J.Org. Chem., Vol. 40, No. 1, 1975 127
Notes addition of base t o the reaction mixture gives t h e nitrile directly (method 13). The choice of base for the elimination reaction t o form nitriles is arbitrary, except for that of the oxime derived from p - nitrobenzaldehyde. In this case, potassium or sodium hydroxide gives a mixture of products, among which are t h e desired nitrile to t h e extent of about 50%, and smaller amounts of p - nitrobenzaldehyde and N-p- nitrophenylformamide. T h e use of triethylamine i n absolute ethanol, however, affords p - nitrobenzonitrile cleanly. T h e results of execution of these procedures with various aldehydes are given in T a b l e I.
(9)(a) T. Sheradsky, G. Salemnick, and Z. Nir. Tetrahedron, 28, 3833 (1972);(b) T. Sheradsky and 2. Nir, TetrahedronLett., 77 (1969);(c)T. Sheradsky, /bid., 1909 (1968);(d) J. Heterocycl. Chem., 4, 413 (1967). (10) (a)Y. Tamara, J. Mlnamlkawa, Y. Klta, J. H. Kim, and M. Ikeda, Tefrahedron, 29, 1063 (1973);(b) Y. Tamara, eta/., J. Org. Chem., 38, 1239 (19733,and references therein. (11)Y. Tamara, H. Fujlwara, K. Samoto, M. Ikeda, and Y. Kita, Synthesis, 215 (1973). (12)(a)T. Sheradsky and 2 . Rappoport, J. Chem. SOC.8, 898 (1967):(b) 0. L. Brady and R. Truszkowki, J. Chern. Soc., 125, 1087 (1924). (13)R. G. Dickinson and N. W. Jacobsen, Chern. Commun., 1719 (1970).
Experimental Section The melting points were determined on a Buchi melting point apparatus and are corrected. The infrared spectra were taken on a Perkin-Elmer infracord spectrophotometer, and in all cases were identical with those of melting points of various derivatives are listed in Table I. Synthetic Procedures. 0-2,4-Dinitrophenylhydroxylamine was prepared either by the method of Sheradskygdor that of Tamara;lob we found the latter method more convenient for our purposes. Nitrile Preparation. ipiethod A. 0-2,4-Dinitrophenylhydroxylamine (0.995 g, 5 mmol) was dissolved in 50 ml of ethanol by warming on a steam bath. Piperonal (0.75 g, 5 mmol) was added, and the solution swirled until it was homogeneous. Two drops of concentrated HCl were added. A precipitate began to form immediately. Cooling followed by filtration gave a light yellow solid (1.3 g, mp 193-195'). Cooling the filtrate in a freezer (-23') overnight gave, after filtration, 0.33 g of fine needles, mp 194-195'. The total yield of piperonal 0-2,4-dinitrophenyloxime was 98%. This oxime derivative (0.5 g, 1.51 mmol) was suspended in 50 ml of 95% ethanol. KOH (20 ml, 0.2 N in 95% ethanol) was added and the solution heated slowly to a gentle reflux. Reflux was maintained for 3 hr, although the color of the phenolate ion developed instantaneously, and the solution was concentrated to 15 ml under reduced pressure. Water (75 ml) and 5% NaOH (15 ml) were added and the resulting suspension extracted with chloroform. Drying, evaporation, and recrystallization from hexanes yielded a white solid in 81%yield; mp 91.5-93.5O; ir 2270 crn-'. In another preparation of the same material, warming of the solution (to effect dissolution of the 0-2,4-dinitrophenyloxime) for 10 min followed by work-up as described above afforded essentially the same yield of nitrile. Stirring the 0-substituted oxime with triethylamine in tetrahydrofuran for 12 hr, however, gave no reaction. Method B. 0-2,4-Dinitrophenylhydroxylamine (0.199 g, 1 mmol) was dissolved in 30 ml of ethanol by warming on a steam bath. 10-Undecylenic aldehyde (Aldrich, 0.168 g, 1 mmol) was added followed by one drop of concentrated HCl. The solution was allowed to cool, and it was stirred at room temperature for 30 min. Two equivalents of triethylamine was added, and the solution was heated to gentle reflux; a dark yellow color developed. After 5 min the solution was poured into 75 ml of 5% aqueous sodium bicarbonate and extracted with ether. Drying and evaporation of the ethereal solution left a light yellow liquid. Bulb-to-bulb distillation gave a colorless liquid (153 mg, 93%):ir 2260 cm-1.
