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J.Org. Chem., Vol. 39, No. 19, 1974
Garst and Schmir
3. Syn chloride (unlabeled 9): 30 mg, 9.5% yield; mp and mmp1° 144-145'. B. With Labeled 4.2 The reaction was carried out as described in A, above, to give the following. 1. A mixture of pure syn and anti acetates 5 and 6: 64.3% yield; ratio of syn:anti 1~3.3. 2. Pure anti chloride 10 (25.9%yield): the pmr spectrum showed no methine at 6 5.18 (anti chloride) which confirmed deuterium at the methine carbon; mass spectral analysis showed 95.2% monodeuterated species and 4.8% unlabeled species. 3. Pure syn chloride (1.5% yield): mass spectral analysis showed 63.2% nondeuterated, 32.7%monodeuterated, and 4.1% dideuterated species; the pmr spectrum (using a computer of average transients) gave an apparent triplet centered at 6 5.97 for anti H (9) which integrated for -0.5H us. aromatic H. Analysis of the label in acetates 5 and 6 was conducted on the pure alcohols obtained by hydroly~is.~ The syn alcohol (mp and mmp 158-159°)9 showed by mass spectral analysis 82.7% unlabeled and 17.3% monodeuterated species; the pmr spectrum (CDC13) showed, subsequent to treatment of a sample with DzO to eliminate overlapping signals due to OH, a quartet at 6 5.33 (methine H) which integrated to 0.85 H us. the aromatic H. The anti alcohol (mp and mmp 205-206°)9 showed by mass spectral analysisls 97.4% dl and 2.6% dp species; pmr showed no observable methine resonance. Reaction of 4 with p-toluenesulfonyl chloride was carried out as previously described10 to give only syn tosylate (m 122-123O from ether);20no anti tosylate10 was detected. The mass spectrum of this product showed 97.5% d l and 2.5% dz species; pmr (CDCl3) showed one proton (methine H)at 8 6.35.$
Mass Spectrometry by Biomedical Research Branch of NIH under Grant R-330 is also gratefully acknowledged. The authors would also like to thank Professor V. J. Traynelis, Department of Chemistry, University of West Virginia, for helpful discussions of this work.
Registry No.-4 (unlabeled), 25907-81-7; 4 (labeled), 5182005-4; syn-5 acetate, 51933-62-1; syn-5 alcohol, 25866-36-8; anti-6 acetate (unlabeled), 52078-88-3; a n t i 4 acetate (labeled), 5215191-4; anti-6 alcohol (labeled), 52079-43-3; syn-7 tosylate, 3778125-2; syn-9, 37781-27-4; anti-10 (unlabeled), 52019-95-1; anti-10 (labeled), 52078-89-4; acetic anhydride, 108-24-7; acetyl chloride, 75-36-5; p-toluenesulfonyl chloride, 98-59-9.
(IO) W. E. Parham, K. B. Sloan, K. R. Reddy, and P. E. Olson, J. Org. Chem.,
Acknowledgments. The authors would like to express their appreciation to Dr. David Rosenthal and Mr. Fred Williams, Chemistry and Life Sciences Division, Research Triangle Institute, for advice and technical assistance in regard to determination of 2H and l80labels by mass spectral analysis. Support for the Research Triangle Center for
References and Notes Supported in part by the National Science Foundation Grant No. GP 35429.
For the precedlng article In this series, see W. E. Parham, P. E. Olson, and K. R. Reddy, J. Org. Chem., 2432 (1974). (a) E. Ochiai, "Aromatic Amine-Oxides,''Transl. by D. V. Mizoguchi. Elsevier, Amsterdam, 1967; (b) V. J. Traynelis in "Mechanisms of Molecular Migrations," Vol. 2, B. S. Thyagarajan, Ed., Interscience, New York, N. Y., 1969, pp 1-42; (c)A. R. Katritsky and J. M. Lagowsky, "Chemistry of Heterocyclic N-oxides," Academic Press, New York, N. Y., 1971, pp 349-367.
