HK1159114B - Process for preparing amines from alcohols and ammonia - Google Patents

Abstract

The present invention provides novel ruthenium based catalysts, and a process for preparing amines, by reacting a primary alcohol and ammonia in the presence of such catalysts, to generate the amine and water. According to the process of the invention, primary alcohols react directly with ammonia to produce primary amines and water in high yields and high turnover numbers. This reaction is catalyzed by novel ruthenium complexes, which are preferably composed of quinolinyl or acridinyl based pincer ligands.

Description

Process for preparing amines from alcohols and ammonia

Technical Field

The present invention relates to novel ruthenium catalysts and to a process for preparing primary amines by reacting alcohols with ammonia in the presence of such catalysts.

Background

Amines are very important in chemistry and biologyA kind of compound is provided. They are widely used in the production of pharmaceuticals, fine chemicals, agrochemicals, polymers, dyes, pigments, emulsifiers and plasticizers (1). In amines, terminal primary amines (e.g. RNH)₂Where R is an organic group) are the most useful, but their selective synthesis is challenging due to their high reactivity.

Conversion of alcohols to amines by conventional methods typically involves two to three steps, each of which typically requires isolation and purification, making the process cumbersome for even small scale synthesis (2). Less processes are known for the stepwise one-pot conversion of alcohols to primary amines, but such processes are not environmentally friendly and are not suitable for large-scale production (3-6). Existing methods for the preparation of primary amines typically utilize stoichiometric amounts of toxic reagents and result in poor selectivity and very low atom economy (7-9). An attractive process for the preparation of linear secondary and tertiary amines by hydroaminomethylation of internal olefins is reported. Amines are also prepared by reduction of amides, usually under severe conditions that produce a mixture of products (11). Iridium and rhodium catalyzed preparation of amines from aldehydes has also been reported (12). Although high hydrogen pressures were required to reductively aminate the aldehyde and form the alcohol as a byproduct, the present method represents the first homogeneous catalytic reductive amination process with ammonia. Lewis acid catalyzed reductive amination processes (13, 14) for the synthesis of amines are also known. Recently, the synthesis of aromatic amines was achieved by palladium-catalyzed arylation of ammonia in dioxane (15). The primary amine may be alkylated with an alcohol to obtain the secondary amine (16). Iridium-catalysed polyhydrocarbylation of ammonium salts with alcohols for the synthesis of secondary and tertiary amines is reported, but the selective synthesis of primary amines remains a difficult task to accomplish (17).

In processes for the commercial production of amines (1, 18), to date, the largest and most utilized are based on the reaction of alcohols with ammonia. However, the solid acid-catalyzed reaction of alcohols with ammonia requires very high temperatures (300-. The metal oxide catalyzed reaction of alcohols and amines at high temperature and pressure also produces a mixture of amines and must be carried out under hydrogen pressure for catalyst stability. Furthermore, the reaction forms alkanes as a result of the CO evolution. (18)

The catalytic coupling of ammonia to organic substrates for the direct preparation of aryl and primary hydrocarbyl amines is considered to be two of the ten greatest challenges in catalysis (19). The atom economy approach of activating amines (instead of the Mitsunobu process) to perform direct nucleophilic substitution excluding azides and hydrazines and "N" -centered chemistry is one of the most desirable processes in the pharmaceutical industry (20). The selective catalytic synthesis of primary amines is an unreasonable challenge because primary amines are more nucleophilic than ammonia and compete with ammonia in the reaction with electrophiles such as hydrocarbyl halides or aldehydes to produce secondary amines (21), which can also react, leading to the formation of a mixture of products.

Thus, the selective catalytic synthesis of primary amines directly from alcohols and ammonia without generating waste products with concomitant dehydration under relatively mild conditions is highly economically and environmentally desirable. However, such a simple method is not known.

The pincer complexes may have outstanding catalytic properties (22, 23). Applicants of the present invention previously reported dehydrogenation of alcohols catalyzed by PNP-and PNN-Ru (II) hydride complexes (24). While secondary alcohols produce ketones (25, 26), primary alcohols are efficiently converted to esters and dihydrogen (25-26). Dearomatized PNN pincer complexes are particularly efficient (28); which catalyses the process under neutral conditions in high yield in the absence of an acceptor or co-catalyst. U.S. application publication No. US 2009/0112005, which is the applicant of the present invention, describes a process for preparing amides by reacting a primary amine and a primary alcohol in the presence of a ruthenium catalyst to form an amide compound and molecular hydrogen.

Given the general importance of amines in biochemical and chemical systems, efficient syntheses that avoid the disadvantages of the prior art methods are highly desirable.

Summary of The Invention

The present invention provides novel ruthenium-based catalysts, and methods for producing primary amines by reacting a primary alcohol and ammonia in the presence of such catalysts to produce a primary amine compound and water. As encompassed herein, the inventors have discovered a novel process for preparing amines in which primary amines are prepared directly from primary alcohols and ammonia under mild conditions, which obviates the need for stoichiometric amounts of toxic reagents, high pressures and harsh experimental conditions. The reaction is homogeneously catalyzed by novel ruthenium pincer complexes which are stable to air and can be carried out in water, in various organic solvents, in the absence of solvents or in heterogeneous or homogeneous mixtures of water and organic solvents. The simplicity, versatility and excellent atom economy of the present process make it attractive for the conversion of alcohols to amines both in small-scale applications and large-scale applications.

The process of the present invention, i.e. the direct catalytic conversion of alcohol and ammonia to amine and water, is shown in scheme 1. This novel environmentally benign reaction can be used to produce a variety of amines from very simple substrates, has high atom economy and does not use any stoichiometric amount of activator, and therefore does not produce waste.

Scheme 1:

the applicant of the present invention has surprisingly found that novel ruthenium complexes catalyze the reaction of primary alcohols with ammonia to form primary amines and H₂And O. In one embodiment, the ruthenium catalyst is represented by the structure of formula a:

wherein

L₁And L₂Each independently selected from the group consisting of: phosphine (PR)^aR^b) Amine (NR)^aR^b) Imines, Sulfides (SR), thiols (SH), sulfoxides (S (═ O) R), heteroaryl groups containing at least one heteroatom selected from nitrogen and sulfur; arsine (AsR)^aR^b)、(stibine)(SbR^aR^b) And an N-heterocyclic carbene represented by the following structure:

L₃is a monodentate, two-electron donor, e.g. CO, PR^aR^bR^c、NO⁺、AsR^aR^bR^c、SbR^aR^bR^c、SR^aR^bNitrile (RCN), isonitrile (RNC), N₂、PF₃CS, heteroaryl (e.g., pyridine, thiophene), tetrahydrothiophene, and N-heterocyclic carbenes;

R¹and R²Each is hydrogen or together with the carbon to which they are attached represents a phenyl ring fused to the quinolinyl moiety of formula a to form an acridinyl moiety;

R、R^a、R^b、R^c、R³、R⁴and R⁵Each is independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;

y being a monoanionic ligand, e.g. halogen, OCOR, OCOCF₃、OSO₂R、OSO₂CF₃、CN、OH、OR、NR₂(ii) a Neutral solvent molecule NH₃、NR₃Or R₂NSO₂R, wherein R is as defined above. Note that when Y is middleWhen it is used, the whole molecule carries a positive charge.

