WO2025111343A1

WO2025111343A1 - Processes for preparing 6-anilino-2,2,4-trimethyl-1,2-dihydroquinoline

Info

Publication number: WO2025111343A1
Application number: PCT/US2024/056676
Authority: WO
Inventors: Malik Hani AL-AFYOUNI; Judicael Jacques Chapelet; Donald L. Fields Jr.; Jonathan Michael Penney; Ralph Dale Triplett Ii
Original assignee: Flexsys America LP
Current assignee: Flexsys America LP
Priority date: 2023-11-20
Filing date: 2024-11-20
Publication date: 2025-05-30
Anticipated expiration: 2026-05-20

Abstract

The present disclosure provides a method of preparing Compound (1): (Formula1), or salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, diacetone alcohol, a compound of Formula (I): (Formula I), wherein R1 and R2 are as defined in the specification, or a combination thereof; in the presence of a catalyst and, optionally, a solvent; at a reaction temperature of from about 50 °C to about 180 °C. The present disclosure also provides compositions comprising Compound (1), or a salt or solvate thereof, prepared by the methods disclosed herein.

Description

PROCESSES FOR PREPARING 6-ANILINO-2,2,4-TRIMETHYL-l,2- DIHYDROQUINOLINE

BACKGROUND

Field

[0001] The present disclosure provides methods and processes for preparing compounds, e.g., 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline, having anti degradant, e.g., antiozonant, antioxidant and/or antifatigue, properties, that are useful additives for vulcanized rubber articles, compositions comprising elastomers, lubricants, fuels, and other compositions which require such properties or in compositions which are themselves useful as compositions to impart such properties.

Background

[0002] Many materials such as plastics, elastomers, elastomeric products (tires, belts, hoses, bushings, mounts, vibration isolators, etc.), lubricants and petroleum products (such as hydraulic fluids, oils, fuels and oil/fuel additives for automotive and aviation applications) are prone to degradation upon prolonged exposure to light, heat, oxygen, ozone, repetitive mechanical actions and the like.

[0003] Anti degradants useful in the manufacture of articles formed from elastomers, plastics and the like require a very specific combination of qualities that can be difficult to achieve. While the anti degradants must obviously have commercially acceptable efficacy, they must also exhibit that efficacy over prolonged periods of time associated with use of the article, particularly at exposed surfaces of the article where degradation from environmental factors such as light, oxygen and ozone primarily occurs. Just as important to the protection of surface exposed components, efficacy in protecting imbedded components of composite materials from the effects of oxidative aging and repetitive mechanical action are critically important. The anti degradants must achieve these results while not negatively impacting other additives' efficacy or desirable characteristics in the final article. Further, anti degradants which provide or improve the mechanical fatigue life after an article has been in service, aged oxidatively or by exposure to ozone are highly valued since these will inherently improve the useful mechanical service life of article. Consequently, elastomeric articles which undergo repeated mechanical flexure, extension, or compression during service would greatly benefit from such a discovery.

[0004] Articles formed from general purpose elastomers such as natural rubber, in particular tires, are especially prone to degradation from both oxygen and ozone. As discussed in U.S. Patent No. 2,905,654, the effect on rubber from degradation by oxygen is different from the effect from degradation from ozone; however, both effects can be detrimental to tire performance, appearance and life expectancy. Fatigue and crack propagation are also issues of specific concern, in particular for steel belt edge areas and tire sidewalls which are subject to significant stresses and stretching forces while flexed whether inflated, partially inflated, uninflated and throughout the service life of the tire. U.S. Patent No. 8,833,417 describes an antioxidant system that purportedly increases long-term resistance to fatigue and crack propagation over the known antioxidants discussed immediately below.

[0005] Materials with antidegradant efficacy are known in the art for use in tire applications and are commercially available. For example, A,A-disubstituted- paraphenylenediamines such as those sold under the trademark Santoflex® are generally favored by many tire manufacturers for this purpose. EP 3147321 Al discloses rubber compositions, tires, amine compounds, and anti -aging agents, and in particular, a rubber composition that is said to be suitable for use in tread rubber or sidewall rubber of a tire.

[0006] U.S. Patent Nos. 3,362,929 and 3,362,930 disclose 6-anilino-2,2,4-trimethyl-l,2- dihydroquinoline and its corresponding tetrahydroquinoline, methods for preparing these compounds, and their use as an antiozonant in elastomeric compositions. However, there remains a need to develop efficient, scalable, high yield processes for preparing 6-anilino- 2,2,4-trimethyl-l,2-dihydroquinoline and related compounds.

BRIEF SUMMARY

[0007] The present disclosure provides a method of preparing Compound (1):

[0008] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, [0009] with acetone, mesityl oxide, a compound having Formula (I):

^R OR²

(I),

[0010] or a combination thereof;

[0011] in the presence of a catalyst and, optionally, a solvent;

[0012] at a reaction temperature of from about 50 °C to about 300 °C,

[0013] wherein:

[0014] R¹ and R² are independently selected from C1-C12 alkyl; or

[0015] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8- membered heterocyclo.

[0016] The present disclosure also provides a composition comprising Compound (1), or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0017] with acetone, mesityl oxide, a compound having Formula (I):

^R OR²

(I),

[0018] or a combination thereof;

[0019] in the presence of a catalyst and, optionally, a solvent;

[0020] at a reaction temperature of from about 50 °C to about 300 °C,

[0021] wherein:

[0022] R¹ and R² are independently selected from C1-C12 alkyl; or

[0023] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8- membered heterocyclo.

[0024] Additional embodiments and advantages of the disclosure will be set forth, in part, in the description that follows, and will flow from the description, or can be learned by practice of the disclosure. The embodiments and advantages of the disclosure will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.

[0025] It is to be understood that both the foregoing summary and the following detailed description are exemplary and explanatory only, and are not restrictive of the invention as claimed. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Fig. 1 is a line graph depicting the yield of Compound (1) as a function of the molar ratio of acetone to 4-aminodiphenylamine in the initial reaction mixture.

[0027] Fig. 2 is a line graph depicting the yield of Compound (1) as a function of the molar ratio of catalyst to 4-aminodiphenylamine in the initial reaction mixture.

[0028] Fig. 3 is a line graph depicting the yield of Compound (1) as a function of the mole fraction of mesityl oxide in the initial reaction mixture.

[0029] Fig. 4 is a line graph depicting the yield of Compound (1) as a function of reaction temperature.

[0030] Fig. 5 is a LCMS chromatogram representative of a crude reaction mixture obtained from the procedure described in Example 19 comprising Compound (1) and the structures of observed impurities.

DETAILED DESCRIPTION

[0031] The present disclosure provides a method of preparing Compound (1):

[0032] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0033] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

(I),

[0034] or a combination thereof;

[0035] in the presence of a catalyst and, optionally, a solvent;

[0036] at a reaction temperature of from about 50 °C to about 180 °C,

[0037] wherein:

[0038] R¹ and R² are independently selected from C1-C12 alkyl; or

[0039] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8- membered heterocyclo.

[0040] The present disclosure also provides a composition comprising Compound (1):

[0041] or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0042] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R OR²

(I),

[0043] or a combination thereof;

[0044] in the presence of a catalyst and, optionally, a solvent;

[0045] at a reaction temperature of from about 50 °C to about 180 °C,

[0046] wherein:

[0047] R¹ and R² are independently selected from C1-C12 alkyl; or

[0048] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo.

[0049] The present disclosure also provides a method of preparing Compound (1):

[0050] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0051] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

(I),

[0052] or a combination thereof;

[0053] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours; and

[0054] (ii) in the presence of a second catalyst at a reaction temperature of from about

50 °C to about 180 °C for 1-48 hours;

[0055] wherein:

[0056] R¹ and R² are independently selected from C1-C12 alkyl; or [0057] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo.

[0058] The present disclosure also provides a composition comprising Compound (1):

[0059] or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0060] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R ,OR²

(I),

[0061] or a combination thereof;

[0062] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours; and

[0063] (ii) in the presence of a second catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0064] wherein:

[0065] R¹ and R² are independently selected from C1-C12 alkyl; or

[0066] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8- membered heterocyclo.

[0067] In some embodiments, the first catalyst is the same as the second catalyst.

In some embodiments, the first catalyst is different than the second catalyst.

[0068] The present disclosure also provides a method of preparing Compound (1):

[0069] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0070] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R OR²

(I),

[0071] or a combination thereof; [0072] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0073] (ii) in the presence of a second catalyst at a reaction temperature of from about

50 °C to about 180 °C for 1-48 hours; and

[0074] (iii) in the presence of a third catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0075] wherein:

[0076] R¹ and R² are independently selected from C1-C12 alkyl; or

[0077] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo

[0078] The present disclosure also provides a composition comprising Compound (1):

[0079] or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0080] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R ,OR²

(I),

[0081] or a combination thereof;

[0082] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0083] (ii) in the presence of a second catalyst at a reaction temperature of from about

50 °C to about 180 °C for 1-48 hours; and

[0084] (iii) in the presence of a third catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0085] wherein:

[0086] R¹ and R² are independently selected from C1-C12 alkyl; or

[0087] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo. Reagents

[0088] As described herein, Compound (1) is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, diacetone alcohol, a compound of Formula (I), e.g., 2,2-dimethoxypropane, or a combination thereof.

[0089] 4-Aminodiphenylamine has the following structure:

and may also be referred to as d-phenylbenzene-Cd-diamine or 4-ADPA.

[0090] 2-Aminodiphenylamine has the following structure:

[0091] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, further comprises 2-aminodiphenylamine, or a salt or solvate thereof. In some embodiments, the composition comprising 4-aminodiphenylamine comprises from about 95 wt/wt % to about 99.9 wt/wt % of 4-aminodiphenylamine and from about 0.1 wt/wt % to about 2 wt/wt% 2-aminodiphenylamine. In some embodiments, the composition comprising 4-aminodiphenylamine comprises about 99.2 wt/wt % of 4-aminodiphenylamine and about 0.3 wt/wt % 2-aminodiphenylamine.

[0092] Mesityl oxide has the following structure:

and may also be referred to as 4-methylpent-3-en-2-one or 4-methyl-3-penten-2-one.

[0093] Acetone has the following structure:

and may also be referred to as propan-2-one or 2-propanone.

[0094] Compounds having Formula (I) have the following structure:

^R OR²

(I), wherein:

[0095] R¹ and R² are independently selected from C1-C12 alkyl;

[0096] or R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8-membered heterocyclo.

[0097] In some embodiments, R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

[0098] In some embodiments, R¹ and R² are methyl.

[0099] In some embodiments, R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8-membered heterocyclo.

[0100] In some embodiments, R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

[0101] In some embodiments, the compound having Formula (I) is selected from the group consisting of:

[0102] In some embodiments, the compound having Formula (I) is 2,2- dimethoxy prop ane .

[0103] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with acetone.

[0104] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with acetone and mesityl oxide.

[0105] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with mesityl oxide.

[0106] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with a compound having Formula (I).

[0107] In some embodiments, the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 1 : 1, from about 1 : 10 to about 5: 1, from about 1 : 10 to about 10: 1, from about 1 : 10 to about 25: 1, from about 1 : 10 to about 50:1, from about 1 : 1 to about 5: 1, from about 1 : 1 to about 10: 1, from about 1 : 1 to about 25: 1, from about 1 : 1 to about 50: 1, from about 5: 1 to about 10: 1, from about 5: 1 to about 25: 1, from about 5: 1 to about 50: 1, from about 10: 1 to about 25: 1, from about 10: 1 to about 50: 1, or from about 25: 1 to about 50: 1. In some embodiments, the molar ratio of acetone to mesityl oxide is from about 2:1 to about 4:1, from about 2: 1 to about 6:1, from about 2: 1 to about 8:1, from about 2: 1 to about 10:1, from about 4: 1 to about 6:1, from about 4: 1 to about 8:1, from about 4: 1 to about 10:1, from about 6: 1 to about 8:1, from about 6: 1 to about 10: 1, or from about 8:1 to about 10:1. In some embodiments, the molar ratio of acetone to mesityl oxide is from about 2: 1 to about 4:1.

[0108] In some embodiments, the molar ratio of acetone to mesityl oxide is about 1:10, about 1:5, about 1:1, about 2:1, about 4:1, about 3:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 15:1, about 20:1, about 25:1, about 30:1, about 40: 1, or about 50: 1. In some embodiments, the molar ratio of acetone to mesityl oxide is about 3:1.

[0109] In some embodiments, the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 10 to about 1:1, from about 1 : 10 to about 2:1, from about 1:10 to about 10:1, from about 1:10 to about 25:1, from about 1:10 to about 50:1, from about 1:10 to about 75:1, from about 1:10 to about 100:1, from about 1:1 to about 2:1, from about 1 : 1 to about 10:1, from about 1 : 1 to about 25: 1, from about 1 : 1 to about 50:1, from about 1:1 to about 75:1, from about 1:1 to about 100:1, from about 2:1 to about 10:1, from about 2:1 to about 25:1, from about 2:1 to about 50:1, from about 2:1 to about 75:1, from about 2:1 to about 100:1, from about 10:1 to about 25:1, from about 10:1 to about 50:1, from about 10:1 to about 75:1, from about 10:1 to about 100:1, from about 25:1 to about 50:1, from about 25:1 to about 75:1, from about 25:1 to about 100:1, from about 50: 1 to about 75: 1, from about 50: 1 to about 100: 1, or from about 75: 1 to about 100:1. In some embodiments, the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 1 to about 2:1, from about 1 : 1 to about 4:1, from about 1 : 1 to about 6:1, from about 1 : 1 to about 8:1, from about 2: 1 to about 4:1, from about 2: 1 to about 6:1, from about 2: 1 to about 8:1, from about 4: 1 to about 6:1, from about 4: 1 to about 8: 1, or from about 6: 1 to about 8: 1. In some embodiments, the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1:1 to about 4:1.

[0110] In some embodiments, the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 1:1, about 1:2, about 1:4, about 1:8, about 1:10, about 1:25, about 1:50, about 1:75, or about 1 : 100. In some embodiments, the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8:1. [0111] In some embodiments, the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 10 to about 1:1, from about 1 : 10 to about 2:1, from about 1:10 to about 10:1, from about 1:10 to about 25:1, from about 1:10 to about 50:1, from about 1:10 to about 75:1, from about 1:10 to about 100:1, from about 1:1 to about 2:1, from about 1 : 1 to about 10:1, from about 1 : 1 to about 25:1, from about 1 : 1 to about 50:1, from about 1:1 to about 75:1, from about 1:1 to about 100:1, from about 2:1 to about 10:1, from about 2: 1 to about 25: 1, from about 2: 1 to about 50: 1, from about 2: 1 to about 75: 1, from about 2: 1 to about 100: 1, from about 10: 1 to about 25: 1, from about 10:1 to about 50:1, from about 10:1 to about 75:1, from about 10:1 to about 100:1, from about 25:1 to about 50:1, from about 25:1 to about 75:1, from about 25:1 to about 100:1, from about 50: 1 to about 75: 1, from about 50: 1 to about 100: 1, or from about 75: 1 to about 100:1. In some embodiments, the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1:1 to about 2:1, from about 1 : 1 to about 4:1, from about 1 : 1 to about 6:1, from about 1 : 1 to about 8:1, from about 2: 1 to about 4:1, from about 2: 1 to about 6:1, from about 2: 1 to about 8:1, from about 4: 1 to about 6:1, from about 4: 1 to about 8: 1, or from about 6: 1 to about 8: 1. In some embodiments, the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 4: 1 to about 1 : 1/

[0112] In some embodiments, the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 10:1, about 5:1, about 3:1, about 1.5:1, about 1.3:1, about 1.1:1, about 1:1, about 1:2, about 1:4, about 1:8, about 1:10, about 1:25, about 1:50, about 1:75, or about 1:100. In some embodiments, the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2:1.