Acknowledgment. T h i s work was supported by the National Institute of General Medical Sciences. Marvin Miller would like to acknowledge support by a National Institutes of Health Training Grant. Registry No.-I,
17508-17-7,
References and Notes (1) V. P. Kukhar and V. I. Pasternak, Synthesis, 563 (1974). (2)R. W. Binkley, TetrahedronLett., 2085 (1970). (3) H. G. Foley and D. R. Dalton, J. Chem. SOC., Chem. Commun., 628 (1973). (4)R. Appel, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 104,2025 (1971). (5)For a review of the aldehyde-to-nitrile conversion, see Z. Rappoport, Ed., "The Chemistry of the Cyano Group," interscience, New York, N.Y., 1970. (6)R. F. Smith and L. E. Walker, J. Org. Chem., 27,4372 (1962). (7)L. A. Carpino, Accounts Chem. Res., 6, 191 (1973) (8)(a) L. A. Carpino, C. A. Giza, and 6.A. Carplno, J. Amer. Chem. SOC., 81,955 (1959);(b) L. A. Carpino, ibid., 82, 3133 (1960).
A Reagent for the a,@Reduction of Conjugated Nitriles James A. Profitt and David S. Watt* Department of Chemistry, University of Colorado, Boulder, Colorado 80302
E. J. Corey Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138
The reduction of a,@-unsaturatednitriles 1 t o saturated nitriles 2 often proceeds with concomitant reduction of t h e nitrile moiety,l decyanation,2 h y d r o d i m e r i ~ a t i o n ,a~n d polymerization.4 Those procedures reported t o afford predominantly the nitrile 2 suffer from poor yields5 and limited6 or uncertain7 scope. We now wish, t o report a general procedure for effecting t h e transformation 1 -+ 2 in high yield. Ri
x;;
R2
1
-
x:N
Ri
R2
2
The reduction of 1 t o 2 using magnesium in methanol was compatible with various substitution patterns and, in t h e limited cases examined, with other functional groups (see Table I). A particular advantage of this method over catalytic hydrogenation was the regioselective reduction of a conjugated double bond in the presence of a nonconjugated double bond. The principal side reaction observed i n only a few instances was decyanation to afford olefins.8
Experimental Section Infrared spectra were determined on a Perkin-Elmer Infracord spectrometer. Nmr spectra were determined on a Varian A-60A spectrometer. Mass spectra were determined on a Varian-Mat CH5 mass spectrometer. Elemental analyses were performed by Atlantic Microlabs, Atlanta, Ga. The following is a typical experimental procedure. 3-Phenylbutyronitrile. To 188 mg (1.31 mmol) of 3-phenyl-2'butenitrile9 (E/Z = 9/11 in 13.1 ml of methanol was added 1.27 g (52.4 mmol, 40 equiv) of magnesium turnings. The exothermic reaction which ensued after 10 min was moderated with an ice bath. The reaction was stirred 1 hr a t 0' and 5 hr a t 25O. To the reaction a t Oo was added 24 ml of 6 N hydrochloric acid over a 1-hr period to afford a clear solution which was extracted with three 20-ml portions of ether. The ether solutions were combined, washed with 20 ml of brine, dried over anhydrous magnesium sulfate, and evaporated to afford 196 mg of oil. The oil was chromatographed on a 20 X 20 cm preparative layer Merck silica gel F254 plate in 1:9 ether-hexane to afford 183 mg (96%)of 3-phenylbutyronitrile, (Rf 0.20): ir (TF)4.48 (CN) and 6.25 fi (arom); nmr (CCl.4) 6 1.42 (d, J = 7 Hz, 3, CHCHB),2.35-2.55 (m, 2, CHzCN), 2.80-3.35 (m, 1, CHCH3), and 7.23 (5, s, ArH); mass spectrum (70 eV) mle (re1 intensity) 51 (12), 77 (32), 78 (81, 79 (161, 103 (15), 104 (6), 105 (loo), 106 (111,and 145 (22).
128
J. Org. Chem., Vol. 40, No. 1, 1975
Notes
Table I The Magnesium in Methanol Reduction of a,@-UnsaturatedNitriles RlR&=CRaCN Isolateda
R1
R2
R3
Registry NO.
yield of nltrlle 2, %
Registry No.