X represents one, two, three, four, five, six or seven substituents located on any carbon atom of the acridinyl moiety (in which R is¹And R²In the case where together with the carbon to which they are attached represent a benzene ring fused to the quinolinyl moiety of formula a); or one, two, three, four or five substituents located on any carbon atom of said quinolinyl moiety (wherein R is¹And R²Each being hydrogen) and is selected from the group consisting of: hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, inorganic supports (e.g., silica) and polymeric moieties (e.g., polystyrene).

In one embodiment, R¹And R²Each is H, and the ruthenium catalyst is represented by the following structure:

in another embodiment, R¹And R²Together with the carbon atom to which they are attached form a benzene ring fused to a quinolinyl moiety to form an acridinyl moiety, and the ruthenium catalyst is represented by the following structure:

several non-limiting embodiments of the ruthenium catalyst of the present invention are:

substituent R^aAnd R^bEach is independently hydrocarbyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydrocyclohydrocarbyl, hydrocycloaryl, hydrocycloheterocyclyl, or hydrocycloheteroaryl. Some non-limiting examples are methyl, ethyl, isopropyl, t-butyl, cyclohexyl, cyclopentyl, phenyl, 2, 4, 6-trimethylphenyl, and the like.

The substituent Y being a monoanionic ligand, e.g. halogen, OCOR, OCOCF₃、OSO₂R、OSO₂CF₃CN, OH, OR OR NR₂Wherein R is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl. Some non-limiting examples are F, Cl, Br, I, OCOCH₃、OCOCF₃、OSO₂CF₃And other anionic ligands. The presently preferred Y ligand is halogen, such as Cl. Y may also be a neutral solvent molecule, NH₃、NR₃、R₂NSO₂R, and the like. When Y is neutral, the complex is charged, as exemplified below for the embodiment where Y is a solvent ligand:

examples of solvent ligand molecules (i.e., Y ═ solvent molecules) include, but are not limited to, acetone, dihydrocarbyl ketones (e.g., 2-butanone), cyclic ketones (e.g., cyclohexanone), THF, anisole, dimethyl sulfoxide, acetonitrile, CH₂Cl₂Toluene, water, pyridine, and the like.

In a presently preferred embodiment, L₃Is CO.

In a particular embodiment, the ruthenium catalyst is represented by the structure of formula 1 below:

in an alternative embodiment, the ruthenium catalyst is prepared by reacting complex A with sodium borohydride (NaBH)₄) Borane derivative of the catalyst of formula a obtained by the reaction. The borane derivatives are represented by the structure of formula B.

In a particular embodiment, the borane derivative is represented by the structure of formula 3. Complex 3 is sometimes referred to herein as "RuH (BH)₃)(A-ⁱPr-PNP)(CO)”。

The term "primary alcohol" as used herein refers to RCH of the formula₂A compound of OH, wherein R is an organic group. A wide variety of primary alcohols may be used in the process of the present invention. In one embodiment, the alcohol is represented by the formula R⁶CH₂OH represents wherein R⁶Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl and hydrocarbyloxy alkyl. In certain exemplary embodiments, the alcohol is selected from the group consisting of: methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, benzyl alcohol, o-methoxybenzyl alcohol, m-or p-methoxybenzyl alcohol, o-halobenzyl alcohol, m-or p-halobenzyl alcohol, pyridin-2-yl-methanol, 2-furanylmethanol, 2-phenylethanol, 2-methoxyethanol, 2-methyl-1-butanol, cyclohexylmethanol and 3-methyloxetan-3-yl) methanol.

The term "ammonia" as used herein refers to the compound "NH₃". Usually, ammonia is used as the gasThe application is as follows. However, in an alternative embodiment, the present invention contemplates the use of ammonium hydroxide (NH) when water is used as the reaction solvent₄ ⁺OH^-) An aqueous solution of (a). Thus, according to this embodiment, ammonia is provided as an aqueous solution of ammonium hydroxide.

As used herein, the term "primary amine" refers to the formula RNH₂Wherein R is an organic group. The primary amine is typically of the formula RNH₂Wherein R is an organic group. Preferably, the primary amine is of the formula RCH₂NH₂Wherein R is an organic group. A wide variety of primary amines can be prepared in the process of the invention. In one embodiment, the primary amine obtained by the process of the invention is of the formula R⁶CH₂NH₂Is represented by, wherein R⁶Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl and hydrocarbyloxy alkyl.

The process of the invention may be carried out in the presence or absence of a solvent. When present, the solvent may be aqueous (i.e., water), an organic solvent, or a mixture thereof. When mixtures of water and organic solvents are used, the solvent system may form a homogeneous solution or a heterogeneous mixture. Some non-limiting examples of organic solvents are benzene, toluene, o-, m-or p-xylene and mesitylene (1,3, 5-trimethylbenzene), dioxane, THF, DME (dimethoxyethane), anisole and cyclohexane.

The ammonia and primary alcohol may be used in equimolar amounts, however, it is preferred to add an excess of ammonia.

In another embodiment, the present invention provides a precursor for preparing the ruthenium catalyst of the invention. In one embodiment, the precursor is represented by the structure of formula 2A:

wherein

Each R is independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;

R¹and R²Each is hydrogen, or together with the carbon to which they are attached represents a benzene ring fused to a quinolinyl moiety to form an acridinyl moiety; and is

X represents one, two, three, four, five, six or seven substituents located on any carbon atom of the acridinyl moiety (in which R is¹And R²In the case where together with the carbon to which they are attached represent a benzene ring fused to the quinolinyl moiety of formula a); or one, two, three, four or five substituents located on any carbon atom of said quinolinyl moiety (wherein R is¹And R²Each being hydrogen) and is selected from the group consisting of: hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, inorganic supports (e.g., silica) and polymeric moieties (e.g., polystyrene).

A particular embodiment of formula 2A is where each R is isopropyl, R¹And R²Together with the carbon to which they are attached represent a compound fused to a quinolinyl moiety to form a benzene ring of an acridinyl moiety, and the compound has the structure of formula 2:

detailed description of the invention

The present invention relates to novel ruthenium catalysts and to a process for preparing primary amines by reacting a primary alcohol and ammonia in the presence of such catalysts to produce ammonia and water as the only products.

