DE2053738A1 - Gamma-phenyl, hydroxy-crotonolactams - as intermediates from agamma-phenyl, halo-crotonolactones and primary amines - Google Patents

Abstract

Cpds. of the general formula (I) as an extension of the prodn. of cpds. (Ia) of DT 1770042 : (where R is H, an aliphatic, cycloaliphatic aromatic or heterocyclic residue; X is halogen; Y is halogen or an S-linked aromatic residue) are inters. for plant-protective agents, CNS-active pharmaceuticals, dyestuffs and polymers for artificial fibres, partic. for paper sie and adhesives. Prepd. from gamma-phenyl-gamma-halo-crotonolactones and ammoni or primary amines at -20 to +20 degrees.

Description

Process for the production of γ-phenyl-γ-hydroxy-croton lactams Addendum to patent. ... ... (patent application P 17 70 042.4-44).

Subject of the main patent. ... ... (patent application P 17 70 042.4-44) is a process for the production of a, ß-dihalo-γ-hydroxy-crotonalctamen of the general formula in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical and the individual radicals X can be the same or different and each denote a halogen atom, by reaction of mucohalogen acid halides of the general formula wherein X has the aforementioned meaning, with ammonia or primary amines of the general formula R - NH2 III, in which Et has the aforementioned meaning, at a temperature between -20 and + 20 ° C.

It has been found that the process of the main patent develop further and the process for the preparation of T-phenyl-Y-hydroxy-croton lactams of the general formula in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical, X denotes a halogen atom and Y denotes a halogen atom or an aromatic radical bonded via a sulfur atom, generalization can be made if instead of the mucohalogen acid halides of the general formula II y-phenyl-Y-halogen-crotone lactones of the general formula in which X and Y have the aforesaid meaning used.

If phenylmucochloric acid chloride and cyclohexylamine are used, the reaction can be represented by the following equation: The starting materials used are compounds of general formula IV. Preferred starting materials IV and correspondingly preferred end products I are those in whose formulas X denotes a chlorine atom or bromine atom and Y denotes a chlorine atom, bromine atom or one bonded via a sulfur atom, optionally by being inert under the reaction conditions Groups and / or atoms such as chlorine atoms, alkoxy groups with 1 to 4 carbon atoms substituted phenyl radical.

For example, the following starting materials IV can be used: Phenylmucochloric acid chloride, Phenylmucobromic acid chloride, a-ip-Methoxyphenylmercapti -ß-chloro-7-phenyl-7-chloro-y-crotone lactone, a-ip-chlorophenylmercapti -B-chloro-Y-phenyl-Y-chloro-Y-croton lactone; analogous T-bromine compounds.

Otherwise, the procedure is carried out under the conditions of the procedure carried out according to the main patent, e.g. with regard to temperature, solvent, Reaction conditions, amounts of starting materials, starting material III and thus the meaning of R. Preferred amines III and correspondingly preferred end products I are those in whose formula R is an alkyl, alkenyl, cycloalkyl, aralkyl, Aryl radical each with up to 12 carbon atoms or a 5- or 6-membered one heterocyclic ring, the 1 nitrogen atom and / or 1 oxygen atom or 2 nitrogen atoms and to which a benzene nucleus can optionally also be fused, denotes. The radicals and rings mentioned can still be inert under the reaction conditions Groups and / or atoms, e.g. hydroxy groups, alkyl, alkoxy, hydroxyalkyl, dialkylamino, Hydroxyalkyl mercapto and aminoalkyl groups each having 1 to 4 carbon atoms per alkyl radical, amino groups attached to the phenyl ring, piperazino, piperidyl, morpholinyl groups, be substituted. The starting amine can be used in a stoichiometric amount or in excess, generally in an excess of up to 15% by weight above the stoichiometric amount, be reacted with starting material II.

For example, the following amines can be used as starting materials III: Ammonia, ethylamine, tryptamine, cyclohexyl-, cyclooctyl-, benzylamine, p-anisidine, p-nitroaniline, 2-aznino-pyrimidine, 2-aminopyrrole, 2-aminopyridine, cyclododecylamine, 1-hydroxyethyl-4-aminoethyl-piperazine, 4-amino-propyl-morpholine.

Except for those already mentioned in the main application, which are to be used appropriately Solvents are also carboxamides such as acetamide, dimethylformamide; Alkanols such as ethanol, ß-ethylhexanol, isobutanol advantageous.

