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.Found 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 0.435 mol of sodium naphthalenide solution was added 19.5 g (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 (0.024 mol, 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. Found C, 83.37;H , 6.87. Reaction of Ethyl Benzoate with Sodium Naphthalenide. To 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, 80/90 mesh, 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,5628209-8;l-ethanoyl-1,4-dihydronaphthalene, 56282-10-1; benzil, 13481-6;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 systems." Doxy1 (4,4-dimethyloxazoline-N-oxyl) nitroxides 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 eOwing .~ 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 vWhen .~ the phenylhydrazine reduction was carried 91-20-3; sodium, 7440-23-5; ethyl dimethylpropanoate, 3938-95-2; out on a more concentrated solution of 1 (65.7 mg in 0.2 ml 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
3146 J. Org. Chem., Vol. 40, No. 21, 1975
Notes
Table I 100-MHz R'MR S p e c t r a (CDCl3) of S e v e r a l N-Hydr0x.v A m i n e s a n d N i t r o n e 5 C0np.i
Spectrum
2
6 1.17 (6 H,s ) , 1.22 (6 H,S ) , 1.3-2.1 (4 H, m ) , 4.01 (1 H,m) 6 0.89 (3 H, m ) , 1.21 (3 H,s), 1.25 (3 H,s ) , 1.33 (3 H,s ) , 1.1-1.7 (8 H,m ) , 3.59 (1 H,d , J = 9 Hz),3.65 (1 H,d , J = 9 Hz) 6 0.8-1.0 (6 H,m ) , 1.20 (6 H,s), 1.1-1.9 (10 H, m), 3.50 (2 H, s) 6 0.90 (6 H,m ) , 1.24 (6 H , s ) , 1.2-1.8 (20 H,m ) , 3.63 (2 H, s) 6 0.89 (3 H, m), 1.19 (3 H,s), 1.23 (3 H,S I , 1.11.9 (8 H,m ) , 3.69 (2 H,s ) , 5.25 (1 H, m, J A B = 2, JAc = 11 Hz),5.42 (1 H,m , JAB = 2, JBC = 18 Hz),6.13 (1 H,d Of d , JAc = 11, J,c = 18 Hz) 6 0.90 (3 H,m ) , 1.60 (6 H,s), 1.1-1.8 (6 H,m ) , 2.65 (2 H, m ) , 3.73 (2 H,s ) , 5.45 (1 H,d , J = 11 Hz), 5.52 (1 H,d, J = 17 Hz), 5.99 (1 H,d of d , J = 11, 17 Hz) 6 0.88 (3 H,t , J = 7 Hz),1.13 (3 H,S I , 1.16 (3 H,s ) , 1.1-1.7 (6 H, m )
-
4a
4b 4c 4d
5
7
158"). S t r u c t u r e assignments of t h e other N - h y d r o x y amines were verified by comparison of t h e respective NMR spectra with those of t h e crude substances synthesized by t h e nitrone m e t h ~ d . Additionally, ~,~ nitroxides 1 and 3a were recovered from t h e NMR experiments by copper-catalyzed o ~ i d a t i o n ~of , ~ t' h e N-hydroxy amines 2 a n d 4a in 90% yield after preparative TLC a n d shown t o be identical with t h e original nitroxides by melting point in t h e case of 1 a n d by ir a n d mass spectral fragmentation pattern12 in t h e case of 3a. W h e n vinyl nitroxide 3d5 was reduced with phenylhydrazine, a time-dependent NMR spectrum was observed
? I
OH
OH
I
CHCI
2
1 PhNHSH,+ CDCl,
I
b
or
CHCI,
3
4
a, R = CH, c, R = CH,(CH,),
5. E x p e r i m e n t a l Section NMR spectra were recorded on a Varian XL-100 spectrometer using MedSi as an internal standard. Phenylhydrazine was freshly distilled. A fresh standard solution (0.03 M ) of phenylhydrazine in CDCls was made up prior to each series of experiments and used within a 0.5-hr period owing to the known slow reaction of phenylhydrazine with CHC1s.13The progress of the reduction could be monitored visually by the disappearance of the yellow-orange color of the nitroxide. Comparative runs with crude phenylhydrazine gave identical NMR spectra but the resulting reduced solutions were always colored. The use of 0.5 molar equiv of phenylhydrazine minimizes the extraneous absorption in the aromatic region of the NMR spectrum. Otherwise, an excess of reagent has no undesirable effects. General Phenylhydrazine Reduction Procedure. To a solution of -5 mg of the nitroxide in 0.3 ml of CDC13 in an NMR tube was added -0.5 ml (0.50 molar equiv) of 0.03 M phenylhydrazine in CDCls. After -15 min at 25O the yellow-orange color had faded and the NYR spectrum was that of the corresponding N-hydroxy amine (Table I). Alternatively, a small drop of phenylhydrazine can be added directly to the nitroxide-CDCls solution without using the standard solution when absorptions in the 6 -7.3 region are not of interest. General Procedure for Recovery of the Nitroxide after Reduction. The solvent was evaporated from the reduced NMR sample. The residue was dissolved in 1 ml of MeOH containing 1mg of cupric acetate monohydrate5$" and stirred under air for -1 hr. The solution quickly became dark purple and then slowly changed to the characteristic yellow-orange color of the nitroxide. Concentration followed by preparative TLC over silica gel gave the pure nitroxide in high yield. A c k n o w l e d g m e n t . This investigation was supported by t h e National Science Foundation (09413) a n d Public H e a l t h Service Research Grant CA-17338from t h e National Cancer Institute.
