DE1039518B - Process for the preparation of basic substituted 8-oxyquinolines - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

kl. 12p 1/10

INTERNAT. KL. C 07 d

PATENT OFFICE

EXPLAINING PUBLICATION 1039 518

F9240IVb / 12p

REGISTRATION DATE: 11 JUNE 1952

NOTICE
THE REGISTRATION
AND ISSUE OF THE
EDITORIAL: SEPTEMBER 25, 1958

J. H. Burckhalter and W. H. Edgerton (J. Am. Chem. Soc, 73, 4837) have published 5-halo-7-diethylaminomethyl-8-oxyquinolines described as amoebic compounds.

It has been found that basic substituted 8-oxyquinolines of the general formula

R "

CO

R '

N-CH ₂ - _%

HO

are much more effective and more tolerable. In this formula, R and R 'are the same or different normal or branched alkyl radicals which are interrupted by heteroatoms or by oxy groups, dialkylamino groups or can be substituted by an aryl radical, where R and R 'together with the neighboring Nitrogen atom can also mean a saturated heterocyclic radical, while R ″ a represents optionally substituted aromatic or heterocyclic radical, either directly with the Carbonyl group is connected or an alkylene or alkenylene group mediating the connection with the carbonyl group wearing.

According to the invention, the compounds are prepared by an in 7-position unsubstituted 8-oxyquinoline of the general formula

R "

CO

HO

R '

HN,

wherein R and R 'are as defined above. Method of manufacture basic, substituted 8-oxyquinolines

Applicant:

Paint factories Bayer Aktiengesellschaft, Leverkusen-Bayerwerk

Dr. Ernst Schxaufstätter, Wuppertal-Elberfeld, and Dx. Mairianne Bock, Wuppertal-Sonnborn,

have been named as inventors

According to the invention, however, one can also proceed in such a way that a base-substituted 5-aceto-8-oxyquinoline is used the general formula

CH ₃

2 * CO

R '

N-CH ₂ - ,.

HO

wherein R and R 'have the above meaning, an optionally substituted aromatic or heterocyclic one Aldehyde can act.

If this procedure is used, compounds of the narrower general formula are obtained

R '"

CH

1 CH

CO

where R "has the above meaning with formaldehyde and a secondary amine of the general formula R '

HO

where R '"represents an optionally substituted aromatic or heterocyclic radical.

# 19 639/459

3 4

The compounds can, as such as well as in the form of an analog, from 5-cinnamoyl-8-oxyquinoline with di-

their salts with inorganic or organic acids butylamine the S-cinnamoyl ^ -dibutylaminomethyl-S-oxy used will. quinoline (mp 51 to 53 ° C), with di (oxyethyl) amine that

5-cinnamoyl-7-di (oxyethyl) aminomethyl-8-oxychmoline

Example 1 5 (mp 136 ° C), with as-triethyl-ethylenediamine the 5-Cinn-

- amoyl-7- [N- (diethylaminoethyl) -N-ethylaminomethyl] -

8.3 g of 5-benzoyl-8-hydroxyquinoline, 3.5 g of 30 ° / ₀ sodium formaldehyde 8-oxyquinoline (F. 85 to 90 ° C) and with bis (diäthylhydlösung, 3 g of 50% dimethylamine solution and 200 cc aminoethyl ) -amine the 5-cinnamoyl-7-bis- (diethylamino-alcohol are refluxed for 4 hours. ethyl) -aminomethyl-8-oxyquinoline (mp 85 to 90 ° C) er-Then the alcohol is distilled off, the residue keep io.

stirred with 3 ⁰ / "acetic acid, filtered and the FII Beisp'el 5

joined with ammonia precipitated. After suction and

Recrystallization from 4D ⁰ IfJLgSm alcohol shows that 9.2 g of S-cinnamoyl-S-oxyquinol, 3.5 g of 30% form-

Holding S-benzoyl ^ -dimethylaminomethyl-S-oxyquinoline aldehyde solution, 4.1 g of N-methyl-N-benzylamine and 400 ecm a melting point of 113 ° C. If the alcoholic 15 alcohol are refluxed for 5 hours. Hydrogen chloride is added to the solution of this substance, it is then filtered off while hot, and the alcohol is evaporated in this way the hydrochloride precipitates, which is a decomposition agent and the residue from a benzene-ligroin mixture point at about 135 to 140 ° C. recrystallized. The 5-cinnamoyl-7- (N-

When using as-triethyl-ethylene-methyl-N-benzyl-aminomethyl) -8-oxyquinoline melts analogously diamine instead of dimethylamine is 5-benzoyl-20 at 124 ° C, the hydrochloride decomposes at 227 ° C. 7- [N- (diethylaminoethyl) -N-ethyl-aminomethyl] -8-oxy- Analog is obtained from 5-cinnamoyl-8-oxyquinoline and

Quinoline obtained from m.p. 54 to 56 ° C. N-methyl-N-dodecylamine 5-cinnamoyl-7- (N-methyl-

N-dodecyl-aminomethyl) -8-oxyquinoline (m.p. 76 ° C) geBeExample 2 forms.

