DE2361604A1 - PROCESS FOR THE PRODUCTION OF N, N-DISUBSTITUTED CARBONIC ACID AMIDES - Google Patents

Description

I) R. STEPHAN G ..- BESZEDES '

S. r

PATENT Attorney PATENT Attorney.

. I, _Λ 803 OACHAU «bei.MÖNCHEN. . · &"-

BOX 1168 ~ '

Τ <. AT HEIDEWEG 2

5 " TELEPHONE: DACHAU 4371

χ. , Postal checking account, MuiVctien 1368

Bank account Mr. 90 637 bei'dcr Kreis and S'adtsparkasse Dachau-Indersdorf

Be s c h r e, i ι η η .g

for patent application

ESZAIiMAGYARORSZAGI VEGYIMÜVEK

Saj obabony, Hungary

concerning

Process for the preparation of N, N-disubstituted

Carboxylic acid amides

The invention relates to a method for producing Ν, Ν-disubstituted carboxylic acid amides of the general formula

.R,

- N

'YRO c,' *

^ i

S0982571,093 Ι '

..J. . ί · ·· - ".- -« 'is worxn

_E for one, optionally by 1 or

^Λ '■ <■' · '< ^: - ^; more halogens 'or' phenyl residues ^

'; .- ■ * ■■ - <> ^; substitutedi -straight-or ver '

- ^f üL ■ - · ■ · branched aliphatic Eest with 1 to 18

ff; < ^! ~: ¹ . ■. - ^; ^ Carbon atoms, a phenyl radical, ex-

W ^} ..% - ■ -f '■' · '·'"hen chlorine phenyl radical, a dichloro- * i

f Γ '. 'V - ^{: i} -äphenylrest, a liitrophenylrest, a ". ^

J. ..'_ '. 'Dinitrophenyl radical or a trimethoxy,

ψ rJ ίφ.ν, 'phenyl radical or a nitrogen atom /

I ^ ί Ά, ■■ - - 'having unsaturated 6-membered

J '* ^; _t KW ..... - ■■ heterocyclic Eest stands and

I * and E, which can be the same or different,

^: straight-chain or branched aliphatic radicals with 1 to 4 carbon atoms or, f optionally by 1 or more ali-

I phatic residues with 1 to 4 carbon

f atoms substituted, phenyl radicals

^! interpret or together with the nitrogen

atom to which they are bound, one nitrogen and one oxygen atom represent having 5-membered heterocyclic radical.

Examples of aliphatic radicals, optionally substituted by 1 or more halogens or phenyl radicals

^! p * ^ itl bis'iS ^ orlSgiweiJe- 2 to 18, Kohlens, ppätdmen1, ffor ^ ^; : § ", Ä! Ie R ₁ stand L · ^ are Alkylx-este, *** ^ ** & ^ ZQ.- . ^ G || mi ^^ S and-Pentadelylresi ^, ^^ ό ^^ Ι ^ Μ ^ ψψ ^^ - ^ ^

^! § | f ipMrmethyirest, ^
f "c _; .:; C | 3phenyläthylreste / '" ■ ^l - ¹ ^': "', *'. /"'. .. ₍ . ί '^ _; ,, φ | _; | <2

p. g; f | f | ^ ;;:% _as piele for ^ containing a nitrogen atom ^: unge | attxgte ^^ | ^ ylj ^ -Slieder-he'terocyclic radicals, 'for which E ^ can stand ^ "^ ggp

509825/1093 '^ " ³ "' %

.are pyridyl residues.

Examples of ,, aliphatic res; be, miifc. 1 to 4 carbon atoms ^. For the R ₂₄ ^ d ₁ R ₇ . are ^ LEVERAGING or through which can be represented by R ₂ and R _5, the phenyl radicals can be substituted, are alkyl radicals such as methyl, Ithyl-,% ■ £ "i, propyl and butyl radicals, and alkoxyalkyl, -As Methoxyf "J methyl, kthoxymethyl and butoxymethyl radicals.

jt An example of a nitrogen and an oxygen atom

6-membered heterocyclic radicals which can be represented by R ₂ and *> R _x together with the nitrogen atom to which they are attached, is the morpholine radical.

Among the compounds of formula I are extremely '' t many important pesticides and pharmaceuticals. The "- plant protection agents of the formula I are distinguished by their very favorable selective herbicidal action. The substances of the formula I which can be used as medicaments include sedatives or tranquilizers and also substances and tonics or analeptics which are well suited for the treatment of arteriosclerosis.

The compounds of formula I can be Ν, Ν-disubstituted Carboxamides, but also al σ acylated amines

to be eaten. Domentsprechend exist for their preparation two main options: 1 ') acylating the secondary; v, amines μηΛ, * 2, _-), which .A ^ kylieren of carboxamides.. -,

<}: -, The, ira ;. Fachschriftenverlag turn the .organischen chemistry, described · l _'ti' 'surrounded -zahliieichen opportunities for acylating amines. * "in Houben- ^ oyl, Methods of Organic Chemistry, 8, 1/18

I.1952J. For example, the acylation of ^fl '' with carbonic anhydride or carboric acid is known, where, in addition to the acylic acid, Am, n is a carboxylic acid; relational. a. Al-., Γ-

Γ 509825 / 10.93 - - -

>;. _{Γ (} , -, γ # 361604

alcohol is formed. The disadvantage of this method is there daring that e ^ s in general only with primary amines with lower Carbon, atomic number is useful (A. Kaufmann: Ber. ^; 5,480fi909}; H. Hon | cka: Soc., | 9, 428 p]

The acylation can be carried out more cheaply and with a higher yield using carboxylic acid chlorides. However, this reaction is strongly exothermic and for control purposes the heat of reaction must be removed. Furthermore, the hydrochloric acid formed must be bound, since it reacts with the amine used as the starting material, and this reduces the yield of the reaction. In addition, the production and purification of carboxylic acid chlorides of greater chain length is laborious (Ch. E. Gaspari: Am. Soc. 27, 305 (39023 j W. Weaver, WM Whaley: Am. Soc. 69, Λ 144 [1947]).