The present reaction is catalyzed by novel ruthenium complexes, preferably based on quinolyl or acridinyl ligands, and does not require a base or acid promoter.

In one embodiment, the ruthenium catalyst is represented by the structure:

wherein

L₁And L₂Each independently selected from the group consisting of: phosphine (PR)^aR^b) Amine (NR)^aR^b) Imines, Sulfides (SR), thiols (SH), sulfoxides (S (═ O) R), heteroaryl groups containing at least one heteroatom selected from nitrogen and sulfur; arsine (AsR)^aR^b)、(SbR^aR^b) And an N-heterocyclic carbene represented by the following structure:

L₃is a monodentate, two-electron donor, e.g. CO, PR^aR^bR^c、NO⁺、AsR^aR^bR^c、SbR^aR^bR^c、SR^aR^bNitrile (RCN), isonitrile (RNC), N₂、PF₃CS, heteroaryl (e.g., pyridine, thiophene), and tetrahydrothiophene;

R¹and R²Each is hydrogen, or together with the carbon to which they are attached represents a phenyl ring fused to the quinolinyl moiety of formula a to form an acridinyl moiety;

R、R^a、R^b、R^c、R³、R⁴and R⁵Each is independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;

y being a monoanionic ligand, e.g. halogen, OCOR, OCOCF₃、OSO₂R、OSO₂CF₃、CN、OH、OR、NR₂(ii) a Neutral solvent molecule NH₃、NR₃Or R₂NSO₂R, wherein R is as defined above. Note that when Y is neutral, the entire molecule carries a positive charge.

X represents one, two, three, four, five, six or seven substituents located on any carbon atom of the acridinyl moiety (in which R is¹And R²In the case where together with the carbon to which they are attached represent a benzene ring fused to the quinolinyl moiety of formula a); or one, two, three, four or five substituents located on any carbon atom of said quinolinyl moiety (wherein R is¹And R²Each being hydrogen) and is selected from the group consisting of: hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, inorganic supports (e.g., silica) and polymeric moieties (e.g., polystyrene).

In one embodiment, R¹And R²Each is H, and the ruthenium catalyst is represented by the following structure:

in another embodiment, R¹And R²Together with the carbon atom to which they are attached to form fused quinolinesThe quinoline moiety thereby forms a benzene ring of the acridinyl moiety, and the ruthenium catalyst is represented by the following structure:

several non-limiting embodiments of the ruthenium catalyst of the present invention are:

substituent R^aAnd R^bEach is independently hydrocarbyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydrocyclohydrocarbyl, hydrocycloaryl, hydrocycloheterocyclyl, or hydrocycloheteroaryl. Some non-limiting examples are methyl, ethyl, isopropyl, t-butyl, cyclohexyl, cyclopentyl, phenyl, 2, 4, 6-trimethylphenyl, and the like.

The substituent Y being a monoanionic ligand, e.g. halogen, OCOR, OCOCF₃、OSO₂R、OSO₂CF₃CN, OH, OR OR NR₂Wherein R is alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl. Some non-limiting examples are F, Cl, Br, I, OCOCH₃、OCOCF₃、OSO₂CF₃And other anionic ligands. The presently preferred Y substituent is halogen, such as Cl. Y may also be a neutral solvent molecule, NH₃、NR₃、R₂NSO₂R, and the like. When Y is neutral, the complex is charged, as exemplified below for the embodiment where Y is a solvent:

examples of embodiments in which Y is a solvent include, but are not limited to, acetone, dihydrocarbyl ketones (e.g., 2-butanone), cyclic ketones (e.g., cyclohexanone), THF, anisole, dimethyl sulfoxide, acetonitrile, CH₂Cl₂Toluene, water, pyridine, and the like.

In a presently preferred embodiment, L₃Is CO.

In a particular embodiment, the ruthenium catalyst is represented by the structure of formula 1 below:

in one embodiment, the ruthenium catalyst is prepared by reacting compound A with sodium borohydride (NaBH)₄) The borane derivative of the catalyst of formula a obtained by the reaction is illustrated in scheme 2 below. The borane derivatives are represented by the structure of formula B:

scheme 2

In one embodiment, the borane derivative is represented by the structure of formula 3:

the borane derivatives of formula 3 can be obtained by the procedure set forth in scheme 3:

it is understood that when the catalyst includes one or more chiral centers, all stereoisomers are included within the scope of the present invention.

A wide variety of primary alcohols may be used in the process of the present invention. In one embodiment, the alcohol is represented by the formula RCH₂OH represents, wherein R is an organic group. In another embodiment, the alcohol is represented by the formula R⁶CH₂OH represents wherein R⁶Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkylaryl, alkyl heterocyclyl, alkyl heteroaryl, aryloxyalkyl and hydrocarbyloxyalkyl. In certain exemplary embodiments, the alcohol is selected from the group consisting of: methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, benzyl alcohol, o-methoxybenzyl alcohol, m-or p-methoxybenzyl alcohol, o-halobenzyl alcohol, m-or p-halobenzyl alcohol, (pyridin-2-yl) methanol, 2-furanyl methanol, 2-phenylethanol, 2-methoxyethanol, 2-methyl-1-butanol, cyclohexylmethanol and (3-methyloxetan-3-yl) methanol.

Various primary amines can be prepared in the process of the invention. In one embodiment, the primary amine obtained by the process of the invention is of the formula RNH₂Wherein R is an organic group. In another embodiment, the primary amine obtained by the process of the invention is of the formula RCH₂NH₂Wherein R is an organic group. Preferably, the primary amine obtained by the process of the invention is of the formula R⁶CH₂NH₂Is represented by, wherein R⁶Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl and hydrocarbyloxy alkyl.

The process of the invention may be carried out in the presence or absence of a solvent. When present, the solvent may be aqueous (i.e., water), an organic solvent, or a mixture thereof. When mixtures of water and organic solvents are used, the solvent system may form a homogeneous solution or a heterogeneous mixture. Non-limiting examples of organic solvents are benzene, toluene, o-xylene, m-xylene orP-xylene mesitylene (1,3, 5-trimethylbenzene), dioxane, THF, DME, anisole and cyclohexane. In one embodiment, the present invention contemplates the use of ammonium hydroxide (NH) when water is used as the reaction solvent⁴⁺OH^-) An aqueous solution of (a).

