Patent GB-942195-A (GB)
Title: Method of preparing compounds containing the group
IPC: C07C237/00
Filed: 1960-01-18
Abstract: Compounds containing the grouping: <FORM:0942195/C2/1> as a structural element are prepared by reacting an isonitrile with an imonium ion, viz. a compound containing the structural element: <FORM:0942195/C2/2> in the presence of a nucleophilic reaction partner comprising a compound in which the molecule is negatively charged or electrically neutral and has at least one free electron pair. The reaction proceeds via the formation of a labile primary adduct having a structural element <FORM:0942195/C2/3> which stabilizes itself by secondary reaction and/or rearrangement. Specified nucleophilic reaction partners are water, amines, carboxylic acids and salts thereof, aminoacids, polycarboxylic acids, betamines, carbamates, metal sulphides, hydrogen selenide, selenides, thiosulphates, cyanates, thiocyanates, azides, hydrazoic acid, phosphates and stable complex metal hydrides. Specified isonitriles are ortho-isocyano benzoic acid and isopropyl, n-butyl, tertiary-butyl, cyclohexyl, benzyl, pyridyl and 2,6-dimethylphenyl isocyanides. Imonium ions may be provided by means of compounds in which such ions are present, e.g. Vilsmeier adducts or hydrastinine hydrochloride, or by addition of a proton to a Schiff's base, an eneamine, a diene-amine, an aminol or any such compound formed in situ, e.g. from an amine and a carbonyl compound or from a compound containing both carbonyl and amino groups, such as gamma-methylaminovaleraldehyde. The nucleophilic reaction partner may also be present in the form of a functional group of one of the added reaction partners, especially of the compound containing the imonium ion or the carbonyl group and/or the amino group used to form the imonium ion, examples thereof being succinaldehyde acid, phthalmonaldehyde, beta-alanine and orthoisocyano-benzoic acid.  If water, hydrogen selenide or an amine is used as a nucleophilic reaction partner, the primary adduct stabilizes itself by means of a proton displacement according to the following scheme: <FORM:0942195/C2/4> wherein X represents O, Se or N-, respectively. If thiosulphate is used as a nucleophilic reaction partner, imido thiosulphates are first formed which are hydrolyzed to form thioamides according to the following scheme:- <FORM:0942195/C2/5> When azides are used as nucleophilic reaction partners an imido azide is formed, which is transformed to a tetrazole by ring formation according to the following scheme:- <FORM:0942195/C2/6> Through simultaneous use of cyanate and a primary amine (for the formation of the imonium ion) the iminoacyl isocyanate first formed is converted to a hydantoin imine by intermolecular acylation.  Thiocyanate reacts analogously in the presence of a primary amine to give a thiohydantoin imine.  The reaction schemes are as follows:- <FORM:0942195/C2/7> Through simultaneous use of a thiocyanate and a secondary amine the imino acyl isothiocyanate first formed is stabilized by the addition of a further molecule of thiocyanate and subsequent intramolecular acylatrion to form a cyclic thiourea derivative according to the following scheme:- <FORM:0942195/C2/8> Through simultaneous use of a carboxylic acid and a primary amine an imino carboxylic acid anhydride is formed which yields an acyl amino acid amide by intramolecular acylation according to the following scheme:- <FORM:0942195/C2/9> If the imonium ions also carry a carboxyl group, a cyclic imino anhydride will be formed which is converted to a lactam through transanular transfer of the an acyl group. Such a reaction may be used for building up the penicillin system according to the following reaction scheme:- <FORM:0942195/C2/100> <FORM:0942195/C2/111> The examples describe the preparation of N-piperidino acetic acid cyclohexylamide, diethylamino-aceto-2,6-xylidide, alpha- (n-propylamino)-propioanilide, n-butylaminoaceto-2-chloro - 6 - methylanilide, piperidino - aceto - 2,6 - xylidide, alpha - piperidino - isovaleric acid cyclohexylamide, N-phenyl-N-methyl-glycine-N1-cyclohexyl-amide, N-nbutyl-glycine-N1-cyclohexyl - amide, N, N-dimethylamino-thioacetic acid, N1-benzylamide, N,N-dimethylamino - thioacetic acid N1 - cyclohexylamide, diethlamino thioaceto 2,6-dimethylanilide, alpha piperidino - seleno - isovaleric acid cyclohexylamide, 5-piperidinomethyl - 1 - cyclohexyl - tetrazole, 5 - (11 - piperidino - 21 - methyl - 11 - propyl - 1 - cyclohexyl - tetrazole, 5 - (N - 211 - propylamino - 21 - propyl) - 1 - cyclohexyl - tetrazole, 2 - (piperidino - benzyl) - 1 - cyclohexyl - tetrazole, 1 - cyclohexyl - 5 - (11 - (piperidino) - 11 - cyclohexyl) - tetrazole, 1 - cyclohexyl - 4 - piperidino - methyl - 4 - thiocyano - 1,3 - diaza-thio - 2 - cyclobutanone, N-acetylamino - isovaleric acid N1 - cyclohexylamide, N-acetyl - N - cyclohexyl - amino - phenyl - acetic acid N1 - cyclohexylamide, 1 - acetyyl - 2 - phenyl - 4,4 - dimethyl - thiazolidine - 5 - cyclohexyl carboxamide, N - formylamino - isovaleric acid N1 - cyclohexylamide, N1 - (N - n - butylcarbamyl -) - N1 - n - butylamino - isovaleric acid N11 - cyclohexylamide, alpha - isopropyl - N - beta - cyclohexyl - amino - ethyl - piperidine, a mixture of methyl benzoate and piperidino-isovaleric acid cyclohexylamide, a mixture of tetraethylpyrophosphate and piperidino - isovaleric acid cyclohexylamide, and compounds of the formulae. <FORM:0942195/C2/122> <FORM:0942195/C2/133> <FORM:0942195/C2/144> <FORM:0942195/C2/155> <FORM:0942195/C2/166> <FORM:0942195/C2/177> <FORM:0942195/C2/188> <FORM:0942195/C2/199> <FORM:0942195/C2/200> <FORM:0942195/C2/211> <FORM:0942195/C2/222> <FORM:0942195/C2/233> <FORM:0942195/C2/244>ALSO:Compounds containing the grouping: <FORM:0942195/C3/1> as a structural element are prepared by reacting an isonitrile with an imonium ion, viz. a compound containing the structural element: <FORM:0942195/C3/2> in the presence of a nucleophilic reaction partner comprising a compound in which the molecule is negatively charged or electrically neutral and has at least one free electron pair.  In examples a compound of the formula:- <FORM:0942195/C3/3> is prepared by reacting a mixture of formalin and N, N1-dimethyl-octamethylene diamine hydrochloride with octamethylene diisocyanide in a dimethyl formamide solvent; a compound of the formula:- <FORM:0942195/C3/4> is prepared by saturating a solution of dodecamethylene diamine in dimethyl formamide and methanol with carbon dioxide and adding thereto isobutyraldehyde and n-butyl isocyanide; a compound of the formula:- <FORM:0942195/C3/5> is prepared by adding n-butyl isocyanide to a mixture of octamethylene diamine, adipic acid, isobutyraldehyde and dimethyl sulphoxide; a polyamide resin having properties similar to those of nylon is prepared by condensing equimolar amounts of hexamethylenediamine and adipic acid in the presence of isobutyraldehyde and cyclohexyl isocyanide; and a compound of the formula:- <FORM:0942195/C3/6> is prepared by reacting a mixture of d -aminocaproic acid, isobutyraldehyde and n-butyl-isocyanide together in a mixture of methanol and dimethylformamide.