In the case of primary amines and short-chain carboxylic acid, this succeeds dje acylation of the amines at high temperatures too with carboxylic acids, with the resulting water being contimidated is removed, for example by distilling off in the azeotropic Mixture with xylene. However, this procedure is only available as a laboratory

■ fcorium method and also only applicable for primary amines, An additional condition is that the amines and the carboxylic acid must be insensitive to heat. Acylating primary amines with carboxylic acids in the presence of phosphorus trichloride has been published by M. Grimmel in J. Am = Soc * 68) 539 1 ^ 946J described. In this reaction forms., First 'the amine with the H) osphörtrichlorid a phosphorus compound; as an intermediate product from which the amine acylated by the carboxylic acid is formed.

There is also acylation with phosphorus oxychloride phosphorus pentoxide or etraniethylphosphate and carboxylic acids known, in which the implementation via the formation of -phosphorus

^; 509825/1093 " ^5th

esteramide !! runs.

In Hungarian patent specification 159 044- the chloroacylation is secondary amines using chlorocarboxylic acids and phosphorus trichloride ".

The fact that acid aides can be prepared by hydrolysis of carboxylic acid nitriles is known, although less important in practice. (C. Exigler: Ann. ,, 14-9 ■> 306 [-1869) ·

The second main group of processes for the preparation of IJ, N-disubstituted carboxamides is, according to the technical script: fttura, the alkylation of acid araids. In this case, the carboxylic acid amide is first prepared from the carboxylic acid with ammonia and this is then treated with one of the known alkylating agents (such as alkyl halides, dialkyl sulfates or potassium alkyl sulfates) (A. Y /. Titherley: Soc. 79, 393 [1901J) . In some cases the acid amide is first reacted with sodium amide in an inert solvent to form sodium salt and this is then alkylated. According to this process, a monosubstituted acid amide can be produced in the first stage; this is converted again to Natriura- L- .z and the latter is alkylated, whereby the N _t N-disubstituted acid amide is obtained.

The specialist literature deals in great detail with those which can be prepared from primary amines by phosgenation in the cold Carbamoyl chlorides (substituted carbamic acid chlorides), which occur as intermediate products in the production of isocyanates. Strangely enough, however, are over the Carbaiiioylchloride, which in the phosgenation of secondary Amines are formed, and hardly any publications can be found on the further reactions of these compounds.

508825/1093

According to W. Price (Soc * 1 ££, 115 [1924J) the with • secondary amines made carbamoyl chlorides with alcohols urethanes. It is also known that it substituted with amines Urea derivatives or carbamides result (Houben-Y / eyl, 8, 118 [i952 *]).

Finally, it is known that the carbamoyl chlorides mentioned under the conditions of the Friedel-Crafts reaction in the common solvents at temperatures from 50 to 80 ° C with aromatic compounds to form ^ Carboxamides react (Houben-Weyl, 8, 380 1952j) <

It has now been found that the N, N- disubstituted Carboxamides of the formula I by the following process are much simpler than described in the specialist literature and can be practically produced in 1 step.

The invention therefore provides a process for the preparation of Ν, ΓΓ-disubstituted carboxylic acid amides of the general formula

for one, optionally by 1 or more halogens or substituted phenyl radicals, straight-chain or branched aliphatic radical with 1 to 18 carbon atoms, a phony radical, a chlorophenyl radical, a dichlorophenyl radical, a nitrophenyl radical, a dinitrophenyl radical or a l'rimethoxyphenylrost or a Unsaturated nitrogen atoms

509825/1093 " ⁷ ~

"'6-membered heterocyclic residue stands and

Rp and R, which can be the same or different, straight-chain or branched aliphatic radicals with 1 to 4 carbon atoms or, optionally by 1 or more aliphatic radicals having 1 to 4 carbon atoms substituted, phenylresiE signifi-

J [J x _t \ _'.,::: /' * '^"., Ten or together with the Stickstoffafcon to"■' φ '- ■' ^tj ~ " '" which they are attached, eirien3ein''"P nitrogen and an oxygen atom

P "■ '■' pointing 6-membered heterocyclic. ^IA , ■"'·. .% est represent which is identified by it- ■■

is that a carboxylic acid of the general 'formula

0
R ₁ - G ^ ' II,

, y / orin R ,, as specified above,

a) with a secondary amine of the general formula

J ^ N - H ΙΙΪ, ^R 5

v / orin Rp and R- are as defined above, and Phoügen at 50 to ISO ⁰ C, preferably

- 8 - 509825/1093

50 to 150 ⁰ O, in particular 80 to 100 ⁰ O, optionally in the presence of an inert solvent, is reacted or

V) with a Garbawioylchloriä the general formula

Cl - C - N (I IV,

I ^x

wherein R ₀ and R- are as defined above

_ _? ei $

lf are at a temperature of

100 to 500 ⁰ G, preferably 110 to 220 ⁰ G, is reacted under Kohlendioxyd- r_ f cleavage and

obtained ■ iTjN-di substituted carboxamide in itself is isolated from the reaction mixture in a known manner.