The stoichiometric ratio of ammonia to primary alcohol can vary and depends on the particular alcohol and solvent used for the reaction. In one embodiment, the ammonia and alcohol may be added in equimolar amounts. However, in a preferred embodiment, an excess of ammonia is used. Exemplary amounts of ammonia are between 1atm and about 1000atm, such as between 5 and 500atm, between 5 and 100atm, between 5 and 20atm, preferably between 7 and 10atm, such as 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 atm. Exemplary corresponding amounts of alcohol are between 1 and 100mmol or higher, such as 100 and 500mmol, preferably between 1 and 10mmol, more preferably between 1 and 5 mmol.

The reaction of the present invention may be carried out for a length of time necessary to effect conversion of the primary alcohol to the primary amine, for example, from 1 hour to 24 hours or longer than 24 hours. The temperature range may vary from room temperature to heated conditions, for example up to 200 ℃.

In another embodiment, the process of the present invention may be used to prepare secondary amines by the reaction of a primary amine and a primary alcohol. The primary alcohol may be of the formula R as described above⁶CH₂Any of OH alcohols. The primary amine may have, for example, the formula R⁷NH₂Wherein R is⁷Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl and hydrocarbyloxy alkyl. In certain exemplary embodiments, the primary amine is selected from the group consisting of: methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, benzylamine, cyclohexylamine, and the like. According to this embodiment, the resulting secondary amine has the formula R⁶CH₂NR⁷H. Typically, the reaction between a primary and a primary amine to form a secondary amine is carried out at elevated temperatures (e.g., 160-Ranging from a period of 24 hours to 72 hours. However, it will be apparent to those skilled in the art that the reaction conditions may be optimized as deemed appropriate by those skilled in the art.

Chemical definition

As used herein, the term hydrocarbyl, when used alone or as part of another group, refers to "C" in one embodiment₁To C₁₂Hydrocarbyl "and means linear and branched, saturated or unsaturated (e.g., alkenyl, alkynyl) groups and can contain mixed structures, the unsaturated groups being only when the number of carbon atoms in the hydrocarbyl chain is greater than or equal to two. Preferably a hydrocarbon radical (C) containing 1 to 6 carbon atoms₁To C₆A hydrocarbyl group). Preferably a hydrocarbon radical (C) containing 1 to 4 carbon atoms₁To C₄A hydrocarbyl group). Examples of saturated hydrocarbyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, and hexyl. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, butenyl, and the like. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, and the like. Similarly, the term "C₁To C₁₂Alkylene "means a divalent group of 1 to 12 carbons.

The hydrocarbyl group may be unsubstituted or substituted with one or more substituents selected from the group consisting of: halogen, hydroxy, alkoxy, aryloxy, hydrocarbylaryloxy, heteroaryloxy, oxo, cycloalkyl, phenyl, heteroaryl, heterocyclyl, naphthyl, amino, alkylamino, arylamino, heteroarylamino, dihydrocarbylamino, diarylamino, hydrocarbylarylamino, hydrocarbylheteroarylamino, arylheteroarylamino, acyl, acyloxy, nitro, carboxy, carbamoyl, carboxamide, cyano, sulfonyl, sulfonylamino, sulfinyl, sulfinylamino, thiol, hydrocarbylthio, arylthio, or hydrocarbylsulfonyl group. Any substituent may be unsubstituted or further substituted with any of these aforementioned substituents. By way of illustration, a "hydrocarbyloxyhydrocarbyl group" is a hydrocarbyl group substituted with a hydrocarbyloxy group.

The term "cycloalkyl" as used herein alone or as part of another group means "C₃To C₈Cycloalkyl "and means any saturated or unsaturated (e.g., cycloalkenyl, cycloalkynyl) monocyclic or polycyclic group. Non-limiting examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Examples of cycloalkenyl groups include cyclopentenyl, cyclohexenyl, and the like. The cycloalkyl group may be unsubstituted or substituted with any one or more of the substituents defined above for the cycloalkyl group. Similarly, the term "cycloalkylene" means a divalent cycloalkyl group as defined above, wherein the cycloalkyl group is bonded at two positions linking two separate additional groups together. A hydrocarbyl cycloalkyl group refers to a hydrocarbyl group bonded to a cycloalkyl group.

The term "aryl" as used herein alone or as part of another group denotes an aromatic ring system containing from 6 to 14 ring carbon atoms. The aromatic ring may be monocyclic, bicyclic, tricyclic, and the like. Non-limiting examples of aryl groups are phenyl, naphthyl, including 1-naphthyl and 2-naphthyl, and the like. The aryl group may be unsubstituted or substituted through available carbon atoms by one or more groups as defined above for the hydrocarbyl group. An alkylaryl group refers to an alkyl group (e.g., benzyl) bonded to an aryl group.

The term "heteroaryl" as used herein alone or as part of another group denotes a heteroaromatic system containing at least one heteroatom ring atom selected from nitrogen, sulfur and oxygen. Heteroaryl groups contain 5 or more ring atoms. Heteroaryl groups can be monocyclic, bicyclic, tricyclic, and the like. Also included in this expression are benzoheterocycles. If the ring atom is nitrogen, the present invention also encompasses N-oxides of nitrogen-containing heteroaryl groups. Non-limiting examples of heteroatoms include thienyl, benzothienyl, 1-naphthothienyl, thianthrenyl, furyl, benzofuryl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, indazolyl, purinyl, isoquinolyl, quinolyl, acridinyl, naphthyridinyl, quinoxalyl, quinazolinyl, cinnolinyl, piperidinyl, carbolinyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, and the like. Heteroaryl groups may be unsubstituted or substituted by one or more groups as defined above for hydrocarbyl through available atoms. An alkylheteroaryl group refers to an alkyl group bonded to a heteroaryl group.

The term "heterocycle" or "heterocyclyl" as used herein alone or as part of another group denotes a five to eight membered ring having 1 to 4 heteroatoms, such as oxygen, sulfur and/or nitrogen. These five-to eight-membered rings may be saturated, fully unsaturated or partially unsaturated. Non-limiting examples of heterocycles include piperidinyl, pyrrolidinyl, pyrrolinyl, pyrazolinyl, pyrazolidinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl, piperazinyl, indolinyl, dihydrofuranyl, tetrahydrofuranyl, dihydrothienyl, tetrahydrothienyl, dihydropyranyl, tetrahydropyranyl, and the like. The heterocyclyl group may be unsubstituted or substituted by one or more groups as defined above for the hydrocarbyl group, through available atoms. A hydrocarbyl heterocyclyl group refers to a hydrocarbyl group bonded to a heterocyclyl group.