[0113] In some embodiments, the molar ratio of the compound of Formula (I), e.g., 2,2-dimethoxypropane, to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 10 to about 1:1, from about 1 : 10 to about 2:1, from about 1 : 10 to about 10:1, from about 1:10 to about 25:1, from about 1:10 to about 50:1, from about 1:10 to about 75: 1, from about 1 : 10 to about 100: 1, from about 1 : 1 to about 2:1, from about 1 : 1 to about 10:1, from about 1:1 to about 25:1, from about 1:1 to about 50:1, from about 1:1 to about 75:1, from about 1:1 to about 100:1, from about 2:1 to about 10:1, from about 2:1 to about 25: 1, from about 2: 1 to about 50: 1, from about 2: 1 to about 75: 1, from about 2: 1 to about 100:1, from about 10:1 to about 25:1, from about 10:1 to about 50:1, from about 10:1 to about 75:1, from about 10:1 to about 100:1, from about 25:1 to about 50:1, from about 25: 1 to about 75: 1, from about 25: 1 to about 100:1, from about 50: 1 to about 75: 1, from about 50: 1 to about 100: 1, or from about 75: 1 to about 100:1. In some embodiments, the molar ratio of the compound of Formula (I), e.g., 2,2-dimethoxypropane, to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 :1 to about 2: 1, from about 1 : 1 to about 4: 1, from about 1 : 1 to about 6: 1, from about 1 : 1 to about 8: 1, from about 2: 1 to about 4: 1, from about 2: 1 to about 6: 1, from about 2: 1 to about 8: 1, from about 4: 1 to about 6: 1, from about 4: 1 to about 8: 1, or from about 6: 1 to about 8: 1. In some embodiments, the molar ratio of the compound of Formula (I), e.g., 2,2- dimethoxypropane, to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 1 to about 4: 1.

[0114] In some embodiments, the molar ratio of the compound of Formula (I), e.g., 2,2-dimethoxypropane, to 4-aminodiphenylamine, or a salt or solvate thereof, is about 10: 1, about 9: 1, about 8: 1, about 7:1, about 6: 1, about 5: 1, about 1 : 1, about 1 :2, about 1 :4, about 1 :8, about 1 : 10, about 1 :25, about 1 :50, about 1 :75, or about 1 : 100. In some embodiments, the molar ratio of the compound of Formula (I), e.g., 2,2- dimethoxypropane, to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8: 1.

Catalysts

[0115] In some embodiments, the catalyst comprises a homogeneous catalyst. In some embodiments, the catalyst is a homogeneous catalyst. In some embodiments, the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

[0116] Non-limiting examples of homogeneous catalysts include iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride, boron trifluoride diethyl etherate, boron trifluoride tetrahydrofuran complex, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

[0117] In some embodiments, the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, hydrobromic acid, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride. In some embodiments, the homogeneous catalyst is pyridinium perbromide. In some embodiments, the homogeneous catalyst is methane sulfonic acid. In some embodiments, the homogenous catalyst is hydrobromic acid.

[0118] In some embodiments, the homogeneous catalyst is present in an amount of from about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof. In some embodiments, the homogeneous catalyst is present in an amount of from about 1 mol% to about 5 mol%, from about 1 mol% to about 10 mol%, from about 1 mol% to about 15 mol%, from about 1 mol% to about 20 mol%, from about 1 mol% to about 25 mol%, from about 1 mol% to about 30 mol%, from about 1 mol% to about 40 mol%, from about 5 mol% to about 10 mol%, from about 5 mol% to about 15 mol%, from about 5 mol% to about 20 mol%, from about 5 mol% to about 25 mol%, from about 5 mol% to about 30 mol%, from about 5 mol% to about 40 mol%, from about 5 mol% to about 50 mol%, from about 10 mol% to about 15 mol%, from about 10 mol% to about 20 mol%, from about 10 mol% to about 25 mol%, from about 10 mol% to about 30 mol%, from about 10 mol% to about 40 mol%, from about 10 mol% to about 50 mol%, from about 15 mol% to about 20 mol%, from about 15 mol% to about 25 mol%, from about 15 mol% to about 30 mol%, from about 15 mol% to about 40 mol%, from about 15 mol% to about 50 mol%, from about 20 mol% to about 25 mol%, from about 20 mol% to about 30 mol%, from about 20 mol% to about 40 mol%, from about 20 mol% to about 50 mol%, from about 25 mol% to about 30 mol%, from about 25 mol% to about 40 mol%, from about 25 mol% to about 50 mol%, from about 30 mol% to about 40 mol%, from about 30 mol% to about 50 mol%, or from about 40 mol% to about 50 mol%, relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof. In some embodiments, the homogeneous catalyst is present in an amount of from about 5 mol% to about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0119] In some embodiments, the homogeneous catalyst is present in an amount of about 1 mol%, about 2.5 mol%, about 5 mol%, about 7.5 mol%, about 12.5 mol%, about 15 mol%, about 20 mol%, about 25 mol%, about 30 mol%, about 40 mol%, or about 50 mol%, relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof. In some embodiments, the homogeneous catalyst is present in an amount of about 10 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0120] In some embodiments, the catalyst comprises a heterogeneous catalyst. In some embodiments, the catalyst is a heterogeneous catalyst. In some embodiments, the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

[0121] Non-limiting examples of acid treated resins include a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

[0122] Non-limiting examples of solid-supported acids include micro-meso-macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on y-AhCh, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, para-toluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SChH.

[0123] Non-limiting examples of solid acids include heteropolyacids and metal-organic frameworks.

[0124] Non-limiting examples of base catalysts include ZrCh/MgO.

Solvent

[0125] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted without any additional solvents, i.e., acetone and/or mesityl oxide and/or the compound of Formula (I), e.g., 2,2-dimethoxypropane, are used as both reagents and solvents, i.e., the reaction is run "neat."

[0126] In some embodiments, the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted in the presence of a solvent.

[0127] Non-limiting examples of solvents include methanol, ethanol, isopropanol, acetonitrile, chloroform, di chloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, and combinations thereof. In some embodiments, the solvent is methanol. In some embodiments, the solvent is acetonitrile. In some embodiments, the solvent is chloroform. In some embodiments, the solvent is toluene.

Reaction Conditions

[0128] In some embodiments, the reaction temperature is from about 50 °C to about 60 °C, from about 50 °C to about 70 °C, from about 50 °C to about 80 °C, from about 50 °C to about 100 °C, from about 50 °C to about 105 °C, from about 50 °C to about 120 °C, from about 50 °C to about 140 °C, from about 50 °C to about 160 °C, from about 50 °C to about 180 °C, from about 50 °C to about 200 °C, from about 50 °C to about 250 °C, from about 50 °C to about 300 °C, from about 60 °C to about 70 °C, from about 60 °C to about 80 °C, from about 60 °C to about 100 °C, from about 60 °C to about 120 °C, from about 60 °C to about 140 °C, from about 60 °C to about 160 °C, from about 60 °C to about 180 °C, from about 60 °C to about 200 °C, from about 60 °C to about 250 °C, from about 60 °C to about 300 °C, from about 70 °C to about 80 °C, from about 70 °C to about 100 °C, from about 70 °C to about 120 °C, from about 70 °C to about 140 °C, from about 70 °C to about 160 °C, from about 70 °C to about 180 °C, from about 70 °C to about 200 °C, from about 70 °C to about 250 °C, from about 70 °C to about 300 °C, from about 80 °C to about 100 °C, from about 80 °C to about 120 °C, from about 80 °C to about 140 °C, from about 80 °C to about 160 °C, from about 80 °C to about 180 °C, from about 80 °C to about 200 °C, from about 80 °C to about 250 °C, from about 80 °C to about 300 °C, from about 100 °C to about 120 °C, from about 100 °C to about 140 °C, from about 100 °C to about 160 °C, from about 100 °C to about 180 °C, from about 100 °C to about 200 °C, from about 100 °C to about 250 °C, from about 100 °C to about 300 °C, from about 120 °C to about 140 °C, from about 120 °C to about 160 °C, from about 120 °C to about 180 °C, from about 120 °C to about 200 °C, from about 120 °C to about 250 °C, from about 120 °C to about 300 °C, from about 140 °C to about 160 °C, from about 140 °C to about 180 °C, from about 140 °C to about 200 °C, from about 140 °C to about 250 °C, from about 140 °C to about 300 °C, from about 160 °C to about 180 °C, from about 160 °C to about 200 °C, from about 160 °C to about 250 °C, from about 160 °C to about 300 °C, from about 180 °C to about 200 °C, from about 180 °C to about 250 °C, from about 180 °C to about 300 °C, from about 200 °C to about 250 °C, from about 200 °C to about 300 °C, or from about 250 °C to about 300 °C. In some embodiments, the reaction temperature is from about 80 °C to about 100 °C.

[0129] In some embodiments, the reaction temperature is about 50 °C, about 60 °C, about 70 °C, about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 110 °C, about 120 °C, about 130 °C, about 140 °C, about 150 °C, about 160 °C, about 170 °C, about 180 °C, about 190 °C, about 200 °C, about 225 °C, about 250 °C, about 275 °C, or about 300 °C. In some embodiments, the reaction temperature is about 90 °C.

[0130] In some embodiments, the reacting is performed for from about 0.5 h to about 2 h, from about 0.5 h to about 6 h, from about 0.5 h to about 12 h, from about 0.5 h to about 18 h, from about 0.5 h to about 24 h, from about 0.5 h to about 36 h, from about 0.5 h to about 48 h, from about 2 h to about 6 h, from about 2 h to about 12 h, from about 2 h to about 18 h, from about 2 h to about 24 h, from about 2 h to about 36 h, from about 2 h to about 48 h, from about 6 h to about 12 h, from about 6 h to about 18 h, from about 6 h to about 24 h, from about 6 h to about 36 h, from about 6 h to about 48 h, from about 12 h to about 18 h, from about 12 h to about 24 h, from about 12 h to about 36 h, from about 12 h to about 48 h, from about 18 h to about 24 h, from about 18 h to about 36 h, from about 18 h to about 48 h, from about 24 h to about 36 h, from about 24 h to about 48 h, or from about 36 h to about 48 h. In some embodiments, the reacting is performed for from about 0.5 h to about 24 h.

[0131] In some embodiments, the reacting is performed for about 0.5 h, about 1 h, about 2 h, about 4 h, about 6 h, about 8 h, about 12 h, about 16 h, about 18 h, about 24 h, about 36 h, or about 48 h. In some embodiments, the reacting is performed for about 12 h.

[0132] In some embodiments, the reacting is performed at elevated pressure. In some embodiments, the reacting is performed in a pressurized vessel, e.g., an autoclave.

Reaction Performance

[0133] In some embodiments, the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 50%, from about 40% to about 60%, from about 40% to about 70%, from about 40% to about 80%, from about 40% to about 90%, from about 50% to about 60%, from about 50% to about 70%, from about 50% to about 80%, from about 50% to about 90%, from about 50% to about 100%, from about 60% to about 70%, from about 60% to about 80%, from about 60% to about 90%, from about 60% to about 100%, from about 70% to about 80%, from about 70% to about 90%, from about 70% to about 100%, from about 75% to about 100%, from about 80% to about 90%, from about 80% to about 100%, or from about 90% to about 100%, based on the amount of unreacted 4-aminodiphenylamine. In some embodiments, the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0134] In some embodiments, the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 85%, about 90%, about 95%, about 98%, about 99%, or about 100%, based on the amount of unreacted 4-aminodiphenylamine. In some embodiments, the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is about 80%, based on the amount of unreacted 4-aminodiphenylamine.

[0135] In some embodiments, the purified yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 60%, from about 45% to about 70%, from about 45% to about 80%, from about 45% to about 85%, from about 45% to about 90%, from about 45% to about 95%, from about 45% to about 99%, from about 60% to about 70%, from about 60% to about 80%, from about 60% to about 85%, from about 60% to about 90%, from about 60% to about 95%, from about 60% to about 99%, from about 65% to about 99%, from about 70% to about 80%, from about 70% to about 85%, from about 70% to about 90%, from about 70% to about 95%, from about 70% to about 99%, from about 80% to about 85%, from about 80% to about 90%, from about 80% to about 95%, from about 80% to about 99%, from about 85% to about 90%, from about 85% to about 95%, from about 85% to about 99%, from about 85% to about 90%, from about 85% to about 95%, from about 85% to about 99%, from about 90% to about 95%, from about 90% to about 99%, or from about 95% to about 99%, based on the starting amount of 4-aminodiphenylamine. In some embodiments, the purified yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0136] In some embodiments, the purified yield of Compound (1), or a salt or solvate thereof, is about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 90%, about 95%, about 97%, about 98%, or about 99%, based on the starting amount of 4-aminodiphenylamine. In some embodiments, the purified yield of Compound (1), or a salt or solvate thereof, is about 85% based on the starting amount of 4-aminodiphenylamine. [0137] In some embodiments, 30% to about 95%, from about 40% to about 50%, from about 40% to about 60%, from about 40% to about 70%, from about 40% to about 80%, from about 40% to about 90%, from about 40% to about 95%, from about 50% to about 60%, from about 50% to about 70%, from about 50% to about 80%, from about 50% to about 90%, from about 50% to about 95%, from about 60% to about 70%, from about 60% to about 80%, from about 60% to about 90%, from about 60% to about 95%, from about 70% to about 80%, from about 70% to about 90%, from about 75% to about 90%, from about 70% to about 95%, from about 80% to about 90%, from about 80% to about 95%, or from about 90% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof. In some embodiments, from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0138] In some embodiments, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof. In some embodiments, about 80% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

Additional Reaction Products

[0139] In some embodiments, the crude reaction product comprises an oligomer of

Compound (1). In some embodiments, the oligomer of Compound (1) has the structure:

wherein n is an integer from 0 to 10. In some embodiments, n is an integer from 0 to 3. [0140] In some embodiments, the oligomer of Compound (1) has a molecular weight that is a multiple of about 264 g/mol, e.g., about 528 g/mol, about 792 g/mol, about 1,056 g/mol, or about 1,320 g/mol.

[0141] In some embodiments, the selectivity for Compound (1) over other reaction products is from about 55% to about 99%. In some embodiments, the selectivity for Compound (1) over other reaction products is from about 55% to about 60%, from about 55% to about 70%, from about 55% to about 80%, from about 55% to about 90%, from about 55% to about 95%, from about 60% to about 70%, from about 60% to about 80%, from about 60% to about 90%, from about 60% to about 95%, from about 60% to about 99%, from about 70% to about 80%, from about 70% to about 90%, from about 70% to about 95%, from about 70% to about 99%, from about 80% to about 90%, from about 80% to about 95%, from about 80% to about 99%, from about 90% to about 95%, from about 90% to about 99%, or from about 95% to about 99%.

[0142] In some embodiments, the selectivity for Compound (1) over other reaction products is about 90%. In some embodiments, the selectivity for Compound (1) over other reaction products is about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 95%, about 97%, about 98%, or about 99%.

Further Reaction

[0143] In some embodiments, Compound (1), or a salt or solvate thereof, is reduced to produce Compound (2):

or a salt, solvate, or stereoisomer thereof.

[0144] In some embodiments, Compound (1) is reduced with hydrogen in the presence of a metal catalyst. In some embodiments, metal catalyst comprises nickel, platinum, palladium, rhodium, or ruthenium. In some embodiments, the metal catalyst comprises palladium, e.g., the metal catalyst is palladium on carbon (Pd/C), e.g., the metal catalyst is 10% Pd/C.

[0145] In some embodiments, Compound (1) is reduced using a hydride donor catalyst, e.g., triethylsilane/trifluoroacetic acid. [0146] Compound (1) may also be reduced using other reduction/hydrogenation methods known in the art.

