DE2104377A1 - Indoleninium salts prepn - by alkylating indoles in presence of solvent - Google Patents

Abstract

Salts of formula (I) : (where R1 is an aliphatic residue; R2 and R3 are aliphatic or araliphatic residues or are joined to form an alicyclic ring; R4 is H, an aliphatic residue, halogen, alkoxy or NO2; and X is -O-SO2-OR1 or -OS2R5 in which R5 is an aromatic residue), are prepd. by reacting a substd. indole of formula (II) : (where R6 is H or R3) with an alkylating agent R1-X in the presence of oxides and/or salts with weak acids of Gp. II metals and (novel feature) also of an organic solvent which is inert under the conditions of the reaction, giving better heat-transfer and temp. regulation conditions and the starting material (II) does not have to be isolated from the crude soln. thereof in an organic solvent resulting from its prodn. by Fisher indole synthesis.

Description

Process for the preparation of i, 2,3,3-tetrasubstituted indolenine salts Addendum to patent. ... ... (patent application P 19 49-293.4).

Subject of the main patent. ... ... (patent application P 19 49 293.4) is a process for the preparation of 1,2,3,3-tetrasubstituted indoleninium salts of the general formula in which R1 denotes an aliphatic radical, R2 and R3 know to be the same or different and each denote an aliphatic or araliphatic radical or together with the carbon atoms adjacent to them denote members of an alicyclic ring, R4 denotes an aliphatic radical, a halogen atom, an alkoxy group, a Nitro group or a hydrogen atom and X is the radical -OS02R5, in which R5 is an aromatic radical, or the radical where R1 has the aforementioned meaning, denotes by reaction of a substituted indole of the general formula where R2 and R4 have the aforementioned meaning, r has the aforementioned meaning of R3 and can also stand for a hydrogen atom, with an alkylating agent of the general formula R1 - X I1I, in which R1 and X have the aforementioned meaning, in the presence of oxides and / or weak acid salts of metals of Group II of the Periodic Table.

It has now been found that the process of the main patent continues Can be designed when the reaction in the presence of one of the reaction conditions inert organic solvent is carried out.

It is expedient to use solvents which are insoluble or in water only up to 10% by weight, based on the amount of water, are soluble. Advantageously suitable are solvents with a boiling point at normal pressure or at a pressure of up to 10 at above 100 ° C, preferably between 100 and 1900C, in particular between 110 and 150 ° C. For example, the following can be used as solvents: Aromatic hydrocarbons, e.g. o-, m-, p-xylene, chlorobenzene, benzene, toluene, ethylbenzene, isopropylbenzene, p-dichlorobenzene; Halogenated hydrocarbons, especially chlorinated hydrocarbons, e.g. tetrachlorethylene, tetrachloroethane, carbon tetrachloride, chloroform, trichlorethylene, Pentachloroethane, cis-dichloroethylene, bromobenzene, 1,2-dichloroethane; Ether, e.g. n-butyl ethyl ether, Di-n-butyl ether, di-isoamyl ether, diisopropyl ether, anisole, phenetole, cyclohexyl methyl ether; aliphatic or cycloaliphatic hydrocarbons, e.g. hexane, heptane, nonone, a-pinene, pinane, o-, m-, p-cymene, gasoline fractiobes within the aforementioned boiling point range, Cy methylcyclohexane, decalin, ligroin, 2,2,4-triineL1cd @, 2,3-trimethylpentane, 2,3,3-trimethylpentane, Ge appropriate mixtures. Expediently, one uses medium in an amount of 50 to 100%, preferably from 60 to 80% by weight, based on starting material II.

The rest of the process is carried out under the conditions of the process carried out close to the main patent, in particular with regard to the starting materials, catalysts, Reaction conditions and implementation of the reaction. Compared to the procedure after According to the main patent, temperature management and control are simpler and more reliable. The process according to the invention also allows a preferred, particularly economical one Embodiment: The starting material II is made from the corresponding phenylhydrazine and a concrete, e.g. in sulfuric acid, aqueous solution at one temperature between 70 and 100 ° C, and then sets the reaction mixture according to the invention Solvent as extractant too. After appropriate extraction of the raw Starting indoles II, the organic phase is separated off from the aqueous phase and washed optionally with aqueous ammonia solution and distilled from the organic extract the rest of the water. The solution of the starting material II produced in this way is optionally with the addition of further amounts of organic solvent, then under implemented the conditions of the procedure according to the main patent. You save yourself With this method of operation, an expensive and cumbersome isolation of the starting material II after its manufacture.

