Patent GB-782936-A (GB)
Title: Diammonio esters containing two heterocyclic groups
IPC: C07D295/088
Filed: 1955-03-25
Abstract: The invention comprises compounds of the formula <FORM:0782936/IV (a)/1> wherein n and m are integers from 1 to 6 inclusive, R represents a pyridyl radical or an <FORM:0782936/IV (a)/2> group wherein <FORM:0782936/IV (a)/3> represents a piperidyl, morpholinyl or pyrrolidyl radical and R1 represents an alkyl radical containing 1 to 6 carbon atoms inclusive and the anions are non-toxic.  Such compounds are obtained by reacting a compound having the formula <FORM:0782936/IV (a)/4> with pyridine, N-lower alkyl piperidine, N-lower alkyl-morpholine or N-lower alkyl-pyrrolidine, where the lower alkyl group contains 1 to 6 carbon atoms inclusive and X is chlorine, bromine or iodine.  Alternatively the corresponding ditertiary aminoester is quaternized with an alkylating agent.  In examples: (1) and (2) 2 - (1 - methylpiperidinio) ethyl 3 - (1 - methylpiperidinio) propionate di-iodide is prepared by quaternization of the 2-(1-piperidyl)-ethyl 1-piperidinepropionate with methyl iodide. Similarly obtained are (3) 1-methyl-2-(1-methyl-piperidinio) ethyl 3-(1-methyl-piperidinio) propionate di-iodide; (4) 1-methyl-2-(4-methyl-morpholinio) ethyl 3-(4-methyl-morpholinio) propionate di-iodide; (5) 1-methyl-2-(1-methyl-pyrrolidinio) ethyl 3-(1-methyl-pyrrolidinio)-propionate di-iodide.  In Example (6), the product of Example (5) is converted to the dinitrate by passage over an ion-exchange column which had been previously washed with normal nitric acid.  Other anions, e.g. of citric, picric, phosphoric or lactic acids can be similarly introduced. In Example (7) 2-bromoethyl 3-bromopropionate is refluxed with dry pyridine to give 2 - pyridinioethyl 3 - pyridiniopropionate dibromide.  Compounds with methyl, propyl, isopropyl, butyl, isobutyl, pentyl or hexyl radicals in place of the ethyl groups in the compounds prepared in the examples can be similarly obtained.  Starting compounds. 2-Chloroethyl 3-chloropropionate refluxed in methyl ethyl ketone with sodium iodide gives 2-iodoethyl 3-iodopropionate.  This compound, on standing with piperidine in benzene solution gives 2-(1-piperidyl) ethyl 1-piperidinepropionate, which is converted to the hydrochloride.  2-Bromo-ethanol is reacted with 3-bromopropionyl chloride to give 2-bromoethyl 3-bromopropionate.  2 - (Piperidyl) ethyl 1 - piperidinepropionate is prepared by refluxing 2-bromoethyl 3-bromopropionate with piperidine in benzene.  1-Bromo-2-propanol is obtained by reacting propylene oxide with 48 per cent hydrobromic acid at 28 DEG  to 31 DEG  C.  2 - Bromo - 1 - methylethyl 3 - bromopropionate is prepared by reacting 3-bromopropionyl chloride with 1-bromo-2-propanol.  This product, refluxed with piperidine or morpholine, respectively, gives 1-methyl-2-(1-piperidyl)-ethyl 3 - (1 - piperidino) propionate and 1 - methyl - 2 - (4-morpholino) ethyl 4 - morpholinepropionate.  a  - Methyl - 1 - pyrrolidine - ethanol is prepared by reacting pyrrolidine and propylene oxide.  1 - Methyl - 2 -(1 - pyrrolidinyl) ethyl acrylate is obtained by reacting a -methyl-1-pyrrolidine-ethanol with acrylyl chloride.  1 - Methyl - 2 - (1 - pyrrolidinyl) ethyl - 1 - pyrrolidine-propionate is prepared by refluxing 1-methyl-2-(pyrrolidinyl) ethyl acrylate with pyrrolidine.