The compounds preparable by the process of the invention are valuable intermediate products for the production of pesticides, pharmaceuticals (stimulating effect on the central nervous system), dyes and polymers on the Plastic area. They are particularly valuable as intermediate products for manufacture of paper glues and adhesives. There are 0.1 to 3 percent additions of copolymers of the end product with styrene and vinyl ethers to the paper pulp, good glue effects at the same time good ink absorption capacity of the paper.

The parts mentioned in the examples are parts by weight.

Example 1 (preparation of starting material IV) 735 parts of phenylmucochloric acid are with the addition of 50 parts of dimethylformamide 4 hours at 850C in 15,000 Parts of toluene treated with 6,000 parts of phosgene. The mixture is filtered off, concentrated, cooled to OOC and the solid which has been filtered off with suction is recrystallized from cyclohexane. Yield of phenylmucochloric acid chloride: 6,500 parts (82 to 83% of theory), Fp 7500.

Phenylmuco-a-bromo-ß-chloric acid chloride can be prepared from phenylmucobromic acid in a completely analogous manner (Mp 67 to 680C), from phenylmercapto-ß-chloro-y-phenyl-y-hydroxy-y-croton lactone α-Phenylmercapto-ß-chloro-γ-phenyl-γ-chloro-γ-crotonlactone (mp 88 up to 89 ° C), from α- [p-methoxyphenyl-mercapto] -ß-chloro-γ-phenyl-γ-hydroxy-γ-crotanoactone α- [p-Methoxy-pheny Y-phenyl-y-chloro-y-crotone lactone (mp 62 to 63 ° C) and from α- [p-Chlorophenylmercapto] -β-chloro-γ-phenyl-γ-chloro-γ-croton-] actone α- [p-Chlorophenylmercapto] -γ-chloro-γ-phenyl-γ-chloro-γ-crotonlaction (Mp 11 @ to 114 ° C).

The elemental analysis is correct here and in the following examples the error limits correspond to the calculated values.

Example 2 In a solution of 527 parts of phenylmucochloric acid chloride in 5,000 parts of benzene at 10 ° to 200 ° C., 100 parts of ammonia are converted into 100 parts of ammonia within one hour initiated. The mixture is filtered off with suction, the filter residue is washed with water, dried and recrystallized from toluene. Yield of a, B-dichloro-y-phenyl-yhydroxy-crotone lactam: 340 parts $ (70% of theory), m.p. 175 to 177 ° C.

Example 3 To 132 parts of phenylmucochloric acid chloride in 700 parts At 15 to 1800, dimethylformamide becomes 61 parts of ethanolamine in 100 parts of dimethylformamide admitted. After 20 hours the mixture is poured into ice water. The secluded N- (ß-hydroxyethyl) -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam is filtered off with suction, dried and recrystallized from benzene. Yield: 136 parts (95 ffi of theory), m.p. 145 to 14700.

Example 4 To 263 parts of phenylmucochloric acid chloride in 800 parts 104 parts of allylamine are added to benzene. After stirring for two days at 17 to 19 ° C, the mixture is filtered off with suction, the filtrate is concentrated and the residue (N-allyl-α, ß-dichloro-γ-phenyl-γ-hydroxycrotonlactam) recrystallized from benzene. Yield: 260 parts (92% of theory), melting point 133 to 13500.

Example 5 To 263 parts of phenylmucochloric acid chloride in 3,000 parts 427 parts of n-etradecylamine are added to benzene. The mixture will last for 24 hours Stirred from 16 to 1700, then filtered off with suction, the filtrate was concentrated and the residue (N-n-Tetradecyl-α, ß-dichloro γ-phenyl-γ-hydroxy-crotonlactam) recrystallized from cyclohexane.

Yield: 290 parts (66% of theory), melting point 70 to 71.degree.

Example 6 263 parts of phenylmucochloric acid chloride and 538 parts of stearylamine are stirred for 20 hours at 14 to 19 ° C in 3,500 parts of benzene.

The mixture is filtered off with suction, the filtrate is concentrated and the residue (N-stearyl-a, ß-dichloro-y-phenyl-y-hydroxy-crotonlactam) recrystallized from petroleum ether. Yield: 320 parts (64% of theory), melting point 68 to 70.degree.