9.4 g 5- (4'-chlorobenzoyl) -8-oxyquinoline (mp 216 ° C; her- Example 6

made from 8-hydroxyquinoline and 4-chlorobenzoyl chloride 9.2 g of S-cinnamoyl-S-oxychinolm, 3.5 g of 30 ⁰ / "sodium form

according to Friedel-Crafts), 3.5 g of 30% formaldehyde-aldehyde solution, 2.5 g of pyrrolidine and 400 ecm of alcohol solution, 3 g of 50% dimethylamine solution and 500 ecm are refluxed for 8 hours. Then alcohol is refluxed for 5 hours. After 30 the alcohol is evaporated and the residue with dilute evaporation of the alcohol, the residue is extracted cold with tertiary acetic acid. After filtering, the dilute hydrochloric acid is added, filtered off and the filtrate extract is precipitated with ammonia, the precipitate is filtered off with ammonia. After recrystallization from and recrystallized from alcohol. The 5-cinnamoyl-60 ° / ₀ sodium alcohol melts the 5- (4'-chlorobenzoyl) - 7-pyrrolidinomethyl-8-oxyquinoline melts at 178 ° C 7-dimethylaminomethyl-8-oxyquinoline at 92 ° to 93 ° C. under 35 Decomposition. The hydrochloride decomposes at The hydrochloride begins to decompose from 140 ° C. 232 ° C.

In the same way, 5-cinnamoyl-8-oxyquinoline becomes

Example 3 with piperidine the S-cinnamoyl ^ -piperidinomethyl-S-oxy-

quinoline (m.p. 71-72 ° C; m.p. of the hydrochloride 220 ° C

a) 9.2 g of 5-cinnamoyl ~ 8-oxyquinoline are in 400 ecm 40 with decomposition) and with N-methylpiperazine the 5-Cinnboiler Dissolved alcohol and after adding 3.5 g of amayl-7- (N'-methyl-piperazinomethyl) -8-oxyquinoline 30% formaldehyde solution and 3 g 50% dimethyl (mp 181 ° C; mp of the hydrochloride 203 to 204 ° C below amine solution refluxed for 5 hours, with decomposition) obtained.

the new connection formed fails. One sucks hot

and thus receives the S-cinnamoyl ^ -dimethylamino- 45 Example 7

methyl-8-oxyquinoline of 193 ° C.

b) 8.4 g of S-Aceto ^ -dimethylaminomethyl-S-oxychino-10.3 g of 5- (4'-chlorocinnamoyl) -8-oxyquinoline (mp 197 ° C; lin hydrochloride (melting point 225 ° C with decomposition, prepared from 5-aceto-8-oxyquinoline and 4-chlorobenzy Heating of 5-aceto-8-oxyquinoline with dialdehyde in an alcoholic-alkaline solution), 3.5 g of 30% strength methylamine hydrochloride and paraformaldehyde in Al-50 formaldehyde solution, 3 g of 50% dimethylamine solution alcohol) are dissolved in 100 ecm of water, with 50 ecm and 400 ecm of alcohol are refluxed for 5 hours 10% sodium hydroxide solution was added and the mixture was boiled with 3 ecm Benz. It is suctioned off hot and evaporated to dryness. aldehyde shaken for several hours. The precipitate. After recrystallization from alcohol, the 5- (4'-is separated, dissolved in dilute acetic acid and treated with chlorocinnamoyl) -7-dimethylaminomethyl-8-oxyquinoline Ammonia pleases. After recrystallization, the 55 melts at 183 ° C. The hydrochloride decomposes at 215 Product at 193 ° C and is identical to the above up to 216 ° C. S-Cinnamoyl-y-dimethylaminomethyl-S-oxyquinoline Example 8

table. ^

Example 4 ^ ^as 5 - (^ - Phenyl-propionyl) -7-dimethylaminomethyl-

60 8-oxyquinoline is prepared analogously to Example 4 from 5 - (^ - phenyl-

9.2 g of S-cinnamoyl-S-oxychmolin, 3.5 g of 30 ⁰ / "sodium form propionyl) -8-oxyquinoline, formaldehyde and dimethyl

aldehyde solution, 2.5 g of diethylamine and 400 ecm of alcohol amine. The compound melts at 88 to 9O ⁰ C.

are refluxed for 4 hours. Then "-

the alcohol example 9 is used regardless of any precipitated substance evaporated and the residue cold with dilute 65

Extracted hydrochloric acid. After filtration, the extract S-cinnamalaceto ^ -dimethylammomethyl-S-oxyquinoline is precipitated with ammonia, the 5-cinnamoyl-7-di- is made from S-cinnamalaceto-S-oxyquinoline as ethylaminomethyl-8-oxyquinoline (F. 85 to 9O ⁰ C) ER- (F. 129 ° C; obtained from 5-aceto-8-oxyquinoline and Zimthalten the melting point of the hydrochloride is aldehyde by alkaline condensation), formaldehyde at 180 to 185 ° C (with decomposition).. 70 and dimethylamine produced. The connection is melting

after recrystallization from ligroin at 73 to 74 ° C, the Hydrochloric! decomposes above 140 ° C.

