Patent GB-674072-A (GB)
Title: Haloamines and their salts
Filed: 1949-05-13
Abstract: Haloamines of the formula <FORM:0674072/IV (b)/1> where A is hydrogen, alkyl or methoxy, R is hydrogen or methyl, X is halogen and B is alkyl, benzyl, 1-naphthylmethyl, 2-phenoxyethyl, 2-toloxyethyl or 2-(methoxyphenoxy)-ethyl, are prepared by reacting a halide of the formula <FORM:0674072/IV (b)/2> with a 2-alkylamino-ethanol, 2-benzylaminoethanol, 2 - menaphthyl - (11) - amino - ethanol, 2-amino-ethanol ( 1/2 mol.) or corresponding 1-substituted-2-propanol, and treating the product with a halogenating agent such as thionyl chloride or bromide. Alternatively, the said halide may be reacted with NH2-CH2-CHR-OH, the product reacted with BX and finally halogenated as before.  The amine hydrochloride or hydrobromide thus obtained may be treated with an alkali (e.g. potassium carbonate) to liberate the free base, from which other salts may be produced, e.g. the sulphate, hydrochloride, hydrobromide, nitrate, phosphate, methylsulphonate, ethylsulphonate or propylsulphonate.  Examples describe the preparation of the following substituted aminoethanols and conversion into the hydrochlorides of the corresponding amino-chlorethanes:-(1) N-2-phenoxyethyl-N-benzyl; (2) N : N-bis-2-phenoxyethyl; (3) N : N-bis-2-o-tolyloxyethyl; (4) N : N-bis-2-p-tolyloxyethyl; (5) N-2 - o - tolyloxyethyl - N - 1 - menaphthyl; (6) N - 2 - (o - isopropylphenoxy - ethyl) - N - benzyl; (7) N - 2 - (o - ethylphenoxy - ethyl) - N - benzyl; (8) N - 2 - o - tolyloxyethyl - N - ethyl; (9) N - 2 - o - tolyloxyethyl - N - benzyl; (10) N - 2 - o - anisyloxyethyl - N - benzyl; (11) N - 2 - o - anisyloxyethyl - N - 2 - o - tolyloxyethyl; (12) N - 2 - p - anisyloxyethyl - N - benzyl; and (13) N - 2 - o - anisyloxyethyl - N - ethyl.  Example (14) describes the preparation of N : N-bis-2-o-tolyloxyethyl-1-amino-2-propanol and conversion into the hydrochloride of the corresponding 1-amino-2-chlorpropane. Example (15) describes the preparation of the free base of N-2-o-tolyloxyethyl-N-benzyl-1-amino-2-chlorethane and conversion into the methanesulphonate.  A sample has been furnished under Sect 2 (5) of the hydrobromide of N-2-(o-isopropylphenoxy) - ethyl - N - benzyl - 1 - amino - 2 - bromoethane, prepared from the corresponding ethanol and thionyl bromide.  The following N-substituted-2-aminoethanols are obtained by reacting 2-aminoethanol with the appropriate halogen compound:-N - menaphthyl - (11) -, N - 2 - (o - isopropylphenoxy) - ethyl -, N - 2 - (o - ethylphenoxy) - ethyl-, N-2-o-anisyloxyethyl- and N-2-p-anisyloxyethyl-.  2 - Chlorethyl o - tolyl ether, 2 - chlorethyl p - tolyl ether and 2-chlorethyl o-anisyl ether are prepared from the corresponding hydroxy compounds and thionyl chloride.  2- Bromoethyl o - isopropyl - phenyl ether, 2-bromoethyl o-anisyl ether and 2-bromoethyl p-anisyl ether are obtained by reacting ethylene dibromide with o-isopropylphenol, guaiacol and hydroquinone monomethyl ether respectively.  Ethylene glycol mono-o-tolyl and mono-o-anisyl ethers are made by reacting ethylene chlorhydrin with o-cresol and guaiacol respectively.  The Specification as open to inspection under Sect. 91 refers to compounds of the first general formula above where R is any alkyl radical.  Hydrogen bromide is also specified as a halogenating agent.  It is also stated that when a halide A-C6H4-O-CH2-CH2X is reacted with 2-aminoethanol or 1-amino-2-propanol to introduce two aryloxyethyl radicals, this reaction may be carried out in two steps. This subject-matter does not appear in the Specification as accepted.