Patent GB-573509-A (GB)
Title: Urea derivatives
IPC: C07C273/18
Filed: 1943-08-23
Abstract: Substituted ureas of the general formula <FORM:0573509/IV/1> in which R is an alkyl radical having from 2 to 4 carbon atoms and R1 is a halogenated phenyl, benzyl or phenethyl radical which may be substituted in the nucleus by one or more alkyl or alkoxy radicals containing less than 8 carbon atoms, are prepared by reacting secondary amines having the general formula R-NH-R1, where R and R1 have the meaning given above with nitrourea.  In the case of a phenyl radical, the ring is directly bound to the N and in the case of a benzyl or phenethyl radical the ring is aliphatically bound to the N by -CH2- or -CH2CH2-.  The products have sedative, hypnotic or an sthetic properties.  The reaction is carried out by warming the reactants in alcoholic solution, using excess nitro urea; the substituted urea product is best separated by steam distillation from saturated salt solution, whereby most of the amine is removed and the urea obtained by recrystallization of the residue.  The secondary amines employed as starting materials are prepared by alkylation of halogenated aromatic amines using alkyl sulphates or alkyl toluene sulphonates in preference to alkyl bromides or iodides as alkylating agents.  In examples: (1) N-n-propyl-N-(4-bromo-2-methylphenyl) urea is prepared from n-propyl-4-bromo-2-methyl aniline and nitrourea; (2) N-n-butyl-N-(4-bromo-2-methyl phenyl) urea from nitrourea and n-butyl-4-bromo-2-methylaniline which is itself prepared by reacting 4-bromo-2-methylaniline with n-butyl toluene sulphonate; (3) N-ethyl-N-(5-chloro-2-methylphenyl) urea from ethyl - 5 - chloro - 2 - methyl - aniline and nitrourea; (4) N-ethyl-N-(3-chloro-2-methylphenyl) urea from ethyl-3-chloro-2-methylaniline and nitrourea; and (5) N-ethyl-N-(3-bromo-6-ethoxyphenyl) urea from nitrourea and ethyl-3-bromo-6-ethoxyaniline which is prepared by brominating acet-o-phenetidine, hydrolysing the product and N-ethylating the amine with diethyl sulphate.  Other specific examples of the products are N-ethyl-N-(2-chlorophenyl) urea, N - ethyl - N - (4 - bromo - 2 - ethylphenyl) urea, and N-ethyl-N-(3-bromo-4-ethoxy phenethyl) urea. Samples have been furnished under Sect. 2 (5) of compounds prepared as described in examples 1, 3, 4 and 5, and also a sample of N-ethyl-N-(3-bromo-4-methoxy benzyl) urea prepared from nitrourea and N - ethyl - N - (3 - bromo - 4 - methoxybenzyl) amine, itself prepared by brominating N-ethylanisylamine.  According to the Provisional Specification, substituted ureas of the general formula <FORM:0573509/IV/2> in which R represents an alkyl radical having less than 8 carbon atoms, R1 and R11 each represent hydrogen or alkyl radicals having less than 8 carbon atoms and which may or may not be the same, and R111 is a haloaryl or haloaralkyl radical which may be further substituted by one or more alkyl or alkoxy radicals of less than 8 carbon atoms each and in which R and R111 together contain at least 8 carbon atoms, are prepared by converting N-alkylated halogenated aryl or aralkyl amino compounds to the corresponding ureas by known methods, for example, by reacting them with nitrourea or substitution products thereof.  In examples, additional to those described above, (6) N-methyl-N-(3-bromo-4-methoxybenzyl) urea is prepared from nitrourea and 3 - bromo - 4 - methoxybenzyl methylamine; (7) N-methyl-N-(3 - chloro - 4 - methoxy phenethyl) urea from nitrourea and 3-chloro-4-methoxy phenethyl methylamine itself obtained by chlorination of methylhomoanisylamine.  Other specified examples of the products are N-methyl-N-(2-bromo - 4 - ethylphenyl) urea, N - methyl - N - (2-bromo-5-ethoxybenzyl) urea and N-methyl-N-(2-bromo-5-methoxyphenethyl) urea.