Example 10

a) 18.8 g 5- (2'-chlorobenzoyl) -8-oxyquinoline (mp 127 to 128 ° C; prepared from 8-oxyquinoline and 2-chlorobenzoyl chloride according to Friedel-Crafts), 200 ecm alcohol, 7 g 30% formaldehyde solution and 7 g of 50 ° / ₀ sodium dimethylamine solution are boiled for 2 hours under reflux. It is filtered off hot and the hydrochloride of 5- (2'-chlorobenzoyl) -7-dimethylaminomethyl-8-oxyquinoline precipitates from the filtrate with alcoholic hydrochloric acid, which, after recrystallization from alcohol, melts at 207 ° C. with decomposition.

b) Analogously to the procedure of Example 10, a) is prepared from 5- (2 ', 4'-dichlorobenzoyl) -8-oxyquinoline (mp 196 ° C;) from 8-oxyquinoline and 2,4-dichlorobenzoyl chloride) 5- (2 ', 4'-dichlorobenzoyl) -7-dimethylaminomethyl-8-oxyquinoline obtained with formaldehyde and dimethylamine, which was isolated in the form of its hydrochloride (mp 222 ° C with decomposition).

Example 11

8.3 g of 5- (3 ', 4'-dimethoxycinnamoyl) -8-oxyquinoline (mp 185 ° C; obtained by alkaline condensation of S-aceto-S-oxyquinoline with veratrumaldehyde) are mixed with 250 ecm alcohol, 2 cooked, 5 g of 30% formaldehyde solution and 2.5 g of 50 ° / ₀ dimethylamine solution for 90 minutes under reflux. It is then filtered off while hot and the filtrate is allowed to crystallize. The 5- (3 ', 4'-dimethoxycinnamoyl) -7-dimethylaminomethyl-8-oxyquinoline obtained in this way melts at 132 ° C. and forms a hydrochloride which melts at 232 ° C. with decomposition. Average same. In contrast, the yields naturally vary between 40 and 90% in the individual examples, depending on the starting materials used

Claims (1)

PATENT CLAIM: Process for the preparation of basic substituted 8-oxyquinolines of the general formula R " Example 12 35 6.8 g of S-Furfurylidenaceto-S-oxyquinoline (F. 154 ° C; prepared from S-Aceto-S-oxyquinoline and furfural in alkaline solution), 250 cc of alcohol, 2.6 g of 30 ° / ₀ formaldehyde solution and 2 , 6 g of 50% strength dimethylamine solution are heated on a water bath for 1 hour. Is then cooled, filtered off with suction and the residue is recrystallized from alcohol to give the 5-Furfurylidenaceto-7-dimethylaminomethyl-8-oxyquinoline mp. 190 ⁰ C is obtained, the hydrochloride decomposes at 220 ° C. 45 Example 13 8.8 g of 5- (5'-nitro-furfurylidenaceto) -8-acetoxy-quinoline (m.p. 190 ° C; produced by heating S-aceto-S-oxyquinoline with 5-nitrofurfurol in acetic anhydride), 5 g 50% strength of dimethylamine, 2.5 g of 30 ° / ₀ formaldehyde solution and 400 cc of alcohol are boiled for 2 hours under reflux. It is filtered off hot and the hydrochloride of 5- (5'-nitro-furfurylidene-aceto) -7-dimethylaminomethyl-8-oxyquinoline is precipitated with alcoholic hydrochloric acid. Example 14 6.5 g S- ^ quinolyty-io '^ - acryloyl-S-oxyquinoline (m.p. 210 ° C; obtained by condensation of S-aceto-S-oxyquinoline with quinoline-6-aldehyde in alkaline solution), 150 ecm of alcohol , 2 g of 30 ° / ₀ formaldehyde solution and 2 g of 50% dimethylamine solution are boiled for 2 hours under reflux. It is filtered off hot and the 5 - [(quinolyl) - (6 ')] - acryloyl-7-dimethylaminomethyl-8-oxyquinoline is allowed to crystallize out in the filtrate up to 265 ° C. The yields of end products are according to the two embodiments of the claimed process in CO R ' N-CH, "N ' HO wherein R and R 'are identical or different normal or branched alkyl radicals which are through heteroatoms interrupted or substituted by oxy groups, dialkylamino groups or by an aryl radical may be, or where R and R 'together with the adjacent nitrogen atom form a saturated heterocyclic Radical, while R "denotes an optionally substituted aromatic or heterocyclic one Represents a radical which is either directly linked to the carboxyl group or a compound with the carbonyl group-mediating alkylene or alkenylene group, characterized in that one in a known manner either a) an 8-oxyquinoline which is unsubstituted in the 7-position the general formula R "
CO HO where R "has the above meaning with formaldehyde and a secondary amine of the general formula hn; R ' converts, in which R and R 'have the above meaning, or that one b) to a basic substituted 5-aceto-8-oxyquinoline of the general formula R ' HO wherein R and R 'have the above meaning, an optionally substituted aromatic or heterocyclic one Aldehyde can act. ® 809 639/459 9.58