3144
J. Org. Chem., Vol. 40, No. 21, 1975
Notes Table I Reaction of Sodium Naphthalenide with Aliphatic Estersn
Reactions of Sodium Naphthalenide with Aromatic a n d Aliphatic Esters Manhar Vora and Norman Holy*
Naphthalcnide:
Department of Chemistry, Western Kentucky University, Bouling Green, Kentucky 42101 Received March 4 , 1975
The considerable attention devoted to the chemistry of sodium naphthalenide has derived, in part, from observations that this radical anion is both a strong basel and a powerful reducing agent.2 Its reactions with esters were of interest to us from several respects. (1) Naphthalenides have been used as bases for condensation reactions without evaluation of other possible functions, such as electron transfer. (2) It was desirable to determine if the product trend noted in the reactions of carbonyl compounds would be repeated by a closely related functional group.3 (3) Few functional groups have demonstrated competitive proton abstraction and reduction. For esters such a competition was viewed as being clearly possible. (4) Extant reports on the reactions of aromatic radical anions with esters were in ~onflict.~ We have found that deprotonation is the main reaction for esters in which the a carbon possesses a hydrogen. This
I
-C-CO,Et
I
THF.-10”
‘C=C-OEt
/O-
/
H observation is based upon the disappearance (GLC) of ethyl ethanoate and ethyl hexanoate upon addition of these esters to a sodium naphthalenide solution. The major portion of these esters was regenerated upon quenching the reactions with water, followed by adjustment of the pH to 5-7 with dilute hydrochloric acid and GLC analysis. However, proton abstraction was not the only reaction which occurred. Aliphatic esters (Table I) also formed acylation products of naphthalene. While the yields of these products were not high, the fact that they were formed at all is significant, This type of naphthalene product has not been recorded previously. Machtinger reported the reaction of ethyl laurate with sodium naphthalenide to yield the analogous ketone containing a fully aromatic naphthalene moiThis is clearly not the case for the esters we have examined; the NMR spectra are in accord only with the 1,4dihydro derivatives. The products we have observed are analogous to the adduct reported by Kaplan et al. in their study of the reaction of sodium biphenylide with ethyl laurate.4b The reaction of ethyl benzoate (Table 11) provides a striking contrast to the reactions of alkyl esters. No acylation products of naphthalene could be detected. The only ester-derived products were benzil and benzoin.
0
Ph-C-C-Ph
0
0
II It
+
OH
I I
Ph-C-CH-Ph
The following conclusions are apparent. (1) Sodium naphthalenide interacts with aliphatic esters in a capacity other than strictly as a base; its use to effect enolate formation is not advised. (2) The differing fates of aliphatic and aromatic esters are analogous to those observed for the reactions of aliphatic and aromatic carbonyl compound^.^ Deprotonation and acylation occur with aliphatic esters. In
Compd
Yield,
ester
Product
Ethyl hexanoate
2:l
35
Ethyl ethanoate
2:l
11
Ethyl dimethylpropanoate
2:l
13
6 H
a
Yields are based upon ester.
