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Conversion of 2-amino-2-deoxy-D -glucose diethyl dithioacetal hydrochloride into 2-s-ethyl-2-thio-D -glucose
Cmaohydme Research Elsevier PublishingCompany,
299
Anuterdam
RintcdiIlBelgium
CONVERSION ACETAL
A.
OF
2-AMINO-2-DEOXY-D-GLUCOSE
HYDROCHLORIDE
INTO
DIETHYL
DITHIO-
2-S-ETHYL-2-THIO+GLUCOSE*t
E. EL ASHMAWY, D. HORTON l*, LIGAYA G. MAGBANUA, AND’J. M. J. TRONCHET
Department
of Chemistry,
The Ohio State
Uninersity,
Columbus,
Ohio 43210 (U.S.A.1
(Received October 25th, 1967)
ABSTRACT
Treatment
of 2-amino-2-deoxy-D-glucose
diethyl dithioacetal hydrochloride
(1)withnitrous acid in aqueous hydrochloric acid gives 2-S-ethyl-2-thio-D-glucose (2) as the principal product, and an anhydro-D-hexose diethyl dithioacetal is not formed. Substance 2 was characterized by conversion into the phenylhydrazone (3) and further into D-arabino-hexdose phenylosazone (6); n.m.r. spectroscopy confirmed that 2 was an aldose having the D-gluco configuration. Acetylation of 2 gave the anomeric pyranose tetraacetates (4 and 5), and the n.m.r. spectrum of the P-D tetraacetate (4) further confirmed the structure assigned to 2. Nitrous acid in aqueous acetic acid converted 1 into a mixture of 2 and an anhydro-D-hexose diethyl dithioacetal. INTRODUCTION
Primary alkylamines react with nitrous acid by carbonium ion-type processes2. The reaction possesses great driving force under mild conditions. The net reaction path observed may vary widely as the structure and stereochemistry of the starting amine are varied. In derivatives of the 2-amino-2-deoxyllexoses the course of the reaction3 is profoundly influenced by the structure of the group at C-l. For example, 2-amino-2-deoxy-D-glucose4.‘, or its methyl a-~ or /?-D-glycoside6, react with aqueous nitrous acid to give 2,5-anhydro-D-mannose’, whereas 2-amino-2-deoxy-D-gluconic acid reacts to give 2,5-anhydro-D&conic acid’. The corresponding alditol, 2-amino%deoxy-D-glucitol, reacts to give 2-deoxy-D-arabino-hexose’. In the first example, inversion at C-2 takes place, presumably by rearside attack at C-2 by O-5 as a nitrogen molecule leaves from C-2. A net double inversion, by initial formation of an a-lactone, *Part of a series “Action of Nitrous Acid on Derivatives of Amino Sugars”. For a preliminary report, see ref. 1. *Supported by Grant No. GM-l 1976-03 from the National Institute of General Medicine, theNational Institutes of Health, U.S. Public Health Service, (The Ohio State University Research Foundation Project 1820), and by a Grant from the Parke-Davis Company, Ann Arbor, Michigan (The Ohio State University Development Fund, Grant No. 52-2102). The n.m.r. spectrometers were provided through Grants from the National Science Foundation, Washington, DC. **To whom inquiries should be addressed. Civbuhyd.
Res., 6 (1968) 299-309
~-S-E~YL-~-THIO-D-GLUCOSE
309
D-glucose diethyl dithioacetal triacetate, Defaye’j reported (60 MHz, chloroform-d) r 8.7 (CH, of Et), 7 7.43 (CHz of ethyl), and 7 7.92 (acetyls). For the O-deacetylated analog in chloroform-d, Defayet3 reported 5 4.78 (doublet, J,,, 8 Hz, H-l), T 6.79 (quartet, J2,3 4.5 Hz, H-2). ACKNOWLEDGMENTS
The authors thank R. H. Bell and J. H. Lauterbach for n.m.r. spectral measurements and the Parke-Davis Company for laboratory facilities (for L.G.M.) during part of this investigation. REFERENCES 1 D. HORTON, LIGAYA G. MAGBANUA, AND J. M. J. TRONCHET, C!tem. Ind. (London), (1966) 1718. 2 P. A. S. SMITH AND D. R. BAER, Org. Reactions, 11 (1960) 157; A. STREITWIESER. JR., AND W. D. SCHAEFFER,J. Am. Chem. Sot., 79 (1957) 2888. 3 S. PEAT, Aduan. Carbohydrate Cbem ., 2 (1946) 37; F. SHAFIZADEH, ibid., 13 (1958) 43. 4 P.A.LEVENEANDF.B.LAFORGE. J.Biol.C~em..21(1915)345,351;P.A.L~vnv~,ibid.,36(1918) 89; A. B. GRANT, New Zealand J. Sri. Tecbnol., 37 (1956) 509. 5 B. C. BERA, A. B. FOSTER, AND M. STACEY, J. C/tern. Sot., (1956) 4531. 6 B. C. BERA, A. B. FOSTER, D. HORTON, AND KERSTIN D. PHILIPS, unpublished data. 7 F. TIEMANN AND R. HAARMAN, Bet., 19 (1886) 1257; E. FISCHER AND F. TIEMANN, ibid., 27 (1894) 138. 