(a) V. J. Traynelis and P. L. Pacini, J. Amer. Chem. SOC., 86, 4917 (1964); (b) S. Oae, S. Tamagaki, T. Negoro, K. Ogino, and S. Kozuka. Tetrahedron Len., 917 (1966); (c) S. Oae, S. Tamagaki, T. Negoro, and S. Kozuka, Tefrahedron, 26, 4051 (1970): (d) V. J. Traynelis, A. I. Gallagher, and R. F. Martello, J. Org. Chem., 26, 4365 (1961); (e) C. W. Muth and R. S. Darlak, /bid., 30, 1909 (1965). Attempts to confirm the anhydrobase at the a-carbon atom have been unsuccessful;however, there is spectral evidence for the corresponding anhydrobase in reactions leading to 4-substituted pyridines; cf. V. J. Traynelis and A. I. Gallagher, J. Org. Chem., 35, 2792 (1970). (6) R. Bodalsky and A. R. Katritsky, J. Chem. SOC.6,831 (1968). (7) (a) S. Oae, T. Kitao and Y. Kitaoka, J. Amer. Chem. SOC., 84, 3359 (1962); (b) S. Kozuka, S. Tamagaki,T. Negoro and S. Oae, Tetrahedron Len., 923 (1968). (6) T. Koenig, J. Amer. Chem. SOC.,88, 4045 (1966); cf. formula 13 in this paper. (9) W. E. Parham, R. W. Davenport, and J. B. Biasotti. J. Org. Chem., 35, 3775 (1969). 38, 927 (1973). (11) No chlorides were detected on prolonged (138.5 hr) treatment of syn and anti acetates with refluxing acetyl chloride. (12) D. Rosenthal, private communication. (13) Calculations were performed by modified method of S. Oae and coworkers: cf. ref 7. (14) Return of an acetate ion pair associated with the activated complex
(15) ( 16) (17) (18)
may be analogous to results obtained with acetyl chloride. Silica gel, petroleum etherl8-ether (3:2) as eluent.
BP 30-60'. BP 60-90'. K. Biemann, "Mass Spectrometry; Organic Chemical Applications." McGraw-Hill, New York, N. Y., 1962, pp 204-250. (19) Silica gel developed with petroleum etherlB-ether(85: 15).
(20) The syn tosylate melts at 104-107° when crystallized from chloroform-
petroleum etherI6and is analytically pure. When the material is crystallized from ether, the mp is 122-123'.
Hydrolysis of 2-Methoxyfuranl John E. Garst and Gaston L. Schmir* Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510 Received April 23,1974 The acid-catalyzed hydrolysis of 2-methoxyfuran in aqueous dimethyl sulfoxide results in the formation of crotonolactone (4, 55-65%), methyl succinate semialdehyde ( 5 , 16-23%), and methyl cis -4-hydroxycrotonate (6, 16%),as determined by nmr spectroscopy. These findings are not in agreement with an earlier report2 and require revision of the proposed mechanism of hydrolysis of 2-methoxyfuran.
The acid-catalyzed hydrolysis of 2-methoxyfuran (1) has been reported2 to yield the enol 2 of the methyl ester of succinic acid semialdehyde, presumably arising uia a tetrahedral addition intermediate3 (eq 1). The proposed inter6.0
H
4 cOH7 COPCHJ 4.*
7.8
3.0
1
2
(1)
mediate is similar in structure to those believed to be formed in many acyl transfer reactions: and in particular to those of ester hydrolysis5 and formatiom6 It seemed of special interest to determine whether the direction of decomposition of the addition intermediate would be pH dependent, as had been found with the closely related intermediates generated during the lactonization of coumarinic acids,6 and if so, to measure the partitioning ratio of the different ionic species of the intermediate. While attempting to obtain this information, we have found that the hy-
J. Org. Chem., Vol. 39, No. 19, 1974 2921
Hydrolysis of 2-Methoxyfuran Table I Hydrolysis of 2-Methoxyfuran
0.001 0.003 0.005
0.01 0.08 0.25
1.64, 1.68 4.70, 5.46 8.05, 8.20, 8.38 k H = 1.66 iZI-' sec-'
0.28' 0.24' 2.8' 2.4d 11.2, 12.5' 7.8, 9.6' kD = 0.033 M' sec-'
a At 25", 0.8% CHsCN-HzO, g = 0.1. *At 32.5", 41 mol % dimethyl sulfoxide-&-deuterium oxide. c Disappearance of 2-methoxyfuran. Appearance of 4.
drolysis of 2-methoxyfuran is appreciably more complex than hitherto reported.2 Results and Discussion The identification2 of the enol 2 as the product of hydrolysis of 2-methoxyfuran was based on the interpretation of the nmr spectrum of the reaction product (in 50 mol % dimethyl sulfoxide) as shown in eq 1. That the assigned structure 2 is probably incorrect is revealed by the published7a nmr spectrum (in CCld) of the corresponding enolic methyl ether 3 (Chart I). On the other hand, the measured chemical shifts and coupling constants assigned2 to structure 2 correspond closely to those determined in this laboratory for 4-hydroxycrotonic acid lactone (4) in 50 mol % dimethyl sulfoxide-water.8 In the same solvent, the methyl group of methanol had a chemical shift of 3.23 ppm relative to tetramethylsilane. Chart I 4.48
7 .e4
H
591
H
_Xi:ggg CO,CH,.
OCH,
4'92
616
,
266
CH,-CH CHO
H
950
162"