40
COC,H,-f ”.[
Table I1 Reaction of Sodium Naphthalenide with Ethyl Benzoate R a t i o naphtha1enide:benzoate
% benzil
% benzoin
4:l 1:l
5 38
86
27
its reaction with ethyl benzoate, sodium naphthalenide functions exclusively as a reducing agent. (3) Conceptually, the naphthalene acylation products may arise via a number of routes; those analogous to the alternatives described for the reactions of carbonyl compounds are most likely.3 These possibilities involve either electron transfer or nucleophilic attack as key steps. The routes to benzil and benzoin are not certain but the “unified acyloin condensation mechanism” discussed recently by Bloomfield, Owsley, Ainsworth, and Robertson must be considered as an attractive alternative to the traditional radical coupling or dianion mechanisms. Experimental Section All melting points are uncorrected and were taken with a FisherJohns melting point apparatus. Ir spectra were determined on a Perkin-Elmer Model 710 infrared spectrometer. NMR spectra were recorded on a Varian A-60A spectrometer using MedSi as an internal standard. Mass spectra were determined by the University of Kentucky Mass Spectroscopy Center with a Perkin-Elmer RMU7 spectrometer; the ionizing voltage was 70 eV. Elemental analyses were performed by Galbraith Laboratories, Knoxville, Tenn. Starting Materials. Tetrahydrofuran was purified by distillation under nitrogen from benzophenone sodium ketyl. Reagent grade esters were dried over magnesium sulfate and distilled before use. Reagent grade naphthalene was used directly. Baker Analyzed metallic sodium was cleaned of its oxide coating before use. General Procedure for the Preparation of Sodium Naphthalenide. T o 800 ml of dry, deoxygenated, cooled (-10’) T H F containing 60.0 g (0.47 mol) of naphthalene was added 10.0 g (0.435 mol) of metallic sodium over a 30-min period. The dark green color of the naphthalenide formed within 1 min. The mixture was stirred under nitrogen for 12-15 hr before three 5-ml aliquots were removed, quenched in 50-ml portions of water, and titrated for total base with standardized hydrochloric acid solution to a phenolphthalein end point. General Procedure for the Reaction of Sodium Naphthalenide with Esters. To the sodium naphthalenide solution cooled to ca. -10’ was added via addition funnel a solution of the ester dis-
Notes solved in 50 rnl of dry THF. The temperature rose to about 10' during the 2 min required; the color changed from dark green to dark brown. After 2-5 min ice water was added and the pH adjusted to 5-7 with 6 M hydrochloric acid. The organic products were isolated by extraction with ether, washing with water, and drying over magnesium sulfate. The ethers were evaporated under vacuum and the products were separated by column or thin layer chromatography from silica gel. Some lots of silica gel caused partial decomposition upon column chromatography, so it was necessary to partially deactivate these by first washing the column with 1% ethyl ether-99% petroleum ether. Crude product fractions were combined and further purified by vacuum distillation. Yields are based upon ester. Reaction of Ethyl Dimethylpropanoate with Sodium Naphthalenide. To 0.435 mol of sodium naphthalenide in 800 ml of T H F was added 28.0 g (0.22mol) of ethyl dimethylpropanoate. Isolation of the products as described in the general procedure and elution from a silica gel column with 50% petroleum ether-50% benzene resulted in the isolation of 7.0 g (0.033mol, 15%) of crude l-(2,2-dimethyl-l-propanoyl)-1,4-dihydronaphthalene. Distillation