The term "hydrocarbyloxy" refers to a hydrocarbyl group bonded to an oxygen, such as methoxy, ethoxy, propoxy, and the like. The term "aryloxy" refers to an aryl group bonded to oxygen, such as phenoxy and the like. The term "halogen" refers to F, Cl, Br or I. The term "amide" refers to RCONH₂RCONHR or RCON (R)₂Wherein R is as defined herein. The term "ester" refers to RCOOR, wherein R is as defined herein. The term "cyano" refers to a CN group. The term "nitro" means "NO₂A "group.

The inorganic support to which the pyridine ring in formula a is attached may be, for example, silica gel, glass fiber, titania, zirconia, alumina, and nickel oxide.

The polymer to which the pyridine ring in formula a is attached may, for example, be selected from polyolefins, polyamides, polyethylene terephthalate, polyvinyl chloride, polyvinylidene chloride, polystyrene, polymethacrylate, natural rubber, polyisoprene, butadiene-styrene random copolymer, butadiene acrylonitrile copolymer, polycarbonate, polyacetal, polyphenylene sulfide, cyclic olefin copolymer, styrene-acrylonitrile copolymer, ABS, styrene-maleic anhydride copolymer, chloroprene polymer, isobutylene copolymer, polystyrene, polyethylene, polypropylene, and the like.

As used herein, the term "quinolinyl" refers to a group represented by the following structure:as used herein, the term "acridinyl" refers to a group represented by the following structure:as will be readily understood by those skilled in the art and as described herein, a quinolinyl or acridinyl functional group can be attached to the ruthenium catalysts of the present invention.

An exemplary procedure:

benzyl alcohol was reacted with ammonia in the presence of ruthenium catalyst 1(0.1 mol%) in refluxing mesitylene (boiling point 163 ℃ C.). As shown in entries 1-3 of Table 1, 98% conversion of the alcohol was observed after 1 hour to give 69% benzylamine and 28% N-benzylidene benzylamine. At longer reaction times, a slightly higher yield of benzylamine was observed. Similar results were obtained after 3 hours in refluxing p-xylene (boiling point 138 ℃) at lower temperatures (table 1, entry 4). When the reaction was carried out in toluene (b.p. 110.5 ℃) for the same time, the conversion efficiency of benzyl alcohol was lower (table 1, entry 5), but after 13h 99% conversion of benzyl alcohol occurred to provide 87% yield of benzylamine and N-benzylidene benzylamine (12%). Using dioxane (boiling point 100 ℃) as solvent and further lowering the reaction temperature resulted in lower conversion (table 1, entry 7).

Table 1. Benzylamine was synthesized directly from benzyl alcohol and ammonia catalyzed by ruthenium complex 1. Complex 1(0.01mmol), benzyl alcohol (10mmol), ammonia (7.5atm) and solvent (3ml) were heated to reflux in a Fischer-Porter flask. The conversion of alcohol and the yield of product were analyzed using Gas Chromatography (GC).

^aThe reaction is carried out in a refluxing solvent.^bTemperature of the oil bath.

To test whether increasing the concentration of ammonia relative to alcohol can reduce imine formation (e.g., by trapping the contemplated intermediate aldehyde and preventing it from reacting with the primary amine), complex 1(0.01mmol), benzyl alcohol (2.5mmol), and ammonia (8atm) in toluene were heated at reflux in a Fischer-Porter tube for 130 minutes to give benzylamine (64.6%) and N-benzylidene benzylamine (19.3%), while the conversion of benzyl alcohol was 84.7% (compare with entry 6 of table 1). Thus, increasing the concentration of ammonia does not affect the extent of imine formation.

1-hexanol was chosen as the benchmark substrate for the study of the direct amination reaction of simple fatty alcohols (benchmark). 1-hexylamine and dihexylamine were formed, the latter yield increasing at higher reaction temperatures and longer reaction times (Table 2). When the reaction was carried out in refluxing toluene for 15h, 1-hexylamine was obtained in 63% yield, while the major by-product was the corresponding imine (table 2, entry 3). When the same reaction was extended to 24h, the yield of dihexylamine increased from 3% to 18% and the yield of 1-hexylamine decreased to 58% (table 2, entry 4).

Table 2. The direct synthesis of 1-hexylamine from 1-hexanol and ammonia was catalyzed by ruthenium complex 1. Complex 1(0.01mmol), 1-hexanol (10mmol), ammonia (7.5atm) and solvent (3ml) were heated to reflux in a Fischer-Porter flask. The conversion of the amine and the yield of the product were analyzed using GC.

^*The corresponding imine is the major by-product.Trihexylamine is formed as a by-product.

The range of direct amination of the alcohol with ammonia catalyzed by complex 1(0.1 mol%) in refluxing toluene was investigated relative to the alcohol (table 3). The arylcarbinols undergo an easy reaction to provide benzylamine in good yield. Benzyl alcohol with electron donating groups on the benzene ring reacted faster (table 3, entries 1, 2) than benzyl alcohol with electron withdrawing groups (table 3, entry 3). Electron-rich heteroaryl carbinols exhibit excellent selectivity towards primary amines. Pyridin-2-yl-methanol and 2-furanylmethanol were converted to the corresponding primary amines in 96% and 94.8% yields, respectively (table 3, entries 4, 5). Like 1-hexanol, 1-pentanol also reacted to result in the formation of 1-pentylamine (61%) and dipentylamine (34.6%) (table 3, entry 6). 2-Phenylethanol reacted similarly, but the formation of secondary amines was less favorable (Table 3, entry 7). 2-methoxyethanol exhibited very good selectivity to the primary amine, providing 2-methoxyethylamine in 94.5% yield (table 3, entry 8). Good selectivity for the synthesis of aryl and heteroarylmethylamines is obtained. Increasing the steric hindrance at the beta position of the hydrocarbon alcohol reduces the formation of imines and the corresponding secondary amines and thus increases the selectivity and yield of primary amines (table 3, entries 9-11). Notably, the strained (strained) 4-membered ring in (3-methyloxetan-3-yl) methanol (table 3, entry 9) remained intact, resulting in high yields of primary amines. The reaction also takes place efficiently in pure alcohol, without the need for added solvent (table 3, entries 6, 9).

Table 3. The amine was synthesized directly from alcohol and ammonia catalyzed by ruthenium complex 1. Complex 1(0.01mmol), alcohol (10mmol), ammonia (7.5atm) and toluene (3ml) were heated in a Fischer-Porter. The conversion of alcohol and the yield of product were analyzed using GC.

^*Clean Reaction (Neat Reaction).The corresponding imine is the major by-product in all reactions (analyzed by GC-MS and MS (esi)); the yield was not determined.Yield of dipentylamine.