The reaction of the carboxylic acid of the formula II with the secondary amine of the formula III is expediently carried out in \ . stb'chiometric & r amount together with an equimolar amount of phosgene. The reaction takes place within a short period of time. Thereafter, the solvent is usually removed by distillation and the reaction mixture is separated by vacuum distillation or the N, N-disubstituted carboxylic acid amide is precipitated by pouring the reaction mixture into water and then separated by filtration.

50982B / 1093

2,361

When the carboxylic acid of the formula II is reacted with the Carbamoyl chloride of the formula IV disfigured as already mentioned carbon dioxide as a by-product and the end of the reaction is indicated by the cessation of gas evolution. The other The reaction mixture can be worked up as described above.

Thus, the two manufacturing process variants require the compliance with different temperature ranges, because the reaction of the carboxylic acid of formula II with the secondary amine of the formula III and phosgene is carried out at temperatures of 50 to 16O ⁰ C, preferably 50 to 150 ⁰ C, in particular 80 to 100 ⁰ C. , carried out while the reaction of the carboxylic acid of the formula II with the carbamoyl chloride of the formula IV at temperatures of 100 to 100 ⁰ C, preferably 110 to 220 ⁰ C, is carried out accessible and easy to handle starting materials in 1 step in good yield pure Ν, Ν-disubstituted carboxamides can be prepared. It can be described as extremely favorable that a wide range of ΪΤ, Ν-disubstituted carboxamides can be prepared by the process according to the invention. Thus, the carboxylic acid from which they are derived can be a straight-chain or branched alkyl carboxylic acid with 2 to 19 carbon atoms, but amides of halocarboxylic acids, aryl carboxylic acids or aryl carboxylic acids substituted in the aryl radical as well as 'further' heterocyclic carboxylic acids can also be produced the secondary amines that can be used as starting materials are equally extensive.

If the reaction is carried out in the absence of solvents, then there is a particular advantage of the reaction in that the gaseous by-products from the Ν, Ν-disubstituted acid amide, which is a solid substance, escape and therefore their removal does not have any particular

509825/1093 '. -10-

• ν

- 10 -

■ f '' Λ

, took required.

The method according to the invention tan ^ discontinuixch However, its particular advantage is that it is in the systems customary in the chemical industry can also be carried out continuously. The continuous Implementation only requires a packed column, a felt-no-steam, a felling device and a centrifuge.

The invention is not intended to be limiting to the following Examples to be understood are explained in more detail.

£ 3 — H ti "

'* ■■

ί ', 1teti & Ht ^ ¹ JtA <-. ~, -

5;

ty

\ ; '"'·■''ί -Example 1

^> '' It wurdteiilin, a stirrer, a JThej \ §inen.mit "a condenser, a gas inlet tube and a Gasablei- ψ /" "tung pipe provided 500 cm ^ SK piston 13, of Li (di - n-butyl) -. introduced Y ^ -amine and 25.6 g of palmitic acid This mixture \ / 'vnirde in .200 cnr xylene gelöst.- The reaction mixture was I' · heated -'auf 130 ⁰ C and within about 30 minutes, Y - 11 . g phosgene was introduced After completion of the Gaseinleitens ρ r '', the excess phosgene was removed by heating * a ι *. '- Thereafter, the Response-ionsgemisch was cooled and \, 2 χ 100 cm x ^ v / ater washed the phases. were> separated, the organic phase was dried over sodium sulfate and the solvent was distilled off under reduced pressure. the remaining residue as a yellowish oil ER- i stared on cooling to form white crystals. Thus were j

I received 27.5 g (75% of theory) N, N- (di-n ~ butyl) ~ palmitic acid amide i I with a melting point of 37 ° ^C. . j

■ Analysis: |

; calculated; N - 3.83%; ^!

found: M = 3.77%.

Example 2

ΐ, -r'-j They were placed in a,;) -, 250 Qm ^ | i | lbem. 25 ^ 6 g of plamic acid; and 19.1 g ^, N- (Di-n 1 i ^ carbomo ^ xhlorid introduced. The reaction sgenii sch 'was v. -, heated uniformly to 13Ο C within about 30 minutes, .. f - v; obei one. Gas evolution began. The mixture was kept at 130 to 160 ° ^{C. for 1} hour. After this time, the evolution of gas ceased. The melt was dissolved in 100 cip

5 0 9 82 5/1093,

"Pour old water and with 100 <* 'Benzene. The benzene phase was dried over potassium sulfate and

then the benzene was distilled off under vacuum. That as The gel oil that remained solidified on cooling

S white crystals. Bo were 27.2 _B (74.8% of the ^ e.) _%

^'K: _N - (di-n-butyl) -palmitinsäureamid with a Sohael.punkt ^.

obtained from 37 ⁰ C. - * _:

Analysis:

calculated: N = 3.85%;
found: H = 3.77%

Example 3

There were in a J ₅ O cm? Flask that was “as skeleton” as in Example 1, 15.5 6 H-dsopropyD-aniline ”, 2 B benzoic acid and 150 cm? Introduced o-dichlorobensol. -H 6 phosgene were passed into the Ge-Xh at 140 to 160 ° C within about 50 minutes, excess phosgene was removed by heating, then the solvent was distilled off under vacuum and the residue was stirred in 100 cm? poured cold water. The deposited crystals were nitrated by means of a glass frit, ^{washed with 2 × 20 cm 5 of} water and then dried. So 19.8 B CT * of the theory) E-ClsopropyD-K-Cphenrl) -. Ubenzoic acid amide with a melting point of 55%, 56 °

keep.