I 6H
b. R = CH ,CH,
which, at first, corresponded t o a -3:l mixture of N - h y droxy a m i n e 4d a n d its ring-opened nitrone isomer 5. This l a t t e r substance was also observed as t h e major product when t h e vinyllithium-nitrone reaction5sa was carried o u t a t 0". After about 30 m i n t h e NMR spectrum of t h e phenylhydrazine reduction mixture corresponded t o a -1:2 mixt u r e of 4d and 5 together with some products of decomposition. Interestingly, when 3 d (9.7 mg in 0.3 ml of CDC13) was treated with an eight- t o tenfold excess of 97% hydrazine, t h e r e was n o immediate reaction. After 3 h r t h e yellow color had faded a n d t h e NMR spectrum was that of only 4d plus hydrazine. Evaporation of t h e CDClB a n d t r e a t m e n t of t h e residue with cupric ion in methanol gave back nitroxide 3d in 86% yield after preparative TLC. T h e unusual propensity of 4d t o undergo ring opening t o 5 undoubtedly is related t o t h e a d d e d presence of t h e conjugated system in
Registry No.-1, 2564-83-2; 2, 3637-10-3; 3a, 16263-51-7; 3b, 55011-35-3; 3c, 55011-36-4; 3d, 55011-37-5; 4a, 55011-31-9; 4b, 55011-32-0; 4c, 55011-33-1; 4d, 55011-34-2; 5, 56348-28-8; 6, 56348-29-9; 7,4604-54-0; phenylhydrazine, 100-63-0.
R e f e r e n c e s and N o t e s
d, R = CHL=CH
(1)Alfred P. Sloan Foundation Fellow; NiH Research Career Development Award Rectplent. (2) For reviews, see 0. H. Griffith and A. S . Waggoner. Acc. Chem. Res., 2, 17 (1969);H. M. McConnell and B. G. McFarland, 0.Rev. Biophys., 3, 91 (1970):I. C. P. Smith. "Biological Applications of Electron Spin Resonance Spectroscopy", J. R. Bolton. D. Borg, and H. Schwartz. Ed., Wiley-Interscience. New York, N.Y., 1972,pp 483-539. (3)See, for example, H. Lemaire. J. Chim. Phys., 64, 559 (1967);S. H. Glarum and J. H. Marshall, J. Chem. Phys., 47, 1374 (1967):G. M. Zhidomirov and A. L. Buchachenko, J. Sbuct. Chem., 8, 987 (1967);E. G. Rozantsev. "Free Nitroxide Radicals", Plenum Press, New York. N.Y.. 1973;E. K. Metzner, L. J. Libertini, and M. Calvin, J. Am. Cham. SOC., 96, 6515 (1974). (4) J. F. W. Keana, S. B. Keana, and D. Beetham, J. Am. Chem. Soc., 89,
PhSHNH,
I
CDCl
i
0
6
I
bH
3055 (1967). (5) J. F. W. Keana and T. D. Lee, J. Am. Chem. SOC.,97, 1273 (1975). (6)The NMR spectra of paramagnetic species have been observed using
7
paramagnetic solvents which serve as "spin relaxers"; see R. W. Kreii-
J. Org. Chem., Vol. 40,No. 21, 1975 3147
Notes ich. J. Am. Chem. SOC.,90, 2711 (1968); R. Chiarelli and A. Rassat, Tetrahedron,29, 3639 (1973). (7) Phenylhydrazine has been used by Rosantsev for the high-yield synthesis of Khydroxypiperidine 2 from nitroxide 1 id refluxing methand; see E. G. Rosantsev and U. A. Golubev, Izv. Akad. Nauk SSSR, Ser. Khlm., 891 (1966): Chem. Abstr. 65, 10559 (1966). (8) T. D. Lee and J. F. W. Keana, manuscript in preparation. (9) E. Lund, Nitro Compd., Proc. Int. Symp., 291 (1963): Chem. Abstr., 64, 676 (1966). (10) E. G. Rozantsev, I n . Akad. Nauk SSSR, Ser. Khlm., 2187 (1964); Chem. Abstr., 62, 7721 (1964). (11) R. Bonnett, R. F. C. Brown, V. M. Clark, I. 0. Sutherland, and A. Todd, J. Chem. Soc.. 2094 (1959). (12) S. Chou, J. A. Nelson, and T. A. Spencer, J. Org. Chem., 39, 2356 (1974). (13) W. L. Barnett, J. SOC. Chem. Ind., London, 40, 167 (1921): Chem. Abstr.. 15, 3083 (1921).