[0147] In some embodiments, Compound (2), or a salt, solvate, or stereoisomer thereof, is oxidized to produce Compound (3):

or a salt, solvate, or stereoisomer thereof. Compound (2) may be oxidized using methods known in the art.

[0148] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (5):

or a salt or solvate thereof.

[0149] In some embodiments, the composition comprises less than 10 wt% of Compound (5). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (5).

[0150] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (6):

[0151] In some embodiments, the composition comprises less than 10 wt% of Compound (6). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (6).

[0152] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (7):

(7), or a salt, solvate, or stereoisomer thereof.

[0153] In some embodiments, the composition comprises less than 10 wt% of Compound (7). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (7).

[0154] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (4):

or a salt, solvate, or stereoisomer thereof.

[0155] In some embodiments, the composition comprises less than 10 wt% of Compound (4). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (4).

[0156] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (8):

or a salt, solvate, or stereoisomer thereof.

[0157] In some embodiments, the composition comprises less than 10 wt% of Compound (8). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (8).

[0158] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (9):

(9), or a salt or solvate thereof. [0159] In some embodiments, the composition comprises less than 10 wt% of Compound (9). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (9).

[0160] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (10):

or a salt, solvate, or stereoisomer thereof.

[0161] In some embodiments, the composition comprises less than 10 wt% of Compound

(10). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (10).

[0162] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (11):

H I ct.ib

H (11), or a salt or solvate thereof.

[0163] In some embodiments, the composition comprises less than 10 wt% of Compound

(11). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (11).

[0164] In some embodiments, the composition comprising Compound (1) prepared as described herein further comprises Compound (5) and Compound (11).

[0165] In some embodiments, the composition comprises less than 10 wt% of Compound (5) and less than 10 wt% of Compound (11). In some embodiments, the composition comprises less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (5); and less than 5 wt%, less than 3 wt%, less than 1 wt%, or less than 0.5 wt% of Compound (11).

Embodiments

[0166] The disclosure also provides the following numbered embodiments.

[0167] Embodiment 1. A method of preparing Compound (1):

(1),

[0168] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0169] with acetone, mesityl oxide, a compound having Formula (I):

^R OR²

(I),

[0170] or a combination thereof;

[0171] in the presence of a catalyst and, optionally, a solvent;

[0172] at a reaction temperature of from about 50 °C to about 300 °C,

[0173] wherein:

[0174] R¹ and R² are independently selected from C1-C12 alkyl; or

[0175] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8-membered heterocyclo.

[0176] Embodiment 2. The method of Embodiment 1, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

[0177] Embodiment 3. The method of Embodiment 2, wherein R¹ and R² are methyl.

[0178] Embodiment 4. The method of Embodiment 1, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

[0179] Embodiment 5. The method of Embodiment 1, wherein the compound having Formula (I) is selected from the group consisting of:

[0180] Embodiment 6. The method of Embodiment 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone. [0181] Embodiment 7. The method of Embodiment 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone and mesityl oxide.

[0182] Embodiment 8. The method of Embodiment 7, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

[0183] Embodiment 9. The method of Embodiment 8, wherein the molar ratio of acetone to mesityl oxide is about 4: 1 to about 8: 1.

[0184] Embodiment 10. The method of any one of Embodiments 6-9, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2: 1 to about 100: 1.

[0185] Embodiment 11. The method of Embodiment 10, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8: 1.

[0186] Embodiment 12. The method of Embodiment 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide.

[0187] Embodiment 13. The method of any one of Embodiments 7-12, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 1 to about 100:1.

[0188] Embodiment 14. The method of Embodiment 13, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2: 1.

[0189] Embodiment 15. The method of any one of Embodiments 1-14, wherein the catalyst is a homogeneous catalyst.

[0190] Embodiment 16. The method of Embodiment 15, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

[0191] Embodiment 17. The method of Embodiment 15, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

[0192] Embodiment 18. The method of Embodiment 17, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, hydrobromic acid, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride.

[0193] Embodiment 19. The method of Embodiment 18, wherein the homogeneous catalyst is pyridinium perbromide or hydrobromic acid.

[0194] Embodiment 20. The method of any one of Embodiments 1-19, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0195] Embodiment 21. The method of Embodiment 20, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 25 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0196] Embodiment 22. The method of Embodiment 21, wherein the homogeneous catalyst is present in an amount of about 10 mol% to about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0197] Embodiment 23. The method of any one of Embodiments 1-14, wherein the catalyst is a heterogeneous catalyst.

[0198] Embodiment 24. The method of Embodiment 23, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

[0199] Embodiment 25. The method of Embodiment 24, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

[0200] Embodiment 26. The method of Embodiment 24, wherein the solid- supported acid is micro-meso-macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn2+, Sn2+, and Cu2+ exchanged tungstophosphoric acid (TP A) supported on y-A12O3, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, paratoluenesulfonic acid (p-TSA)/ZnC12, or WO3/activated carbon/SO3H.

[0201] Embodiment 27. The method of Embodiment 24, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, EhSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine.

[0202] Embodiment 28. The method of Embodiment 24, wherein the solid acid is a heteropolyacid or a metal-organic framework.

[0203] Embodiment 29. The method of Embodiment 24, wherein the base catalyst is

ZrCh/MgO.

[0204] Embodiment 30. The method of any one of Embodiments 1-29, wherein the reaction temperature is from about 50 °C to about 180 °C.

[0205] Embodiment 31. The method of Embodiment 30, wherein the reaction temperature is from about 85 °C to about 105 °C.

[0206] Embodiment 32. The method of any one of Embodiments 1-31, wherein the method comprises reacting in the presence of a solvent.

[0207] Embodiment 33. The method of Embodiment 32, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

[0208] Embodiment 34. The method of any one of Embodiments 1-33, wherein the reacting is performed for from about 0.5 h to about 24 h.

[0209] Embodiment 35. The method of any one of Embodiments 1-34, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0210] Embodiment 36. The method of Embodiment 35, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0211] Embodiment 37. The method of any one of Embodiments 1-36, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4-aminodiphenylamine. [0212] Embodiment 38. The method of Embodiment 37, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0213] Embodiment 39. The method of any one of Embodiments 1-38, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0214] Embodiment 40. The method of Embodiment 39, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0215] Embodiment 41. The method of any one of Embodiments 1-40, wherein the crude reaction product comprises an oligomer of Compound (1).

[0216] Embodiment 42. The method of any one of Embodiments 1-41, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%.

[0217] Embodiment 43. The method of Embodiment 42, wherein the selectivity for

Compound (1) over other reaction products is from about 65% to about 90%.

[0218] Embodiment 44. The method of any one of Embodiments 1-43, wherein the method further comprises reducing Compound (1), or a salt or solvate thereof, to produce Compound (2):

or a salt, solvate, or stereoisomer thereof.

[0219] Embodiment 45. The method of Embodiment 44, wherein the reducing comprises reacting Compound (1), or a salt or solvate thereof, with hydrogen in the presence of a metal catalyst, to produce Compound (2), or a salt, solvate, or stereoisomer thereof.

[0220] Embodiment 46. The method of Embodiment 45, wherein the metal catalyst comprises nickel, platinum, palladium, rhodium, or ruthenium.

[0221] Embodiment 47. The method of any one of Embodiments 44-46, wherein the method further comprises oxidizing Compound (2), or a salt, solvate, or stereoisomer thereof, to produce Compound (3):

(3), or a salt, solvate, or stereoisomer thereof.

[0222] Embodiment 48. The method of any one of Embodiments 1-43, wherein the method further comprises oxidizing Compound (1), or a salt or solvate thereof, to produce Compound (4):

or a salt, solvate, or stereoisomer thereof.

[0223] Embodiment 49. The method of any one of Embodiments 1-48, wherein the composition comprising 4-aminodiphenylamine comprises about 99.2 wt/wt % of 4- aminodiphenylamine and about 0.3 wt/wt % 2-aminodiphenylamine.

[0224] Embodiment 50. The method of any one of Embodiments 1-22 or 30-49, wherein the catalyst is not hydrochloric acid or iodine.

[0225] Embodiment 51. A composition comprising Compound (1):

[0226] or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0227] with acetone, mesityl oxide, a compound having Formula (I):

(I),

[0228] or a combination thereof;

[0229] in the presence of a catalyst and, optionally, a solvent;

[0230] at a reaction temperature of from about 50 °C to about 300 °C,

[0231] wherein:

[0232] R¹ and R² are independently selected from C1-C12 alkyl; or

[0233] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to

8-membered heterocyclo. [0234] Embodiment 52. The composition comprising Compound (1) of Embodiment 51 further comprising Compound (5):

or a salt or solvate thereof.

[0235] Embodiment 53. The composition comprising Compound (1) of Embodiment

52, wherein the composition comprises less than 10 wt% of Compound (5).

[0236] Embodiment 54. The composition comprising Compound (1) of any one of

Embodiments 51-54, further comprising Compound (6):

or a salt, solvate, or stereoisomer thereof.

[0237] Embodiment 55. The composition comprising Compound (1) of Embodiment

54, wherein the composition comprises less than 10 wt% of Compound (6).

[0238] Embodiment 56. The composition comprising Compound (1) of any one of

Embodiments 51-55, further comprising Compound (7):

or a salt, solvate, or stereoisomer thereof.

[0239] Embodiment 57. The composition comprising Compound (1) of Embodiment

56, wherein the composition comprises less than 10 wt% of Compound (7).

[0240] Embodiment 58. The composition comprising Compound (1) of any one of

Embodiments 51-57, further comprising Compound (4):

or a salt, solvate, or stereoisomer thereof.

[0241] Embodiment 59. The composition comprising Compound (1) of Embodiment

58, wherein the composition comprises less than 10 wt% of Compound (4). [0242] Embodiment 60. The composition comprising Compound (1) of any one of Embodiments 51-59, further comprising Compound (8):

or a salt, solvate, or stereoisomer thereof.

[0243] Embodiment 61. The composition comprising Compound (1) of Embodiment

60, wherein the composition comprises less than 10 wt% of Compound (8).

[0244] Embodiment 62. The composition comprising Compound (1) of any one of

Embodiments 51-61, further comprising Compound (9):

or a salt or solvate thereof.

[0245] Embodiment 63. The composition comprising Compound (1) of Embodiment

62, wherein the composition comprises less than 10 wt% of Compound (9).

[0246] Embodiment 64. The composition comprising Compound (1) of any one of

Embodiments 51-63, further comprising Compound (10):

or a salt, solvate, or stereoisomer thereof.

[0247] Embodiment 65. The composition comprising Compound (1) of Embodiment

64, wherein the composition comprises less than 10 wt% of Compound (10).

[0248] Embodiment 66. The composition comprising Compound (1) of any one of

Embodiments 51-65, further comprising Compound (11):

or a salt or solvate thereof.

[0249] Embodiment 67. The composition of Embodiment 66, wherein the composition comprises less than 10 wt% of Compound (11).

[0250] Embodiment 68. The composition of any one of Embodiments 51-67, wherein the composition is prepared by reacting the composition comprising 4- aminodiphenylamine, or a salt or solvate thereof, with the compound of Formula (I).

[0251] Embodiment 69. The composition of Embodiment 68, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

[0252] Embodiment 70. The composition of Embodiment 69, wherein R¹ and R² are methyl.

[0253] Embodiment 71. The composition of Embodiment 68, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

[0254] Embodiment 72. The composition of Embodiment 68, wherein the compound having Formula (I) is selected from the group consisting of:

[0255] Embodiment 73. The composition of any one of Embodiments 51-67, wherein the composition is prepared by reacting the composition comprising 4- aminodiphenylamine, or a salt or solvate thereof, with acetone.

[0256] Embodiment 74. The composition of any one of Embodiments 51-67, wherein the composition is prepared by reacting the composition comprising 4- aminodiphenylamine, or a salt or solvate thereof, with acetone and mesityl oxide.

[0257] Embodiment 75. The composition of Embodiment 74, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

[0258] Embodiment 76. The composition of Embodiment 75, wherein the molar ratio of acetone to mesityl oxide is about 4: 1 to about 8:1. [0259] Embodiment 77. The composition of any one of Embodiments 73-76, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2: 1 to about 100: 1.

[0260] Embodiment 78. The composition of Embodiment 77, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8: 1.

[0261] Embodiment 79. The composition of any one of Embodiments 51-67, wherein the composition is preparing by reacting the composition comprising 4- aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide.

[0262] Embodiment 80. The composition of any one of Embodiments 74-79, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 1 to about 100: 1.

[0263] Embodiment 81. The composition of Embodiment 80, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2:1.

[0264] Embodiment 82. The composition of any one of Embodiments 51-81, wherein the catalyst is a homogeneous catalyst.

[0265] Embodiment 83. The composition of Embodiment 82, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

[0266] Embodiment 84. The composition of Embodiment 82, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

[0267] Embodiment 85. The composition of Embodiment 84, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride. [0268] Embodiment 86. The composition of Embodiment 84, wherein the homogeneous catalyst is pyridinium perbromide.

[0269] Embodiment 87. The composition of any one of Embodiments 82-86, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0270] Embodiment 88. The composition of Embodiment 87, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0271] Embodiment 89. The composition of Embodiment 88, wherein the homogeneous catalyst is present in an amount of about 10 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0272] Embodiment 90. The composition of any one of Embodiments 51-81, wherein the catalyst is a heterogeneous catalyst.

[0273] Embodiment 91. The composition of Embodiment 90, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

[0274] Embodiment 92. The composition of Embodiment 91, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

[0275] Embodiment 93. The composition of Embodiment 91, wherein the solid- supported acid is micro-meso-macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on y-AhCh, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, paratoluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SOsH.

[0276] Embodiment 94. The composition of Embodiment 91, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, EhSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine. [0277] Embodiment 95. The composition of Embodiment 91, wherein the solid acid is a heteropolyacid or a metal-organic framework.

[0278] Embodiment 96. The composition of Embodiment 91, wherein the base catalyst is ZrCh/MgO.

[0279] Embodiment 97. The composition of any one of Embodiments 51-96, wherein the reaction temperature is from about 50 °C to about 180 °C.

[0280] Embodiment 98. The composition of Embodiment 97, wherein the reaction temperature is from about 85 °C to about 95 °C.

[0281] Embodiment 99. The composition of any one of Embodiments 51-98, wherein the compositing is prepared by reacting a composition comprising 4- aminodiphenylamine, or a salt or solvate thereof, in the presence of a solvent.

[0282] Embodiment 100. The composition of Embodiment 99, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

[0283] Embodiment 101. The composition of any one of Embodiments 51-98, wherein the reacting is performed for from about 0.5 h to about 24 h.

[0284] Embodiment 102. The composition of any one of Embodiments 51-101, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4- aminodiphenylamine.

[0285] Embodiment 103. The composition of Embodiment 102, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0286] Embodiment 104. The composition of any one of Embodiments 51-103, wherein the yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0287] Embodiment 105. The composition of Embodiment 104, wherein the yield of

Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine. [0288] Embodiment 106. The composition of any one of Embodiments 51-105, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0289] Embodiment 107. The composition of Embodiment 106, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0290] Embodiment 108. The composition of any one of Embodiments 51-107, wherein the crude reaction product comprises an oligomer of Compound (1).

[0291] Embodiment 109. The composition of any one of Embodiments 51-108, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%.

[0292] Embodiment 110. The composition of Embodiment 109, wherein the selectivity for Compound (1) over other reaction products is from about 65% to about 90%.

[0293] Embodiment 111. A composition comprising Compound (2):

or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by reducing the composition of any one of Embodiments 51-110.

