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GB793899A - Organic nitrogen compounds and process for producing the same - Google Patents

Organic nitrogen compounds and process for producing the same

Info

Publication number
GB793899A
GB793899A GB20069/56A GB2006956A GB793899A GB 793899 A GB793899 A GB 793899A GB 20069/56 A GB20069/56 A GB 20069/56A GB 2006956 A GB2006956 A GB 2006956A GB 793899 A GB793899 A GB 793899A
Authority
GB
United Kingdom
Prior art keywords
prepared
piperazine
compounds
pentanol
product
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB20069/56A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Parke Davis and Co LLC
Original Assignee
Parke Davis and Co LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Parke Davis and Co LLC filed Critical Parke Davis and Co LLC
Publication of GB793899A publication Critical patent/GB793899A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205Radicals derived from carbonic acid

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention comprises compounds of the formula: <FORM:0793899/IV (b)/1> (wherein R is an allyl group or an alkyl group of 1 to 4 carbon atoms, Z is hydrogen or an aliphatic carboxylic acyl group of 1 to 4 carbon atoms, and n is 3, 4, 5 or 6), their acid addition salts and their preparation by the following methods: (1) reacting a N-(R-mercaptophenyl)-N1-unsubstituted piperazine with a compound of formula Halogen-(CH2)OZ, preferably by refluxing 2 equivalents of the piperazine with 1 equivalent of the halogen compound in an anhydrous organic solvent; (2) for the compounds in which Z is an acyl group, by acylation of the free alcohols, e.g. with an acyl halide or anhydride in an inert, anhydrous organic solvent or, when acetic anhydride is used, in acetic acid, preferably at reflux temperature; (3) for the compounds in which Z is hydrogen, by hydrolysis or alcoholysis of their esters, e.g. with an aqueous alkali or alkaline earth metal hydroxide in an organic solvent or with catalytic amounts of an alkali metal alcoholate in an anhydrous organic solvent, preferably at reflux temperatures; (4) for the compounds in which Z is hydrogen, by reduction of compounds of the above general formula wherein the -(CH2)nOZ group is replaced by a group -Y-(CH2)n-2-COOR1 (Y being -CH2- or -CO- and R1 an alkyl group of 1 to 4 carbon atoms) e.g. by using sodium and an alcohol or lithium aluminium hydride in an anhydrous non-hydroxylic organic solvent; and (5) for the compounds wherein n is 3, by reacting an N-(R - mercaptophenyl) - N1 - unsubstituted piperazine with allyl alcohol in presence of an alkali metal alcoholate of allyl alcohol, preferably at 75 DEG to 150 DEG C. The free base and acid-addition salt forms of the compounds of the invention are interconvertible by conventional procedures. In examples: (1) 1-o-methylmercapto-phenylpiperazine (prepared from o-methylmercaptoaniline and bis-(b -bromethyl) amine hydrobromide) and 5-bromopentan-1-ol acetate (prepared by heating acetyl bromide and tetrahydropyran in presence of granulated zinc and hydrogen bromide) give 4-o-methylmercaptophenyl - 1 - piperazine pentanol acetate which is subsequently hydrolysed to the free pentanol; (2) 1-o-ethylmercaptophenylpiperazine (prepared from bis-(b -bromoethyl)amine hydrobromide and o-ethylmercapto aniline, the latter being prepared from 2-amino benzenethiol and diethyl sulphate) and methyl acrylate at 23-25 DEG C. give a product which on reduction with lithium aluminium hydride yields 4-o-ethylmercaptophenyl - 1 - piperazine propanol; (3) 5 - carbomethoxyvaleryl chloride (prepared from monomethyl valerate and thionyl chloride) is reacted with 1-o-ethylmercaptophenylpiperazine and the product is reduced with lithium aluminium hydride to give 4-o-ethylmercaptophenyl - 1 - piperazine hexanol which on esterification with acetic anhydride in acetic acid gives the acetate; (4) 4-o-ethylmercaptophenyl - 1 - piperazine pentanol acetate is prepared as in (1) and is then hydrolysed to the free pentanol; (5) 1-o-ethylmercaptophenyl piperazine and diethyl adipate are reacted together at 100 DEG C. and the product reduced to give the hexanol of (3); (6) 1-o-methylmercaptophenyl piperazine and deltabromovaleronitrile are refluxed in toluene and the product is then treated with absolute alcohol and anhydrous hydrogen chloride and subsequently refluxed in the presence of water to give a product which on reduction yields 4 - o - methylmercaptophenyl - 1 - piperazinepentanol; (7) 1-o-methylmercaptophenyl piperazine, sodium and allyl alcohol are refluxed to give 4 - o - methylmercaptophenyl - 1 - piperazinepropanol; (8) the pentanol product of (4) is prepared from 1-o-ethylmercaptophenylpiperazine and pentamethylene bromohydrin; (9) 4 - o - allylmercaptophenyl - piperazine pentanol acetate is prepared from 1-o-allylmercaptophenylpiperazine (prepared from bis(b - bromoethyl)amine hydrobromide and o-allylmercapto aniline, the latter being prepared from 2-aminobenzene thiol and allyl bromide) by the method of (1) and is then hydrolysed to the free pentanol; (10) 4-o-butylmercaptophenyl-1-piperazine pentanol acetate is prepared as in (1), the 1-o-butylmercaptophenylpiperazine starting material being prepared from o-butylmercaptoaniline, itself prepared from 2-aminobenzenethiol and butyl bromide, and is hydrolysed to the free pentanol; (11) 1 - o - ethylmercaptophenylpiperazine and ethyl gammabromobutyrate give a product which on reduction yields 4-o-ethylmercaptophenyl - 1 - piperazinebutanol. Acid - addition salts of some of the products are described. Starting materials. Compounds of the formula: <FORM:0793899/IV (b)/2> (R1 being an alkyl group of 1 to 4 carbon atoms) are prepared from the corresponding phenylpiperazines and (1) a compound Halogen-(CH2)n-1-CN, followed by treatment of the product with an anhydrous alcohol hydrohalic acid and subsequent hydrolysis, or (2) a compound Halogen-(CH2)n-1-COOR1, or (3) when n is 3, an acrylic acid ester CH2== CHCOOR1. Compounds of the formula: <FORM:0793899/IV (b)/3> are prepared from the appropriate phenylpiperazine and a compound Y1-CO-(CH2)n-2 -COOR1 wherein Y1 is a halogen atom or an alkoxy group of 1 to 4 carbon atoms.
GB20069/56A 1955-06-29 1956-06-28 Organic nitrogen compounds and process for producing the same Expired GB793899A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US793899XA 1955-06-29 1955-06-29

Publications (1)

Publication Number Publication Date
GB793899A true GB793899A (en) 1958-04-23

Family

ID=22150243

Family Applications (1)

Application Number Title Priority Date Filing Date
GB20069/56A Expired GB793899A (en) 1955-06-29 1956-06-28 Organic nitrogen compounds and process for producing the same

Country Status (1)

Country Link
GB (1) GB793899A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2976290A (en) * 1959-04-24 1961-03-21 Parke Davis & Co Piperazine derivatives and methods for their production

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2976290A (en) * 1959-04-24 1961-03-21 Parke Davis & Co Piperazine derivatives and methods for their production

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