Analysis ^:

"Calculated: N = 5.86%; *

found: U - 5.98%.

- 13 -5 0 9 -8 2-5 / 10 9 3; ;

There were provided in a groove with a gas discharge pipe

5 ^ ¹⁸⁰ ** ⁰ ^ "'

It were in a nut

250 _Cra 5 flasks 5.5 S benzoic acid and 5 S ^

HphenyD-carbamoyl chloride introduced and xnnerhalb _{two hours} ^above Gtwicklung <^ z

HphenyDcarbamoylchl

heated to 140 ^ü C, with a gas evolution <^ zte. Jas's reaction genasch was kept at 140 to ι / υ υ for about 1 hour. After this time, the evolution of gas ceased. The melt was stirred in 1 ₅ 0 cm? Poured in water. The deposited crystals were nitrated by means of a glass frame, 2 ml, each 20 cm? Washed with water and then dried. Thus 5.7 S (78% of theory) N = (Isopro _P yl) - * ~ - (phenyl) -benzoic acid amide with a melting point of 55 to 56 ° C. were obtained.

Analysis:

calculated: N = 5.86%;
found: N = 5.98%.

Example 5

135 g of N- (isopropyl) aniline, 98 g of monochloroacetic acid and 500 cm ^ of benzene were introduced into a 1,500 cur ^{5 flask equipped as described in Example 11.} The solution was adjusted to 70 to 80 ⁰ G heated and there were introduced over 2 hours 110 g of phosgene, with careful attention to uniform feeding. After the introduction of gas had ended, the reaction mixture was stirred for a further 1 hour at 80.degree. C., after which the excess phosgene was removed by passing dry air through. The benzene was removed by distillation under atmospheric pressure and the residue was poured into 800 cmr of water. The precipitated crystals were filtered using a glass filter, twice with 150 cm 'of water each time

- 14 509825/1093

- 14 -

washed and then dried, 172 g (81% of theory) of N- (isopropyl) -N- (phenyl) -chloroacetamide with a melting point of 71 to 76 ^° C. were obtained.

Analysis:

calculated: Cl = 16.74%, N = 6.61%; found: Cl = 16.58%, N = 6.77%.

fp example 6

ί 'were in a with a stirrer, a thermometer, I / a condenser, a gas inlet tube ujid a Casablei- - f tung pipe provided 250 cm ^ flask 67.6 g of N- (isopropyl). -

, -aniline and 46.8 g of monochloroacetic acid melted together. 55 g of phosgene were introduced hour within 0 Ij <In the melt at 70 to 100 ⁰ C. The reaction mixture was then stirred for a further Λ hour. The excess phosgene was expelled by introducing dry air and then the melt was poured into 400 crar of water. The eliminated

7th

Crystals were filtered off, washed twice with 100% water each time and then dried. Thus 50 g (48% of theory) of N- (isopropyl) -IT- (phenyl) -chloroacetamide were obtained with a melting point of 72 ⁰ C. The filtrate was made alkaline, recovering 53 g of N- (isopropyl) aniline.

Analysis:

calculated: Cl = 16.74%, N = 6.61%; found: Cl = 16.57%, N .- = 6.75%

- 15 509825/1093

Example ?

. 9.88 g of N- (isopropyl) -N- (phenyl) -carbamoyl chloride and 5.02 g of ionochloroacetic acid were placed in a 250 cm ^{5 flask provided with a gas discharge tube.} The reaction mixture was ^{heated to 120 °} C. and kept at this temperature for 1 hour with stirring until the evolution of gas ceased. The melt was then ^{poured into 100 cm 5 of} water. The deposited crystals were filtered off, ^{washed twice with de 20 cm 5 of} water and then dried. Thus f 5 g (1/3 of theory) N- (isopropyl) -N- (phenyl) chloroacetamide with a melting point of 76.5 ° C. were obtained.

Analysis:

calculated; Cl = 16.74%, 'N = 6.61%; found: Cl = 16.97%, N = 6.87%.

Example 8

There were in a 1,000 cnr flask, which was equipped as described in Example 1, 52.6 g (4-5 cur) IT, N-lpi-n-butyl) - -amine, 25 / l · g monochloroacetic acid and 400 cur xylene introduced. The reaction mixture was ^{heated to 80 to 100 °} C. and then 50 g of phosgene were passed in over the course of about 1 hour. After the introduction of gas had ended, stirring was continued for a further 2 hours at the same temperature. The excess fhosgene was then expelled by passing dry air through and the xylene was distilled off. The product was purified by fractional vacuum distillation. So were «fj? g (87% of theory) of N, H- (di-n-butyl) chloroacetamide with a boiling point of 155 ° C./16 Torr.

- 16 509825/1093

Analysis:

calculated: found:

Gl = 17.5%, · N = 6.85%; Cl = 17.42%, Ν = 6.78%.

