Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1988-05-11
1989-08-29
Hollrah, Glennon H.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D21702
Patent
active
048618888
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The invention relates to a new process for the preparation of 3,4-dihydroisoquinoline.
BACKGROUND OF INVENTION
The isoquinoline derivatives, which are unsubstituted in 1-position, are very important starting materials as well as intermediates in the synthesis of different substituted and condensed isoquinolines. By using the Reissert compounds obtained from the 3,4-dihydroisoquinolines many substituted isoquinolines may be prepared (J. Org. Chem. 35, 3119, 1970). The 3,4-dihydroisoquinolines are suitable also for the preparation of condensed isoquinolines which also are found in nature (Chem. Ber. 98, 557, 1965).
The above mentioned synthesis were, however, performed only with 6,7-dialkoxy derivatives since the 3,4-dihydroisoquinolines, which contain an electron donor substituent in 6-position, may be prepared easily by the Bischler-Napieralsky synthesis. The 3,4-dihydroisoquinoline of the invention may be prepared by the Bischler-Napieralsky synthesis only in a very low yield since the starting material, the N-formyl-2-phenylethylamine does not contain an electron donor substituent in para-position and during the reaction mainly the undesired by-products are formed (Ann. 382, 369, 1911).
Therefore those synthesis routes were mainly studied for the preparation of the 3,4-dihydroisoquinoline which are based on the partially dehydrogenation of the easily available 1,2,3,4-tetrahydoisoquinoline. This reaction cannot be stopped, however, at a degree of partial dehydrogenation while using oxidizing agent and so isoquinoline will be formed (Arch. Pharm. 274, 153, 1936). Therefore this method is suitable only for the preparation of the N-substituted derivatives where, due to partial dehydrogenation, quaternary 3,4-dihydroisoquinolinium salts are formed (J. Am. Chem. Soc. 71, 3408 1949). In the newest literature some oxidation methods are described whereby 3,4-dihydoisoquinoline may be obtained. In these processes special oxidizing agents and catalysts (e.g. ruthenium+tert.-buthylhydroperoxyd) are, however, needed so that the widespread use of this process is restricted (J. Chem. Soc. Chem. Comm. 1985, 615). Also isoquinolines are formed in the dehydrogenation reaction performed in the presence of noble metal catalysts (Chem. Ber. 60, 2602, 1927).
An improved process for the preparation of the compound of the invention is described in our earlier application according to which the 3,4-dihydroisoquinolines were prepared by Bischler-Napieralsky synthesis in the presence of Lewis-acids (published Hungarian patent application Nr. T25,548). Although by this process the 3,4-dihydroisoquinolines substituted in the 1-position could be obtained in very high yield, in the case of 3,4-dihydroisoquinoline unsubstituted in the 1-position the corresponding hexachlorostannate is formed only in a 62% yield, from which the base may be set free with some additional loss.
DESCRIPTION OF THE INVENTION
Our invention, by which the selective dehydrogenation of 1,2,3,4-tetrahydroisoquinoline is realized, eliminates the disadvantages of the known processes and provides a method for the preparation of 3,4-dihydroisoquinoline in large amounts and high purity which is more simple and can be carried out easier than the processes known in the art. It has been found that 1,2,3,4-tetrahydroisoquinoline may be selective dehydrogenated to 3,4-dihydroisoquinoline with elemental sulphur in a solvent at 50.degree. to 150.degree. C. In the reaction the end product is obtained in very high yield, in high purity. As solvents alcohols, aromatic hydrocarbons, ethers, etc. may be used.
According to a preferred embodiment of our invention the reaction is performed in toluene or butanol at the boiling point of the solvent. In the reaction 1-mercapto-1,2,3,4-tetrahydroisoquinoline is formed as an intermediate, which cannot be isolated and by hydrogen sulfide elimination it will be spontaneously transformed to 3,4-dihydroisoquinoline. In the dehydrogenation reaction 1 to 10 moles of sulphur is used per 1 mole of the tetrahydroisoquino
REFERENCES:
patent: 3135759 (1964-06-01), Whittaker
patent: 3796715 (1974-03-01), Weimgruber et al.
patent: 4656279 (1987-04-01), Okazaki et al.
Ajzert Ilona K.
Fleischer Judit
Kellner Katalin M.
Puskas Mariann E.
Rimai Jozsef
Chinoin Gyogyszer - es Vegyeszeti Termekek Gyara Rt.
Dubno Herbert
Hollrah Glennon H.
Turnipseed James H.
LandOfFree
Process for the preparation of 3,4-dihydroisoquinoline does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of 3,4-dihydroisoquinoline, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of 3,4-dihydroisoquinoline will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2239556