Table I Rate Constants for Decomposition of tert-Butyl p-Nitrophenylperacetate (1) and tert-Butyl Phenylperacetate (2) in Cumene at 85' k x lo5, s e d
P , atm
Perester
1
1
2000
3.10 2.74 2.73 2.65 2.71 2.02 13.2 12.3
4000
10.6
1250 2000
3000 4000
6000 1
2
rt 0.06 rt 0.04
* 0.07
f 0.04 rt 0.06
0.07
Ranges reported are derived from least-squares analysis of the kinetic data.
One-Bond and Two-Bond Homolytic Scission of tert-Butyl p-Nitrophenylperacetatel Robert C. Neuman, Jr.,* and Richard Wolfe Department of Chemistry, University of California, Riverside, California 92502 Received February 4,1975
It is accepted that some tert- butyl peresters thermally decompose by one-bond scission (eq l a ) while others decompose by simultaneous scission of two bonds (eq l b ) so
R-C--O R-CO-OCMeJ
1I
0
II 0
/T
c
.0CMe3
Re CO! .0CMe3
(la)
- -0.4 -0.8
-
- 1.2-
I
I
I
I
I
(lb)
as to produce carbon dioxide in the primary ~ t e p . ~ How-~ ever, the proposal that a few peresters decompose simultaneously by both pathways4g6remains c o n t r ~ v e r s i a l . ~ . ~ + ~ R groups which can become reasonably stable radicals (R.), such as diphenylmethyl,2,6trityl? tert- b ~ t y 1 , ~ * p-methoxybenzy13,6.11J2and p-methylbenzyl,6J1J2 lead to decomposition via path Ib, while pheny1,2J3 vinyl,14 and ethyl4 groups promote one-bond scission (eq la). One perester which has been proposed to decompose by both routes is tert- butyl p-nitrophenylperacetate (1): O,N+CH,CO,OCM~, 1
In this paper we present the results of a study of the effect of pressure on decomposition of 1 in the solvent cumene. We feel that the data indicate that 1 decomposes only by two-bond scission; however, the results are not unambiguous. Results and Discussion The rates of decomposition of 1 (cumene, 85') a t various pressures are given in Table I along with data for unsubstituted tert-butyl phenylperacetate (2) under the same conditions. The atmospheric pressure data for these two per-
I
I
I
1
U+
Figure 1. Plot of log ( k x l k H ) vs.
for thermal decomposition of ring substituted tert-butyl phenylperacetates where, from left to right, X = p-MeO, p-Me, H, rn-Me, p-C1, rn-C1, and p-NO:, in chlorobenzene at 90.7" (A), cumene at 79.6" ( O ) , and cumene at a50 ( 0 ) . u+
~ ~ ~ ~ ~ J ~
and the fit of this solid point provides justification for comparison of these studies of 1 to the earlier data.11J2 A question had been raised that the apparent positive deviation of Bartlett's point for 1 in chlorobenzene from the best straight line through the other points (Figure 1) might reflect induced decomposition.ll The congruence of our data point for 1 in curnene with that for 1 in chlorobenzene suggests, however, that induced decomposition is probably not important. It seems unlikely that it would occur to the same extent in these two different solvents. The data for 2 were determined a t 85' not only to provide results for the Hammett plot, but to see if the same pressure dependence obtained in the earlier study12 was observed. A comparison of the earlier data for 2 a t 79.6' with those determined here a t 85' (Figure 2) show that this is the case. The data for 1 are plotted in Figure 2 along with those for tert- butyl phenylperacetate, tert- butyl trimethylperacetate? tert- butyl dimethylpera~etate~ and the cis and trans isomers of tert-butyl 2-propyl-2-peroxypentenoate (3).14 These latter two peresters decompose by one-bond EtCH=C(CH2Et)COJCMeJ
2
esters give the solid point in Figure l.15 This Hammett plot for decomposition of ring-substituted tert- butyl phenylperacetates was drawn using data obtained by Bartlett (chlorobenzene, 90.7')" and by Behar (cumene, 79.60)12
3
scission14 (path l a ) while the trimethylperacetate is generally accepted to decompose by two-bond s c i s s i ~ n . ~It~ ~ ~ ~ - ~ J seems to us that two families of curves are visible in this figure and that the data for 1 fall within that family with a
