GB886613A - Manufacture of tetrahydro-ú+ú=ºaquinoline derivatives - Google Patents

Manufacture of tetrahydro-ú+ú=ºaquinoline derivatives

Info

Publication number
GB886613A
GB886613A GB29472/60A GB2947260A GB886613A GB 886613 A GB886613 A GB 886613A GB 29472/60 A GB29472/60 A GB 29472/60A GB 2947260 A GB2947260 A GB 2947260A GB 886613 A GB886613 A GB 886613A
Authority
GB
United Kingdom
Prior art keywords
acid
general formula
formula above
hydrogen
give
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
GB29472/60A
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
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 F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of GB886613A publication Critical patent/GB886613A/en
Expired legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
    • B01J31/08—Ion-exchange resins
    • B01J31/10—Ion-exchange resins sulfonated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations

Abstract

The invention comprises 3,4-dihydroisoquinolines of the general formula <FORM:0886613/IV (b)/1> in which n has the value 1, 2, or 3 and R represents hydrogen or an alkyl group, and a process described below, in which they are intermediates for the manufacture of 1,2,3,4-tetrahydroisoquinoline derivatives of general formula <FORM:0886613/IV (b)/2> in which R and n have the significance stated above, and acid addition salts thereof. The process of manufacture consists of (1) condensing homoveratryl amine, for example, by heating, preferably with the aid of a condensing agent such as a cation-exchange resin in its acid form, with the correctly substituted b -phenylpropionic acid to give the correspondingly substituted b -phenylpropionic acid homoveratryl amide; (2) cyclising the aforesaid amide, especially with the aid of an acidic agent such as phosphorus oxychloride or a mineral acid, to give the 3,4-dihydroisoquinoline derivative of the first general formula above; (3) reducing the aforesaid 3,4-dihydroisoquinoline derivative by treatment with, for example, lithium aluminium hydride or lithium or potassium borohydride or hydrogen and Raney nickel so as to obtain the corresponding 1,2,3,4-tetrahydroisoquinoline derivative; (4) N-methylating the last-mentioned compound (preferably by treatment with formaldehyde followed by reduction with formic acid or with hydrogen in the presence of Raney nickel) to give the compound of the second general formula above; and (5), if desired, converting the free base of the second general formula above into one of its acid addition salts. When R is hydrogen, compounds of the second general formula above contain one asymmetric carbon atom, and examples of resolution by diasteareaoisomer formation using dextrotartaric acid, dibeanzoyldextrotartaric acid, and dextrocamphorsulphonic acid are given. When R is alkyl, compounds of the second general formula above contain 2 asymmetric carbon atoms. Detailed examples are given. Nuclear-halogenated b -phenylpropionic acids may be produced (a) by condensing the appropriately substituted benzaldehyde with malonic acid, decarboxylating the resulting benzylidenemalonic acid, and hydrogenating the product; (b) by reacting the correctly substituted benzyl halide with a sodium malonic ester (optionally alkylated), saponifying, and decarboxylating the product; and (c) reacting sodio diethyl acetoacetate with a nuclear halogenated benzyl halide, and splitting off the acetyl group from the resulting benzylacetoacetic acid diethyl ester by hydrolysis with concentrated alkalis, the ester having been alkylated prior to hydrolysis, if desired. Detailed examples are given. Specification 862,052 is referred to.
GB29472/60A 1959-12-09 1960-08-26 Manufacture of tetrahydro-ú+ú=ºaquinoline derivatives Expired GB886613A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH886613X 1959-12-09

Publications (1)

Publication Number Publication Date
GB886613A true GB886613A (en) 1962-01-10

Family

ID=4545319

Family Applications (1)

Application Number Title Priority Date Filing Date
GB29472/60A Expired GB886613A (en) 1959-12-09 1960-08-26 Manufacture of tetrahydro-ú+ú=ºaquinoline derivatives

Country Status (1)

Country Link
GB (1) GB886613A (en)

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