4786-38-3 53153- 63- 2 53153- 64-3 53153- 65-4 53153-66- 51 53153-67- 6 53153- 68- 7 4360-47- 8 14799-78- 1 3531-24-6 53153-69-8 53153-70- 1 50400-28-7 53153- 71 - 2 53153- 72- 3 531 53- 73-4 53153- 74- 5 53153- 75-6 4435- 18- 1 53153- 76- 7 53153- 77- 8 53153-78-9 53153-79-0 53 153- 80- 3 53153-81-4 53153- 82- 5 53153- 83-6 5146-66-7 53153- 84-7 53153- 85- 8 53153-86-9 53 153- 87-0
72 77 75 84 68 100 95 85 96 67 95 95 73 92 70 77 83 66 74 91 95 87 90 100 84 93 78 75 65 9O b 93 74
53153- 89- 2 53153-90-5 53153-91-6 53193-92-7 42144-33-2 53153- 93- 8 531 53- 94- 9 645-59-0 20132-76-7 2286-54-6 53153- 95-0 53153-96-1 53153- 97-2 53153- 98-3 53153- 99-4 53154- 00-0 29770-74-9 53154-01- 1 4435- 14- 7 53154-02-2 4634- 62- 2 53 154- 03- 3 53154- 04-4 53154- 05- 5 53154-06-6 53154-07-7 531 54- 08- 8 51566-62-2 53 154- 09- 9 53 154- 10-2 53154-11-3
53153-88- 1
74c
18214-14-7
a All products were isolated by preparative layer chromatography on Merck silica gel F254 and had infrared, nmr, and mass spectral data in accord with assigned structures. Isolated as the methyl ester. C Isolated as the ketone.
Anal. Calcd for C l o H d : C, 82.72; H, 7.64. Found: C, 82.64; H,
7.67.
Acknowledgment. We (J.A.P. and D.S.W.) wish to thank the Research Corporation for their generous support. Registry No.-(Z)-3-Phenyl-2-butenenitrile, 14799-79-2.
References and Notes (1) (a) (Electrolysis at Pb cathode /H2S04)T. Nonaka and K. Sugino, J. Nectrochem. SOC., 114, 1255 (1967); (b) (electrolysis at Pb cathode IH3P04) Y. D. Smirnov, L. 1. Saltykova, and A. P. Tomilov, Zh. PrM Khim. (Leningrad),.43, 1620 (1970); Chern. Abstr., 72, 8 7 3 5 1 ~ (1970). (2) (Pd-CIA'-pmethene) K. Kindier and K. Luhrs, Chem. Ber., 99, 227 (1966). (3) For e i e c t r ~ c h e m i c a and i ~ ~ ~sodium ~ hydrodimerization: (a) A. P. Tomilov, V. A. Klimov, S.L. Varshavskii, Khim. Prom. (Moscow), 42, 892 (1966); (b) 2. Rappoport, Ed., '[The Chemistry of the Cyano Group," Interscience, New York, N.Y., 1970, p 188; (c) F. Matsuda, Tetrahedron Lett., 6193 (1966); (d) imperial Chemical Industries of Australia and New Zeaiand, French Patent 1,505,117, Dec 8, 1967; Chem. Abstr., 69, 105945q (1968); (e) Y. Arad, M. Levy, and D. Vofsi, South African Patent 67,07,122, June 12, 1968; Chem. Abstr., 70, 57171f (1969); (f) Y. Arad, M. Levy, H. Rosen, and D. Vofsi, J. Polym, Sci., Part 8, 7, 197 (1969); (9) Y. Arad, M. Levy, and D. Vofsi, South African Patent 68,01,325, Aug 1, 1968; Cbem. Abstr., 70, 87075v (1969); (h) M. Kawamata, Kogyo Kagaku Zasshi, 74, 1364 (1971); Chem. Abstr., 75, 76121j (1971); and (i) M. Kawamata, ibid., 74, 2063 (1971); Chem. Abstr., 76, 3379k (1972)). (4) (a) B z H F. ~ G. A. Stone and H. J. Emeieus, J. Cbem. Soc., 2755 (1950); (b)H. J. Emeieus and K. Wade, ibld., 2614 (1960); (c) LiAIH4: N. E. Boyer, Tech. Apskafs, 23, 8 (1980); Chem. Abst., 58, 10309g (1963). (5) (a) R~SnHlhvor A: M. Pereyre, G. Colin, and J. Vaiade, Tefrahedron Lett., 4805 (1967); (b) M. Pereyre, G. Colin, and J. Vaiade, Bull. SOC. Chim. Fr., 3358 (1968); (c) HCO(CO)~: R. W. Goetz and M. Orchin, J. Org. Cbem., 27, 3698 (1962).