A Λ
ι, in the j

Example 9

A 350 cn / flask equipped as described in Example 1 was charged with 13 g of 13% T- (di ~ n-butyD-a & in, 21.1 g of 3,5-dinitrobenzoic acid and 150% of xylene The reaction mixture was heated to 100 to 120 ° C. and 11 g of phosgene were then passed in over 30 minutes. After the gas had been passed in, the reaction mixture was stirred for a further 30 minutes at the same temperature. After cooling, this was a by-product The amine salt formed was washed out by shaking twice with 100 cm ^ of water each time and then the solvent was distilled off. The residue solidified on cooling. Thus, 24 g (74.5% theoretical) of N, N- (Di-n-bu- tyl) -3,5-dinitrobenzoic acid amide with a melting point of 61 to 62 ⁰ C obtained.

Analysis:

calculated: found:

= 13.0%;
= 12.71%.

Example 10

9.58 g of Ti, IT- (di-n-butyl) -carbamoyl chloride and 10.6 g of 3,5-dinitiobezoic acid were weighed into a 25Ο cm ^ flask provided with a gas discharge tube, and the mixture was then taken up 140 to 160 ⁰ C heated, with a gas evolution began. The reaction mixture was up to the end of the evolution of gas, i.e. about 90 times the limit of the above

509825/1083

Maintained temperature and, after cooling, poured into 100 cnr v / water with stirring. Then again with 100 cm ^ of benzene extracted and the separated from the aqueous phase organic Phase dried over sodium sulfate. Breastfeeding after your retirement of the benzene, a residue was obtained which solidified after standing for a short time. So were 12 g (74% of theory) · -i N, N- (di-n-butyl) -3,5 ~ dinitrobenzoic acid amide with a melting point from 61 to 62 ° C.

Analysis:

calculated: N = 13.0%;
found: N = 12.71%.

Example 11

11.0 g of 3,4,5-trimetboxybenzoic acid and 350 cm ^{5 of} xylene were introduced into a 1000 cm ^{5 flask equipped as described in Example 1.} The mixture was heated to 80 ° and 5.0 g of Morpliolin in 50 cm ^{5 of} xylene were added. 5.0 g of phosgene were passed in at the same temperature and the reaction mixture was then stirred for a further 1 hour. The excess phosgene was expelled with dry air. The pale yellow solution was concentrated in vacuo to 30 to 40 cm and then to 50 cm with stirring ⁵ petroleum ether poured in. After ₅ to 10 minutes the removed

Divorced Ki? ^^ 1?

f times with petroleum ether _; washed. and then dried wolves the "

# 2.2 g immmv ^ HMi ^ pi ^^: ^ \ ^^^ '$

teziehun _f sw ^ isejj ^

.-oxazin ^ it a melting point, of lifg.erglten. "'^^ " ■ £ Λ

-18 509 825/109 3

?., .. ^; l . ■ Analysis:
. : **? '*? '"·. - ■" · .. ·· ί - 18th »
I. '"calculated: • "# ^.; /.ϊ emΝ·-

% e fifth; ^ N * »^, 9250.

In a 500 cnr flask fitted with a gas discharge tube, 16.0 g of morpholine carbamoyl chloride and 22.5 g 3,4,5-trimethoxybenzoic acid weighed out. The mixture was on Heated to 120 to 140 ° C and held at this temperature for 90 minutes. After cessation of gas evolution were 100 cm ^ V / water was added and it was allowed to last 10 to 15 minutes heated to boiling under reflux. The reaction mixture was then filtered through a folded filter and the filtrate was collected Chilled 5 ° C. The precipitated crystals were by means of; filtered off a glass frit and dried. So 23.0 g (82>? Of theory) N ~ (3,4,5-trimethoxybenzoyl) -morpholine respectively K- (3,4,5-trimethoxybenzoyl) tetrahydro-1,4- -oxazine with a melting point of 116 ° C.

Analysis:

calculated: K = 4.98%;
found: N = 4

K «fäj? I5äp ' Example 1? ■■ ■ ^ ^{: i}

Iff There were in a Ixe in the example Ί, described ex- _y ^ lusiieten 350 cm ⁵ flasksM? g N, N- (diphenyl) -amiö ^ 9.5 g mono-Γ ■ Woressigsäurö and 150'cm ⁵ xylene introduced. * The reaction - W ^ ^ mixed wurdli ^ f 120 heated to 130 ° 0, and at this Tempe-S ^ Äatir Inirden'innerhaO.b 1 hour 11 g Phosgbn initiated. The * % rf ^ ose surplus was expelled with dry air, the ^

^ Mf- , - ¹ 9 - ■

: M ^% . 509825/1093

Yl.

% £ 8L

Xylene was removed by distillation and the melt was in 1.00 cm! Poured in water. The crystals, \ vurden from - / filtered 2 times / asse_r washed with 20 cirr V and then dried ge _r ^^^.?. Thus 19.5% (94-, 7% of the Theprie) NjlI-ODiphenyi; - obtained chloroacetamide with a melting point of 115 "to 118 ° C.

Analysis:

calculated:
found:

Cl = 14-, 4-2%, N- 5 »71%; Cl = 14-, 635%, N = 5.68%.

Example

It vmrden placed in a 250 cm ^ flask equipped with a gas discharge tube 4-, 62 g of N, H- (diphenyl) ^ carbamoyl chloride and 2.5 g of wonochloroacetic acid. The mixture was heated to 120 to 150 ⁰ C until gas evolution Beendigmg maintained at this temperature, which took about 1 hour to complete. Thereafter, v / urde poured which is to throw in 50 cm water ^J. The deposited crystalline. Substance was filtered off, washed twice with 10 cm 'water each and then dried. So (7% of theory 94-), N, N- (diphenyl) 4, 65 g - -chioracetamid obtained with a melting point 115-118 ⁰ C.