The parts given in the following examples are parts by weight.

Example 1 A mixture of 145.2 parts of 2,3-dimethylindole, 100 parts Chlorobenzene and 150 parts of zinc oxide is heated to 120 to 7250C, with a thin Porridge is made. With stirring, 362 parts of dimethyl sulfate are slowly added, with the onset, exothermic reaction the. Temperature without external heating at 120 holds up to 1250C. The mixture is then stirred for 4 hours at 120 to 12500, then up 850C cooled and slowly mixed with 500 parts of cold water. The reaction mixture is processed directly without isolation of the end product I and at 30 to 35 ° C with 1.5 parts of piperidine as a stabilizer and 730 parts of ammonia water (25 percent by weight) offset. The zinc hydroxide precipitate initially formed dissolves after complete in a short time. The upper layer of the formed two-phase mixture is separated from the lower, aqueous layer and immediately in a vacuum distillation convicted. It is prepared during the separation operations by adding nitrogen Protected from atmospheric oxygen and fractionally distilled at 15 Torr.

1st flow: 25-30 ° C 80 parts (water and chlorobenzene) 2nd flow: 30-120 ° C 2 parts (chlorobenzene and Fischer's base) Main fraction: 120-125 ° C 162 parts (93% of theory) Fischer's base residue: 15 parts The 2nd forerun is the raw one Base of the next batch added.

Example 2 a) Preparation of starting material II: A mixture of 350 Parts of water, 68.2 parts of sulfuric acid (96% by weight) and 113.5 parts of phenylhydrazine is heated to 75 ° C, then slowly with 79.7 parts of methyl ethyl ketone under good Mixing is added, the temperature being raised to 95.degree. C. under gentle reflux holds, and stirred for 3 hours at 950C. 300 parts of chlorobenzene are now slowly added. The mixture is kept at 95 ° C. for a further 15 minutes and the organic ones are then separated at 7000 Phase off. 5 parts of ammonia water (25% by weight) are added to the organic phase and distilled at 50 to 55 Torr to a bottom temperature of 12500 for dehydration.

b) Implementation: The solution of the crude starting material obtained according to Example 2a) II in chlorobenzene is used instead of the isolated starting material II analogously to Example 1 implemented. The same yield of end product is obtained.

Example 3 Analogously to Example 2, phenylhydrazine can be used instead Use an equivalent amount of phenylhydrazine »hydrochloride, the amount of sulfuric acid is reduced to 50 parts.

The same amount of end product I is obtained.

Example 4 The reaction with 120 parts of bromobenzene is carried out analogously to Example 1 instead of chlorobenzene. 160 parts of Fischer's base are obtained.

Example 5 The reaction with 90 parts of anisole is analogous to Example 1 instead of chlorobenzene. 150 parts of Fischer's base are obtained.

Claims (1)

Claim Further embodiment of the process for the preparation of 1,2,3,3-tetrasubstituted indoleninium salts of the general formula in which R1 denotes an aliphatic radical, R2 and R7 can be identical or different and each denote an aliphatic or araliphatic radical or together with the carbon atoms adjacent to them denote members of an alicyclic ring, R4 denotes an aliphatic radical, a halogen atom, an alkoxy group, a Nitro group or a hydrogen atom and X is the radical -OS02R5, in which R5 is an aromatic radical, or the radical where R1 has the aforementioned meaning, denotes by reaction of a substituted indole of the general formula wherein R2 and R4 have the aforementioned meaning, R6 has the aforementioned meaning of R3 and can also stand for a hydrogen atom, with an alkylating agent of the general formula R1 - X III, in which R1 and X have the aforementioned meaning, in the presence of Oxides and / or salts of weak acids of metals of group II of the periodic table, according to patent. ... ... (Patent application P 19 49 293.4), characterized gekennzeichllet that the Reaction in the presence of an organic substance which is inert under the reaction conditions Solvent is carried out.