Since the generation of a stoichiometric amount of water in the reaction does not affect the catalysis of complex 1, the possibility of using water as reaction medium was investigated. Interestingly, direct amination of alcohol with ammonia "on water" by complex 1 performed very well with excellent selectivity for primary amines. While water is the most environmentally friendly possible solvent of nature, its current use in catalysis is limited (28). The presence of a very large excess of water is advantageous because it may already lead to hydrolysis of the imine formed by further reaction of the primary amine and thus enhance the selectivity towards primary amines (table 4, entries 1-3). Benzylamine and 2-phenylethanol are insoluble in water at room temperature, form a homogeneous solution upon heating, and the reaction can therefore be considered "in water". Fatty alcohols, such as 1-hexanol, are not miscible with water even when heated, and the reaction occurs "on water" (29) (table 4, entry 4). Unexpectedly, when the water-soluble alcohols ([ pyridin-2-yl ] methanol and 2-methoxyethanol) "were subjected to a direct amination reaction in water", the reaction became very slow, even after prolonged heating (30h), and the conversion was less efficient, in strong contrast to the excellent reaction in toluene (table 3, entries 4 and 8).

Table 4. The amines were synthesized directly from alcohols and ammonia in water and on water, catalyzed by ruthenium complex 1. Complex 1(0.01mmol), alcohol (10mmol), ammonia (7.5atm) and water (3ml) were heated to reflux in a Fischer-Porter. The conversion of alcohol and the yield of product were analyzed using GC.

The corresponding imine is the major by-product in entries 1-3; the corresponding acids are by-products in entries 6-8.The corresponding acid was found in the aqueous layer.^*CaproamideFound in the aqueous layer.A mixture of 2ml of water and 2ml of toluene was used as solvent.^§A mixture of 1ml of water and 2ml of dioxane was used as solvent.

The inventors of the present invention have further found that borane derivatives of the ruthenium catalysts of the present invention are also useful as catalysts in the process for converting primary alcohols to primary amines according to the present invention. Such borane derivatives are prepared by using sodium borohydride (NaBH)₄) Treating the ruthenium catalyst. For example, complex 3(RuH (BH)₃)(A-ⁱPr — PNP) (CO)) can be used to convert benzyl alcohol to benzylamine in good yield, as shown in scheme 4 below:

scheme 4:

it should be noted that an aqueous solution of ammonium hydroxide may be used instead of ammonia gas. The reaction in water has certain practical advantages, such as separation of the aqueous and organic layers at the end of the reaction upon cooling, and further purification of the product by vacuum distillation. The selectivity of linear primary amines was improved by using co-solvents such as toluene or dioxane in water (table 4, entries 5-7).

In addition to the selective synthesis of commercially important primary amines, the present invention also provides tools for the direct production of amine functionality from alcohols without generating waste in the synthesis of complex natural products and pharmaceuticals.

The disclosures of all cited references are incorporated by reference as if fully set forth herein.

Experimental details section

Example 1

Acridine-based pincer complex RuHCl (A-ⁱPreparation of Pr-PNP) (CO)1

By means of a novel electron-rich tridentate PNP ligand 2 with RuHCl (PPh)₃)₃(CO) reaction in toluene at 65 ℃ for 2h (scheme 5) quantitative preparation of the novel acridine-based pincer complex RuHCl (A-ⁱPr-PNP) (CO) 1. 1 of³¹P{¹H } NMR showed a single peak at 69.35 ppm. 1 of¹The H NMR spectrum showed a triple resonance of Ru-H at-16.09 ppm. The "arm" methylene protons produce two double triplets at 3.50ppm and 5.24 ppm: (²J_HH＝12.8Hz，²J_PH3.7 Hz). A single resonance of C9H for the acridine ring occurs at 8.15ppm, representing a high field shift of 0.46ppm relative to the corresponding proton of ligand 2 (8.61ppm), indicating reduced aromaticity of acridine upon complexation with ruthenium. The structure of complex 1 was determined by single crystal X-ray diffraction studies, which revealed a distorted octahedral geometry around the ruthenium center (30). Upon complexation, the acridine weakens its planarity and becomes bent in the middle of the aryl ring to take the shape of a boat with a dihedral angle of 167.6 °. Complex 1 is stable in air over a period of months for practical use.

Scheme 5. Synthesis of ligand 2 and Complex 1.

Scheme (b): a) i, diisopropylphosphine/MeOH, 50 ℃, 48 h; triethylamine, normal temperature, 1h, 83%. b) RuHCl (PPh)₃)₃(CO)/toluene, 65 ℃, 2h, quantitative or RuHCl (PPh)₃)₃(CO)/THF, normal temperature, 9h, 82%.

Example 2 Synthesis method

General experiments

All experiments with metal complexes and phosphine ligands were performed under a pure nitrogen atmosphere in a vacuum atmosphere glove box equipped with a MO 40-2 inert gas purifier or using standard Schlenk techniques. All solvents were reagent grade or higher. All non-deuterated solvents were refluxed on sodium/benzophenone ketyl (ketyl) and distilled under argon atmosphere. The deuterated solvent is used in the state as received. All solvents were degassed with argon and stored in a glove boxAnd (3) a molecular sieve. Most chemicals used in catalytic reactions are purified by vacuum distillation. However, the same product yields were obtained when commercial grade reagents were used. Will be selected from Barnstead NANOPicture Diamond^TMThe ultrapure water obtained from the water purification system is used for catalytic reaction in water. Preparation of 4, 5-bis (bromomethyl) acridine (31) and RuHCl (CO) (PPh) according to literature procedures₃)₃(32)。

Recording at 500, 100 and 162MHz respectively using a Bruker AMX-500NMR spectrometer¹H、¹³C and³¹p NMR spectrum.¹H and¹³C{¹h } NMR chemical shifts are reported in ppm downfield from tetramethylsilane.³¹P NMR chemical shifts to separate from H₃PO₄Reported at a low field of one part per million and referenced to phosphoric acid at D₂Outer 85% solution in O. Abbreviations used in NMR trace experiments: b, broad peak; s, single multiplet; d, doublet; t, triplet; q, quartet; m, multiplet, v, virtual shift (virtual).

4, 5-bis (bromomethyl) acridine (3A)³⁴：¹H NMR(CDCl₃)：5.31(s，4H，ArCH₂)，7.39(dd，³J_H，H＝8.5Hz，，⁴J_H，H＝7.9Hz，2H，ArH)，7.82(d，³J_H，H＝6.7Hz，2H，ArH)，7.86(d，³J_H，H＝8.5Hz，2H，ArH)，8.65(s，1H，ArH).