Analysis:

14-, 4-2%, Ii = 5.71%; ^!

_: 7 " , γ

Example 15

There were introduced into a tube with a gas outlet provided vex ^, ₇ * 500 cm piston 19, 8 "g N- (isopropyl) -H- (phenyl) ~ carbamoyl-ίή 'chloride and 25.6 g Pal, with acid. The mixture \ ^v, = _ was heated to 14-0 C and then 90 minutes kept at elifer temperature of 140 to 180 ⁰ O long. After completion of the

',' i Q "Z

Gas evolution v / urde cooled to 20 0, treated with 20 at the Ath ^ r and the separated crystalline amine salt removed by filtration. The ethereal solution was evaporated in vacuo and the residue was poured into 50 cnr 'ice water. The product was filtered off and dried to g < ^% . Thus 51 g (84 ·% of theory) of N- (isopropyl) were - -K- (phenyl) -palmitinsäureamid obtained with a Schroelzpunkt of 51 ⁰ C.

Analysis:

; calculated: N = 5.75%;

found: IT = 5 »

Example 16

⁵ flasks 19.1 SN, IT- (di-n-butyl) carbaraoyl chloride and 12.2 ε benzoic acid were introduced into a 550 era 5 flask provided with a gas extraction tube. The reaction mixture was heated to 110 ⁰ C, whereby gas evolution ,, ₃ approximately at a temperature of 110 to 150 ⁰ C for 90 _minutes; lasted, began. The reaction mixture was then ^{poured into 100 cm 5 of} water and extracted with 100 cm ^{5 of} benzene. The benzene phase was separated from the aqueous phase and dried over sodium sulfate. The solvent was distilled off and the product obtained was passed through

- 21 509825/1093

purified fractional vacuum distillation. In this way, 18.0 s (77.5% of theory) _N , N- (di-butyl) -enzoic acid amide were obtained. The product was a colorless oil, the boiling point of which was 1 ^ W ° C / 14 Torr.

Analysis:

calculated: N = 6.0%;
found: N = 5.95%

Example 17

There were introduced into a container provided with a gas discharge pipe 350 cm5 piston 15 S Morpholx ηcarbamoylchlorid and 12.5 g of benzoic acid. ■ The Reakfcionegemisch was heated to 150 to 160 ⁰ C. After \ ^ hour the gas evolution ceased. The melt vvuiie poured into 50 cm of water J ₁ and then extracted with 50 cm ^{5 of} benzene. The - ^} phases were separated and the organic phase was over | dried sodium sulfate. By fractional vacuum. ^ J

distillation were 17 S (89% of theory) N- (benzoyl) - \ J | -morpholine or N- (benzoyl) -tetrahydro »1, ^ - _; |

xazin received. The product was a colorless oil with |

a boiling point of 178 to 182 ° C / 15 torr. '''\

Analysis: ■ · '-;>? -'

calculated; N = 8.5%; '' J ^

found: N = 8.5%.

Example 18

It vAirden in a provided with a gas discharge pipe

~ 22 -

. 500 cm ^ flask placed 24.6 g of nicotinic acid and 28.5 g of N, N- (DiSthyl) - -carbamoyl chloride. The reaction mixture was' heated to 190 to 22O ⁰ C maintained for about 20 to 30 minutes until the evolution of gas at this temperature. The brown melt was separated by vacuum distillation the transferred at 155 to 160 ° C / 10 Tox ^ r fraction. 51.0 g (87.5% of theory) of N, N- (diethyl) nicotinic acid amide or nicotinic acid diethyl amide were thus obtained.

Analysis:

calculated: N = 15.7%;
found: N = 15.5%.

S ^: example 19

«· It v / are connected to a gas discharge pipe

* "See 100 cnr flask 1.25 S diphenylacetic acid and 1.0 g !!, N-iDimethyl ^ carbamoyl chloride was introduced. That

ί -Reaktionsgeiaisch was heated to 120 to 140 ⁰ C and t $ hour held at this temperature. After that it was

Poured \ cooled to 80 ⁰ C in 20 cm ^ melt water. The precipitated crystals are filtered off, washed with a little water and then dried. 1.4 g (100% of theory) (N, N-dimethyl) - [i, 1- (diphenyl) -acet "amide] ^: or 1,1- (diphenyl) -iT, N" (dimethyl) -acefara'i.d with a melting point of 128 to 129 ° C.

Analysis:

calculated: N = 5.85%; ■ '.>: ■.

found: N = 5.96%.

- 23 -50S825 / 1033

Example 20

51.5 g of 2-chlorobenzoic acid and Z] , 1 g of N, i ;- (diethyl) -carbamoyl chloride were introduced into a flask equipped with a gas discharge tube. The reaction mixture vmrde to I50 to 14O ⁰ C and heated for 4 5 minutes held at this temperature. The cooled mixture was poured into 200 cm of water and then with ⁵ 100 cnr benzene

^ g. extracted. The benzene phase was over sodium sulfate

1 | i f dried and then the benzene by distilling off μη-cer vacuum removed. So were 53 g (90.5% of theory) N, E- (diethyl) -2-chlorobenzoic acid amide respectively

f \. 2-chlorobenzoic acid diethylamide in the form of a yellowish brown | - Obtain oil.

