2614
J. Org. Chem., VoZ. 58, No. 16, 197.9
RICHTER AND ULRICH
The Reaction of Phenyl Isocyanate with N-Methyl-2-pyrrolidinone REINHARD RICHTER"AND HENRIULRICH Donald S. Cilmore Research Laboratories, The Upjohn Company, North Haven, Connecticut 06478 Received February 16, 1973 The reaction of l-methyl-2-pyrrolidinone with phenyl isocyanate at 140 and 210' was studied. Besides 1methyl-Zphenyliminopyrrolidine (2), a pyrroline carbanilide (7) and pyrroloquinolines (10, 11) and pyrrolopyrimidines (12, 13) are formed. The reaction mechanism is discussed and earlier reported findings on this reaction are corrected.
Aryl isocyanates react at elevated temperature with a variety of compounds containing carbonyl groups to give imines and carbon dioxide. The method is used for the preparation of azomethines, ketimines, amidines, and guanidines from the corresponding aromatic aldehydes, benzophenones, and N-persubstituted amides and In some cases, other products are obtained owing to successive interaction of the formed imines with excess isocyanate. Good examples are the extensively studied reactions of N,N-dimethylformamide6-8 and N,N-dimethylacetamides with aryl isocyanates. I n connection with thermostability studies of Nmethyl-2-pyrrolidinone (NMP, 1)-isocyanate mixtures, we found that phenyl isocyanate reacts with 1 a t temperatures above 100'. Generation of carbon dioxide was observed when an equimolar mixture of the two components was kept at 140' for 16 hr. During the reaction the isocyanate was consumed completely (as shown by the disappearance of the NCO band at 2270 cm-1 in the ir) while about 65% of 1 remained unchanged, N-Methyl-2-phenyliminopyrrolidine(2)) expected to be the main product, can be isolated after removal of unreacted 1 from the semisolid reaction mixture by distillation in only 18% yield (based on converted 1). From the residue seven solid compounds were isolated by repeated fractional crystallization from different solvent combinations (see Table I and Scheme I). Carbanilide, triphenyl isocyanurate, the pyrroline-3carboxanilide 7 and the hexahydropyrrolopyrimidine 12 are the major products, whereas the pyrroloquinolines 10 and 11 and the hexahydropyrrolopyrimidine 13 together account for only 1-2%. Structure assignments of the new compounds are based on elemental analysis, nmr, ir, and in some cases mass spectroscopy (see Experimental Section) ; the known compounds (carbanilide, triphenyl isocyanurate, and 2) were compared with authentic samples. The yields given vary somewhat with work-up methods but are correct in the order of magnitude. The product ratio can be changed drastically by increasing the reaction temperature. For example, a 1 : 1 mixture of 1 and phenyl isocyanate kept for 4 hr (1) E. Niwa, H. hoki, H. Tanaka, K . Munakata, and M. Namiki, Chem. Ber., 99,3932 (1966). (2) H. Staudinger and R. Endle, B e y . Deut. Chem. U e s . , 60, 1042 (1917). (3) R . Richter, Chem. Ber., 108, 938 (1969). (4) M. L. Weiner, J. Org. Chem., 26, 2245 (1960). (6) P.A. Argabright and V. J. Sinkey, Chem. Ind. (London), 857 (1966). (6) H. Ulrich, B. Tucker, F. A. Stuber, and A. A. R. Sayigh, J. Org. Chem., 88, 3928 (1968). (7) E. Dyer, T. E. Majewski, and J. D. Travis, J. Org. Chem., 8 8 , 3931
(1968). (8) R. Richter and H. Ulrich, J. 0 7 0 . Chem., 8 6 , 2005 (1971). (9) E.Dyer, T. E. Majewski, T . J. Nycz, and J. D. Travis, J. Helerocycl.
Chem., 9,955 (1972).