[0294] Embodiment 112. The composition of Embodiment 111, wherein the reducing comprises reacting Compound (1), or a salt or solvate thereof, with hydrogen in the presence of a metal catalyst, to produce Compound (2), or a salt, solvate, or stereoisomer thereof.

[0295] Embodiment 113. The composition of Embodiment 112, wherein the metal catalyst comprises nickel, platinum, palladium, rhodium, or ruthenium.

[0296] Embodiment 114. A composition comprising Compound (3):

or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by oxidizing the composition of any one of Embodiments 111-113.

[0297] Embodiment 115. A composition comprising Compound (4):

(4), or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by oxidizing the composition of any one of Embodiments 51-110.

[0298] Embodiment 116. The composition of any one of Embodiments 51-115, wherein the composition comprising 4-aminodiphenylamine comprises about 99.2 wt/wt % of 4-aminodiphenylamine and about 0.3 wt/wt % 2-aminodiphenylamine.

[0299] Embodiment 117. The composition of any one of Embodiments 51-81 or 90- 116, wherein the catalyst is not hydrochloric acid or iodine.

[0300] The disclosure also provides the following numbered embodiments relating to two-stage reactions, wherein a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I), or a combination thereof, for a period of time in the presence a first catalyst and for a period of time in the presence of a second catalyst to give Compound (1).

[0301] Embodiment 1 A. A method of preparing Compound (1):

[0302] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0303] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R OR²

(I), or a combination thereof;

[0304] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours; and

[0305] (ii) in the presence of a second catalyst at a reaction temperature of from about

50 °C to about 180 °C for 1-48 hours;

[0306] wherein:

[0307] R¹ and R² are independently selected from C1-C12 alkyl; or [0308] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo.

[0309] Embodiment 2 A. The method of Embodiment 1 A, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

[0310] Embodiment 3 A. The method of Embodiment 2 A, wherein R¹ and R² are methyl.

[0311] Embodiment 4 A. The method of Embodiment 1 A, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

[0312] Embodiment 5 A. The method of Embodiment 1 A, wherein the compound having Formula (I) is selected from the group consisting of:

[0313] Embodiment 6 A. The method of Embodiment 1 A, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone.

[0314] Embodiment 7 A. The method of Embodiment 1 A, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone and mesityl oxide.

[0315] Embodiment 8 A. The method of Embodiment 7 A, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

[0316] Embodiment 9 A. The method of Embodiment 8 A, wherein the molar ratio of acetone to mesityl oxide is about 4: 1 to about 8: 1.

[0317] Embodiment 10 A. The method of any one of Embodiments 6 A- 9 A, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2: 1 to about 100: 1.

[0318] Embodiment 11 A. The method of Embodiment 10 A, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8: 1.

[0319] Embodiment 12 A. The method of Embodiment 1 A, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide. [0320] Embodiment 13 A. The method of any one of Embodiments 7 A- 12 A, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1 : 1 to about 100: 1.

[0321] Embodiment 14 A. The method of Embodiment 13 A, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2: 1.

[0322] Embodiment 15 A. The method of any one of Embodiments 1 A- 14 A, wherein the first catalyst or second catalyst comprises a homogeneous catalyst.

[0323] Embodiment 16 A. The method of Embodiment 15 A, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

[0324] Embodiment 17 A. The method of Embodiment 15 A, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

[0325] Embodiment 18 A. The method of Embodiment 17 A, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, hydrobromic acid, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride.

[0326] Embodiment 19 A. The method of Embodiment 18 A, wherein the homogeneous catalyst is hydrobromic acid.

[0327] Embodiment 20 A. The method of any one of Embodiments 1 A- 19 A, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0328] Embodiment 21 A. The method of Embodiment 20 A, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 25 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof. [0329] Embodiment 22 A. The method of Embodiment 21 A, wherein the homogeneous catalyst is present in an amount of about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0330] Embodiment 23 A. The method of any one of Embodiments 1 A- 14 A, wherein the first catalyst or second catalyst comprises a heterogeneous catalyst.

[0331] Embodiment 24 A. The method of Embodiment 23 A, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

[0332] Embodiment 25 A. The method of Embodiment 24 A, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

[0333] Embodiment 26 A. The method of Embodiment 24 A, wherein the solid- supported acid is micro-meso-macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on y-AhCh, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, paratoluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SOsH.

[0334] Embodiment 27 A. The method of Embodiment 24 A, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, EhSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine.

[0335] Embodiment 28 A. The method of Embodiment 24 A, wherein the solid acid is a heteropolyacid or a metal-organic framework.

[0336] Embodiment 29 A. The method of Embodiment 24 A, wherein the base catalyst is ZrCh/MgO.

[0337] Embodiment 30 A. The method of any one of Embodiments 1 A-29 A, wherein the reaction temperature is from about 50 °C to about 180 °C.

[0338] Embodiment 31 A. The method of Embodiment 30 A, wherein the reaction temperature is from about 95 °C to about 105 °C. [0339] Embodiment 32 A. The method of any one of Embodiments 1 A-31 A, wherein the method comprises reacting in the presence of a solvent.

[0340] Embodiment 33 A. The method of Embodiment 32 A, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

[0341] Embodiment 34 A. The method of any one of Embodiments 1 A-33 A, wherein the reacting is performed for from about 0.5 h to about 24 h.

[0342] Embodiment 35 A. The method of any one of Embodiments 1 A-34 A, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0343] Embodiment 36 A. The method of Embodiment 35 A, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0344] Embodiment 37 A. The method of any one of Embodiments 1 A-36, A wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0345] Embodiment 38 A. The method of Embodiment 37 A, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0346] Embodiment 39 A. The method of any one of Embodiments 1 A-38 A, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0347] Embodiment 40 A. The method of Embodiment 39 A, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0348] Embodiment 41 A. The method of any one of Embodiments 1 A-40 A, wherein the crude reaction product comprises an oligomer of Compound (1).

[0349] Embodiment 42 A. The method of any one of Embodiments 1 A-41 A, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%. [0350] Embodiment 43 A. The method of Embodiment 42 A, wherein the selectivity for Compound (1) over other reaction products is from about 65% to about 90%.

[0351] The disclosure also provides the following numbered embodiments relating to three-stage reactions, wherein a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, is reacted with acetone, mesityl oxide, a compound having Formula (I), or a combination thereof, for a period of time in the presence a first catalyst, for a period of time in the presence of a second catalyst, and for a period of time in the presence of a third catalyst to give Compound (1).

[0352] Embodiment I B. A method of preparing Compound (1):

[0353] or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof,

[0354] with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I):

^R OR²

(I),

[0355] or a combination thereof;

[0356] (i) in the presence of a first catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0357] (ii) in the presence of a second catalyst at a reaction temperature of from about

50 °C to about 180 °C for 1-48 hours; and

[0358] (iii) in the presence of a third catalyst at a reaction temperature of from about 50 °C to about 180 °C for 1-48 hours;

[0359] wherein:

[0360] R¹ and R² are independently selected from C1-C12 alkyl; or

[0361] R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo.

[0362] Embodiment 2 B. The method of Embodiment 1 B, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

[0363] Embodiment 3 B. The method of Embodiment 2 B, wherein R¹ and R² are methyl. [0364] Embodiment 4 B. The method of Embodiment 1 B, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

[0365] Embodiment 5 B. The method of Embodiment 1 B, wherein the compound having Formula (I) is selected from the group consisting of:

[0366] Embodiment 6 B. The method of Embodiment 1 B, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone.

[0367] Embodiment 7 B. The method of Embodiment 1 B, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone and mesityl oxide.

[0368] Embodiment 8 B. The method of Embodiment 7 B, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

[0369] Embodiment 9 B. The method of Embodiment 8 B, wherein the molar ratio of acetone to mesityl oxide is about 4: 1 to about 8:1.

[0370] Embodiment 10 B. The method of any one of Embodiments 6 B-9 B, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2: 1 to about 100: 1.

[0371] Embodiment 11 B. The method of Embodiment 10 B, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8:1.

[0372] Embodiment 12 B. The method of Embodiment 1 B, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide.

[0373] Embodiment 13 B. The method of any one of Embodiments 7 B-12 B, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1:1 to about 100:1.

[0374] Embodiment 14 B. The method of Embodiment 13 B, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2:1. [0375] Embodiment 15 B. The method of any one of Embodiments 1 B-14 B, wherein the first catalyst, second catalyst, and/or third catalyst comprises a homogeneous catalyst.

[0376] Embodiment 16 B. The method of Embodiment 15 B, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

[0377] Embodiment 17 B. The method of Embodiment 15 B, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

[0378] Embodiment 18 B. The method of Embodiment 17 B, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, hydrobromic acid, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride.

[0379] Embodiment 19 B. The method of Embodiment 18 B, wherein the homogeneous catalyst is hydrobromic acid.

[0380] Embodiment 20 B. The method of any one of Embodiments 1 B-19 B, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0381] Embodiment 21 B. The method of Embodiment 20 B, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 25 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0382] Embodiment 22 B. The method of Embodiment 21 B, wherein the homogeneous catalyst is present in an amount of about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

[0383] Embodiment 23 B. The method of any one of Embodiments 1 B-14 B, wherein the first catalyst, second catalyst, and/or third catalyst comprises a heterogeneous catalyst. [0384] Embodiment 24 B. The method of Embodiment 23 B, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

[0385] Embodiment 25 B. The method of Embodiment 24 B, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

[0386] Embodiment 26 B. The method of Embodiment 24 B, wherein the solid- supported acid is micro-meso-macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on y-AhCh, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, paratoluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SOsH.

[0387] Embodiment 27 B. The method of Embodiment 24 B, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, EhSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine.

[0388] Embodiment 28 B. The method of Embodiment 24 B, wherein the solid acid is a heteropolyacid or a metal-organic framework.

[0389] Embodiment 29 B. The method of Embodiment 24 B, wherein the base catalyst is ZrCh/MgO.

[0390] Embodiment 30 B. The method of any one of Embodiments 1 B-29 B, wherein the reaction temperature is from about 50 °C to about 180 °C.

[0391] Embodiment 31 B. The method of Embodiment 30 B, wherein the reaction temperature is from about 95°C to about 105 °C.

[0392] Embodiment 32 B. The method of any one of Embodiments 1 B-31 B, wherein the method comprises reacting in the presence of a solvent.

[0393] Embodiment 33 B. The method of Embodiment 32 B, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

[0394] Embodiment 34 B. The method of any one of Embodiments 1 B-33 B, wherein the reacting is performed for from about 0.5 h to about 24 h.

[0395] Embodiment 35 B. The method of any one of Embodiments 1 B-34 B, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0396] Embodiment 36 B. The method of Embodiment 35 B, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

[0397] Embodiment 37 B. The method of any one of Embodiments 1 B-36, B wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0398] Embodiment 38 B. The method of Embodiment 37 B, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

[0399] Embodiment 39 B. The method of any one of Embodiments 1 B-38 B, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0400] Embodiment 40 B. The method of Embodiment 39 B, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

[0401] Embodiment 41 B. The method of any one of Embodiments 1 B-40 B, wherein the crude reaction product comprises an oligomer of Compound (1).

[0402] Embodiment 42 B. The method of any one of Embodiments 1 B-41 B, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%.

[0403] Embodiment 43 B. The method of Embodiment 42 B, wherein the selectivity for Compound (1) over other reaction products is from about 65% to about 90%.

Definitions

[0404] The term "alkyl" as used herein by itself or as part of another group refers to a straight- or branched-chain aliphatic hydrocarbon containing one to twelve carbon atoms, i.e., a C1-C12 alkyl, or the number of carbon atoms designated, e.g., C1-C3 alkyl such as methyl, ethyl, propyl, or isopropyl; a C1-C4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or t-butyl; and so on. In one embodiment the alkyl is a straight-chain alkyl. In another embodiment, the alkyl is a branched-chain alkyl. In one embodiment, the alkyl is a Ci-Cs alkyl. In another embodiment, the alkyl is a Ci-Ce alkyl. In another embodiment, the alkyl is a C1-C4 alkyl. In another embodiment, the alkyl is a C1-C3 alkyl. Non-limiting exemplary C1-C12 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, ec-butyl, /e/7-butyl, zso-butyl, 3-pentyl, hexyl, heptyl, octyl, nonyl, and decyl.

[0405] The term "heterocyclo" as used herein by itself or as part of another group refers to a saturated monocyclic group containing five to eight ring members, i.e., a 5- to 8- membered heterocyclo, comprising at least three carbon atoms and two oxygen atoms. The heterocyclo- may be unsubstituted or substituted with one or more, e.g., one, two, three, or four, C1-C4 alkyl groups. Non-limiting exemplary 5- to 8-membered heterocyclo groups include:

[0406] As used herein, the term "stereoisomers" is a general term for all isomers of an individual molecule that differ only in the orientation of their atoms in space. It includes enantiomers and isomers of compounds with more than one chiral center that are not mirror images of one another (diastereomers).

[0407] In some embodiments, a compounds disclosed herein comprises a mixture of E and Z stereoisomers, e.g., as illustrated for Compound (4) below:

„ . . .. E stereoisomer Z stereoisomer

Compound (4) [0408] In some embodiments, a compound disclosed herein comprises a mixture of E and Z stereoisomers, wherein the E:Z ratio is 500: 1 to 1 :500. In some embodiments, the E:Z ratio is 100: 1 to 1 : 100. n some embodiments, the E:Z ratio is 10: 1 to 1 : 10. In some embodiments, the E:Z ratio is 5:1 to 1 :5. In some embodiments, the E:Z ratio is 3: 1 to 1 :3. In some embodiments, the E:Z ratio is 2: 1 to 1 :2. In some embodiments, the E:Z ratio is about 10: 1, about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4:1, about 3: 1, or about 2: 1. In some embodiments, the E:Z ratio is about 1 : 10, about 1 :9, about 1 :8, about 1 :7, about 1 :6, about 1 :5, about 1 :4, about 1 :3, or about 1 :2. In some embodiments, the E:Z ratio is about 1 : 1.

[0409] In some embodiments, a compound disclosed herein comprises only the E stereoisomer, i.e., there is no detectable amount of the Z stereoisomer as measured by HPLC.

[0410] In some embodiments, a compound disclosed herein comprises only the Z stereoisomer, i.e., there is no detectable amount of the E stereoisomer as measured by HPLC.

[0411] The term "chiral center" or "asymmetric carbon atom" refers to a carbon atom to which four different groups are attached.

[0412] The terms "enantiomer" and "enantiomeric" refer to a molecule that cannot be superimposed on its mirror image and hence is optically active wherein the enantiomer rotates the plane of polarized light in one direction and its mirror image compound rotates the plane of polarized light in the opposite direction.

[0413] The term "racemic" refers to a mixture of equal parts of enantiomers and which mixture is optically inactive.

[0414] The term "absolute configuration" refers to the spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description, e.g., R or S.

[0415] The stereochemical terms and conventions used in the specification are meant to be consistent with those described in wre & Appl. Chem 65:2193 (1996), unless otherwise indicated.

[0416] The term "enantiomeric excess" or "ee" refers to a measure for how much of one enantiomer is present compared to the other. For a mixture of R and S enantiomers, the percent enantiomeric excess is defined as | R - S | * 100, where R and S are the respective mole or weight fractions of enantiomers in a mixture such that R + S = 1. With knowledge of the optical rotation of a chiral substance, the percent enantiomeric excess is defined as ([a]obs/[a]max)*100, where [a]obs is the optical rotation of the mixture of enantiomers and [a]max is the optical rotation of the pure enantiomer. Determination of enantiomeric excess is possible using a variety of analytical techniques, including NMR spectroscopy, chiral column chromatography, or optical polarimetry.