'i _rj analysis:

calculated: N = 6.65%, Cl = 16.8%; found: Ή = 6.41%, Cl «16.21%.

t, " Example 21
f 1

There v / ere into a container provided with a gas discharge pipe 250 cnr piston 51 "5 g of 4-chlorobenzoic acid and 27i1 g N, N- (diethyl) carbamoyl chloride were charged and the mixture was heated on the oil bath for 50 minutes at 140 to 16O ⁰ C . After cooling, the reaction mixture was poured into about 200 cc v / water and then extracted with 100 cnr petroleum ether. The petroleum ether was distilled off from the organic phase in vacuo. Thus, 52 g (76.5% of theory) of N, N- (diethyl) -4 «chlorobenzoic acid amide or 4-chlorobenzoic acid diethylamide were ex-hold in the form of a yellow oil.

_ 24 508825/1093

- Pu -

Analysis:

calculated: W = 6.65%, Cl = 16.8%; found: N = 6.55%, Cl ^ 16.6%.

I. Example 22

• j They have been fitted with a gas discharge pipe in a

j see 250 em "* flask 19.1 g of 5,4-dichlorobenzoic acid and MfA '■ · -:' 15.5 g of li, W- (diethyl) - carbamoyl chloride introduced.

- .j mixture was heated on the oil bath at 140 to 160 ⁰ C "and ■■ '- 30 minutes, maintained at this temperature the iTach, the cooling was Reaktionsgernisch in 100 cm ^ V / ater a ··.' Gegoscen ' and then with 50 cnr 'petroleum ether extracts _the;. organic phase was dried and the solvent' was removed So were 22 b (89.5% of Theoide) 'N, N- (diethyl) ~ 5 ^ -dichlorbenzoesäurearaid beziehungsv / ice. / 5,4-Diclilcrbenzoesäurediethylari; id obtained in - ^ orm of an orange oil.

Analysis:

t calculated: N = 5.70%, Cl = 28.8%;

J found: N = 5.41%, Cl = 28.4%.

example

There were in one with a gas discharge pipe

, see 250 cra ^ flasks 19.1 g of J ^ l-dichlorobenzoic acid and 19.1 g of N, N ~ (diisobutyl) -carbanioyl chloride introduced. The mixture was ^{heated to 140 °} C. and held at 160 to 180 ^° C. for 50 minutes. After cooling, the melt was

i - 25 -

ί. 509825/1093

Λ. W ■ Αι

calculated: N = 5.30%, '' Cl = 13 ', 35% · .- '. '■ "- ■' - , * .- / » i * ί ^s ''"' - found: 'N' = '5.4-1%,' Cl = 12.94% .; ' ■ -; "- '·' - fi 0 ^J. , -

rt-

Poured in 100 cnr water. The separated 'crystals

were filtered off with a glass frit, twice with 20 cm- '' of water; gev; ash and then dried. The: crude product was recrystallized from petroleum ether. Thus, 25 g (83.5% of theory) N, N- (diisobutyl) .- 3,4-dichlorobenzoic acid amide or 3,4-dichlorobenzoic acid diisobutyl- '' \ uid with a melting point of. 74 to 76 ⁰ C obtained. ! ^J P <i

Analysis:

calculated: Έ = 4.68%, Cl = 23.6%; ·, R

found: N = 4.78%, Cl = 24.07%.

Example 24

15.5 g of 2-chlorobenzoic acid and 19.1 g of N, N ~ (diisobutyl) carbamoyl chloride were introduced into a 250 cm ^{5 flask provided with a gas discharge tube.} The mixture was melted and held at 140 to 160 ^° C. for ^ hours. After cooling, the reaction mixture was poured into 100 oar V / a.syer and then extracted with 50 cia ^ petroleum ether. The organic phase was dried and the solvent was distilled off in vacuo. Thus, 22.5% (85.5% of theory) N, N ~ (diisobutyl) -2-chlorobenzoate amide or S-chlorobenzoic acid diisobutylamide were obtained in the form of a dark red oil. \ ■ ' ^j χ * "

Analysis: ^ .._% ■, - - \\\. ' - V

calculated: "'N' =" 5.30%, ί '"01 =

. ■ \ "ι * ²⁶ - 'K

Hf, " _κ , _e ρ

■ t

"ty:

- 26 -

\ Mfl

"ι elii%

_j Example, 25

It vAirden in a veraohenen with a gas discharge pipe 250 cm ^ piston 19 j1 S 3 »^ - JDichlorbenzoesäure and 19» 1 g of N, N ~ (Disek.butyl) carbamoyl chloride introduced Pas mixture was' heated to 120 ⁰ C and 30 Maintained at a temperature of 120 to 130 ⁰ O for minutes. After the evolution of gas had ceased, the reaction mixture was poured into about 100 cnr water, the N _t N- (disec.butyl) -3,4-dichloro , benzoic acid amide or 3 * 4-dichlorobenzoic acid _amide; disek.butylamid in solid form parted * The product was ^ filtered off with a glass frit \ washed twice with 20 cnr. water and then dried. Thus 2'I- g (80% of theory) of product were obtained with a melting point 176-180 ⁰ C.

Analysis: W = calculated: N = found:

Cl = 23.60;

Gl = 24.07%.

ff ..,

ml

-% ne

ü.er, .eine Flüs.i

Continuously senior to

ils Reakticnsgcfäß a "it Easohlaringen filled _a with ei _Dem He.i _ZMD tel" rsehen, Glanlcolouno "t exoer I, _K n of 400 mm and a ftneüta **""""™ l-? 7" ^^ naeb S. had a ^! # «1 ^ -α e at the o ^ e end,

spe _r re _;

- 27 -

S09825 / 1093

ι /

j§ <'■%"g -i vapor he escaped enamel reached a 2,000 cm ^

fl i- ^% ife precipitation vessel made of glass, which is equipped with a 'stirrer and a con- .... · *' * | Ί
t '. ^: >->, fitcontinuous V / ass.erzuleitung was provided, and -from there

I || ty * -J | n a continuously operating centrifuge.