Example 7 263 parts of phenylmucochloric acid chloride are used in 2,500 Parts of cyclohexane dissolved and 226 parts of 4-methylcyclohexylamine at 10 to 1500 slowly shifted. After stirring for 15 hours, the mixture is filtered off with suction and the at Concentrate the filtrate, the residue which remains from a benzene-petroleum ether mixture recrystallized. Yield of N- [4'-methylcyclohexyl} -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam 250 parts (73% of theory), m.p. 137 to 13800.

Example 8 263 parts of phenylmucochloric acid chloride in 2,000 parts Dioxane are charged at 0 to 500 with 146 parts of n-butylamine in 500 parts of dioxane. The mixture is stirred overnight, poured into water and extracted with methylene chloride. The organic phase is extracted with saturated sodium chloride solution and dried and narrowed. The residue (N-n-butyl-α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam) is recrystallized from petroleum ether.

Yield: 190 parts (63% of theory), melting point 99 to 1000 ° C.

Example 9 To 263 parts of phenylmucochloric acid chloride in 2,000 parts 366 parts of cyclododecylamine are added to benzene. After 2 days at 12 to 18 ° C the mixture is worked up as in Example 5.

310 parts (75% of theory) of N-cyclododecyl-α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam are obtained ; Mp 198-200 ° C.

Example 10 a) 527 parts of phenylmucochloric acid chloride in 2,000 parts Benzene is mixed with 626 parts of 5-diethylamino-2-aminopentane and 2 days at Stirred at 15 to 19 ° C. The organic phase is washed with water and delivers on concentration 740 parts of N0 (4'-diethylamino-1'-methyl) -butyl-α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam.

b) From corresponding starting materials III, analogously to Example 10a N- [2'-Dimethylaminoethyl [-α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (Yield: 74% of theory, melting point 133 ° to 134 ° C.), N- [2'-diethylasminoethyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (yield: 63% of theory, Mp 79 to 81 ° C), N- {3'-diethylaminopropyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (Yield: 62% of theory, Ep 83 to 84 ° C), N- [3'-piperidino-propyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (yield: 54% of theory, Mp 114 to 115 ° C), N- [3'-morpholino-propyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (Yield: 57% of theory, melting point 107 to 109 ° C.).

Example 11 527 parts of phenylmucochloric acid chloride in 9,500 parts Chloroform with 484 parts of ß-hydroxy-ethyl-ß'-amino-ethyl sulfide at 10 to 200C added and stirred for 30 hours. The reaction mixture is extracted with water, the organic phase is concentrated and the residue is recrystallized from benzene. Man receives 570 parts (82% of theory) N -'-hydroxy-ethyl-mercapo-ethy7 α, ß-dichloro-γ-phenyl-γ-hydroxy-croton-lactam. Mp 112 to 114 ° C example 12 a) 263 parts of phenylmucochloric acid chloride in 2,500 parts of benzene are mixed with 374 Parts of 1- [2'-hydroxyethyl] -4- [3 "-aminopropyl] piperazine are added after work-up analogously to Example 10, 260 parts of N- [4'-hydroxyethyl-piperazion-propyl] -α are obtained, ß-dichloro-γ-phenyl-γ-hydroxy-crotonlactam (63% of theory) from mp 106 to 1070C (from cyclohexane / benzene).

b) Analogously, one obtains from phenylmucochloric acid chloride and m-cyanobenzylamine N- [m-Cyanbenzy] -α, ß-dichloro-γ-phenyl-γ-hydroxycrotonlactam (yield 42% of theory, melting point 170 to 172 ° C.), from phenylmucochloric acid chloride and p-phenetidine N- [n-Ethoxyphenyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-croton-lactam (Yield 82% of theory, mp 203-205 ° C), from phenylmucochloric acid chloride and N, N-Dimethyl-p-phenylenediamine N- [p-Dimethylaminophenyl] -α, ß-dichloro-γ-phenyl-γ-hydroxy-croton-lactam (Yield 71% of theory; mp 219-220 ° C.), from phenylmucochloric acid chloride and n ß-naphthylamine N- [ß-naphthyl] -α, ß-dichloro-γ-phenyly-hydroxy-crotonlactam (Yield 84% of theory; mp 208-2090C) and from phenylmucochloric acid chloride and m-xylidine N- [3'.5'-dimethyl-phenyl] -α, ß-dichloro-γ-phenyl-γ-hydroxycrotone lactam (Yield 71% of theory; melting point 228 to 2300 ° C.).

