CS239426B1 - Lactam acylation products and processes for their preparation - Google Patents

Abstract

Acylation products of ω-amino acid lactams and a method for their preparation. The acylation products of ω-amino acid lactams contain two acyl groups in the molecule and have the general formula I. Compounds of general formula I can be prepared from compounds of general formula II by the action of a metallating agent, e.g. an alkali metal hydride or amine or an organometallic of general formula RMe, in an aprotic organic solvent at a temperature of 193 to 343 K, preferably at a temperature of 243 to 283 K, and the corresponding metal derivative of compound II is acylated with a halide or carboxylic acid anhydride R2COOH, the resulting compound of general formula I is isolated from the reaction mixture after neutralization or acidification.

Description

Products of acylation of lactams of ω-amino acids and their preparation.

The ω-amino acid lactam acylation products contain two acyl groups per molecule and have the general formula I

Ar-C-N

Wn

I 2

C-O-C-R *

(I) a thioic organic solvent at a temperature of 193 to 343 K, preferably at a temperature of 243 to 283 K, and the corresponding metal-derivative of compound II is acylated with a carboxylic acid halide or anhydride R ² COOH, the resulting compound of formula I is isolated from neutralization or acidification.

Compounds of formula I may be prepared from compounds of formula II, θ 0 (II),

I i

Ar-CN C 1, (CH ₂ ) _n CR'H x - (CH ₂ ) _m by treatment with a metallating agent such as an alkali metal hydride or amine or an organometallic compound of the formula RMe, in apro239426

The invention relates to ω-amino acid lactam acylation products and to a process for their preparation.

In studying the mechanism of anionic polymerization of ω-amino acid lactams, it is believed that side acylation reactions of growth centers or polymerization activators produce, inter alia, lactam derivatives acylated at the nitrogen and carbon atom adjacent to the carbonyl group (see, e.g., J. Sebenda in Comprehensive Chemical Kinetics, Vol 15. Non-Radical Polymerisatien, edited by CH Bamford, CPH Tipper, Elsevier, New York 1976, 409). These derivatives were synthesized in aromatic and heteroaromatic series only recently in the Czech Republic. Certificate No. 239425.

At the same time, a process has been found for the preparation of compounds of formula (1) which have not yet been described and which are the object of the present invention.

The invention relates to ω-amino acid acylation products which contain two acyl groups in the molecule and have the general formula 1 (I)

L -........

/

^(C12 > m

Wherein R is hydrogen or methyl, R is an alkyl moiety of 1 to 12 carbon atoms, or an aryl moiety of up to 10 carbon atoms which may be substituted with an alkyl or alkoxy group of 1 to 5 carbon atoms, an aryl group of up to 10 atoms C is cyano or nitro or halogen, Ar is an aromatic radical having 6 to 14 carbon atoms, which may be substituted by alkyl or alkoxy groups of up to 5 C atoms, cyano or nitro, or halogen, X is a single chemical bond, oxygen, sulfur or a group CHR 6 or CR 6 wherein R 6 is alkyl of 1 to 5 carbon atoms or phenyl aq and q are 0 to 10, wherein m + n is equal to or greater than one.

2

It has been found that compounds of formula I wherein R, R, Ar, X, and n are as defined above can be prepared by the process of the invention from compounds of formula 11,

O O

I /

Ar-C-N-C

(CH -) _ CR'H \ /

X- (0¾).

wherein R *, Ar, X, fl and a are as defined above by treatment with a metallating agent, e.g. an alkali metal hydride or amine or organometallic of the formula RMe, wherein R is an alkyl or aryl of 1 to 10 carbon atoms, or an aliphatic secondary amine residue , Me is an alkali metal, in an aprotic organic solvent at a temperature of 193 to 343 K, preferably at a temperature of 243 to 283 X, and the corresponding metal derivative of compound II is acylated with 2 carboxylic acid halide or anhydride R COOH, wherein R is as defined above; The resulting compound of formula (1) is isolated from the reaction mixture after neutralization or acidification by known methods.