[0417] The present disclosure encompasses the preparation and use of salts and solvates, e.g., hydrates, of the compounds described herein. Salts of the compounds described herein can be prepared during the final isolation and purification of the compounds or separately by reacting the compound with an acid having a suitable cation. Salts of the compounds described herein can be acid addition salts formed with acceptable acids. Examples of acids which can be employed to form salts include inorganic acids such as nitric, boric, hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. Non-limiting examples of salts of the compounds described herein include, but are not limited to, the hydrochloride, hydrobromide, hydroiodide, sulfate, bisulfate, 2-hydroxyethansulfonate, phosphate, hydrogen phosphate, acetate, adipate, alginate, aspartate, benzoate, bisulfate, butyrate, camphorate, camphorsulfonate, di gluconate, glycerolphosphate, hemi sulfate, heptanoate, hexanoate, formate, succinate, fumarate, maleate, ascorbate, isethionate, salicylate, methanesulfonate, mesitylenesulfonate, naphthylenesulfonate, nicotinate, 2naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3phenylproprionate, picrate, pivalate, propionate, tri chloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, paratoluenesulfonate, undecanoate, lactate, citrate, tartrate, gluconate, methanesulfonate, ethanedi sulfonate, benzene sulfonate, and ptoluenesulfonate salts. In addition, available amino groups present in the compounds described herein can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. In light of the foregoing, any reference to the compounds described herein appearing herein is intended to include the compounds as well as salts, hydrates, or solvates thereof.

[0418] The present disclosure encompasses the preparation and use of solvates of the compounds described herein. The term "solvate" as used herein is a combination, physical association and/or solvation of a compound described herein with a solvent molecule such as, e.g., a disolvate, monosolvate or hemisolvate, where the ratio of solvent molecule to compound is about 2: 1, about 1 : 1 or about 1 :2, respectively. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate can be isolated, such as when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. Thus, "solvate" encompasses both solution-phase and isolatable solvates. The compounds described herein can be present as solvated forms with a solvent, such as water, methanol, and ethanol, and it is intended that the disclosure includes both solvated and unsolvated forms of the compounds described herein.

[0419] One type of solvate is a hydrate. A "hydrate" relates to a particular subgroup of solvates where the solvent molecule is water. Preparation of solvates is known in the art. See, for example, M. Caira et al, J. Pharmaceut. Sci., 93(3):601-611 (2004), which describes the preparation of solvates of fluconazole with ethyl acetate and with water. Similar preparation of solvates, hemisolvates, hydrates, and the like are described by van Tender et al., AAPS Pharm. Sci. Tech., 5 7):Article 12 (2004), and A.L. Bingham et al., Chem. Commun. 603-604 (2001). A typical, non-limiting, process of preparing a solvate would involve dissolving a compound described herein in a desired solvent (organic, water, or a mixture thereof) at temperatures above 20°C to about 25°C, then cooling the solution at a rate sufficient to form crystals, and isolating the crystals by known methods, e.g., filtration. Analytical techniques such as infrared spectroscopy can be used to confirm the presence of the solvent in a crystal of the solvate.

[0420] The use of the terms "a", "an", "the", and similar referents in the context of describing the disclosure (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated. Recitation of ranges of values herein merely are intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended to better illustrate the disclosure and is not a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosure.

[0421] The term "wt/wt %" as used herein refers to the mass of one component in a composition or blend, e.g., a composition comprising a first compound and a second compound, divided by the combined mass of all components in the composition or blend, times 100. For example, a composition comprising 9 g of Compound (1) and 1 g of Compound (2) comprises 90 wt/wt% of Compound (1) and 10 wt/wt% of Compound (2).

[0422] The term "crude reaction product" as used herein refers to the product of a chemical reaction before it has been isolated and/or purified to remove reagents, impurities and/or solvents that may be present.

[0423] The term "purified yield" as used herein refers to the yield of a product after it has been isolated from all reagents, impurities and/or solvents present in the crude reaction product. A product may be isolated using methods known in the art, such as column chromatography, high-performance liquid chromatography (HPLC), size-exclusion chromatography, and/or recrystallization.

[0424] The term "molar quantity" as used herein refers to the amount of a compound present in a composition, e.g., a reaction mixture, expressed in units of moles.

[0425] The term "molar ratio" as used herein refers to the ratio of the molar quantity of a first compound, e.g., Compound A, to the molar quantity of a second compound, e.g., Compound B. For example, a composition, e.g., a reaction mixture, comprising 1 mole of Compound A and 3 mole of Compound B has a molar ratio of Compound A to Compound B of 3 : 1.

[0426] The term "selectivity" as used herein refers to the molar quantity of a desired reaction product over the molar quantity of all reaction products. For example, a reaction yielding 8 mole of Compound (1), 1 mole of Compound (2), and 1 mole of Compound (3) has a selectivity of (8 mole)/(8 mole + 1 mole + 1 mole) x 100% = 80% for Compound (1).

[0427] The term "conversion" as used herein refers to the molar quantity of a desired product obtained in a reaction based on the amount of a specific starting material. For example, a reaction yielding 8 mole of Compound (1) starting from 10 mole of the starting material 4-aminodiphenylamine has a conversion of (8 mole)/(10 mole) x 100% = 80%.

[0428] The term "mole fraction" as used herein refers to the molar quantity of a given compound in a composition, e.g., a reaction mixture, divided by the combined molar quantity of all compounds in the composition; or, when specified as being relative to specific compound(s), the molar quantity of a given compound in a composition, e.g., a reaction mixture, divided by the combined molar quantity of specific compound(s) in the composition. For example, a composition, e.g., a reaction mixture, comprising 8 mole of Compound A, 1 mole of Compound B, and 1 mole of Compound C has a mole fraction of Compound A of (8 mole)/(8 mole + 1 mole + 1 mole) = 0.8. The mole fraction of Compound A relative to Compound B in the same composition is (8 mole)/(8 mole + 1 mole) = 0.89.

[0429] The phrase "in the presence of a catalyst" refers to reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I), or a combination thereof, with one catalyst or more than one catalyst. In some embodiments, the phrase "in the presence of a catalyst" is refers to reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I), or a combination thereof, with one catalyst, e.g., methane sulfonic acid. In some embodiments, the phrase "in the presence of a catalyst" is refers to reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, diacetone alcohol, a compound having Formula (I), or a combination thereof, with two catalysts, e.g., hydrobromic acid and Amberlyst 15 acidic resin.

[0430] The phrase "a catalyst" and the like refers to a single catalyst or the combination of two or more different catalysts. In some embodiments, the phrase "a catalyst" refers a single catalyst, e.g., methane sulfonic acid. In some embodiments, the phrase "a catalyst" refers the combination of two different catalysts, e.g., hydrobromic acid and Amberlyst 15 acidic resin. In some embodiments, the phrase "a catalyst" refers the combination of three different catalysts.

EXAMPLES

EXAMPLE 1

Comparative Example - Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline according to U.S. Patent No. 3,362,930 (1966)

Synthesis

[0431] Charged 46.0 g of 4-aminodiphenylamine (0.25 moles; 99% purity) and 2.1 mL concentrated hydrochloric acid (0.025 moles, 37%, 5 = 1.18) catalyst to 500-mL reactor equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver. Heated to 120°C under nitrogen with stirring. Fed 110 mL acetone (1.5 moles, 99.5+%, 5 = 0.784) from addition funnel to stirred reactor over 1.5 hours at 120°C. Transferred 91 mL acetone collected in receiver back to addition funnel and fed to reactor over another 1.5 hours at 120°C. Collected another 88 mL acetone in receiver. Recovered 57.9 g of 41.1% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline (this compound may also be referred to as 2,2,4-trimethyl-N-phenyl-l,2-dihydroquinolin-6- amine) and 32.0% 4-aminodiphenylamine by HPLC. Yield was 36.0% and conversion of starting material was 57.9%.

HPLC Analysis

[0432] Chromatograms were obtained using an Agilent 1100 series HPLC system equipped with a Poroshell 120 column (EC-C18 4.6 x 50 mm, 2.7 pm) kept at 25 °C with 5 L injection volume. An ultraviolet detector was used to measure absorption of each component at 280 nm. Multiple-level calibration standards were prepared from column- purified 4-aminodiphenyl amine and 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline for accurate quantification of results. The mobile phase (1 mL/min flow rate) consisted of 5 mmol/L aqueous ammonium formate (Solvent A) and acetonitrile (Solvent B) using the following gradient shown in Table 1 below.

Table 1. HPLC Gradient

EXAMPLE 2

Comparative Example - Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline according to JP Patent No. 48011103 B (1973)

[0433] Charged 92.0 g of 4-aminodiphenylamine (0.50 moles; 99% purity), 5.3 g concentrated hydrochloric acid (0.05 moles, 37%) catalyst, and 15 mL toluene to 500-mL reactor equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with Dean-Stark trap. Filled trap with toluene to just below overflow. Heated to 145°C under nitrogen with stirring. Water was collected in the bottom of the trap and condensate was allowed to flow back into the reactor. Fed 75.0 g acetone (1.3 moles, 99.5+%) from addition funnel to stirred reactor over 4 hours at 145°C. Recovered 148.8 g of 47.3% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 16.1% 4- aminodiphenylamine by HPLC. Yield was 53.3% and conversion of starting material was 74.1%.

EXAMPLE 3

Comparative Example - Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline according to Journal of Medicinal Chemistry, 1972, 15, 77, pp. 1177-1179

[0434] Charged 21.3 g of 4-aminodiphenylamine (0.12 moles; 99% purity), 13.7 g mesityl oxide (0.14 moles, 99% purity, ca. 93% alpha isomer), and 0.6 g iodine (0.002 moles) to 50-mL reactor equipped with magnetic stirrer, temperature control, nitrogen inlet, and condenser. Heated to reflux with stirring. Held under reflux for 7 hours. Recovered 32.6 g of 22.9% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 30.0% 4- aminodiphenylamine by HPLC. Yield was 24.4% and conversion of starting material was 54.3%.

EXAMPLE 4

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Catalyst Screening

[0435] Charged 0.183-0.187 g of 4-aminodiphenylamine (1.0 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 0.1 mmol of catalyst to a test tube as indicated in Table 2 below. Sealed test tubes under air atmosphere. Heated to 60°C with stirring. Held at 60°C for 24 hrs. Analyzed by HPLC. Results are summarized in order of activity, from highest to lowest, in Table 2. Activity is measured by calculating the ratio of product (Compound (1)) to starting material (4-aminodiphenylamine).

Table 2. Summary of Catalyst Types, Amounts and Activity for Example 4

EXAMPLE 5

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Catalyst Screening II [0436] Charged 1.550-1.555 g of 4-aminodiphenylamine (8.4 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 0.8 mmol of catalyst to a test tube as indicated in Table 3 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 60°C for 24 hrs. Analyzed by HPLC. Results are summarized in order of increasing to decreasing 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline yield in Table 3.

Table 3. Summary of Reaction Charges and Yield, Conversion for Example 5

EXAMPLE 6

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Stoichiometry

[0437] Charged 4-aminodiphenylamine (99%), pyridinium perbromide (90%), and 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe to a test tube as indicated in Table 4 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 4 and Fig. 1.

Table 4. Summary of Reaction Charges and Yield, Conversion for Example 6.

EXAMPLE 7

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Catalyst Charge

[0438] Charged 1.550-1.555 g of 4-aminodiphenylamine (8.4 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and pyridinium perbromide (90%) catalyst to a test tube as indicated in Table 5 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 60°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 5 and Fig. 2. Table 5. Summary of Reaction Charges and Yield, Conversion for Example 7.

EXAMPLE 8

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline with Mesityl Oxide and 2,2-Dimethoxypropane

[0439] Charged 1.610-1.615 g of 4-aminodiphenylamine (8.8 mmol; 99%), 4 mL mesityl oxide (35 mmol, 99%, ca. 93% alpha isomer, 5 = 0.86) via syringe, and 0.9 mmol of catalyst to a test tube as indicated in Table 6 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 6.

Table 6. Summary of Reaction Charges and Yield, Conversion for Example 8.

[0440] Charged 1.505 g of 4-aminodiphenylamine (8.2 mmol; 99% purity), 4 mL 2,2- dimethoxypropane (32 mmol, 99+%, 5 = 0.85) via syringe, and 0.2604 g pyridinium perbromide (0.7 mmol, 90%) catalyst to a test tube. Sealed test tube under air atmosphere. Heated to 70°C with stirring. Held at 60°C for 24 hrs. Analyzed by HPLC. Yield was 38.7% and conversion of starting material was 93.8%.

EXAMPLE 9

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline with Ketone Mixtures [0441] Charged 4-aminodiphenylamine (99%), pyridinium perbromide (90%), acetone

(99.5+%), and mesityl oxide (99%) to a test tube as indicated in Table 7 below.

Table 7. Summary of Reaction Charges and Yield, Conversion for Example 9.

[0442] Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 8 and Fig. 3.

Table 8. Summary of Reaction Charges and Yield, Conversion for Example 9.

EXAMPLE 10

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline -

Variation of Water Content

[0443] Charged 1.550-1.552 g of 4-aminodiphenylamine (8.4 mmol; 99%), 0.270-0.272 g pyridinium perbromide (0.8 mmol, 90%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784), and water via syringe to a test tube as indicated in Table 9 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 9. Table 9. Summary of Reaction Charges and Yield, Conversion for Example 10.

[0444] All examples contained herein have been run in the presence of reaction water up to 2 moles per mole of starting material at 100% conversion.

EXAMPLE 11

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Use of Dessicants

[0445] Charged 1.550-1.552 g of 4-aminodiphenylamine (8.4 mmol; 99%), 0.270-0.272 g pyridinium perbromide (0.8 mmol, 90%), magnesium sulfate desiccant as indicated in Table 10 below, and 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe to a test tube. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 10.

Table 10. Summary of Reaction Charges and Yield, Conversion for Example 11.

EXAMPLE 12

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Solvent

[0446] Charged 0.310-0.312 g of 4-aminodiphenylamine (1.7 mmol; 99%), 0.054-0.055 g pyridinium perbromide (0.2 mmol, 90%), and 10 mL of solvent to a test tube as indicated in Table 11 below. Sealed test tubes under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 11.

Table 11. Summary of Reaction Charges and Yield, Conversion for Example 12.

EXAMPLE 13

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Atmosphere

[0447] Charged 1.550-1.552 g of 4-aminodiphenylamine (8.4 mmol; 99%), 0.270-0.272 g pyridinium perbromide (0.8 mmol, 90%), and 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) to a test tube as indicated in Table 12 below. Sealed one test tube after evacuation of the headspace with nitrogen. Sealed the other test tube under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 12.

Table 12. Summary of Yield, Conversion for Example 13.

EXAMPLE 14

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Temperature

[0448] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 6.4 g pyridinium perbromide (0.02 moles, 90%), 69.6 g acetone (1.20 moles, 99.5+%), and 19.6 g mesityl oxide (0.20 moles, 99%) to sealed Parr autoclave. Blanket headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to the temperature indicated in Table 13 below. Held at temperature for 24 hrs. Analyzed by HPLC. Results are summarized in Table 13 and Fig. 4.

Table 13. Summary of Yield, Conversion for Example 14.

EXAMPLE 15

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with PyHBn at 95 °C

[0449] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 6.4 g pyridinium perbromide (0.02 moles, 90%), 118 mL acetone (1.60 moles, 99.5+%, 5 = 0.784), and 27 mL mesityl oxide (0.24 moles, 99%, 5 = 0.86) to sealed 300-mL Parr autoclave. Blanket headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to 95°C. Held at temperature for 24 hrs. Analyzed by HPLC. Yield was 73.1% and conversion of starting material was 92.9%.

EXAMPLE 16

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with AlCh at 95°C

[0450] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 2.6 g aluminum

(III) chloride (0.02 moles, 99%), 92.8 g acetone (1.60 moles, 99.5+%), and 23.0 g mesityl oxide (0.24 moles, 99%) to sealed 300-mL Parr autoclave. Blanket headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to 95°C. Held at temperature for 18 hrs.