It M h in the preheated to 8O ⁰ C packed column in the Wf% $ ', written V / else assembled apparatus were per ||| ·; Γ f hour Ί05 g of monochloroacetic acid and 135 g of N- (isopropyl) - ^' - . ^ aniline in ^z K) 0 cur benzene and 110 g of Phos- W ^ ■ kΛ ■; 'gen introduced at the column bottom. With the laboratory working ^{at 120 0 C.} ; | Cilmeinaampfer, the benzene was distilled from the reaction mixture from IV. The melt came from the film evaporator

1 into the precipitation vessel, in which the crystalline product is in '

jj passer from 20 to 25 ° C said goodbye. By centrifugation, wa-

Ijschen, renewed separation and drying were 170 g per hour

ψ ^J (ß% of theory) N- (isopropyl) -N- (phenyl) chloroacetainide with

I obtained a melting point of 72 ° C.

'" Analysis:

ί calculated: W = 6.61%, Cl = 16.72%; found: N - 6.41%, Cl = 16.60%.

In a Cm ⁵¹ KoIbIn 2% G g N - [(2-methyl ~ 6-ethyl) -phenyl] -N- (ethoxyl K ^^^ m ' _e -tiliyi) ¹ - ^; 6arbamö'ylchiörid and 10 g Monochloressigsäixre incorporated- M 'i ^^ brought / on ^r? 120 ⁰ C and 30 minutes heated to 120 Läng ^bis-; Mt ^^ Zf-O ⁰ C held. After the evolution of gas had ceased, the reaction was poured into 50 cubic meters of water and ^{extracted with 50 cm 5 of} benzene. The benzene phase was separated off (82% of theory) of N - [(2-methyl 'IU rf' * ^ 6-ethyl) -phenyl] 3-N- (ä ⁱ bhbx; yjnethyl) - ch.3.oracetamid in the form of 'egg ^; pl ^!% ^ it obtained dark yellow oil.

P * ' 509825/1093

' Analysis:'. :.,

calculated N = 5.2%, Cl = 13.3%; '-, found: Jf = *% Q3% l Cl = 12.97%

Example 28

it t

It was provided with a gas discharge tube in a fc, ± cr. '! } ^ 50 cm ⁵ flask 29.8 g of N- {(2,6-diethyl) -phenyl) - (N-buto ^ - 'methyl) -car ^ amoylchlorid and 10 g rionochloressigsr.ur?''Introduced to 120 ^{Heated to 0} G and held at up to / 140 ° C for 30 to 40 minutes. The reaction mixture was in Example 2? described way worked up. Thus, 25 g (80.5% of theory) N- [(2,6 ~ diethyl) -phenyl / -N- (butoxymetüyl) - -chloroacetamide were obtained in the form of a dark brown oil

Analysis:

calculated: N - 4.51%, Cl = 11.4%; found: N = 4.39%, Cl - 10.9%.

Claim

509825/1093

Claims (1)

Claim. Process for the preparation of ΪΓ, Ν-disubstituted Carboxylic acid amides of the general formula Il - C - N Il / ^B 2 ' ^E 5 I .._, "in what. % '■■ .. ■; äR ^ for a., possibly through. 1 _P:; or more. Halogens respectively f '< ^v phenyl radicals substituted, straight 5 chain or branched aliphatic ■ £ see remainder with 1 to 18 carbon [· __ atoms, a phenyl radical, a Chlorophenyl radical, a dichloro \ phenyl radical, a nitrophenyl radical, 'q is a dinitrophenyl radical or a • Trimethoxyphenyl radical odex · a cirs. \ Nitrogen atom containing un- "saturated 6-membered heterocyclic see rest poses and I Rp and R-, which may be the same or different \: -. can, straight-chain or branched ; . te aliphatic residues with 1 to ^L \ i. Carbon atoms or, given if by 1 or more aliphatic radicals with 1 to 4 carbon atoms substituted phenyl radicals or together with the nitrogen atom to which they are bonded, one 5 09825/1093 -30- one nitrogen and one oxygen atom on v / iron 6-membered
• represent heterocyclic radical,
characterized in that one
a carboxylic acid of general
formula OH _x , v / ie ötien 'is fixed, ■ ^ H - H III - 51
509825/1093 a) with a secondary amine ~ J _T , "j ·, of the general formula. = _ihi ? _t »% wherein R ₂ and R ₇ v / ie o "ben feet are set, and Phosgene "at ^ O to 160 ^G G, t preferably 50 to 1 ^ 0 C, '' in particular 80 to 10O ⁰ Q ,,,% possibly in counter- ■. waiting for an inert solution ^ ■ ': ■■ | by means of, implements or '" ' S * ¹ \ r J-Ij, 'ti ,! • b) with a .carbamoyl chloride the general I'orr .R ₂ wherein R ₂ and R _{5 are} as above
are feet,} / b. with one
Temperature% from "100" to 500 C, preferably 110 Ms 220 C,
with elimination of carbon dioxide implements ^ ^d %. the resulting li ^ I-disubstituted carboxamide in an For any known way isolated from the reaction mixture. 509825/1093