Up to now, it has been known that metalation and subsequent substitution takes place in the tertiary aromatic or heteroaromatic amides on the nucleus, preferably to the ortho position to the Crbonyl group (see, e.g., P. Beak, RA Brown: J. Org. Chem. £ 2) 34 ( 1982); U. Iwao, Κ. K. Mahalanabis, M. Watanabe, S. 0. de Silva, V. Snieckus: Tetrahedron 22, 1955 (1983)). Although the starting compounds of formula (II) of the present invention are also tertiary aromatic amides, preferably the oxygen of the carbonyl attached to the aliphatic portion of the molecule is acycled. When the metal derivative of the compound of formula (II) is acylated with an aromatic or heteroaromatic carboxylic acid halide or anhydride, it is formed under the conditions set forth in U.S. Pat. of the certificate No. 239425 also, or exclusively, the N, α-diacyl derivative of the corresponding ω-omino acid lactam. Under the conditions of preparation according to the invention, it is also formed

2 is exclusively an acylation product of formula I wherein R, R, Ar, X, s and a are as defined above.

In the preparation of the compounds of the formula I according to the invention, the starting compounds of the formula Ij may be those N-acylated lactam derivatives of m-emino acids in which the carbon atom adjacent to the exocyclic carbonyl does not carry a hydrogen atom and cannot be metalated and subsequently substituted, N-benzoyl lactam derivatives such as N-benzoyl-2-pyrrolidone, N-benzoyl-2-piperidone, N-benzoyl-4-phenyl-2-azetidinone, N-benzoyl-ε-caprolactam, N-benzoyl-6, 6-dimethyl-ε-caprolactam, H-benzoyl-2-methyl-ε-caprolactam, N-benzoyl-3-oxa-ε-caprolactam, R-benzoyl-8-octanlactam, R-benzoyl-12-dodanoclactam and others and N-acyl derivatives derived from substituted benzoic acids, naphthalenecarboxylic acids and heterocyclic carboxylic acids, e.g. pyridine carboxylic acids, thiefenecarboxylic acids, etc. Using N-acyl lactams of ω-amino acids having a substitutable hydrogen atom on the carbon adjacent to the carbonyl group By means of an acyl group, in addition to the products of the formula I, products are also acylated on the oxygen of this exocyclic acyl group. These compounds have very similar properties to the products of the formula I according to the invention and are difficult to separate from them.

Alkali metal hydrides and amides, such as sodium hydride and potassium amide, alkyl and aryl metals, in particular n-butyllithium, tert-butyllithium, methyllithium, naphthylnatrium, preferably in the presence of cryptands or tetramethylethylenediamine, and in particular alkali metal amides, are used as metallating agents. e.g., lithium dimethylamide or lithium diisopropylamide.

The reaction proceeds in inert solvents, preferably of bipolar nature, such as tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, or in aliphatic and aromatic hydrocarbons.

The substitution of the metal derivatives of the compounds of the formula II can be carried out according to the invention with halides, in particular chlorides or anhydrides of aliphatic, aromatic and heteroaromatic carboxylic acids, e.g. benzoyl chloride, acetic anhydride, propionyl chloride, propionic anhydride, 4-nitrobenzoyl chloride, 2-naphthoyl chloride, 2-thiophenecarboxylic acid chloride .

2

The lactam acylation products of formula I, wherein R, R, Ar, X, 3 and 3 are as defined above, are strong acylating agents which, by reaction with nucleophilic compounds such as an amine or an alcohol, yield two molecules of the respective amide or ester and lactam ω -amino acids. As such, they can be used as activators of anionic polymerization of lactams, which have the advantage of not undergoing further acylation reactions.

The preparation process of the present invention is illustrated in more detail by the following non-limiting examples and conditions.

He did

To a solution of 0.43 cm @ ³ (0.003 mol) of diisopropylamine in 15 cm @ ^{3 of} absolute tetrahydrofuran at 298 K, 3 cm @ ³ of n-butyllithium solution of 1 mol.cm @ ^{3 was added} . After 20 minutes, the mixture was cooled to 253 K, and 0.625 g (0.003 mol) of N-benzoyl-ε-caprolactam in 5 cm ^{3 of} absolute tetrahydrofuran was added gradually with stirring. The stirring was carried out at 253 K for 2 hours. The yellowish suspension of the metal derivative was cooled to 197 K, 0.40 µm ³ (0.003 mol) of benzyl chloride was added thereto, and the mixture was stirred at 197 K for one hour and gradually warmed to room temperature for one hour. hydrochloric acid and water, the ethereal solution was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The syrupy residue contained 0.593 g of N, O-dibenzyl derivative of ε-caprelactam, i.e. 61.4% of theory, which was isolated by chromatography on a poly (oxyethylene) impregnated silica gel column in a yield of 0.497 g, i.e. 51.5%, as determined by liquid chromatography. as a crystalline substance; mp 358-359 K after crystallization from diethyl ether.