Analyzed by HPLC. Yield was 71.6% and conversion of starting material was 88.4%.

EXAMPLE 17

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with MgBr? at 95°C

[0451] Charged 18.4 g of 4-aminodiphenylamine (0.10 moles; 99%), 2.7g magnesium (II) bromide (0.015 moles, 98%, anhydrous), 96 mL acetone (1.30 moles, 99.5+%, 5 = 0.784), and 24 mL mesityl oxide (0.20 moles, 99% 5 = 0.86) to sealed 300-mL Parr autoclave. Blanket headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to 95°C. Held at temperature for 24 hrs. Analyzed by HPLC. Yield was 65.2% and conversion of starting material was 75.0%.

EXAMPLE 18

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with LABSA at 95°C

[0452] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 6.4 g 4- dodecylbenzene sulfonic acid (0.02 moles, 99%), 12.0 g magnesium sulfate (0.10 moles, 99%), 116.0 g acetone (2.00 moles, 99.5+%), and 39.2 g mesityl oxide (0.40 moles, 99%) to sealed 300-mL Parr autoclave. Blanket headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to 95°C. Held at temperature for 48 hrs. Analyzed by HPLC. Yield was 62.2% and conversion of starting material was 81.1%.

EXAMPLE 19

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with PyHBn at 95°C

[0453] Charged 55.2 g of 4-aminodiphenylamine (0.30 moles; 99%) and 9.6 g pyridinium perbromide (0.03 moles, 90%) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 95°C under nitrogen with stirring. Fed 200 mL acetone (2.70 moles, 99.5+%, 5 = 0.784) mixed with 40 mL mesityl oxide (0.35 moles, 99%, 5 = 0.86) over 4 hours. Held for 2 hours at 95°C after end of acetone/mesityl oxide feed. Removed 136 mL of condensate throughout reaction and hold steps. Recovered 96.6 g of 52.7% 6-anilino-2,2,4-trimethyl-l,2- dihydroquinoline and 4.8% 4-aminodiphenylamine by HPLC. Yield was 64.2% and conversion of starting material was 91.5%. Fig. 5 is a representative LC chromatogram of a crude reaction mixture obtained using this procedure.

EXAMPLE 20

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with AlCh at 95°C

[0454] Charged 64.4 g of 4-aminodiphenylamine (0.35 moles; 99%) and 4.7 g aluminum (III) chloride (0.03 moles, 99%) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 95°C under nitrogen with stirring. Fed 155 mL acetone (2.10 moles, 99.5+%, 5 = 0.784) mixed with 40 mL mesityl oxide (0.35 moles, 99%, 5 = 0.86) over 5 hours. Held for 1 hour at 95°C after end of acetone/mesityl oxide feed. Removed 134 mL of condensate throughout reaction and hold steps. Recovered 106.1 g of 51.7% 6-anilino- 2,2,4-trimethyl-l,2-dihydroquinoline and 12.3% 4-aminodiphenylamine by HPLC. Yield was 59.3% and conversion of starting material was 79.7%. EXAMPLE 21

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with MgBrc at 95°C

[0455] Charged 18.4 g of 4-aminodiphenylamine (0.10 moles; 99%) and 2.7 g magnesium (II) bromide (0.015 moles, 98%, anhydrous) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 95°C under nitrogen with stirring. Fed 95 mL acetone (1.30 moles, 99.5+%, 5 = 0.784) mixed with 24 mL mesityl oxide (0.20 moles, 99%, 5 = 0.86) over 4 hours. Held for 2 hours at 95°C after end of acetone/mesityl oxide feed. Removed 70 mL of condensate throughout reaction and hold steps. Recovered 34.4 g of 49.7% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 4.0% 4-aminodiphenylamine by HPLC. Yield was 64.3% and conversion of starting material was 92.5%.

EXAMPLE 22

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with PyHBn at 95°C and variable feed rate

[0456] Charged 64.4 g of 4-aminodiphenylamine (0.35 moles; 99%) and 11.2 g pyridinium perbromide (0.035 moles, 90%) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 95°C under nitrogen with stirring. Fed 130 mL acetone (1.75 moles, 99.5+%, 5 = 0.784) mixed with 60 mL mesityl oxide (0.525 moles, 99%, 5 = 0.86) over 5 hours, adjusting the feed rate so that 12 mL of the acetone/mesityl oxide mixture was fed during the first hour of the reaction and 35 mL total was fed during the first two hours. Held for 1.5 hours at 95°C after end of acetone/mesityl oxide feed. Removed 121 mL of condensate throughout reaction and hold steps. Recovered 114.8 g of 55.0% 6-anilino- 2,2,4-trimethyl-l,2-dihydroquinoline and 3.5% 4-aminodiphenylamine by HPLC. Yield was 68.3% and conversion of starting material was 93.6%. EXAMPLE 23

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Catalyst Screening III

[0457] Charged 1.838-1.844 g of 4-aminodiphenylamine (10.0 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 1.0 mmol of catalyst to a test tube as indicated in Table 14 below. Sealed test tubes under air atmosphere. Heated to 95°C. Not stirred. Held at 95°C for 24 hrs. Analyzed by HPLC. Results are summarized in order of increasing to decreasing 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline yield in Table 14.

Table 14. Summary of Reaction Charges and Yield, Conversion for Example 23.

EXAMPLE 24

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Catalyst Screening IV [0458] Charged 1.844 g of 4-aminodiphenylamine (10.0 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 0.098 g methane sulfonic acid (1.0 mmol) to a test tube. Sealed test tube under air atmosphere. Heated to 80°C with stirring. Held at 80°C for 24 hrs. Analyzed by HPLC. Yield was 46.1% and conversion of starting material was 62.2%.

[0459] Charged 1.551 g of 4-aminodiphenylamine (8.4 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 0.271 g 4-dodecylbenzene sulfonic acid (0.8 mmol) to a test tube. Sealed test tube under air atmosphere. Heated to 70°C with stirring. Held at 70°C for 24 hrs. Analyzed by HPLC. Yield was 43.2% and conversion of starting material was 52.0%.

[0460] Charged 1.550 g of 4-aminodiphenylamine (8.4 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 0.081 g sulfamic acid (0.8 mmol) to a test tube. Sealed test tube under air atmosphere. Heated to 80°C with stirring. Held at 80°C for 24 hrs. Analyzed by HPLC. Yield was 15.0% and conversion of starting material was 34.3%.

[0461] Results are summarized in order of increasing to decreasing 6-anilino-2,2,4- trimethyl-l,2-dihydroquinoline yield in Table 15.

Table 15. Summary of Reaction Charges and Yield, Conversion for Example 24.

EXAMPLE 25

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Heterogeneous Catalyst [0462] Charged 50.0 g aluminosilicate zeolite (Sigma catalog number 96096), 112.0 g deionized water, 3.8 g -toluene sulfonic acid monohydrate, and 13.0 g hydrobromic acid (48% aqueous) to reactor. Stir for 4 hrs. Soak for 16 hrs. without agitation. Filtered. Dried solids overnight in 105°C oven.

[0463] Charged 46.0 g of 4-aminodiphenylamine (0.25 moles; 99), 26.0 g prepared zeolite catalyst, 58.0 g acetone (1.00 moles, 99.5+%), and 24.5 g mesityl oxide (0.25 moles, 99%) to sealed 300-mL Parr autoclave. Blanketed headspace with 20 psi nitrogen. Heated with stirring (250 rpm) to 160°C. Held at temperature for 24 hrs. Analyzed by HPLC. Yield was 39.1% and conversion of starting material was 67.2%.

EXAMPLE 26

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Catalyst Charge II (Magnesium Bromide)

[0464] Charged 1.842-1.846 g of 4-aminodiphenylamine (10.0 mmol; 99%), 2 mL acetone (27 mmol, 99.5+%, 5 = 0.784) and 2 mL mesityl oxide (18 mmol, 99%, ca. 93% alpha isomer, 5 = 0.86) via syringe, and magnesium bromide hexahydrate catalyst to a test tube as indicated in Table 16 below. Sealed test tubes under air atmosphere. Heated to 80°C. Not stirred. Held at 80°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 16.

Table 16. Summary of Reaction Charges, Yield, and Conversion for Example 26.

EXAMPLE 27

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Catalyst Charge III (Hydrobromic Acid)

[0465] Charged 1.842-1.848 g of 4-aminodiphenylamine (10.0 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and hydrobromic acid (48% aqueous) catalyst to a test tube as indicated in Table 17 below. Sealed test tubes under air atmosphere. Heated to 80°C with stirring. Held at 80°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 17.

Table 17. Summary of Reaction Charges, Yield, and Conversion for Example 27.

EXAMPLE 28

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline with Ketone Mixtures II (Hydrobromic Acid)

[0466] Charged 4-aminodiphenylamine (99%), hydrobromic acid (48% aqueous), acetone

(99.5+%), and mesityl oxide (99%) to a test tube as indicated in Table 18 below.

Table 18. Summary of Reaction Charges and Yield, Conversion for Example 28.

[0467] Sealed test tubes under air atmosphere. Heated to 90°C with stirring. Held at 90°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 19.

Table 19. Summary of Reaction Charges, Yield, and Conversion for Example 28.

EXAMPLE 29

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline with Ketone Mixtures III (Magnesium Bromide)

[0468] Charged 4-aminodiphenylamine (99%), magnesium bromide hexahydrate, acetone

(99.5+%), and mesityl oxide (99%) to a test tube as indicated in Table 20 below.

Table 20. Summary of Reaction Charges and Yield, Conversion for Example 29.

[0469] Sealed test tubes under air atmosphere. Heated to 80°. Not stirred. Held at 80°C for 22.5 hrs. Analyzed by HPLC. Results are summarized in Table 20.

Table 21. Summary of Reaction Charges and Yield, Conversion for Example 29.

EXAMPLE 30

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline with Mesityl Oxide, 2,2- Dimethoxypropane and Diacetone Alcohol and Ketone Mixtures IV (Magnesium Bromide)

[0470] Charged 1.845-1.847 g of 4-aminodiphenylamine (10.0 mmol; 99%), 0.187-0.189 g magnesium bromide (1.0 mmol, anhydrous), and cyclizing reagent to a test tube as indicated in Table 22 below. Sealed test tubes under air atmosphere. Heated to 90°C with stirring. Held at 90°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 22.

Table 22. Summary of Reaction Charges, Yield, and Conversion for Example 30.

EXAMPLE 31

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Water Content II (Magnesium Bromide)

[0471] Charged 1.843-1.848 g of 4-aminodiphenylamine (10.0 mmol; 99%), 3 mL acetone (40 mmol, 99.5+%, 5 = 0.784) and 2 mL mesityl oxide (18 mmol, 99%, 5 = 0.86), 1 mmol magnesium bromide catalyst, and water via syringe to a test tube as indicated in Table 23 below. Sealed test tubes under air atmosphere. Heated to 80°C. Not stirred. Held at 80°C for 24 hrs. Analyzed by HPLC. Results are summarized in Table 23. Table 23. Summary of Reaction Charges and Yield, Conversion for Example 31.

EXAMPLE 32

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Acidic Resins

[0472] Charged 1.843-1.846 g of 4-aminodiphenylamine (10.0 mmol; 99%), 0.100-0.109 g hydrochloric acid (1.0 mmol, 37% aqueous), 3 mL acetone (40 mmol, 99.5+%, 5 = 0.784) and 2 mL mesityl oxide (18 mmol, 99%, 5 = 0.86) to each of three individual test tubes. Added 1.993 g Amberlyst 15 acidic resin to one of the tubes before the reaction was started. Sealed test tubes under air atmosphere. Heated to 90°C with stirring. Held at 90°C for 23.5 hrs. Added 1.969 g Amberlyst 15 acidic resin to another test tube. Held another 0.5 hrs. at 90°C for a total reaction time of 24 hrs. Analyzed by HPLC. Results are summarized in Table 24.

Table 24. Summary of Acidic Resin Treatment, Yield, and Conversion for Example 32.

[0473] Charged 1.838-1.844 g of 4-aminodiphenylamine (10.0 mmol; 99%), 5 mL acetone (68 mmol, 99.5+%, 5 = 0.784) via syringe, and 1.0 mmol of catalyst to a test tube as indicated in Table 25 below. Sealed test tubes under air atmosphere. Heated to 95°C.

Not stirred. Held at 95°C for 24 hrs. Added 0.99-1.01 g Amberlyst 15 acidic resin and held at 95°C for 1 hr. Added another 0.49-0.51 g Amberlyst 15 acidic resin and held at

95°C for another 2 hrs. Analyzed by HPLC. Results are summarized in Table 25.

Table 25. Summary of Reaction Charges and Yield, Conversion for Example 32.

EXAMPLE 33

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline - Variation of Solvent II (Hydrobromic Acid)

[0474] Charged 0.466-0.471 g of 4-aminodiphenylamine (2.5 mmol; 99%), 0.087-0.091 g hydrobromic acid (0.5 mmol, 48% aqueous), and 10 mL of solvent to a test tube as indicated in Table 26 below. Sealed test tubes under air atmosphere. Heated to 80°C with stirring. Held at 80°C for 23 hrs. Analyzed by HPLC. Results are summarized in Table 26.

Table 26. Summary of Reaction Charges and Yield, Conversion for Example 33.

EXAMPLE 34

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with Magnesium Bromide at 95-120°C and Two-Stage Addition

[0475] Charged 73.6 g of 4-aminodiphenylamine (0.40 moles; 99%) and 23.2 g magnesium (II) bromide hexahydrate (0.08 moles) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 120°C under nitrogen with stirring. Fed 62.4 g acetone (1.08 moles, 99.5+%, 5 = 0.784) mixed with 67.8 g mesityl oxide (0.70 moles, 99%, 5 = 0.86) over 6.2 hours. Held for 0.5 hours at 120°C after end of acetone/mesityl oxide feed. Removed 89 mL of condensate throughout reaction and hold steps. Measured 54.1 g of 44.7% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 11.1% 4- aminodiphenylamine in the reaction mixture by HPLC. Yield was 51.3% and conversion of starting material was 81.8%. Charged another 23.2 g magnesium (II) bromide hexahydrate (0.08 moles, 0.16 moles total) to reactor. Heated to 95°C under nitrogen with stirring. Fed another 62.4 g acetone mixed with 67.8 mesityl oxide over 6.9 hours. Held for 0.5 hours at 102°C after end of acetone/mesityl oxide feed. Removed another 77 mL of condensate throughout second reaction and hold steps. Measured 60.7 g of 30.2% 6- anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 0.4% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 57.4% and conversion of starting material was 98.9%.

EXAMPLE 35

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with Magnesium Bromide at 95°C and Multiple-Stage Addition

[0476] Charged 73.6 g of 4-aminodiphenylamine (0.40 moles; 99%) and 11.6 g magnesium (II) bromide hexahydrate (0.04 moles) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver capable of either refluxing back to reactor or removing condensate from system. Heated to 96-98°C under nitrogen with stirring. Fed 96.1 g acetone (1.60 moles, 99.5+%, 5 = 0.784) mixed with 68.5 g mesityl oxide (0.70 moles, 99%, 5 = 0.86) over 4.2 hours. Added another 5.8 g magnesium (II) bromide hexahydrate (0.02 moles, 0.06 moles total) midway through the ketone feed. Held for 0.5 hours at 88- 90°C after end of acetone/mesityl oxide feed. Removed 102 mL of condensate throughout reaction and hold steps. Added another 5.8 g magnesium (II) bromide hexahydrate (0.02 moles, 0.08 moles total). Heated to 96-98°C under nitrogen with stirring. Fed another 47.6 g acetone (0.80 moles, 99.5+%, 5 = 0.784) mixed with 35.5 g mesityl oxide (0.36 moles, 99%, 5 = 0.86) over 2.0 hours. Held for 1.0 hours at 95-100°C after end of second acetone/mesityl oxide feed. Removed 175 mL of condensate (total). Added another 2.9 g magnesium (II) bromide hexahydrate (0.01 moles, 0.09 moles total). Heated to 96-98°C under nitrogen with stirring. Fed another 19.8 g acetone (0.30 moles, 99.5+%, 5 = 0.784) mixed with 21.4 g mesityl oxide (0.20 moles, 99%, 5 = 0.86) over 3.2 hours. Held for 2.0 hours at 105°C after end of third acetone/mesityl oxide feed. Removed 184 mL of condensate (total). Measured 73.7 g of 47.0% 6-anilino-2,2,4-trimethyl-l,2- dihydroquinoline and 0.4% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 69.8% and conversion of starting material was 99.2%.

