Patent GB-770259-A (GB)
Title: Process for the production of new anilides
IPC: C07D295/13
Filed: 1955-06-10
Abstract: The invention comprises compounds of the formula: Ar-NH-CO-R1-X-R2-Am (I) and acid addition salts thereof, in which Ar is an aryl radical substituted at least in the o : o1-positions by an alkyl or alkoxy group containing not more than 3 carbon atoms, or by a halogen atom, R1 and R2 are straight or branched chain alkylene radicals, Am is a primary, secondary or tertiary amino group or a nitrogen atom forming part of the ring system of a heterocyclic base and X represents oxygen, sulphur, SO, SO2, NH, N-alkyl or N-aralkyl.  The compounds may be prepared by reacting a compound of the formula Ar.NH2 (II) or a salt or reactive derivative thereof with an acid of the general formula: HOOC-R1-X-R2-Am (III) or a reactive derivative thereof. Instead of an acid of the formula (III) there may be used acids or functional derivatives thereof which contain an atom or group which can be converted into the amino group Am, such as for example a halogen atom or a alkyl or aryl sulphonoxy radical. Similarly a carbonyl group may be converted into the group Am by reaction with ammonia or amines followed by reduction.  The compounds may also be made by reaction of an anilide Ar-NH-CO-R1-X1 with a compound of the formula X1-R2-Am where one of the symbols X1 represents a reactive radical such as a halogen atom and the other symbol X1 represents one of the hetero atoms or groups X together with hydrogen or another readily removable radical.  The aminoalkylthio carboxylic acid anilides of the formula I may be converted into the corresponding sulphoxide or sulphonyl derivatives by means of oxidizing agents (e.g. H2O2 in glacial acetic acid).  Compounds of the formula I in which Am is unsubstituted or mono-substituted or in which R1 is a hydrogen atom may be further alkylated or aralkylated, by means of reactive esters of alkanols or aralkanols or by treatment with aldehydes or ketones and reducing agents.  Also compounds wherein Am is a quaternary group may be dequaternized by heating, or in some cases, e.g. in the case of benzyl groups, by catalytic hydrogenation. The products obtained include anilides derived for example from 2 : 6-dimethylaniline, 2-chloro-6-methylaniline, 2 : 4 : 6 - trimethylaniline, 2 - bromo - 6 - methylaniline, 2 : 6 - dichloro - 4 - methylaniline and 2 : 6 - dimethoxyaniline by reaction with dimethylaminoethoxypropionic acid, dimethylaminoethoxy acetic acid and dimethylaminoethoxy butyric acid or the corresponding diethylamino-, dipropylamino, dibutylamino, pyrrolidino or piperidino-alkoxyacids.  Similar monosubstituted aminoalkoxy acids may also be used.  The products may be obtained as the free bases or as the acid addition salts of for example sulphuric, hydrochloric, hydrobromic, phosphoric, acetic, glycolic, citric, succinic, fumaric, maleic, dihydroxymaleic, methylsulpuhric or hydroxyethyl sulphuric acids. In examples: (1) diethylaminoethanol is treated with chloracetic acid 2 : 6-dimethylanilide to give diethylaminoethoxy acetic acid 2 : 6-dimethylanilide; (2) b -chloroethoxy acetic acid chloride is reacted with 2 : 6-dimethylaniline and the resulting b -chloroethoxy acetic acid 2 : 6-dimethylanilide is treated with diethylamine to give the product of (1); (3) chloracetic acid-(2-chloro-6-methyl) anilide is reacted with diethylaminoethanol to give b -diethylaminoethoxy acetic acid-(2-chloro-6-methyl)-anilide, the corresponding b  - dimethylaminoethoxy acetic acid - (2 - bromo - 6 - methyl) - anilide may be obtained in the same way; (4) a -chloropropionic acid - (2 - chloro - 6 - methyl) anilide is treated with N-pyrrolidinopropanol-(3) to give a -(3 - N - pyrrolidinopropoxy) - propionic acid - (2 - chloro - 6 - methyl) anilide; (5) chloracetic acid-(2 : 6-dimethyl) anilide is reacted with 2-N-piperidinoethanol to give b -piperidinoethoxy acetic acid-(2 : 6-dimethyl)-anilide; (6) b -chloro-ethoxy acetic acid-(2 : 6-dimethyl) anilide is reacted with n-butylamine to give b -n-butylaminoethoxy acetic acid-(2 : 6-dimethyl) - anilide; (7) b  - aminoethoxy acetic acid - (2 : 6 - dimethyl) - anilide is treated with n-butyraldehyde and hydrogenated in the presence of Raney nickel to give the product of (6); (8) thio - acetic acid - (2 - chloro - 6-methyl anilide is reacted with diethylaminoethyl chloride to give b -diethylaminoethylthioacetic acid (2-chloro-6-methyl)-anilide; (9) chloracetic acid - (2 - chloro - 6 - methyl) anilide is reacted with diethylaminoethylamine to give diethylaminoethylamino acetic acid-(2) chloro - 6 - methyl) anilide; (10) chloracetic acid - (2 - chloro - 6 - methyl) anilide is reacted with N - b  - aminopropyl - pyrrolidine to give N - b  - pyrrolidino - propylamino - acetic acid-(2 - chloro - 6 - methyl) - anilide; (11) dimethylaminoethyl - thio - acetic acid - (2 : 6 - dimethyl) anilide is oxidized by hydrogen peroxide in glacial acetic acid to give diethylaminoethylsulphonyl acetic acid-(2 : 6-dimethyl) anilide; (12) chloracetic acid-(2-chloro-6-methylanilide) is heated with 2-diethylaminoethyl methylamine to give N-b -diethylaminoethyl-N-methylamino-acetic acid-(2-chloro-6-methylanilide) and (13)-(17) the method of 12 is used for the preparation of N-b -diethylaminoethyl-N-ethylaminoacetic acid-(2-chloro-6-methylanilide); N-b -diethylaminoethyl - N - benzylaminoacetic acid - (2 - chloro - 6 - methyl anilide); N-b -diethylaminoethyl - N - benzylaminoacetic acid - (2 : 4 : 6 - trimethylanilide); N-b -pyrrolidinoethyl - N - benzylaminoacetic acid-(2 : 6 - dimethylanilide) and N - b  - pyrrolidinopropyl - N - isopropylaminoacetic acid - (2-chloro-6-methoxyanilide).