Intramolecular cyclisation of 2-phenylethyl isocyanates

Abstract

SL1 4AUCyclisations of 2-phenylethyl isocyanate (2), ( + ) -I -methyl-2-phenylethyI isocyanate (3). and 2,2-diphenylethyl isocyanate (4) have been studied using polyphosphoric acid, aluminium chloride, boron trifluoride-diethyl ether, and triethyloxonium tetrafluoroborate. Depending on the reaction conditions, triethyloxonium tetrafluoroborate, forexample, notonlygavetheexpected isoquinolones (1 4)-(I 6) and other expected products, but in two cases, also gavethe2-N-(2-phenylethyl)formamidyl-3,4-dihydroisoquinolin-l (2H)-ones ( 9) and (1 0). Theisoquinolone (1 5) w a s alkylated with triethyloxonium tetrafluoroborate or methyl fluorosulphonate to give 1 -ethoxy-( 7) or 1met h oxy -3 -met h y I -3,4 -d i hydro i soq u i no I in e ( 8), respective I y . INTRAMOLECULAR cyclisation of isothiocyanates providesa useful synthesis of isoquinolines,l thienopyridines,2 ben~azepines,~ and thieno[3,2-~]azepines.~ Thus, for example, cyclisation of 2-phenylethyl isothiocyanate with triet hyloxonium tetrafluoroborate gives 1 -ethylthio-3,4-dihydroisoquinoline (5) .l These results prompted us to study cyclisations of the corresponding isocyanates with triethyloxonium tetrafluoroborate and other reagents.At the start of our work 6,7-diniethoxy-3,4-dihydroisoquinolin-1 ( 2 H ) -one (corydaldine) had been synthesised by cyclisation of homoveratryl isocyanate with phosphoryl chloride and polyphosphoric acid while the latter reagent had been used also to synthesise other 3,4dihydroisoquinolin-1 (2H)-ones.6 Since then, polyphosplioric acid and boron trifluoride-diethyl ether * have been used successfully to cyclise p-arylethyl isocyanates. A recently reported two-stage treatment with phosphorus oxychloride and tin(rv) chloride appears to be

3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines Display Remarkable Potency and Selectivity as Inhibitors of Phenylethanolamine N-Methyltransferase versus the α2-Adrenoceptor1a

“…( S )-(+)-3,4-Dihydro-3-methyl-7-nitroisoquinolin-1-(2 H )-one (25). Nitration as described above on ( S )-(+)- 24 {mp 143−144 °C, lit 27b. mp 147 °C; [α] D 23 = 91° ( c 0.22, MeOH)} gave a golden-yellow crystalline solid: mp 232−233 °C dec; [α] D 23 = 100° ( c 0.20, MeOH).…”

Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α2-Adrenoceptor1a

“…The α-position on the naphthalene nucleus is more reactive than the β-position, and hence only 26 was obtained. It is interesting to note that failure to form a seven-membered ring in the intramolecular cyclization of isocyanate in the same ring system has been observed . An alternate lengthy method has been reported for the synthesis of 26 .…”

Total Synthesis of (+)‐(8S,13R)‐Cyclocelabenzine

“…The relative configuration of the (-)-isomer l b was determined by an X-ray crystal-structure analysis, and, on the basis of the known absolute configuration of the employed (+)-(3S)-3-amino-3-phenylpropanoic acid, the absolute configuration of the two chiral centers could be assigned. Thus, l b is (-)-@S, 13S)-4,5, 6,7,8,9,12,13 octahydro-8 -phenyl-2,13 -methano-2H-2,7,11-benzotriazacyclopentadecine-l,10-(3H,llH)-dione (see Fig. 2 ) .…”

“…1 -ones (dihydroisocarbostyrils) can be formed by cyclization of the /3-arylethyl isocyanates of the /3-arylethylurethans, respectively. So, to obtain the lactam fragment 13, we attempted to cyclize compound 11 according to literature procedures with polyphosphoric acid [6], POCI,, or POCI, in combination with SnCI4 [7]. However, all attempts utterly failed.…”