EXAMPLE 36

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with Magnesium Bromide at 95°C and Acidic Resin Addition

[0477] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 3.68 g magnesium (II) bromide (0.020 moles, 98%, anhydrous), 51.0 g acetone (0.88 moles, 99.5+%, 5 = 0.784), and 35.3 g mesityl oxide (0.36 moles, 99% 5 = 0.86) to sealed 300-mL Parr autoclave. Blanketed headspace with 20 psi nitrogen. Heated with stirring (250 rpm) to 95°C. Held at temperature for 6.5 hrs. Stopped and cooled to room temperature. Added another 0.75 g magnesium (II) bromide (0.004 moles, 0.024 moles total), 20.4 g Amberlyst 15 resin, and 18.6 g acetone (0.32 moles, 1.20 moles total). Held for 1.5 hrs. at 95°C then another 16 hrs. at 65°C. Stopped and cooled to room temperature. Added another 0.37 g magnesium (II) bromide (0.002 moles, 0.026 moles total), 9.8 g Amberlyst 15 resin, and 9.3 g acetone (0.16 moles, 1.36 moles total). Held for 6 hrs. at 95°C. Analyzed by HPLC. Measured 33.4 g of 22.1% 6-anilino-2,2,4-trimethyl-l,2- dihydroquinoline and 0.7% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 63.2% and conversion of starting material was 97.1%. EXAMPLE 37

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Smaller-Scale Reaction Flask with Magnesium Bromide at 95°C and Two-Stage Addition

[0478] Charged 18.6 g of 4-aminodiphenylamine (101 mmol; 99%) and 1.48 g anhydrous magnesium (II) bromide (8 mmol) to 100-mL reaction flask equipped with magnetic stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver for removing condensate from the system. Heated to 95°C under nitrogen with stirring. Fed 34.9 g acetone (601 mmol, 99.5+%, 5 = 0.784) mixed with 9.9 g mesityl oxide (101 mmol, 99%, 5 = 0.86) over 4.1 hours. Removed 28.8 g of condensate. Measured 15.5 g of 51.7% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 17.2% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 55.2% and conversion of starting material was 73.6%. Charged another 1.49 g anhydrous magnesium (II) bromide (8 mmol, 16 mmol total) to reactor. Heated to 95°C under nitrogen withstirring. Fed another 34.9 g acetone (601 mmol, 99.5+%, 5 = 0.784) mixed with 9.8 g mesityl oxide (100 mmol, 99%, 5 = 0.86) over 6.2 hours. Removed another 41 mL of condensate. Added another 0.54 g mesityl oxide. Held at 95°C for 1 hr. Measured 19.2 g of 58.8% 6-anilino-2,2,4-trimethyl- 1,2-dihydroquinoline and 1.9% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 72.1% and conversion of starting material was 96.7%.

EXAMPLE 38

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Larger-Scale Reaction Flask with Magnesium Bromide at 105°C and Acidic Resin Addition

[0479] Charged 92.1 g of 4-aminodiphenylamine (0.5 moles; 99%) and 14.6 g magnesium (II) bromide hexahydrate (0.05 moles) to 1-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver for removing condensate from the system. Heated to 95°C under nitrogen with stirring. Fed 145.3 g acetone (2.50 moles, 99.5+%, 5 = 0.784) mixed with 49.1 g mesityl oxide (0.50 moles, 99%, 5 = 0.86) over 7.6 hours. Held for 0.25 hours at 95- 100°C after end of acetone/mesityl oxide feed. Removed 149.6 g of condensate throughout reaction and hold steps. Recycle contents of receiver back to addition funnel along with 21.3 g (0.22 moles) fresh mesityl oxide. Charged another 6.3 g magnesium (II) bromide hexahydrate (0.022 moles, 0.072 moles total) to reactor. Heated to 105°C under nitrogen with stirring. Fed recycled condensate/mesityl oxide mixture over 10.5 hours. Held for 0.25 hours at 105°C after end of condensate/mesityl oxide feed. Removed another 148.3 g of condensate throughout second reaction and hold steps. Measured 90.4 g of 59.2% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 10.0% 4- aminodiphenylamine in the reaction mixture by HPLC. Yield was 68.4% and conversion of starting material was 83.4%. Removed another 83.5 g condensate at 88°C at 30-40 Torr over 3 hrs. Added 1.5 g magnesium (II) bromide hexahydrate (0.005 moles, 0.077 moles total), 19.8 g acetone, and 8.0 g mesityl oxide. Held at 55°C for 14 hrs. Added 9.9 g of Amberlyst 15 resin. Held for 6.0 hrs. at 95°C. Measured 92.4 g of 52.1% 6-anilino- 2,2,4-trimethyl-l,2-dihydroquinoline and 1.8% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 69.9% and conversion of starting material was 96.5%.

EXAMPLE 39

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Smaller-Scale Reaction Flask with Hydrobromic Acid at 95°C and Two-Stage Addition

[0480] Charged 18.4 g of 4-aminodiphenylamine (100 mmol; 99%) and 1.68 g hydrobromic acid (10 mmol, 48% aqueous) to 100-mL reaction flask equipped with magnetic stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver for removing condensate from the system. Heated to 95°C under nitrogen with stirring. Fed 34.8 g acetone (600 mmol, 99.5+%, 5 = 0.784) mixed with 9.8 g mesityl oxide (100 mmol, 99%, 5 = 0.86) over 6.1 hours. Removed 18.4 g of condensate, some loss noted. Measured 14.8 g of 59.3% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 18.9% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 56.6% and conversion of starting material was 74.0%. Charged another 1.68 g hydrobromic acid (10 mmol, 20 mmol total) to reactor. Heated to 95°C under nitrogen with stirring. Fed another 34.9 g acetone (601 mmol, 99.5+%, 5 = 0.784) mixed with 9.7 g mesityl oxide (99 mmol, 99%, 5 = 0.86) over 5.3 hours. Removed another 31.0 g of condensate. Added another 1.55 g mesityl oxide. Held at 75°C for 8 hrs. Measured 16.9 g of 54.7% 6-anilino-2,2,4- trimethyl-l,2-dihydroquinoline and 2.0% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 63.8% and conversion of starting material was 96.7%. EXAMPLE 40

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Autoclave with /^-Toluene Sulfonic Acid at 125°C and Molecular Sieves with Incremental Addition

[0481] Charged 36.8 g of 4-aminodiphenylamine (0.20 moles; 99%), 5.51 g /^-toluene sulfonic acid monohydrate (0.029 moles, 98%, anhydrous), 20.0 g molecular sieves (3 A, 1.6 mm), and 92.8 g acetone (1.60 moles, 99.5+%, 5 = 0.784) to sealed 300-mL Parr autoclave. Blanketed headspace with 20 psi nitrogen. Heated with stirring (500 rpm) to 125°C. Held at temperature for 2.0 hrs. Stopped and cooled to room temperature. Added first portion 1.01 g /?-toluene sulfonic acid monohydrate and 5.01 g molecular sieves. Heated with stirring (500 rpm) to 125°C. Held at temperature for 2.0 hrs. or 4.0 hrs. total. Stopped and cooled to room temperature. Added second portion 1.02 g /?-toluene sulfonic acid monohydrate and 5.05 g molecular sieves. Heated with stirring (500 rpm) to 125°C. Held at temperature for 2.0 hrs. or 6.0 hrs. total. Stopped and cooled to room temperature. Added third portion 1.01 g /?-toluene sulfonic acid monohydrate and 5.01 g molecular sieves. Heated with stirring (500 rpm) to 125°C. Held at temperature for 2.0 hrs. or 8.0 hrs. total. Stopped and cooled to room temperature. Added fourth portion 1.00 g /?-toluene sulfonic acid monohydrate, 4.99 g molecular sieves, and 19.1 g acetone. Heated with stirring (500 rpm) to 125°C. Held at temperature for 2.0 hrs. or 10.0 hrs. total. Stopped and cooled to room temperature. Added fifth portion 1.01 g /?-toluene sulfonic acid monohydrate, 5.03 g molecular sieves, 9.9 g acetone, and 2.9 mesityl oxide. Heated with stirring (500 rpm) to 125°C. Held at temperature for 10.0 hrs. or 20.0 hrs. total. Stopped and cooled to room temperature. Added sixth portion 1.02 g /?-toluene sulfonic acid monohydrate, 4.0099 g molecular sieves, 9.9 g acetone, and 2.9 mesityl oxide. Heated with stirring (500 rpm) to 125°C. Held at temperature for 4.0 hrs. or 24.0 hrs. total. Stopped and cooled to room temperature. Analyzed by HPLC. Measured 30.4 g of 17.6% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 2.4% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 57.6% and conversion of starting material was 88.6%. EXAMPLE 41

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with Hydrobromic Acid at 105°C and Multiple-Stage Addition

[0482] Charged 46.0 g of 4-aminodiphenylamine (0.25 moles; 99%) and 4.4 g hydrobromic acid (0.025 moles, 48% aqueous) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver for removing condensate from the system. Heated to 105°C under nitrogen with stirring. Fed 444 mL acetone (6.00 moles, 99.5+%, 5 = 0.784) over 6.8 hours. Held for 0.2 hours at 105°C after end of acetone feed. Removed 309 mL of condensate throughout reaction and hold steps. Recycle contents of receiver back to addition funnel along with fresh acetone for a total charge volume of 395 mL. Heated to 105°C under nitrogen with stirring. Fed acetone mixed with condensate from first reaction step over 6.4 hours. Measured 41.3 g of 62.0% 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 6.0% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 62.5% andconversion of starting material was 91.2%. Charged 9.4 g mesityl oxide (0.096 moles) in three portions over 6 hrs. at 90-95°C then held for an additional 1 hr. under a vigorous nitrogen sweep to remove residual mesityl oxide. Measured 42.4 g of 60.0% 6-anilino- 2,2,4-trimethyl-l,2-dihydroquinoline and 1.4% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 64.1% and conversion of starting material was 97.9%.

EXAMPLE 42

Synthesis of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline in Reaction Flask with Hydrobromic Acid at 105°C and Single-Stage Addition - All Mesityl Oxide

[0483] Charged 55.4 g of 4-aminodiphenylamine (0.30 moles; 99%) and 10.1 g hydrobromic acid (0.060 moles, 48% aqueous) to 500-mL reaction flask equipped with mechanical stirrer, temperature control, addition funnel, nitrogen inlet, and condenser with receiver for removing condensate from the system. Heated to 105°C under nitrogen with stirring. Fed 98.0 g mesityl oxide (1.00 moles, 99.5+%, 5 = 0.784) over 4.7 hours. Held for 0.3 hours at 105°C after end of mesityl oxide feed. Removed 47.5 mL of condensate throughout reaction and hold steps. Held an additional 1 hr. at 80°C under a vigorous nitrogen sweep to remove residual mesityl oxide. Measured 51.5 g of 56.4% 6- anilino-2,2,4-trimethyl-l,2-dihydroquinoline and 1.0% 4-aminodiphenylamine in the reaction mixture by HPLC. Yield was 64.8% and conversion of starting material was 98.4%. Repeated the experiment. Measured 52.0 g of 57.8% 6-anilino-2,2,4-trimethyl- 1,2-dihydroquinoline and 1.6% 4-aminodiphenylamine in the reaction mixture by HPLC.

Yield was 65.4% and conversion of starting material was 97.4%.

EXAMPLE 43

Crystallization of 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline from Heptane

[0484] Charge approximately 1 : 1 acetone and 1 : 1 heptane on a volume/mass basis to any of the crude reaction mass samples described in Examples 34 through 43. Transfer crude reaction mass dissolved in acetone/heptane to a separatory funnel. Neutralize with sodium carbonate (15% aqueous) in slight molar excess (1.05-1.15) over the amount of acid catalyst charged. Allow organic and aqueous phases to separate. Wash with copious amounts of water until pH is neutral. Discard all aqueous portions. Dry organic portion over magnesium sulfate. Filter out solids. Remove residual acetone from filtrate by rotary evaporation. Heat heptane solution containing 6-anilino-2,2,4-trimethyl-l,2- dihydroquinoline to near boiling. Decant hot solution, leaving behind undissolved residue. Cool decanted solution to room temperature with stirring. Transfer the supernatant liquid to another clean flask if non-crystalline solids begin to form. Repeat if necessary. Filter crystallized solids. Wash with room temperature heptane. Dry to constant weight. Recovery of crystallized solids is generally 25-50% after the first pass crystallization. Several repeat cycles of recovery from the mother liquor, extraction from the residue, and re-dissolution of non-crystalline solids can improve the recovery of purified material up to 55-80%.

[0485] Further purification of solids may be achieved by eluting through a silica gel column with a 90: 10 vol/vol mixture of hexane and ethyl acetate. The desired product is isolated after rotary evaporation of the solvent.

[0486] 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline: 'HNMR (DMSO-d6) 5 7.2 (s, 1H, NH:N-amino), 5 7.0-6.2 (m, 8H, H: aromatic), 5 5.3 (s, 1H, NH:N’ -amino), 5 5.0 (s, 1H, H:allyl), 5 1.6 (s, 3H, CH₃:methyl), 5 1.0 (s, 6H, CH₃: di methyl).

[0487] 6-anilino-2,2,4-trimethyl-l,2-dihydroquinoline: ¹³C NMR (DMSO-d6) 5 147.11, 140.13, 131.43, 129.28, 129.19 (2C), 127.65, 122.46, 121.25, 117.51, 117.18, 113.86 (2C), 113.14, 51.36, 30.80 (2C), 18.50. EXAMPLE 44

Synthesis of 2,2,4-trimethyl-N-phenyl-l,2,3,4-tetrahydroquinolin-6-amine

(Compound (2))

[0488] To a solution of 2,2,4-trimethyl-N-phenyl-l,2-dihydroquinolin-6-amine (40.0 g, 0.151 mol) in methanol (400.0 mL, 10.0 vol) was added 10% Pd/C (4.0 g, 10% w/w) in an autoclave and to that was applied hydrogen pressure (15 kg) with stirring for 8 h. After completion of reaction (monitored by TLC), the reaction mass was filtered through a celite bed, the bed was washed with methanol (200.0 mL) and solvent was evaporated under reduced pressure to afford crude compound, which was purified by triturating in n-pentane to afford 26.0 g of 2,2,4-trimethyl-N-phenyl-l,2,3,4-tetrahydroquinolin-6- amine (65 % yield, >96 % pure by HPLC 260 nm, Mass (m/z): 266.99 [M+H]⁺) as grey solid.

