Patent GB-672872-A (GB)
Title: Improvements in or relating to n-pyridyl-n-thenyl-n:n-disubstituted alkylene-diamines
IPC: C07D409/12
Filed: 1947-09-23
Abstract: Diamines of the general formula <FORM:0672872/IV (b)/1> (wherein R1 and R2 each represent hydrogen or an alkyl group of 1-4 carbon atoms, A represents an alkylene group of 2-11 carbon atoms, and R3 and R4 represent alkyl or aralkyl groups or may be joined to form a ring, and together contain a total of not more than 11 carbon atoms) are manufactured by treating at reaction temperatures, in the presence of a solvent which is or contains an acid-binding agent, an a -(R3,R4-aminoalkylamino)-pyridine with an a -halomethylthiophene, or an N-(a -thenyl) - N1 : N1 - R3,R4 - alkylenediamin with an a -halopyridine.  The reaction is preferably carried out in an inert hydrocarbon solvent in the presence of an alkali metal amide or hydride.  The products are useful as chemical intermediates, and in some cases themselves possess physiological activity, e.g. some have anti-histaminic and some local an sthetic properties.  They may be converted into salts, e.g. hydrohalides, sulphates, phosphates, oxalates, succinates, fumarates, maleates, tartrates, gluconates or citrates.  In examples: (1) N-(a -pyridyl)-N1 : N1-dimethyl- or -diethyl-ethylenediamine is refluxed with a -thenyl chloride in benzene in the presence of sodium hydride to produce N - (a  - pyridyl) - N - (a 1 - thenyl) - N1 : N1-dimethyl- or -diethyl-ethylenediamine; (2) N - (a  - pyridyl) - N1 : N1 - dimethylethylenediamine is refluxed with b -methyl-a -thenyl chloride in toluene in the presence of sodamide, yielding N - (a  - pyridyl) - N - (b 1 - methyl - a 1 - thenyl) - N1 : N1 - dimethylethylenediamine; (3) N - (g  - methyl - a  - pyridyl) - N1 : N1 - dimethylethylenediamine is reacted as in (1) to form N - (g  - methyl - a  - pyridyl) - N - (a 1 - thenyl) - N1 : N1 - dimethylethylenediamine.  A list of additional products is given. Specification 606,181 is referred to.  a -(R3,R4-Aminoalkylamino)-pyridines are obtainable by reacting, in an inert hydrocarbon solvent in the presence of an alkali metal amide or hydride, an a -aminopyridine with an o -R3,R4-aminoalkyl halide (e.g. a -aminopyridine or its g -methyl derivative with b -dimethylaminoethyl chloride), or by reacting an a -halopyridine with an N : N-R3,R4-alkylene diamine (e.g. a -bromopyridine with N : N-dimethylethylenediamine in pyridine).  N - (a  - Thenyl) - N1 : N1 - R3,R4 - alkylenediamines are obtainable by reacting an a -halomethylthiophene with an N : N-R3,R4-alkylenediamine in pyridine or in an inert solvent in the presence of an alkali metal amide or hydride.  b -Methyl-a -thenyl chloride is obtainable by treating b -methylthiophene with aqueous formaldehyde and hydrogen chloride. The Specification as open to inspection under Sect. 91 comprises also the manufacture of compounds of the general formula above in which A may be a hydrocarbon group other than alkylene, and R3 and R4 may be hydrogen, and the use of the following additional methods of preparation: (a) the process of Specification 673,633; (b) reaction of a dialkylamine with a compound containing chlorine, bromine, iodine or a hydroxy group in place of the group NR3R4; (c) the action of alkyl halides, sulphates or sulphonates on a compound containing NH2 in place of NR3R4 (obtainable by reduction of the appropriate compound containing a nitro or cyano group). An example of (a) is given.  This subject-matter does not appear in the Specification as accepted.  Reference has been directed by the Comptroller to Specification 675,266.