a t 0.2 mm gave 5.6 g (0.026mol, 12%) of the pure product: bp 113-116'; NMR (CCld) 1.13 (s, 9 H), 3.35 (broad m, 2 H), 4.82(AB, 2 H), 5.93 (m, 2 H), 7.06 ppm (m, 4 H); ir (CClJ 3100, 1680,1650, 750 cm-l; MS m / e (re1 intensity) 214 (3),155 (30),130 (14),129 (IOO), 128 (59),127 (25),85 (lo),57 (54).Anal. Calcd for CljHlsO: C, 84.11;H, 8.41.F o u n d C, 83.68 H, 8.32. Further elution of the silica gel column with 10% ethyl ether90% benzene yielded 14.2 g (0.044 mol, 43% based on ester) of crude 1,4-bis(2,2-dimethyl-l-propanoyl)-1,4-dihydronaphthalene, mp 51-59'. Recrystallization from ethanol yielded 7.3 g (0.024mol, 22%) of the pure product: mp 95-97'; NMR ( C c 4 ) 1.10 and 1.27 (s, 18 H ) , 3.52 (m, 2 H ) , 4.20 (AB, 2 H), 5.97 (m, 2 H), 7.10 ppm (Az'Bz', 4 H); ir (CC14)3100,1680,1650,750 cm-'; MS m / e (re1 intensity) 298 (E),215 (30),119 (42),106 (50), 85 (63),57 (100).Anal. Calcd for C20H2602: C, 80.54;H, 8.72.Found: C, 80.27;H, 8.63. Reaction of Ethyl Hexanoate with Sodium Naphthalenide. To 0.22 mol of sodium naphthalenide in 500 ml of dry T H F was added 15.7 g (0.11mol) of distilled ethyl hexanoate. Isolation as described in the general procedure followed by elution from a silica gel column with 10% ethyi ether-90% benzene resulted in the isolation of 11.5 g (0.50 mol, 46%) of crude l-hexanoyl-1,4-dihydronaphthalene. Distillation resulted in the isolation of 8.4 g (0.38 mol, 33%) of the pure product: bp 113-116' (0.2mm); NMR ( C c 4 ) 0.80-1.62(m, 9 H), 2.10-2.45 (m, 2 H), 3.45 (m, 2 H), 4.33 (AB, 2 H),5.95 (m, 2 H),7.13 ppm (br s, 4 H); ir (cc14) 3070,3050,1700, 1650,670 cm-l; MS m / e (re1 intensity) 228 (4),157 (13),155 (16), 131 (20),130 (53),129 (loo),128 (701,127(23),99 (15).Anal. Calcd for C16H200: C, 84.16;H, 8.83.Found: C, 83.79;H, 8.70. Reaction of Ethyl Acetate with Sodium Naphthalenide. To 0.435mol of sodium naphthalenide solution was added 19.5g (0.22 mol) of distilled ethyl acetate. After 2 min, the reaction was quenched with ice water and the organic materials isolated in the usual manner. The 75 g of crude products was directly distilled without preliminary chromatography to yield 4.2 g (0.024mol, 11%) of l-ethanoyl-1,4-dihydronaphthalene: bp 100-109' (0.5 mm); NMR ( C c h ) 1.85 (s, 31,3.46 (m, 2 H), 4.30 (AB, 2 H), 6.03 (m, 2 H ) , 7.16 ppm (br s, 4 H); ir (CC14) 3100,1700,725 cm-'; MS m / e (re1 intensity) 172 (81, 155 (28),129 (13),128 (93),127 (loo), 126 (441,125 (10).Anal. Calcd for C12H120: C, 83.69;H, 7.02. F o u n d C, 83.37;H , 6.87. Reaction of Ethyl Benzoate with Sodium Naphthalenide. T o 0.435 mol of sodium naphthalenide in 800 ml of T H F was added 16.5 g (0.11mol) of ethyl benzoate. Elution of the column resulted in the isolation of 9.9 g (0.047mol, 86% based on ester) of benzil, mp 130-131', and 0.55 g (0.0026mol, 5% based on ester) of benzoin, mp 94-96'. Proton Abstraction by Sodium Naphthalenide. To two 0.1 M tetrahydrofuran solutions of sodium naphthalenide a t - 1 O O C were added either 1.0equiv of ethyl ethanoate or ethyl hexanoate. Analysis by GLC (10% polyphenyl ether on Anakrom ABS, 80/90mesh, 125', flow 0.5 cm3/sec; 10% FFAP on Chromosorb W ,60/80mesh, 125' flow 0.5 em"/sec) failed to detect either ester. Upon quenching with 10% hydrochloric acid, followed by GLC analysis, the major portion6 of these esters were regenerated.
J . Org. Chem., Vol. 40, No. 21, 1975 3145 thalene, 56282-08-7;l-hexanoyl-1,4-dihydronaphthalene,5628256282-10-1; benzil, 13409-8;l-ethanoyl-1,4-dihydronaphthalene, 81-6;benzoin, 119-53-9.