(a) Cr(i1): C. E. Castro, R. D. Stephens, and S. Moje, J. Amer. Chem. Soc., 88, 4964 (1966); (b) H2) PtC12(AsPh& -I-SnC12: R. W. Adams, G E. Batiey, and J. C.Bailar, Jr.. ibid., 90, 6051 (1968); (c) Hz lnickei boride T. W. Russell, R. C. Hoy, and J. E. Cornelius, J. Org. Chem., 37, 3552 (1972). For catalytic hydr~genation'~-'and electrochemical r e d u c t i ~ n : ~(a) ~-~ Raney Ni: D. V. Sokoi'skii and L. D. Voikova, Izv. Akad. Nauk Kaz. SSR, Ser. Khim., 14, 69 (1964); Chem. Abstr., 82, 3933f (1965); (b) L. D. Voikova and D. V. Sokoi'skii, Izv. Akad. Nauk Kaz. SSR, Ser. Khlm., 15, 52 (1965); Chem. Absff,, 63, 8195a (1965); (c) L. D. Voikova and D. V. Sokol'skii, Tr. Inst. Khirn. Nauk, Akad. Nauk Kaz. SSR,26, 78 (1969); Chem. Abstr., 72, 7 8 1 9 4 ~(1960); (d) P. M.Yakobashvili and A. S. Chegoiya, Tf. Gruz. Polifekh. Inst., 38 (1968); Chem. Abstr., 71, 29817y (1969); (e) Pd-C: L. D. Volkova and D. V. Sokoi'skii, Katal. Reakts. Zhidk. Faze, Tr. Vses. Konf., 2nd, 233 (1968); Chern. Abstr., 69, 2437w (1968); (f) Ru or Ru-C: E. I. du Pont de Nemours and Go., British Patent 1,133,900, Nov 20, 1988; Chem. Abstr., 70, 28410c (1969); (9) RhCi(PPh&: K. C. Dewhirst, US. Patent 3,489,786, Jan 13, 1970; Chern. Abstr., 72, 89833f (1970); (h) Ni or Co: Veb Leuna-Werke, French Patent 1,489,904, July 28, 1967; Chem. Absfr., 89, 76684w (1968); (i) K. Semykai, H. Pallutz, E. Haehner, K. Becker, and W. Stoss, East German Patent 59,559, Jan 5, 1968; Chem. Abstr., 70, 19612t (1969); (i) K. Semykal, H. Pallutz, E. Hahner, K. Becker, and W, Stoss, U.S. Patent 3,453,314, July 1, 1969; Chem. Absfr., 71, 60778k'(1969): (k) reduced NiW04: 8.T. King, British Patent 1,111,958, May 1, 1988; Chem. Absfr., 69, 51664b (1968): (I) NiS WS2: Veb Leuna-Werke, British Patent 898,736, June 14, 1962; Chem. Abstr., 57, 123321 (1962): (m) Zn: A. P. Tomiiov, L. V. Kaabak, and S. L. Varshavskii, Zh. Obshch. Khim., 33, 2811 (1963); (n) Fe: I. L. Knunyants, S. L. Varshavskii, A. P. Tomliov, and L. V. Kaabak, French Patent 1,401,175: Chern. Abstr., 64, 1660c (1966); and (0)Pb, Ni, C, Hg, or P t A. P. Tomilov and V. A. Klimov, Nectrokhimiya, 3, 232 (1967). For example, 1 (R, = R2 = CH2Ph; R3 = CH3) afforded 1,l-dibenzylethyiene in 27% yield. Most @,@-unsaturatednitriles used in this study were prepared by the modified Wittig reaction of R&CO with (R0)2POCHR&N according to W. S. Wadsworth and W. D. Emmons, J. Amer. Chem. SOC., 83, 1733 (1961).