Example 13 85 parts of α- [p-methoxyphenyl-mercapto] -β-chloro-γ-phenyl-γ-chloro-γ-croton-lactone 56 parts of 4-methylcyclohexylamine are added to 500 parts of benzene and 20 Stirred at 10 to 17 ° C for hours. The mixture is filtered off with suction and the filtrate is concentrated and the crystalline residue is recrystallized from cyclohexane / toluene. Yield 80 Parts (78% of theory) N- [4-methyl-cyclohexyl-a-r-methoxyphenylmercaptol -B-chloro-y-phenyl-y-hydroxycrotone lactam; Mp 138-140 ° C.

Example 14 150 parts of phenyl muco - «- bromo-ß-chloroic acid chloride dissolved in 900 parts of benzene and 110 parts of N, N-diethylpropylenediamine with stirring admitted. After stirring for 24 hours, the mixture is extracted by shaking with 1,000 parts of water, the organic phase is concentrated and the residue that remains is recrystallized from petroleum ether. Yield: 145 parts (74% of theory) of N- (diethylamino-propyl) α-bromo-β-chloro-γ-phenyl-7-hydroxy-crotonlactam; Mp 84 to 860C.

Example 15 202 parts of α-phenylmercapto-β-chloro-γ-phenyl-γ-chloro-γ-crotone lactone 88 parts of n-butylamine in 500 parts of toluene are charged in 2,500 parts of toluene. After 30 hours at 8 to 12 ° C., the mixture is filtered off with suction and extracted with water and the residue that remains when the organic phase is concentrated, from petroleum ether / alcohol recrystallized. Yield: 140 parts of N-n-butyl-a-phenylmercapto-ß-chloro-7-phenyl-Y-hydroxy-crotonlactam (62 to 63% of theory), m.p. 129 to 1300C.

Example 16 186 parts of α-phenylmercapto-β-chloro-γ-phenyl-γ-croton lactone in 2,500 parts of acetone with 185 parts of n-dodecylamine in 700 parts of acetone slowly united. After 24 hours at 15 to 170C, the mixture is suctioned off and the residue recrystallized from the concentrated filtrate from petroleum ether.

Yield: 173 parts (41% of theory) of N-n-dodecyl-α-phenyl mercapto-ß-chloro-γ-phenyl-γ-hydroxy-croton lactam; Mp 103 ° C.

Example 17 In 80 parts of α- [p-chlorophenylmercapto] -β-chloro-γ-phenyl-γ-chloro-croton-lactone in 2,000 parts of benzene ethylamine is introduced at 18 to 2000 for one hour. To about 2 hours> -that will be Sucked off mixture and the residue recrystallized from the filtrate from toluene. Yield: 74 parts (90% of theory) N-Ethyla-ip-chlorophenyl-mercapti-β-chloro-y-phenyl-y-hydroxy-crotonlactam; Mp 179 to 181 C.

Example 18 186 parts of a-i-chlorophenylmercapti -B-chloro-Y-phenyl-y-chloro-γ-croton-lactone in 2500 parts of ethyl acetate with 129 parts of n-octylamine in 500 parts of ethyl acetate charged at 12 to 16 ° C.

After 20 hours, the mixture is filtered off with suction and that from the filtrate crystalline residue obtained recrystallized from cyclohexane. Yield: 174 parts (75% of theory) N-n-octyl-α- [pchlorphenylmercapto] -β-chloro-γ-phenyl-γ-hydroxy-crotonlactam; Mp 137 to 1380C.

Claims (2)

Claims Process for the preparation of T-phenyl-Y-hydroxy-croton lactams of the general formula in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical, X denotes a halogen atom and Y denotes a halogen atom or an aromatic radical bonded via a sulfur atom, according to the procedure for the preparation of α, β-dihalogen Y-hydroxy-croton lactams of the general formula in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical and the individual radicals X can be the same or different and each denote a halogen atom, by reaction of mucohalogen acid halides of the general formula wherein X has the aforementioned meaning, with ammonia or primary amines of the general formula R - NH2 III, in which R has the aforementioned meaning, at a temperature between -20 and + 20 ° C according to the patent. ... ... (patent application P 17 70 042.4-44), characterized in that instead of the mucohalogen acid halides of the general formula II, Y-phenyl-y-halo-crotone lactones of the general formula II in which X and Y have the aforesaid meaning used. 2. y-phenyl-y-hydroxy-croton lactams of the general formula in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical, X denotes a halogen atom and Y denotes a halogen atom or an aromatic radical bonded via a sulfur atom.