Carbazole and its derivatives, namely N-ethyl carbazole has wide application in the synthesis of dyes, pigments and insecticide. Carbazole derivatives are also used widely in electrical industry, high heat-resistant polymers, concrete plasticizers and the like. Carbazole is also one of the important constituents of coal tar. High temperature coal tar contains on an average 1.5% carbazole. Carbazole is also obtained as a co-product in the production of anthracene, both by physical separation (extraction with pyridine, ketone, N-methyl pyrrolidone (NMP), dimethylacetamide, dialkyl sulfoxide, dialkyl formamide) or chemical separation (by means of KOH, or concentrated H2SO4 fusion).
Plethora of published literature for the synthesis of chlorocyclohexanone from cyclohexanone is available. Aromatic primary and secondary amines are also available and can be made by reduction of corresponding nitro derivatives. N-ethylcarbazole is an important intermediate product for the preparation of valuable dyestuffs. It is prepared in the industries by reaction of carbazole with potassium hydroxide or potassium carbonate to give the potassium salt of carbazole, which is then ethylated with an ethyl halide or with diethyl sulphate (See DE-B2132961). Other processes for the preparation of N-ethylcarbazole from carbazole use, for example, ethyl benzenesulphonate (Chemical Abstracts, Volume 82, Abstract No. 45003 1975), diethyl N-(o-tolyl) phosphoramidate (Journal of Heterocyclic Chemistry, Volume 18, page 315 (1981)) or 1,1-diethoxyethylium tetrafluoborate, However, these process have no industrial importance.
All the known industrial preparation processes have the disadvantage that large amount of inorganic salts are produced which are to be removed from the process waste waters by evaporation of the waste water in a labour- and energy-intensive manner and then have to be dumped, or which finally enter rivers with the waste waters via clarification plants. These processes are environmentally unfriendly and produce large amount of solid and liquid waste. For example, if the process described in BIOS Final Report 986, page 197 is used, wastewater obtained comprises about 220 kg of potassium chloride per tonne of N-ethylcarbazole produced. By the process described in DE-B-2132961, about 490 kg of potassium sulphate is found in the waste water per tonne of N-ethylcarbazole. The processes in which ethyl halides are used as ethylating agents also have the further disadvantage that a very expensive purification of the waste air must be carried out to avoid emission of organic halogen compounds, since simple combustion of the waste air is not possible because of the halogen content. A content of organic halogen compounds in the wastewater also cannot be avoided in these processes with aqueous working-up of the reaction mixture. Furthermore, both the use of ethyl halides and that of diethyl sulphate require particular measures when handling these substances because of the toxic and carcinogenic properties. An improved process for the preparation of ethylcarbazole would therefore be extremely desirable for both the ecological and industrial hygiene reasons. Instead of alkyl halides or dialkyl sulphates, dialkyl carbonates can in some cases be employed in alkylation of amines; thus, for example, the use of dimethyl carbonate in the presence of phase transfer catalysts, such as crown ethers, instead of dimethyl sulphate for methylation of imidazole is described in Liebigs Annalen der Chemie 1987, page 77. This publication refers to the pronounced difference in reactivity between dimethyl carbonate and diethyl carbonate and in fact under no circumstances has a defined product has been obtained with diethyl carbonate. The different behavior of dimethyl and diethyl carbonate and the poor results achieved with the latter are also discussed, for example, in Synthesis 1986, page 382. Ethylations on the nitrogen atom of amide groups by means of diethyl carbonate are possible. European Patent Application EP-A-410214 mentions the reaction of urethanes with diethyl carbonate in the presence of at least equivalent amounts of alkali metal or alkaline earth metal carbonates and additional phase transfer catalysts, but these reaction properties of amides cannot be compared with those of amines because of the higher acidity of the amides.
Diethyl carbonate in general reacts with amines to give carbamic acid esters (Houben-Weyl, Methods of Organic Chemistry, Volume E 4, page 159; Ullmann's Encyclopaedia of Industrial Chemistry, 4th edition, Volume 14, page 591; DE-B-2160111), and U.S. Pat. No. 4,550,188 discloses ethylation only as a side-reaction.
