Effective formation of indole imines and enamines from imidoyl chlorides

摘要

J. CHEM. SOC. PERKIN TRANS. I 1989 Effective Formation of lndole Imines and Enamines from lmidoyl Chlorides David St. C. Black," Michael C. Bowyer, Anna Choy, Donald C. Craig, and Naresh Kumar School of Chemistry, University of New South Wales, P.O. Box I, Kensington, N.S.W. 2033, Australia lndoles can be converted into their related imine derivatives by imidoyl chloride reagents (derived from phosphoryl chloride and secondary amides), in a reaction superior to the combination of indole carbonyl compounds and primary amines; however, use of N,N'-diacetyl-o-phenylenediamine leads to the effective formation of enamines. Me0 mPhRecent work has focussed attention on the C-7 reactivity of 4,6-dimethoxy-2,3-diphenylindole(1)' towards electr~philes.~-~ We now report that the indole (1) reacts readily with secondary amides (e.g. formanilide, acetanilide, and benzanilide) and lactams (e.g.pyrrolidin-2-one and 5-methylpyrrolidin-2-one) in the presence of phosphoryl chloride in chloroform, followed by mild neutralization with sodium carbonate to give high yields of the irnines (2a-c) (64--92)-f- and (3a-b) (78--86) respectively (Scheme 1).The reactions presumably proceed uia irnidoyl chloride^.^,^ Although the aldimine (2a) can be prepared in modest yield from the corresponding aldehyde and amine, the ketimines (2b,c) cannot be obtained by a similar process. Formation of the dihydropyrroles (3a,b) is especially effective by the imidoyl chloride route. The nickel(n) complex of the dialdimine (4a) has been prepared by the metal template reaction3 of the 7-formylindole t All new compounds gave satisfactory spectroscopic and analytical data.For (2b):79 yield; m.p. 179-180 "C; S(S00 MHz, CDCl,) 2.43 (3 H, s, CH,), 3.78,3.98 (each 3 H, s, OCH,), 6.29 (1 H, s, ArH), 7.1@-7.44 (15 H, m, ArH), and 11.54 (1 H, br s, NH); mjz 446 (M', 12.5).For (3b): 78 yield; m.p. 195-196 "C; 6(500 MHz, CDCl,), 1.39 (3 H, d, J6.7 Hz, CH,), 1.45--1.59 (1 H,m,CH,), 2.13-2.24(1 H,m,CH,), 3.76and 3.94 (each 3 H, s, OCH,), 4.28 (1 H, br q, CH), 6.24 (1 H, s, ArH), 7.18- 7.44 (10 H, m, ArH), and 12.28 (1 H, br s, NH); m/z410 (M+,71). For (5):707; yield; m.p. 201 "C; 6(500MHz, CDCl,) 2.49 (3 H, s, CH,), 3.60, 3.70 (each 3 H, s, OCH,), 5.77 and 5.97 (each 1 H, s, CH,), 6.19 (1 H, s, ArH), 6.94-7.77 (14 H, m, ArH), and 7.93 (1 H, br s, NH); rnjz485 (M', 8 1).RCONH Phbsol; ___) p0c13 Me0 H Me0 H R R b; Me Scheme 1. with o-phenylenediamine but related formation of the complex of the diketimine (4b) failed. Reaction of the indole (1) with N,N'-diacetyl-o-phenylenediaminein the presence of phos-phoryl chloride in chloroform was therefore carried out, but also failed to yield the diketimine (4b): instead, the enamine (5) was produced cleanly in 70 yield. Such enamine formation was J. CHEM. SOC. PERKIN TRANS. I 1989 20 1 Figure. Me0 R (5) R (4) a:H Me b; Me H (6) ( 7) shown to be more general by the production of the enamine (6) from 2-phenylindole.In this case the product gave suitable crystals for an X-ray structure determination (Figure).* Both compounds (5) and (6) showed single resonances in their 'H n.m.r. spectra for the vinylic protons. It has been shown7 that N,N'-diacetyl-o-phenylenediamine undergoes reaction with phosphoryl chloride in dimethyl- formamide at 75 "C to give the chloro enamine (7). This compound is, however, not an intermediate in the formation of ~ ~~~ * Crystal data for (6).C,,H,,N,C,H,OH, M, 395.5, monoclinic, space group P2,jc, a = 8.139(1), h = 21.030(1), c = 14.048(2) A, p = 113.91(1)', U = 2 198.1(5) A3, D,= 1.19 g ~m-~, = 4, pLcu= 5.45Z cm-'. Crystal size 0.1 1 by 0.10 by 0.35 mm, min. and Max. transmission factors 0.80 and 0.95, 20,,,, 140deg;, 4 152 measured reflexions, 2 766 observed (L 3a(l)),measured.Final residuals R,R, were 0.034,0.047. Atomic co-ordinates, bond lengths and angles, and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre. For details of this deposition system, see 'Instructions for Authors (1989),'J. Chem. SOC.,Perkin Trans. 1, 1989, Issue 1. the products (5) and (6). These enamines could possibly be formed via intramolecular carbanion attack in the intermediate nitrilium cation (9) formed from the related imidoyl chloride (8) e.g. formation of (6), Scheme 21. (1) -H -e CH,-C =N ti (9)Scheme 2. Acknowledgements We thank the Australian Research Grants Scheme for support. References 1 D. St. C. Black, N. Kumar, and L. C. H. Wong, Aust. J. Chern., 1986, 39, 15. 2 D. St. C. Black and N. Kumar, J. Chem. Soc., Chenz. Commun., 1984, 441. 3 D. St. C. Black. D. C. Craig, N. Kumar, and L. C. H. Wong, J. Chem. Suc., Chem. Commun., 1985, 1172. 4 D. St. C. Black, N. Kumar, and L. C. H. Wong, Synthesis, 1986, 474. 5 H. Eilingsfeld, M. Seefelder, and H. Weidinger, Angew. Chem., 1960, 72, 836. 6 H. H. Bosshard and H. Zollinger, Helv. Chim. Actu, 1959,42, 1659. 7 0. Meth-Cohn, B. Narine, and B. Tarnowski, J. Chem. Soc., Perkin Trans. I, 1981, 1520. Received 26th August 1988; Paper 8/03464H