References and Notes (1) A few leading references are listed: H. Normant and B. Angelo, Bull. Soc. Chim. Fr., 354 (1960); K. Suga, S. Watanabe, and T. Suzuki, Can. J. Chem., 46, 3041 (1968); J. J. Eisch and W. C. Kaska, J. Org. Chem., 27, 3745 (1962): H. Normant and B. Angelo, Bull. Soc. Chim. Fr., 810 (1962); B. Angelo, ibid., 1848 (1970); H. Normant and B. Angelo, ibid., 354 (1960); K. Suga. S.Watanabe, and T. Suzuki, Can. J. Chem., 46, 3041 (1966). (2) A few leading references are listed: J. F. Garst, J. T. Barbas, and E. Barton, 11, J. Am. Chem. Soc., 90, 7159 (1968); G. D. Sargent and G. A. Lux, ibid., 90, 7160 (1968); S. Bank and J. F. Bank, Tetrahedron Lett., 4533 (1969): J. F. Garst et ai., Acc. Chem. Res., 4, 400 (1971); G.D.Sargent, C. M. Tatus, and R. P. Scott, J. Am. Chem. SOC.,96, 1602 (1974); A. Oku and K. Yagi, ibid., 1966 (1974); Y. J. Lee and W. D. Closson, Tetrahedron Lett., 1395 (1974); J. F. Garst and J. T. Barbas. J. Am. Chem. SOC., 96, 3239, 3247 (1974); J. S.McKennis, L. Brener, J. R . Schwiger, and R . Pettit, Chem. Commun., 365 (1972), G. Levine, J. Jagur-Grodzinski, and M. Szwarc, Trans. Faraday SOC.,67, 768 (1971); G. Levine, J. 92, 2268 (1970); Jagur-Grodzinski, and M. Szwarc, J. Am. Chem. SOC., D.R. Weyenberg and L. H. Toporcer, J. Org. Chem.. 30, 943 (1965); D. R. Weyenberg and L. H. Toporcer, J. Am. Chem. SOC.,84, 2843 (1962). (3) J. W. Stinnett, M. M. Vora, and N. L. Holy, Tetrahedron Lett., 3821 (1974). (4) (a) D. Machtinger, J. Rech. CNRS, 60, 231 (1963); (b) E. P. Kaplan, 2 . I. Kazakova, E. D. Lubuzh, and A. D. Petrov, lzv. Akad. Nauk SSSR, Ser. Khim., 1446 (1966). (5) J. J. Bloomfield, D. C. Owsley, C. Ainsworth. and R. E. Robertson, J. Org. Chem., 40, 393 (1975).
In Situ Reduction of Nitroxide Spin Labels with Phenylhydrazine in Deuteriochloroform Solution. A Convenient Method for Obtaining Structural Information on Nitroxides Using Nuclear Magnetic Resonance Spectroscopy Terry D. Lee and John F. W. Keana*l
Department of Chemistry, Uniuersity of Oregon, Eugene, Oregon 97403 Received March 28. 1975
Stable nitroxide free radicals have enjoyed wide use both in the study of biological systems with spin-labeling technique$ and in studies of the nature of bi- and polyradical nitroxides systems." Doxy1 (4,4-dimethyloxazoline-N-oxyl) are particularly important since the ring system can be either rigidly attached a t the site of a ketone group4 or readily assembled using the reaction of an organometallic reagent with an appropriate n i t r ~ n e Owing .~ to the paramagnetic nature of the nitroxide spin labels, however, one cannot conveniently gain the valuable structural information on these molecules afforded by NMR spectroscopy.6 It occurred to us that essentially the same structural information could be obtained from the NMR spectra of the corresponding N-hydroxy amines, if a convenient method were available to prepare these normally air- and sometimes moisture-sensitive molecules quantitatively from the nitroxide, preferably in the NMR tube. We have therefore investigated the in situ reduction of a series of nitroxides in CDCls using phenylhydra~ine.~ Thus, in situ reduction of the representative nitroxides 1, 3a-c, and 68 in CDC13 with a solution of phenylhydrazine in CDC13 led smoothly to the corresponding N-hydroxy amines 2, 4a-c, and 7B (Table I). The NMR spectrum of 2 was identical, except for absorption a t 6 -7.3 (ArH), with that of pure 2 prepared from 1 by the method of RosRegistry No.-Sodium naphthalenide, 3481-12-7; naphthalene, a n t ~ e v When .~ the phenylhydrazine reduction was carried 91-20-3; sodium, 7440-23-5; ethyl dimethylpropanoate, 3938-95-2; a more concentrated solution of 1 (65.7 mg in 0.2 ml out on ethyl hexanoate, 123-66-0; ethyl acetate, 141-78-6; ethyl benzoate, 93-89-0; l-~2,2-dimethyl-l-propanoyl)-1,4-dihydronaphthalene, of CHC13), N-hydroxy amine 2 precipitated, recrystalliza56282-07-6; 1,4-bis(2,2-dimethyl-l-propanoyl)-1,4-dihydronaph- tion of which gave 53 mg (80%)of 2, mp 155-159' (lit.lo mp