TABLE I YIELDSO OB PRODUCTS OBTAINED IN REACTIONS OF N-METHYL-ZPYRROLIDINONE WITH PHENYL ISOCYANATE A T 140 AND 210" Y Y i e l d , %-140° 210°
Compd
1-Methyl-2-phenyliminopyrrolidine (2) l-Methyl-2-phenylamino-2-pyrrolino-3carboxanilide (7) l-Methyl-4-hydroxy- 1,2-dihydro-3H-pyrrolo[2,3-b]quinoline (10) l-Methyl-4-anilino-l,2-dihydro-3H-pyrrolo[2,3-b]quinoline (11) 7-Methyl- 1,3-diphenyl-2,4-dioxohexahydr o7H-pyrrolo[2,3-d]pyrimidine(12) 7-Methyl- I, 3-diphenyl-4-phenylimino-Zoxohexahydro-7H-pyrrolo [2,341 pyrimidine
18
41
18
0.4 0.8 31
1.8
16 7
300° (from DMF); colorless crystals; ir (KBr) with 100 ml of methanol. On concentrating the filtrate, a second 1638, 1589 cm-l (quinoline); uv (log e) 222 nm (4.47),243 portion of crystals, 51 g (fraction 2), did separate. The remain(4.34),319 (4.17); Rf 0.43 (benzene/DMF, 7:3). ing filtrate was further concentrated and distilled at reduced Anal. Calcd for CIZHIZN~O:C, 71.98; H, 6.04; N, 13.99; pressure, giving 22.5 g of 2 (fraction 3), bp 85-90' (0.01 mm), mol wt, 200. Found: C, 71.90; H, 6.06; N , 13.92; mol wt, which was identical in ir comparison with authentic material.ae 200 (from mass spectral data). Treatment of the distillation residue with methanol gave 7.2 g From the acetone filtrate 5.9 g of 12 and from the D M F (fraction 4), which was collected by filtration and washed with filtrate 5.0 g of triphenyl isocyanurate were obtained. methanol. The combined filtrate and methanol washings gave, on cooling to -10' for 17 hr, another crop of crystals, 5.9 g Fraction 7 did consist of pure 7. (fraction 5), after filtration and methanol washing. Addition of Fraction 8.-Repeated recrystallizations from DMF-diethyl diethyl ether to the filtrate to beginning turbidity and scratching ether gave 1.7 g of l.methyl-4-anilino-1,2-dihydro-3H-pyrrololed to the separation of more crystals, which were collected after [2,3-b]quinoline (11): mp 238'; colorless crystals; ir (KBr) standing for several hours, 12.5 g (fraction 6) after washing with 1640, 1600, 1595, 1574 (quinoline system), 765, 755, 698 cm'l methanol-diethyl ether and finally diethyl ether. Another crop (CH out of plane vibrations for mono- and 1,2-disubstituted of crystalline material, 2.1 g (fraction 7), was obtained on conbenzene); nmr (CDaCOOD) 6 2.40 (t, 2, CHI, J = 8 Hz), 3.15 centrating the filtrate in. vacuo. Filtrate and methanol-diethyl (9, 3, CHa), 3.68 (t, CH2, J = 8 Hz),6.98-8.45 (m, 9,aromatic ether washings were again concentrated at reduced pressure, H), N H exchanged by CDICOOD; uv' : :A (log e) 206 nm which led to the separation of 3.8 g (fraction 8) of colorless (4.51),247 (4.52),330 (4.10); Rr 0.62. crystals. Anal. Calcd for ClsH1,Na: C, 78.51; H, 6.22; N, 15.26; No further solid material could be obtained from the remaining mol wt, 278. Found: C, 78.79; H, 6.29; N, 15.38; mol wt, yellow-brownish resinous residue, Tlc with benzene-acetone 275 (from mass spectral data). (1:l)showed that most of the solid fractions were mixtures of The following total amounts of product were obtained: 22.5 g two or more components. (18%) of 2,38.7 g (18%) of 7,0.6g (0.4%) of 10, 1.7g (0.8%) of Separation of Solid Fractions. Fraction 1.-The mixture was 11, 70.8 g (31%) of 12,O.j g (
