Alkylierungs‐, Acylierungs‐ und Reduktions‐Versuche an 1‐Cyan‐1.2‐dihydro‐ und ‐1.2.3.4‐tetrahydro‐isochinolin‐Derivaten

Abstract

2-Benzoyl-I-cyan-1.2.3.4-tetrahydro-isochinolin(1) kann uber das mit Natriumhydrid in Dimethylformamid entstehende Carbanion 2 durch Einwirkung von Alkyl-oder Acylhalogeniden in I-Stellung alkyliert (3ad) oder acyliert (3eh), durch Umsetzung mit Phenylsenfal thioacyliert (4) oder rnit Acrylnitril cyanlthyliert (5) werden. 2-Methyl-1 -cyan- (7a) kann gleichfalls iiber das Carbanion 10a in I-Stellung zu l l a methyliert werden und liefert rnit Lithiumalanat die Aminomethylverbindung 8a. -2-A1kyl-1 -cyan-] .2-dihydro-isochinoline (16) werden durch Lithiumalanat unter Eliminierung von Cyanwasserstoff zu 2-Alkyl-1.2-dihydro-isochinolinen 19 reduziert. Aus 2 Mol 16a entsteht rnit Natriumhydrid in Dimethylformamid unter Abspaltung von I Mol Cyanwasserstoff ein Dimerisierungsprodukt, fur das auf Grund des NMR-Spektrums die Konstitutionsformel22 vorgeschlagen wird. 1.2.3.4-tetrahydro-isochinolinAkylation, Acylation, and Reduction Reactions in the 1-Cyano-1.2dihydroand -1. 2.3.4-tetrahydroisoquinoline SeriesThe anion 2, generated from 2-benzoyl-I-cyano-1.2.3.4-tetrahydroisoquinoline (1) by treatment with sodium hydride in dimethylformamide, reacts with alkyl or acyl halides to form the corresponding I-alkyl or I-acyl derivatives (3ah). Thioacylation and cyanethylation (+ 4,s) also take place in the 1-position with phenyl isothiocyanate and acrylonitrile, respectively.By the same procedure the carbanion 10a of I-cyano-2-methyl-l.2.3.4-tetrahydroisoquinoline (7a) can be methylated in the I-position to yield lla. With lithium aluminium hydride 7a forms the aminomethyl compound 8a. -2-Alkyl-1-cyano-1.2-dihydroisoquinolines (16) are reduced with lithium aluminium hydride to the 2-alkyl-1.2-dihydroisoquinolines 19 with elimination of hydrogen cyanide. Treatment of 2 moles of 16a with sodium hydride in dimethylformamide results in the elimination of 1 mole of hydrogen cyanide and the formation of a dimerisation product, for which the constitution formula 22 is proposed on the basis of the n.m.r. spectra. Die ,,Dihydro-Reissert-Verbindung" 2-Benzoyl-1-cyan-1.2.3.4-tetrahydro-isochinolin (1) 1) reagierte ahnlich wie das entsprechende 2-Acetylderivat 2) mit Natriumhydrid in Dimethylformamid unter Bildung des Carbanions 2, aus dem rnit Methyl-oder Athyljodid sowie rnit a-halogenierten Athern oder Thioathern die Substitutionsprodukte 3a -d entstanden. Analog bildete 2 rnit Acyl-oder Carbamoylchloriden die 1) I. W. Elliott und J. 0. Lejlore, J. org. Chemistry 28, 3181 (1963). 2) H . Bohme und R . Schweitzer, Arch. Pharmaz. 303, 225 (1970). Analog wurde in der Zwischenzeit auch 6.7-Dimethoxy-2-benzoyl-I -cyan-I .2.3.4-tetrahydro-isochinolin mit Benzylhalogeniden alkyliert: M. Sharnmcr und C . D. J o n w , J. org. Chemistry 35, 31 19 (1970).

Rearrangements Involving alkoxycarbonyl group migration between nitrogen and oxygen.III. Reactions of modified isoquinoline Reissert compounds with aldehydes

“…The nmr spectra of 1,2-dihydroisoquinolines exhibit signals characteristic of olefinic protons, giving rise to an AB quartet located in the region between 5.95-6.9 6 with a coupling constant J = 8 Hz (15,29). As is evident from Table 2, the N-ethoxycarbonyl Reissert a~lalog Bb shows such a quartet centered at 6.0 6 and 6.9 6, with J = 8 Hz.…”

“…However, soiile modified Reissert compounds have been prepared. Thus 1,2,3,4-tetrahydro derivatives, called 'dihydro-Reissert compounds' have been described (9,(12)(13)(14)(15), and others, having acetyl (9,16), sulfonyl (17), alkoxycarbonyl (9> 18,19), carbamoyl (201, and phosphate (21) substituents in the place of benzoyl group are also known.…”

“…The reaction of dihydro isoquinoline Reissert con~pounds in which formation of their anions is needed, such as alkylation and acylation have been investigated in two cases (14,15). The behaviour of these compounds in condensation reactions with aldehydes has not been examined.…”