Patent GB-841330-A (GB)
Title: Basically substituted butyric acid amides and process for their manufacture
IPC: C07C237/00
Filed: 1957-01-28
Abstract: The invention comprises a -amino-b -hydroxybutyric acid amides of the general formula <FORM:0841330/IV(b)/1> wherein R1 represents hydrogen or an alkyl group containing at the most 4 carbon atoms, R2 represents a phenyl group which may be substituted by an alkoxy group containing at the most 4 carbon atoms, R3 represents hydrogen or an alkyl group containing at least 2 carbon atoms or an alkenyl or aralkyl group, and R4 represents an alkyl, alkenyl or aralkyl group, and acid addition salts thereof, and the preparation thereof by treating an a -amino-b -hydroxy-butyric acid amides of the general formula <FORM:0841330/IV(b)/2> R1 and R2 have the above significance, with the required alkylating, alkenylating or aralkylating agent or agents.  Suitable alkylating, alkenylating and aralkylating agents are hydrohalic esters of the required saturated or unsaturated aliphatic alcohols or araliphatic alcohols in which case the reaction is carried out in the presence of an agent capable of binding hydrohalic acid e.g. on alkali metal or alkaline earth metal hydroxide, carbonate or bicarbonate, or a tertiary organic base such as dimethylaniline, trimethylamine or triethylamine.  Suitable alkylating, alkenylating and aralkylating agents mentioned are bromoethane, 1-bromopropane, 2 - iodopropane, 1 - chloro - and 1 - bromo-butane, 2 - bromobutane, 2 - bromo - 2 - methyl-propane, 1 - iodohexane, 2 - bromohexane, bromocyclohexane, benzyl chloride, 1 - bromopentane, 2 - bromo - 2 - methyl - butane, allyl bromide and iodide and 1 - bromo - 3 - methyl-butene -(2).  Suitable a  - amino - b  - hydroxybutyric acid amide reactants are a -amino-b -hydroxy-butyric acid anilide, p-phenetide, o-, m- and p - anisidide, N - methyl - p - phenetidide, N - ethyl - p - phenetidide, N - isopropylanilide, N - n - butyl - p - anisidide, N - isobutyl - anilide and N - propyl - p - phenetidide.  When the procedure outlined above results in the substitution of only one hydrogen atom of the a -amino group, the amino group may be further alkylated in the same manner or by means of formaldehyde in the presence of formic acid or by catalytic hydrogenation in the presence of formaldehyde. Suitable acids for salt formation are hydrohalic-particularly hydrochloric and hydrobromic, sulphuric, phosphoric, amidosulphonic, formic, acetic, lactic, malonic, succinic, tartaric, b -hydroxyethane sulphonic, maleic, ethylenediamine tetraacetic, benzoic, salicylic and aceturic acids.  In the examples the following compounds are prepared: a  - allylamino - b  - hydroxy - butyric acid p-phenetidide, and the corresponding N-methyl - p - phenetidide, a  - benzylamino - b -hydroxy - butyric acid p - phenetidide and the maleate thereof, a  - ethylamino - b  - hydroxybutyric acid p-phenetidide and the hydrochloride thereof and the corresponding a -n-propylamino and a -allyl-methyl-amino compounds, a  - n - butylamino - b  - hydroxy - butyric acid p-phenetidide and the maleate thereof and the corresponding a  - isoamylamino compounds, a - (isoamylene - (2) - yl - amino) - b  - hydroxybutyric acid p - phenetidide, and a  - (isoamylene - (2) - yl - methylamino) - b  - hydroxybutyric acid p-phenetidide and the hydrochloride thereof.