Example 2

Following the procedure of Example 1, in which propionyl chloride (0.26 cm ^3, 0.003 mol) was used instead of benzyl chloride, an oily product was obtained which gradually crystallized. Recrystallization from diethyl ether gave 0.362 g of N-benzoyl-O-propionylderivative ε-caprolactam, i.e. 44.2%; mp 369 to 370 K.

Example 3

Following the procedure of Example 1, in which 0.507 g (0.003 mol) of 3-phenylproplonoyl chloride was used instead of benzyl chloride. A crystalline product was obtained which, after separation on a poly (exyethylene) impregnated silica gel column (molecular weight 400), gave the N-benzyl-O- (3-phenylpropionyl) ε-caprolactam derivative in a yield of 13.2%.

He attaches

Following the procedure of Example 1 wherein the methylation was performed with ethyl lithium at 253 K for 20 minutes, the product containing N, O-dibenzoyl ε-caprelactam was obtained in 27.9% yield by HPLC analysis. The pure product was isolated by chromatography on a silica gel impregnated with poly (oxyethylene).

Example 5

Following the procedure of Example 1, in which propionic anhydride of 0.39 cm ³ (0.003 mol) was used instead of benzyl chloride and the methylation and acylations were carried out at 197 K, 80.2% of N-benzoyl-O was obtained by HPLC analysis. ε-caprolactam propionyl derivative; crystallization from diethyl ether yielded 0.431 g of pure material, i.e. 52.6%.

Example 6

In the same manner as in Example 1, N-benzoyl-8-octanlactam and N-benzoyl-12-dodecanlact were benzoylated. The yields of Ν, an-dibenzoyl derivatives of 8-octanlactam and 12-dodecanlacta are given in the table.

Table

N, O-dibenzoyl derivative Preparative yield,% t. t., K Of 8-octanlactam 21.4 362 to 365 (hexane-ether) 12-dodecanlactam 15.6 do not crystallize the oil

Object of the invention

Claims (4)

1. The lactam acylation products of the ω-amino acids of the general formula 1, Ar-C-N · / <p> 'X - O I, C-O-C-IC CR ¹ I < ^CH2 > m (I) Wherein R is hydrogen or methyl, R is an alkyl moiety of up to 12 carbon atoms or an aryl moiety of up to 10 carbon atoms which may be substituted with an alkyl or alkoxy group of 1 to 5 carbon atoms, an aryl group of up to 10 carbon atoms , cyano or nitro or halogen, Ar is an aromatic radical having 6 to 14 carbon atoms, which may be substituted by alkyl or alkoxy groups of up to 5 C atoms, cyano or nitro, or halogen, X is a single chemical bond, oxygen, sulfur, or a group CHR3 or CR3, wherein R1 is an alkyl of 1 to 5 carbon atoms or phenyl and and R6 are 0 to 10, with m + n equal to or greater than one. 2. A process for the preparation of lactam acylation products of formula (I) according to claim 1, characterized in that: O Ar-CN - / ^(c 2 2> n X - - c = o \, cr'h) -Wm (IX) wherein R, R, Ar, X, and ² are as defined in point 1, are treated with a metallating agent selected from the group consisting of alkali metal hydrides and amides and organometals of the general formula RMe, wherein R is an alkyl or aryl containing up to 10 carbon atoms or an eliphatic secondary amine residue and Me is an alkali metal, in an aprotic organic solvent at a temperature of 193 to 343 K, preferably at a temperature of 243 to 283 K, and the resulting metaloderivative of compound II is acylated the carboxylic acid anhydride R COOH, wherein R 6 is as defined in point 1, and the resulting compound of formula I is isolated after neutralization or acidification. 3. A process according to claim 2 wherein the compound of formula (II) is selected from the group consisting of N-benzoyl-6-caprolactam, N-benzoyl-8-octanlact, N-benzoyl-12-dodecanlactam, N-benzoyl. -2-pyrrolidone, N-benzoyl-2-methyl-ε-caprolactam, N -benzoyl-2-piperidone, and N-benzoyl-4-alkyl-2-azetidinone. 4. A process according to claim 2, wherein the matting agent is an organometallic compound of formula R1, wherein R is methyl, ethyl, n-butyl, isobutyl, phenyl, diethylamino, or diisopropylamino.