4, 5-bis- (diisopropylphosphinomethyl) acridine (2): to an oven-dried 100mL Schlenk flask equipped with a magnetic rotor was added 4, 5-bis (bromomethyl) acridine (3, 2g, 5.48mmol),A colored solid. The residue was washed with diethyl ether (4 × 15mL), and the diethyl ether was removed under reduced pressure to obtain a bright yellow solid. It was recrystallized from a pentane/acetone mixture to obtain 2.0g (83%) of 4, 5-bis [ (diisopropylphosphine) methyl group]Acridine (2).³¹P{¹H}NMR(C₆D₆)：12.35(s).¹H NMR(CDCl₃)：1.03(m，24H，2×P(CH(CH₃)₂)₂)，1.82(m，4H，(P-CH(CH₃)₂)₂)，3.72(d，²J_P，H＝2.4Hz，4H，2×P-CH₂)，7.39(dd，³J_H，H＝7.9Hz，⁴J_H，H＝6.7Hz，2H，ArH)，7.73(d，³J_H，H＝7.9Hz，2H，ArH)，7.81(d，³J_H，H＝6.7Hz，2H，ArH)，8.61(s，1H，ArH).¹³C{¹H}NMR(CDCl₃)：19.45(d，²J_PC＝11.5Hz，P(CH(CH₃)₂)₂)，19.74(d，²J_PC＝13.5Hz，P(CH(CH₃)₂)₂)，23.32(d，¹J_PC＝18.1Hz，2×P-CH₂)，23.75(d，¹J_PC＝14.3Hz，P(CH(CH₃)₂)₂)，125.38(s，C₁，C₈，A-PNP)，125.58(d，⁴J_PC＝2.0Hz，C₂，C₇，A-PNP)，126.59(s，C_8a，C_9a，A-PNP)，129.80(d，³J_PC＝12.3Hz，C₃，C₆，A-PNP)，136.32(s，C₉，A-PNP)，139.44(d，²J_PC＝7.5Hz，C₄，C₅，A-PNP)，148.82(d，³J_PC＝2.9Hz，C_4a，C_10aa-PNP) the attribution of each signal is determined by DEPT 135.

And dried under vacuum overnight to give pure complex 1 in quantitative yield (191 mg).³¹P{¹H}NMR(C₆D₆)：69.35(s).¹H NMR(C₆D₆)：-16.09(vt，²J_PH＝19.2Hz，1H，Ru-H)，0.88(q，³J_PH＝15.6Hz，³J_HH＝7.3Hz，6H，P(CH(CH₃)₂)₂)，1.03(q，³J_PH＝12.8Hz，³J_HH＝6.4Hz，6H，P(CH(CH₃)₂)₂) 1.53 (overlap m, 2H, P (CH))₃)₂)₂)，1.54(q，³J_PH＝13.7Hz，³J_HH＝7.3Hz，6H，P(CH(CH₃)₂)₂)，1.79(q，³J_PH＝14.7Hz，³J_HH＝7.3Hz，6H，P(CH(CH₃)₂)₂)，2.17(m，2H，P(CH(CH₃)₂)₂)，3.50(dt，²J_HH＝12.8Hz，²J_PH＝3.7Hz，2H，-CHHP)，5.24(dt，²J_HH＝12.8Hz，²J_PH＝3.7Hz，2H，-CHHP)，7.06(t，³J_HH＝7.3Hz，2H，ArH)，7.33(d，³J_H，H＝7.3Hz，2H，ArH)，7.48(d，³J_H，H＝8.2Hz，2H，ArH)，8.15(s，1H，ArH).¹³C{¹H}NMR(C₆D₆)：18.60(s，P(CH(CH₃)₂)₂)，19.42(t，²J_PC＝2.9Hz，P(CH(CH₃)₂)₂)，20.86(s，P(CH(CH₃)₂)₂)，21.94(s，P(CH(CH₃)₂)₂)，24.07(t，¹J_PC＝12.6Hz，P(CH(CH₃)₂)₂)，25.83(t，¹J_PC＝10.3Hz，P(CH(CH₃)₂)₂)，31.98(t，¹J_PC＝6.0Hz，2×CH₂P)，124.66(s，C₁，C₈，A-PNP)，129.1(s，C₂，C₇，A-PNP)，134.15(d，²J_PC＝20.12Hz，C₄，C₅，A-PNP)，135.03(t，³J_PC＝3.4Hz，C₃，C₆，A-PNP)，135.70(s，C_8a，C_9a，A-PNP)，142.13(s，C₉，A-PNP)，151.37(t，³J_PC＝2.0Hz，C_4a，C_10a，A-PNP)，203.40(t，²J_PCRu-CO — 11.4 Hz.) signal attribution was determined by DEPT 135. IR (KBr, particles): 2048.7 (v)_RuH)，1881.9(ν_CO)cm，^-1MS(ESI，MeOH)：569(100％，(M-Cl)⁺)；MS(ESI，CH₃CN)：569(42％，M-Cl)⁺，610(100％，[(M-Cl)(CH₃CN)]⁺).

Alternative methods of preparation for 1: to RuHCl (PPh)₃)₃(CO) (95.3mg, 0.1mmol) to a suspension in THF (5ml) was added ligand 2(48mg, 0.11mmol) and the mixture was stirred at room temperature for 9 h. The orange solution was filtered and the filtrate was evaporated to dryness under vacuum. The orange residue was dissolved in minimal THF (0.5mL) and slowly added to pentane (5mL) to precipitate an orange solid which was filtered and dried under vacuum (50mg, 82%).

RuH(BH₃)(A-ⁱSynthesis of Pr-PNP) (CO) (compound 3):

