DE2444519A1 - PROCESS FOR THE PREPARATION OF 1,2-DIHYDRO-QUINOLINE DERIVATIVES - Google Patents

Description

DlpL-Ing. P. WIRTH Dr. V. SCHMIED-KOWARZIK Dipl.-Ing. G. DANNENBERG Dr. P. WE ¹ NHOLD Dr. D. GUDEL.

281) 34 β FBANKFURTAM MAIN

TELEPHONE (0611)

287014 GB. ESCHENHEIMER STRASSE 3Θ

Ca se LP i m / 1102 ^T ./d/Be

LONZA A.G.

Gampel / Wallis, Switzerland

(Management: Basel)

Process for the production of 1,2 ^ dihydro ~ quinoline

Derivatives.

The present invention relates to a method of manufacture of 1,2-dihydroquinoline derivatives.

It is known that 2-oxo-4-methyl-7-amino-quinoline 'of ra-phenylene diamine and ethyl acetoacetate by 19-hour heating in an autoclave at 130 ⁰ C in 45-60 produce 1,2-dihydro i & Lger yield (C. 1938, II, 4240). ,

It has now been found that zw Hei position χ on 1,2-dihydro-2-oxo-4-methyl-7-amino-ohinoline or 1,2-dih3'-dro-2-oxo-4-raethyl _# - 7 -acetoacetic acid amido-quinoline stat !: Acetoacetic ester directly diketene can be used v / erdeh, \ 7obei the process at significant

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lower. Temperatures and without pressure can be carried out and still surprisingly good yields can be achieved (70- · 8 %;%).

The invention therefore relates to a method for production of 1,2 ~ dihydro-quinoline derivatives of the general

CH-

0 0

Il Il

wherein R is hydrogen or the group CH ^ -C-CHp-C- bsueutet, which is now characterized in that one mole of m-phenylenediamine with about / a 1 mol or 2 hol diketene implemented.

For the production of 1,2-dihydro-2-oxo-A-methyl-7-amino-ch.ir olin, which is also referred to as 7-araino-2-oxy-lepidine or 7-amino-lepid.on can, therefore, be 1 mol m-Fhenylindiamin with ^Q twa 1 mole of diketene to, while for the preparation of 1,2-dihydro-2 ~ oxo-4-methyl-7 ~ acetessigsäurea ⁱⁿ ido-quinoline, also known as 7-acetoacetylamino -4-methyl-quinwlon- (2) oc? F =: r 7-Acetoacetylarninolepiao.i denotes v; ground, 1 mol of m-phenylenediamine ^{reacted with e +} wa 2 mol of diketene

The process is expediently carried out in water with the addition of acetic acid as a catalyst, preferably in 10 50 acetic acid. The above reaction can also in organic solvents in which the starting materials are soluble (eg., Methanol, ButylacetPt, carbon tetrachloride, toluene) with addition of et.wa 5% glacial acetic acid or in glacial acetic acid alone at temperatures below 100 ⁰ C, without Application of pressure, possibly under reflux, carried out v / ground.

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example 1

In a sulfonation flask, equipped with anchor stirrer, reflux condenser, dropping funnel, thermometer, and water bath, 43.2 g sodium least 98 ^ 1, 3-Phenylendiam.ln (F 60-62 ⁰ C)? And 100 ml of 10 6ige Essigsäu ^^ filled and Cleans erature amp stirring 35.2 g Dikfecen in the course of about 20 minutes dripped .. the temperature is left under Zuhilfer-imitate the heat of reaction at 60 - 65 ⁰ C and stiffened läcst after completion of diketene were to admit nor i hour at 60 - 65 ° C post-reagent.

Wax cooling to about 15 ° C is filtered with suction and dried in vacuo at 60-70 ⁰ C bib dried to constant weight. It will

49.2 g of yellow-colored 1,2-dihydro-2-oxo -''- methyl-7-arainoquinoline ir. With a melting point of 268 to 269 ° C, which corresponds to a yield of 70.7 % _f calculated on m- Phenylenediamine.

? A single recrystallization from dimethylformamide / HPO (1: 1) or 5 NC 5iger Ersigsäure the product is colorless and has a melting point .on 274.6 to 275.4 ⁰ C and from 274.0 to 274.8 ⁰ C.

Example 2

In a sulfonation flask, equipped with anchor stirrer, reflux condenser, dropping funnel, thermometer and · Viasserbad, 129.6 least 98 #iges 1,3-Phenylendiarain (F 60-62 ⁰ C), 750 ml of 10% ± ge acetic acid and filled with 211.2 g of diketene were added dropwise over the course of 1 to 11/2 hours with stirring at room temperature. The temperature is allowed to rise to 60 to 65 ^° C. with the aid of the heat of reaction. After completion of diketene Zugatc is for 1 hour at 60-65 ⁰ C and allowed to react for then cooled to about 15 ° C.

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BAD OftfäiNAL

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The precipitated product is filtered off and dried in vacuo at 60 to 70 · ⁰ C Me dried to constant weight. There v / ground 257 g of crude, nearly colorless 1,2-dihydro-3-oxo ~ 4-methyl-7-acetoacetamino-quinoline with a melting point of 238 etvra ⁰ C, corresponding to a yield of 83%, calculated on m- Phenylenedipmine.

After one recrystallization from 67% acetic acid the melting point is 246.0 to 247.0 C, after repeated Recrystallization from the dilute acetic acid changes: the melting point does not flourish *.

The 1,2-dihydroquinolium derivatives prepared according to the invention are valuable intermediate products, especially in the pharmaceutical sector or for the production of special pigments,

SAD 509813/1103

Claims (4)

Claims '1. Method of making vrp. 1,2-DiIiycL o-quinoliri derivatives of the general formula; ^: CH, 0 0 ti tf where R "denotes hydrogen or the group CH ₇ -C-CHp-C-, characterized in that 1 M ^ 1 m ~ phenylenediane> i η is reacted with 1 mol or 2 Hol Biketene. 2. The method according to claim 1, characterized in that the reaction takes place in about 10% acetic acid. 3. The method according to claim 1 to 2, characterized in that the reaction is carried out in organic solvents with the addition of catalytically active acetic acid, preferably in an amount of about 5% by weight. 4. The method according to claim 1 to 3, characterized in that the reaction below about 100 ⁰ C, preferably at about 60 to 65 ⁰ C, but at most under reflux • takes place. 509813/110 3