[0489] ¹ H NMR (400 MHz, DMSO ): 5 7.42 (s, 1H), 7.07 (t, J= 7.6 Hz, 2H), 6.85 (s,

1H), 6.76 (d, J= 7.6 Hz, 2H), 6.70 (d, J= 8.0 Hz, 1H), 6.57 (t, J= 7.2 Hz, 1H), 6.41 (d, J=

8.4 Hz, 1H), 5.19 (s, 1H), 2.82-2.79 (m, 1H), 1.68 (dd, J= 12.8, 6.4 Hz, 1H), 1.28 (d, J=

12.4 Hz, 1H), 1.22 (d, J=6.8 Hz, 3H), 1.17 (s, 3H), 1.09 (s, 3H)

[0490] ¹³C NMR (100 MHz, DMSO ): 5 147.36, 140.56, 131.42, 129.39, 125.07,

121.04, 120.87, 117.25, 114.78, 113.94, 48.81, 44.75, 31.38, 27.74, 27.64, 20.95

[0491] Having now fully described the methods, compounds, and compositions herein, it will be understood by those of skill in the art that the same can be performed within a wide and equivalent range of conditions, formulations, and other parameters without affecting the scope of the methods, compounds, and compositions provided herein or any embodiment thereof. All patents, patent applications, and publications cited herein are fully incorporated by reference herein in their entirety.

Claims

What is claimed is:

1. A method of preparing Compound (1):

or a salt or solvate thereof, the method comprising reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, a compound having Formula (I):

^R OR²

(I), or a combination thereof; in the presence of a catalyst and, optionally, a solvent; at a reaction temperature of from about 50 °C to about 300 °C, wherein:

R¹ and R² are independently selected from C1-C12 alkyl; or

R¹ and R² together with the oxygen atoms to which they are attached form a 5- to 8- membered heterocyclo.

2. The method of claim 1, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

3. The method of claim 2, wherein R¹ and R² are methyl.

4. The method of claim 1, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

5. The method of claim 1, wherein the compound having Formula (I) is selected from the group consisting of:

6. The method of claim 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone.

7. The method of claim 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone and mesityl oxide.

8. The method of claim 7, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

9. The method of claim 8, wherein the molar ratio of acetone to mesityl oxide is about 4 : 1 to about 8:1.

10. The method of any one of claims 6-9, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2:1 to about 100:1.

11. The method of claim 10, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8:1.

12. The method of claim 1, wherein the method comprises reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide.

13. The method of any one of claims 7-12, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1:1 to about 100:1.

14. The method of claim 13, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2:1.

15. The method of any one of claims 1-14, wherein the catalyst is a homogeneous catalyst.

16. The method of claim 15, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

17. The method of claim 15, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

18. The method of claim 17, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride.

19. The method of claim 18, wherein the homogeneous catalyst is pyridinium perbromide.

20. The method of any one of claims 1-19, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

21. The method of claim 20, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

22. The method of claim 21, wherein the homogeneous catalyst is present in an amount of about 10 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

23. The method of any one of claims 1-14, wherein the catalyst is a heterogeneous catalyst.

24. The method of claim 23, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

25. The method of claim 24, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

26. The method of claim 24, wherein the solid-supported acid is micro-meso- macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on 7-AI2O3, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, para-toluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SChH.

27. The method of claim 24, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, FbSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine.

28. The method of claim 24, wherein the solid acid is a heteropolyacid or a metalorganic framework.

29. The method of claim 24, wherein the base catalyst is ZrCh/MgO.

30. The method of any one of claims 1-29, wherein the reaction temperature is from about 50 °C to about 180 °C.

31. The method of claim 30, wherein the reaction temperature is from about 85 °C to about 95 °C.

32. The method of any one of claims 1-31, wherein the method comprises reacting in the presence of a solvent.

33. The method of claim 32, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

34. The method of any one of claims 1-33, wherein the reacting is performed for from about 0.5 h to about 24 h.

35. The method of any one of claims 1-34, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

36. The method of claim 35, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

37. The method of any one of claims 1-36, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4-aminodiphenylamine.

38. The method of claim 37, wherein the purified yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

39. The method of any one of claims 1-38, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

40. The method of claim 39, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

41. The method of any one of claims 1-40, wherein the crude reaction product comprises an oligomer of Compound (1).

42. The method of any one of claims 1-41, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%.

43. The method of claim 42, wherein the selectivity for Compound (1) over other reaction products is from about 65% to about 90%.

44. The method of any one of claims 1-43, wherein the method further comprises reducing Compound (1), or a salt or solvate thereof, to produce Compound (2):

or a salt, solvate, or stereoisomer thereof.

45. The method of claim 44, wherein the reducing comprises reacting Compound (1), or a salt or solvate thereof, with hydrogen in the presence of a metal catalyst, to produce Compound (2), or a salt, solvate, or stereoisomer thereof.

46. The method of claim 45, wherein the metal catalyst comprises nickel, platinum, palladium, rhodium, or ruthenium.

47. The method of any one of claims 44-46, wherein the method further comprises oxidizing Compound (2), or a salt, solvate, or stereoisomer thereof, to produce Compound (3):

(3), or a salt, solvate, or stereoisomer thereof.

48. The method of any one of claims 1-43, wherein the method further comprises oxidizing Compound (1), or a salt or solvate thereof, to produce Compound (4):

or a salt, solvate, or stereoisomer thereof.

49. The method of any one of claims 1-48, wherein the composition comprising 4-aminodiphenylamine comprises about 99.2 wt/wt % of 4-aminodiphenylamine and about 0.3 wt/wt % 2-aminodiphenylamine.

50. The method of any one of claims 1-22 or 30-49, wherein the catalyst is not hydrochloric acid or iodine.

51. A composition comprising Compound (1):

or a salt or solvate thereof, wherein the composition is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with acetone, mesityl oxide, a compound having Formula (I):

or a combination thereof; in the presence of a catalyst and, optionally, a solvent; at a reaction temperature of from about 50 °C to about 300 °C, wherein:

R¹ and R² are independently selected from C1-C12 alkyl; or

52. The composition comprising Compound (1) of claim 51 further comprising Compound (5):

or a salt or solvate thereof.

53. The composition comprising Compound (1) of claim 52, wherein the composition comprises less than 10 wt% of Compound (5).

54. The composition comprising Compound (1) of any one of claims 51-53, further comprising Compound (6):

or a salt, solvate, or stereoisomer thereof.

55. The composition comprising Compound (1) of claim 54, wherein the composition comprises less than 10 wt% of Compound (6).

56. The composition comprising Compound (1) of any one of claims 51-55, further comprising Compound (7):

(7), or a salt, solvate, or stereoisomer thereof.

57. The composition comprising Compound (1) of claim 56, wherein the composition comprises less than 10 wt% of Compound (7).

58. The composition comprising Compound (1) of any one of claims 51-57, further comprising Compound (4):

(4), or a salt, solvate, or stereoisomer thereof.

59. The composition comprising Compound (1) of claim 58, wherein the composition comprises less than 10 wt% of Compound (4).

60. The composition comprising Compound (1) of any one of claims 51-59, further comprising Compound (8):

or a salt, solvate, or stereoisomer thereof.

61. The composition comprising Compound (1) of claim 60, wherein the composition comprises less than 10 wt% of Compound (8).

62. The composition comprising Compound (1) of any one of claims 51-61, further comprising Compound (9):

or a salt or solvate thereof.

63. The composition comprising Compound (1) of claim 62, wherein the composition comprises less than 10 wt% of Compound (9).

64. The composition comprising Compound (1) of any one of claims 51-63, further comprising Compound (10):

(10), or a salt, solvate, or stereoisomer thereof.

65. The composition comprising Compound (1) of claim 64, wherein the composition comprises less than 10 wt% of Compound (10).

66. The composition comprising Compound (1) of any one of claims 51-65, further comprising Compound (11):

(H), or a salt or solvate thereof.

67. The composition of claim 66, wherein the composition comprises less than 10 wt% of Compound (11).

68. The composition of any one of claims 51-67, wherein the composition is prepared by reacting the composition comprising 4-aminodiphenyl amine, or a salt or solvate thereof, with the compound of Formula (I).

69. The composition of claim 68, wherein R¹ and R² are methyl, ethyl, propyl, butyl, pentyl, or hexyl.

70. The composition of claim 69, wherein R¹ and R² are methyl.

71. The composition of claim 68, wherein R¹ and R² together with the oxygen atoms to which they are attached form a 5- or 6-membered heterocyclo.

72. The composition of claim 68, wherein the compound having Formula (I) is selected from the group consisting of:

73. The composition of any one of claims 51-67, wherein the composition is prepared by reacting the composition comprising 4-aminodiphenyl amine, or a salt or solvate thereof, with acetone.

74. The composition of any one of claims 51-67, wherein the composition is prepared by reacting the composition comprising 4-aminodiphenyl amine, or a salt or solvate thereof, with acetone and mesityl oxide.

75. The composition of claim 74, wherein the molar ratio of acetone to mesityl oxide is from about 1 : 10 to about 50: 1.

76. The composition of claim 74, wherein the molar ratio of acetone to mesityl oxide is about 4: 1 to about 8:1.

77. The composition of any one of claims 73-76, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 2:1 to about 100:1.

78. The composition of claim 77, wherein the molar ratio of acetone to 4-aminodiphenylamine, or a salt or solvate thereof, is about 8:1.

79. The composition of any one of claims 51-67, wherein the composition is preparing by reacting the composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, with mesityl oxide.

80. The composition of any one of claims 74-79, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is from about 1:1 to about 100:1.

81. The composition of claim 80, wherein the molar ratio of mesityl oxide to 4-aminodiphenylamine, or a salt or solvate thereof, is about 1.2: 1.

82. The composition of any one of claims 51-81, wherein the catalyst is a homogeneous catalyst.

83. The composition of claim 82, wherein the homogeneous catalyst is a Lewis acid, a Bronsted acid, a base, a halogen, a halogen donor, or a combination thereof.

84. The composition of claim 82, wherein the homogeneous catalyst is selected from the group consisting of iodine, pyridinium perbromide, bromine, bismuth(III) trifluoromethane sulfonate, zinc(II) trifluoromethane sulfonate, hydrobromic acid, magnesium(II) bromide, aluminum(III) chloride, p-toluene sulfonic acid monohydrate, N-bromosuccinimide, copper(II) bromide, copper(II) chloride, methane sulfonic acid, benzene sulfonic acid, boron trifluoride diethyl etherate, boron trifluoride dihydrate, hydrochloric acid, copper(II) trifluoromethane sulfonate, iron(III) chloride, magnesium(II) chloride, copper(I) iodide, and zinc(II) chloride, or the salts or solvates thereof.

85. The composition of claim 84, wherein the homogeneous catalyst is selected from the group consisting of pyridinium perbromide, magnesium(II) bromide, magnesium(II) bromide hexahydrate, and aluminum(III) chloride.

86. The composition of claim 85, wherein the homogeneous catalyst is pyridinium perbromide.

87. The composition of any one of claims 82-86, wherein the homogeneous catalyst is present in an amount of about 1 mol% to about 50 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

88. The composition of claim 87, wherein the homogeneous catalyst is present in an amount of about 5 mol% to about 15 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

89. The composition of claim 88, wherein the homogeneous catalyst is present in an amount of about 10 mol% relative to the starting amount of 4-aminodiphenylamine, or a salt or solvate thereof.

90. The composition of any one of claims 51-81, wherein the catalyst is a heterogeneous catalyst.

91. The composition of claim 90, wherein the heterogeneous catalyst is an acid treated resin, a solid-supported acid, a composite catalyst, a solid acid, or a base catalyst.

92. The composition of claim 91, wherein the acid treated resin is a polyfluorinated sulfonic acid resin, a strongly acidic sulfonic acid exchange resin (Amberlyst 15), a macroporous strong acid ion exchange resin, a strong acid ion exchange resin, a solid acidic ion exchange resin (NRW150), a sifted strong acidic ion exchange resin, or a strong acidic ion exchange resin (type A2 acidic resin).

93. The composition of claim 91, wherein the solid-supported acid is micro-meso- macroporous zeolite catalyst H-Y-MMM, strong-acidity molecular sieve H-MCM-22, an organic protonic acid supported by graphene oxide, an organic protonic acid supported by a zeolite, a small pore size zeolite, a heterogeneous acidic silica catalyst, Zn²⁺, Sn²⁺, and Cu²⁺ exchanged tungstophosphoric acid (TP A) supported on 7-AI2O3, tonsil activated earth (acid treated bentonite clay), alumina, titania, zirconia, niobia, silica-alumina, sulfated zirconia, tungstated zirconia, para-toluenesulfonic acid (p-TSA)/ZnCh, or WCh/activated carbon/SChH.

94. The composition of claim 91, wherein the composite catalyst is zirconium doped titania composite oxide catalyst, FbSCh-MoCh-TiCh solid superacid, or p-toluenesulfonic acid/iodine.

95. The composition of claim 91, wherein the solid acid is a heteropolyacid or a metal-organic framework.

96. The composition of claim 91, wherein the base catalyst is ZrCh/MgO.

97. The composition of any one of claims 51-96, wherein the reaction temperature is from about 50 °C to about 180 °C.

98. The composition of claim 97, wherein the reaction temperature is from about 85 °C to about 95 °C.

99. The composition of any one of claims 51-98, wherein the compositing is prepared by reacting a composition comprising 4-aminodiphenylamine, or a salt or solvate thereof, in the presence of a solvent.

100. The composition of claim 99, wherein the solvent comprises methanol, ethanol, isopropanol, acetonitrile, chloroform, dichloromethane, carbon tetrachloride, benzene, toluene, xylene, pentane, hexane, heptane, cyclohexane, dimethyl sulfoxide, dimethyl formamide, ethyl acetate, methyl t-butyl ether, or a combination thereof.

101. The composition of any one of claims 51-100, wherein the reacting is performed for from about 0.5 h to about 24 h.

102. The composition of any one of claims 51-101, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 40% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

103. The composition of claim 102, wherein the conversion of 4-aminodiphenylamine, or a salt or solvate thereof, to Compound (1) is from about 75% to about 100% based on the amount of unreacted 4-aminodiphenylamine.

104. The composition of any one of claims 51-103, wherein the yield of Compound (1), or a salt or solvate thereof, is from about 45% to about 99% based on the starting amount of 4aminodiphenylamine.

105. The composition of claim 104, wherein the yield of Compound (1), or a salt or solvate thereof, is from about 65% to about 99% based on the starting amount of 4-aminodiphenylamine.

106. The composition of any one of claims 51-105, wherein from about 30% to about 95% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

107. The composition of claim 106, wherein from about 75% to about 90% of the crude reaction product comprises Compound (1), or a salt or solvate thereof.

108. The composition of any one of claims 51-107, wherein the crude reaction product comprises an oligomer of Compound (1).

109. The composition of any one of claims 51-108, wherein the selectivity for Compound (1) over other reaction products is from about 55% to about 99%.

110. The composition of claim 109, wherein the selectivity for Compound (1) over other reaction products is from about 65% to about 90%.

111. A composition comprising Compound (2):

or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by reducing the composition of any one of claims 51-110.

112. The composition of claim 111, wherein the reducing comprises reacting Compound (1), or a salt or solvate thereof, with hydrogen in the presence of a metal catalyst, to produce Compound (2), or a salt, solvate, or stereoisomer thereof.

113. The composition of claim 112, wherein the metal catalyst comprises nickel, platinum, palladium, rhodium, or ruthenium.

114. A composition comprising Compound (3):

or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by oxidizing the composition of any one of claims 111-113.

115. A composition comprising Compound (4):

or a salt, solvate, or stereoisomer thereof, wherein the composition is prepared by oxidizing the composition of any one of claims 51-110.

116. The composition of any one of claims 51-115, wherein the composition comprising 4-aminodiphenylamine comprises about 99.2 wt/wt % of 4-aminodiphenylamine and about 0.3 wt/wt % 2-aminodiphenylamine.

117. The composition of any one of claims 51-81 or 90-116, wherein the catalyst is not hydrochloric acid or iodine.