to a suspension of complex 1(121mg, 0.2mmol) in THF (3ml) under a nitrogen atmosphere was added NaBH in THF (2ml)₄(0.21 mmol). The mixture was stirred at room temperature for 2 hours. The colorless solution was filtered and the solvent was evaporated. The complex was dried under vacuum overnight to give AcPNP-borane ruthenium complex (RuH (BH) of formula 3) in quantitative yield (117mg)₃)(A-ⁱPr-PNP) (CO)). By NMR and by single crystal X-rayLine crystal analysis fully characterized the complex.³¹P{¹H } NMR (benzene-d)₆)：51.57(s).¹H NMR (toluene-D)₈，291K)：-9.27(td，²J_PH＝22.0Hz，²J_HH＝2.7Hz，1H，Ru-H)，-5.40(br s，1H，BH₃)，0.78(q，³J_PH＝11.0Hz，³J_HH＝6.4Hz，6H，P(CH(CH₃)₂)₂) 1.22-1.32 (overlap 3q, 18H, P (CH)₃)₂)₂)，1.51(m，2H，P(CH(CH₃)₂)₂)，2.04(m，2H，P(CH(CH₃)₂)₂)，2.35(dt，²J_HH＝13.7Hz，²J_PH＝2.7Hz，2H，-CHHP)，3.47(d，²J_HH＝15.6Hz，1H，Ar-CHH-Ar)，3.63(d，²J_HH＝13.7Hz，2H，-CHHP)，4.85(d，²J_HH＝15.6Hz，1H，Ar-CHH-Ar)，6.53(d，³J_HH＝7.3Hz，2H，ArH)，6.81(t，³J_H，H＝7.3Hz，2H，ArH)，7.01(d，³J_H，H＝7.3Hz，2H，ArH).¹³C{¹H}NMR(C₆D₆)：15.13(t，²J_PC＝2.3Hz，P(CH(CH₃)₂)₂)，19.80(t，²J_PC＝2.0Hz，P(CH(CH₃)₂)₂)，19.84(s，P(CH(CH₃)₂)₂)，20.22(s，P(CH(CH₃)₂)₂)，21.19(t，¹J_PC＝8.6Hz，P(CH(CH₃)₂)₂)，26.75(t，¹J_PC＝14.3Hz，P(CH(CH₃)₂)₂)，32.28(t，¹J_PC＝11.5Hz，2×CH₂P)，38.66(s，C₉，ArCH₂Ar)，124.40(s，C₂，C₇，A-PNP)，127.27(s，C₄，C₅，A-PNP)，127.58(s，C₁，C₈，A-PNP)，129.39(t，³J_PC＝2.9Hz，C₃，C₆，A-PNP)，141.12(s，C_8a，C_9a，A-PNP)，152.18(t，³J_PC＝3.4Hz，C_4a，C_10a，A-PNP)，207.7(t，²J_PC14.3Hz, Ru — CO), IR (KBR particles): 2413, 2357, 2333, 1913, 1462, 1437, 1036cm^-1.C₂₈H₄₄BNOP₂Analytical calculation of Ru: c, 57.54; h, 7.59. found: c57.49; h, 7.56.

General procedure for the catalytic direct amination of alcohols to amines: complex 1(0.01mmol), alcohol (10mmol) and solvent (3mL, if applicable) were added to a 90mL Fischer-Porter tube in a vacuum atmosphere glove box under a pure nitrogen atmosphere. The tubes were removed from the tank and ammonia (7.5atm) was charged to the Fischer-Porter tubes and the reaction mixture was refluxed in an oil bath covered with a protective cover for a specified time (tables 1-3 in the report). After cooling to room temperature, the products were analyzed using GC, with toluene or mesitylene as internal standard, using an HP-5 cross-linked 5% PH ME siloxane column (30m × 0.32mm × 0.25 μm film thickness) on an HP6890 series GC system.

General procedure for the catalytic direct amination of alcohols to amines in water: complex 1(0.01mmol) and alcohol (10mmol) were placed in a volume of 90mL of Fischer-Porter under an atmosphere of pure nitrogen in a vacuum atmosphere glove box. The Fischer-Porter was removed from the glove box and degassed water (3mL) was added under an atmosphere of argon. Ammonia (7.5atm) was charged to the Fischer-Porter and the reaction mixture was refluxed in an oil bath covered with a protective cover for a specified time (Table 4 in the report). After cooling to room temperature, the products were analyzed using GC with mesitylene as an internal standard, using an HP-5 cross-linked 5% PH ME siloxane column (30m × 0.32mm × 0.25 μm film thickness) on an HP6890 series GC system.

While certain embodiments of the present invention have been illustrated and described, it will be clear that the invention is not limited to the embodiments described herein. Numerous modifications, changes, variations, substitutions and equivalents will be apparent to those skilled in the art without departing from the spirit and scope of the invention as described by the following claims.

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Claims (18)

1. A ruthenium catalyst represented by the structure of formula 1:

or by reacting said formula 1 with sodium borohydride (NaBH)₄) The borane derivative of formula 1 obtained by the reaction, wherein the borane derivative is represented by the structure of formula 3:

2. a process for preparing a primary amine comprising the step of reacting a primary alcohol and ammonia in the presence of a ruthenium catalyst of the borane derivative of formula 1 or formula 3 according to claim 1, thereby generating the primary amine.

3. The process of claim 2, wherein the primary alcohol is of the formula R⁶CH₂OH represents wherein R⁶Selected from the group consisting of: alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkyl cycloalkyl, alkyl aryl, alkyl heterocyclyl, alkyl heteroaryl and hydrocarbyloxy alkyl.

4. The process of claim 2, wherein the primary alcohol is selected from the group consisting of: methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, benzyl alcohol, o-methoxybenzyl alcohol, m-or p-methoxybenzyl alcohol, o-, m-or p-halobenzyl alcohol, pyridin-2-yl-methanol, 2-furanylmethanol, 2-phenylethanol, 2-methoxyethanol, 2-methyl-1-butanol, cyclohexylmethanol and (3-methyloxetan-3-yl) methanol.

5. The process of claim 2, wherein the reaction is carried out in the presence of a solvent.

6. The method of claim 5, wherein the solvent is water or an organic solvent selected from the group consisting of: benzene, toluene, o-, m-or p-xylene, mesitylene (1,3, 5-trimethylbenzene), dioxane, THF, DME, anisole and cyclohexane.

7. The method of claim 6, wherein the solvent is water and ammonia is provided as an aqueous solution of ammonium hydroxide.

8. The method of claim 5, wherein the solvent is a mixture of water and an organic solvent.

9. The method of claim 8, wherein the water and the organic solvent form a homogeneous solution.

10. The method of claim 8, wherein the water and the organic solvent form a multiphase mixture.

11. The method of claim 2, wherein the reaction is carried out in the absence of a solvent.

12. The process of claim 2, wherein the process is carried out under heating or under an inert gas.

13. The method of claim 2, wherein excess ammonia is used.

14. Use of a ruthenium catalyst of a borane derivative of formula 1 or formula 3 according to claim 1 for the preparation of an amine by reacting a primary alcohol and ammonia in the presence of the ruthenium catalyst of the borane derivative of formula 1 or formula 3.

15. A compound represented by the structure of formula 2:

wherein PrⁱIs isopropyl.

16. Use of a compound represented by the structure of formula 2 in the preparation of a ruthenium catalyst of formula 1 according to claim 1:

wherein PrⁱIs isopropyl.

17. A method for preparing a ruthenium catalyst represented by the structure of formula 3, comprising reacting the ruthenium catalyst of formula 1 according to claim 1 with sodium borohydride (NaBH)₄) The reaction steps are as follows:

18. a process for preparing a ruthenium catalyst represented by the structure of formula 1 according to claim 1, comprising reacting a compound of formula 2 with RuHCl (PPh)₃)₃(CO) reaction step in toluene at 65 ℃ or in THF at room temperature