DE2441747A1 - General cyclisation process in high B. Pt. solvent - at 200-350 deg. celsius pref. for prepn. of naphthyridines and quinolines - Google Patents

Abstract

General cyclisation process involving partial clearage of the molecule by heating either the molten starting material or a soln. of this material in an appropriate solvent of high b.pt., then mixing it with a much larger quantity of high b.pt. solvent heated to 240-360 degrees C so that the resulting temp. is 200-350 degrees C, then cyclising at this temp. followed by cooling and isolating the product. The larger quantity of solvent is pref. 2 to 12 times, partic. 5-10 times, that used for the starting material. The reaction is pref. carried out in a tubular reactor with rapid agitation. After cyclising, the cooling is carried out either by a heat exchanger or by pouring into a lower boiling point solvent). The method is spec. for preparing naphtyridines or quinolines of formula (I) from cpds. of formula (II) (where R1 is N or CH, R2 and R5 are alkyl; R3 and R4 are alkyl, alkoxy, halogen or together are -OCH2O-, and R6 is H or alkyl).

Description

Process for carrying out ring closure reactions Addition to patent ..... (Patent application P 23 43 462.0) The main patent relates to a generally executable Process for carrying out ring closure reactions with splitting off of a partial molecule which only beS relatively high, above that which can be achieved with the usual solvents Temperatures run off.

The process is particularly suitable for such ring closure reactions in which an aloa: ol is split off from an ester group from the starting material According to the main patent, the process for carrying out ring closure reactions in high-boiling solvents in the temperature range above 200 ° C to 360 ° C below Separation of a partial molecule and cooling of the reaction mixture carried out by that flian the starting compound melted or in solution of a suitable high-boiling point Solvent heated and with a larger amount heated to 240 to 36,000 of the high-boiling solvent mixed at the resulting mixing temperature carries out the cyclization from 200 ° C to 350 ° C and subsequently the reaction mixture cools, whereupon the product is recovered as the solvents will.

What is described is particularly suitable, generally at temperatures from 203 to 360 ° C executable process for the production of polynuclear, or a heterocyclic rings containing several nitrogen atoms as well as the further substituents Unsubstituted or unsubstituted 4-hydroxy-3-carbalkoxy-naphthyridines or quinolines, starting from the correspondingly substituted or unsubstituted Pyridyl or. Phenylaminomethylene malonic esters.

These further substituents cannot yet be used in any occupied positions of the rings occur and be of any kind, provided they are not react in the cyclization.

Such further substituents are therefore alkyl groups and alkoxy groups, especially those with 1 to 4 carbon atoms, aromatic radicals, especially phenyl radicals Halogen atoms, especially chlorine atoms, phenolic OH groups, optionally alcohol, Alkyl substituents containing kato or ether groups and the like are preferred.

Another subject matter of the main patent is a method for implementation of ring closure reactions according to the procedure described, which is characterized is that a hydroxyl group in the 4-position and a carbalkoxy group in the 3-position bearing and in further) positions substituted or unsubstituted napthyridines or quinolines by thermal cyclization in high-boiling solvents appropriately substituted or unsubstituted pyridyl or phenylaminomethylene malonic acid esters be prepared with elimination of 1 mole of alkenol.

The alkoxy group originating from the alkyl malonate can be used here per se can be any but are carbmethoxy, carbethoxy and carbpropoxy groups preferred.

During the reaction, one of the two alkyl ester groups is in the form split off the free alcohol.

It has now been found that, according to the method, others also determined Pyridyl or phenyl aminomethylene malonic esters can be cyclized.

The subject of the invention is therefore a process for the implementation of ring closure reactions in high-boiling solvents in the temperature range of 200 to 360 ° C with cleavage of a partial molecule by the fact that the starting compound melted or heated in solution of a suitable high-boiling solvent and with a larger amount of the high-boiling solvent heated to 240 to 3600C mixed, the cyclization at the resulting mixing temperature of 200 to 3500C executes and then cools the reaction mixture, whereupon the product from the solvent is obtained, according to patent. * ¢ (patent application P 23 43 462.0 ), characterized in that 3,4-methylenedioxy-pyridylaminomethylene maloester or 3,4-methylenedioxy-phenylaminomethylene malonic ester or their N-alkyl derivatives by cyclization into the appropriately substituted naphthyridines or quinolines implemented.

According to the present process, in particular pyridyl or phenyl aminomethylene malonic esters of the formula in which R1 is nitrogen or CH R4 is H or alkyl and R2 and R3 are alkyl, the correspondingly substituted naphthyridines or quinolines of the formula by ring closure with cleavage of RDOH getting produced.

Substituents in other ring positions are possible.

In the case of R4 = H, there is a tautomeric form in which this H in an OH group in position 4 with a formal shift of the double bonds is present, so that the corresponding compounds as 4-hydroxy compounds are designated.

In the case of R4 = alkyl, the compounds formed are 4-oxy compounds to call.

Preferred alkyl substituents R2, R3 and R4 are those with 1 to 4 carbon atoms.

The general and preferred measures mentioned in the main patent and process conditions apply to the present process in the same way.

The products can, like those of the main patent, as preliminary or intermediate products, find use, for example, for the production of hair dyes.

Example 1 3-Carbathoxy-4-hydroxy-6,7-methylenedioxyquinoline 75 Ltr. Dibenzylbenzene are heated to approx. 300 ° C in a 150 liter stirred kettle. While stirring vigorously, one is heated to 150 ° C. within 1 to 2 minutes Solution of 6.0 kg of 3,4-methylenedioxy-anilinomethylene malonic acid diethyl ester in 12 kg of dibenzylbenzene added. The resulting ethanol distills immediately away. The reaction has ended after about 12 to 18 minutes. The reaction solution becomes cooled rapidly, the cyclizate crystallizing out of the still warm solution. The crystallized cyclizate is spun off using a centrifuge, the filter cake washed several times with hexane and the washing liquid combined with the filtrate. The hexane is separated off from this solution by distillation.

4.8 kg of 3-carbethoxy-4-hydroxy-6,7-methylenedioxychino lin (95 Vo yield) were obtained, in which compound the 3,4-methylenedioxy group of the formulation -O-CH2-O- together with the carbon atoms, to which it is bound, the ping forms.

In a corresponding manner, N-ethyl-3,4-methylenedioxy-anilinomethylene melonate can be used be converted to N-ethyl-3-carbethoxy-4-oxo-3-6,7-methylenedioxyquinoline.

Claims (1)

Claim Process for carrying out ring closure reactions in high boiling points Solvents in the temperature range from 200 to 36,000 with splitting off of a partial molecule by having the starting compound melted or in solution of a suitable one heated high-boiling solvent and with a heated to 240 to 3600C larger Amount of high-boiling solvent mixed, at the resulting miso-temperature carries out the cyclization from 200 to 3500C and then the reaction mixture cools, whereupon the product is obtained from the solvents, after one or several of the claims of patent ... (patent application P 23 43 462.0), thereby characterized that 3,4-methylenedioxy-pyridylaminomethylene malonic ester or 3,4-methylenedioxy-phenylaminomethylene malonic esters or their N-alkyl derivatives by cyclization into the appropriately substituted Naphthyridines or quinolines are implemented.