Only in a few cases ethylations occur as the main reaction in the reactions of aromatic amines with diethyl carbonate. DE-A-2618033 also describes, in addition to the reactions of various aniline derivatives with dimethyl carbonate, the reaction of p-phenylenediamine and p-toluidine. Two monoarylamines activated by electron-donating substituents on the ring, with diethyl carbonate in which mixtures of products mono- and bis-ethylated on the nitrogen are formed. The gas phase reaction of aniline, a relatively highly volatile aromatic amine, with diethyl carbonate in the presence of a catalyst comprising polyethylene glycol and potassium carbonate gives a mixture of 56.5% of N-ethylaniline, 19.7% of N-ethoxycarbonyl-N-ethylaniline and 24.4% of aniline (Journal of Organic Chemistry, Volume 52, page 1300, 1987). It clearly observed that a high proportion of starting material remains un-reacted. This method cannot therefore be applied to amines of low volatility. Alkylation of aromatic amines by means, of dialkyl carbonates in the presence of organic iodides as catalysts is mentioned in German Patent Specification DE-C-3007196. However, because of the addition of organic iodides, industrial realization of this process would again necessitate expensive purification of waste air. Further, with aqueous working-up, it would lead to a content of organic halogen compounds in the wastewater. Furthermore, only reactions with dimethyl carbonate, from which mixtures of N-methyl- and N,N-di-methyl-anilines are obtained, are disclosed. There are no indications that diethyl carbonate gives results similar to those with dimethyl carbonate, which has a substantially better alkylating action. The markedly different alkylation capacity of methyl and ethyl groups in carbonic acid esters can also be seen from EP-B-104601 which also discloses the use, in addition to the use of dimethyl carbonate, of the mixed carbonic acid esters with a methyl group and a higher alkyl group, for example, and preferably, an ethyl group, for N-methylation of bis(2,4,6-tribromophenyl)amine to give the desired N,N-bis(2,4,6-tribromophenyl)methylamine. Alkylation proceeding alongside the methylation, in particular ethylation, which would indicate comparable reaction properties of the methyl and ethyl group in this type of reaction of N-alkylation of a diarylamine, is not referred. However, even with dimethyl carbonate, the reaction is also not complete, so that the separation of reactant and product becomes necessary.
N-Ethyl carbazole is used in the synthesis of useful dyes and pigments. It is used as one of the main constituents in the synthesis of Pigment Violet-23 (PV-23) and its demand in printing ink, plastic and paint industry is increasing rapidly. With rising prices of carbazole and intense market competition, it is found essential to substantially reduce the manufacturing cost of PV-23 so as to be very competitive in the growing pigment market. This lead us to study various steps involved in the application of Bischler synthesis for the preparation of carbazole derivative cheaply so as to make our product more competitive.
Synthesis of carbazole and tetrahydro carbazole by Bischler reaction is very well known in the prior art. Application of Bischler synthesis for the preparation of tetrahydrocarbazoles is first mentioned in DE 374098 (1923). The German patent discloses synthesis of tetrahydrocarbazoles by condensing 1,2-halocyclohexanones with primary or secondary aromatic amines. Furthermore, DE947068 discloses synthesis of tetrahydrocarbazoles by reaction of 2-halogen cyclohexanones with primary or secondary aromatic amines having at least one unsubstituted o-position in the atmosphere of an inert gases free from molecular oxygen.
The availability of wide variety of aromatic amines and the ease with which 2-chloro cyclohexanones reacts with it makes the Bischler synthesis a very attractive method for the preparation of tetrahydrocarbazoles.
Rogers and Corson, J. Am. Soc., 69, 2910, 1947, describes one-step synthesis of tetrahydrocarbazole from cyclohexanone and phenyl hydrazine. This is aromatized by heating with chloranil in xylene (Barclay and Campbell, J. Chem. Soc. 530, 1945).
K. Darrell Berlin, Peter E. Clark, Jack Schroeder and Darrell Hopper, Proc. of the Okala. Acad. of sci. for 1966, pg 215-220, reports synthesis of 3-tert-butyl-1,2,3,4-tetrahydrocarbazole with 81% yield in acetic acid after 2.5 hours reflux. When the reaction is run for 5 hours, yield dropped down to 78.8%.
E. Campaigne and R. D. Lake, Journal of Organic Chemistry (1959), 24, 478-87, describes synthesis of 2-N-ethyl anilino cyclohexanone from reaction of N-ethylaniline (0.20 M) with 2-chloro cyclohexanone (0.20 M), quinoline (0.02 M), sodium carbonate (0.30 M) and 150 ml of methylcellosolve (solvent) which gives 42% yield after 45 minutes reflux. The crude tetrahydrocarbazole is purified by converting it to picrates or purified by passing through alumina column which is then dehydrogenated using 30% Pd-carbon catalyst (0.25-0.4 g of 30% Pd—C catalyst per g of N-ethyl tetrahydrocarbazole with 10 ml/g Xylene after 12 hour, reflux.
The processes disclosed in the prior art for the synthesis of N-ethyl tetrahydrocarbazole require solvent or dehydrating agent. Further, the yield and purity of the alkyl carbazole synthesized from tetrahydrocarbazole by the processes disclosed in the prior art are very low. Accordingly, it is desirable to develop a process for the preparation of N-ethyl tetrahydrocarbazole in higher yield and purity from 2-chloro cyclohexanone and N-ethyl aniline in absence of any solvent or dehydrating agent.
USPTO Backgrounds
USPTO Backgrounds