8 Y. MATSUSHIMA. B&I. Chem. Sot. Japan, 24 (1951) 144. 9 A. B. FOSTER, Cilem. Ind. (London), (1955) 627. 10 L. HOUGH AND M. I. TAHA, J. Cbem. Sot., (1957) 3564. 11 R. U. LEMIEUX AND J. D. STEVENS, Can. J. Chem., 44 (1966) 249. 12 M. RUDRU~I AND D. F. SHAW, J. Gem. Sot. (1965) 52. 13 D. HORTON, J. S. JE~ELL, AND KERXIN D. PHILIPS, J. Org. C/rem., 31 (1966) 3843,4022. 14 0. L. CHAphrAN AND R. W. KING, J. Am. Chem. Sot., 86 (1964) 1256. 15 B. CASU, M. REGGIANI, G. G. GALLO, AND A. VIGEVANI, Tetrahedron, 22 (1966) 3061. 16 H. S. EL KHADEM, D. HORTON, AND T. F. PAGE, JR., J. Org. Cbem., 33 (1968) 000. 17 R. U. LEMIEUX AND J. D. STEVENS, Can. J. Cbem., 43 (1965) 2059. 18 J. I. MUSHER AND E. J. COREY, Terrahedron, 18 (1962) 791. 19 C. V. HOLLAND, D. HORTON, MARTHA J. MILLER, AND N. S. BHACCA, J. Org. Chem., 32 (1967) 3077; compare D. HORTON, J. B. HUGHES, J. S. JEWELL, KERXIN D. PHILIPS, AND W. N. TURNER, ibid., 32 (1967) 1073. 20 D. HORTON AND J. S. JEWELL, J. Org. C’bem. 32 (1967) 1818; D. HORTON AND W. N. TURNER, Carbobyd. Res., 1 (1966) 444. 21 P. BRIGL AND R. SCHINLE, Ber., 65 (1932) 1890. 22 H. R. BOLLIGER AND M. D. SCHMIDT, Helu. Chim. Acra, 34 (1951) 1597. 23 J. DEFAYE, Bull. Sot. Chin France, (1967) 1101. Carbohyd. Res.. 6 (1968) 299-309
299
Anuterdam
RintcdiIlBelgium
CONVERSION ACETAL
A.
OF
2-AMINO-2-DEOXY-D-GLUCOSE
HYDROCHLORIDE
INTO
DIETHYL
DITHIO-
2-S-ETHYL-2-THIO+GLUCOSE*t
E. EL ASHMAWY, D. HORTON l*, LIGAYA G. MAGBANUA, AND’J. M. J. TRONCHET
Department
of Chemistry,
The Ohio State
Uninersity,
Columbus,
Ohio 43210 (U.S.A.1
(Received October 25th, 1967)
ABSTRACT
Treatment
of 2-amino-2-deoxy-D-glucose
diethyl dithioacetal hydrochloride
(1)withnitrous acid in aqueous hydrochloric acid gives 2-S-ethyl-2-thio-D-glucose (2) as the principal product, and an anhydro-D-hexose diethyl dithioacetal is not formed. Substance 2 was characterized by conversion into the phenylhydrazone (3) and further into D-arabino-hexdose phenylosazone (6); n.m.r. spectroscopy confirmed that 2 was an aldose having the D-gluco configuration. Acetylation of 2 gave the anomeric pyranose tetraacetates (4 and 5), and the n.m.r. spectrum of the P-D tetraacetate (4) further confirmed the structure assigned to 2. Nitrous acid in aqueous acetic acid converted 1 into a mixture of 2 and an anhydro-D-hexose diethyl dithioacetal. INTRODUCTION
Primary alkylamines react with nitrous acid by carbonium ion-type processes2. The reaction possesses great driving force under mild conditions. The net reaction path observed may vary widely as the structure and stereochemistry of the starting amine are varied. In derivatives of the 2-amino-2-deoxyllexoses the course of the reaction3 is profoundly influenced by the structure of the group at C-l. For example, 2-amino-2-deoxy-D-glucose4.‘, or its methyl a-~ or /?-D-glycoside6, react with aqueous nitrous acid to give 2,5-anhydro-D-mannose’, whereas 2-amino-2-deoxy-D-gluconic acid reacts to give 2,5-anhydro-D&conic acid’. The corresponding alditol, 2-amino%deoxy-D-glucitol, reacts to give 2-deoxy-D-arabino-hexose’. In the first example, inversion at C-2 takes place, presumably by rearside attack at C-2 by O-5 as a nitrogen molecule leaves from C-2. A net double inversion, by initial formation of an a-lactone, *Part of a series “Action of Nitrous Acid on Derivatives of Amino Sugars”. For a preliminary report, see ref. 1. *Supported by Grant No. GM-l 1976-03 from the National Institute of General Medicine, theNational Institutes of Health, U.S. Public Health Service, (The Ohio State University Research Foundation Project 1820), and by a Grant from the Parke-Davis Company, Ann Arbor, Michigan (The Ohio State University Development Fund, Grant No. 52-2102). The n.m.r. spectrometers were provided through Grants from the National Science Foundation, Washington, DC. **To whom inquiries should be addressed. Civbuhyd.
Res., 6 (1968) 299-309
~-S-E~YL-~-THIO-D-GLUCOSE
309
D-glucose diethyl dithioacetal triacetate, Defaye’j reported (60 MHz, chloroform-d) r 8.7 (CH, of Et), 7 7.43 (CHz of ethyl), and 7 7.92 (acetyls). For the O-deacetylated analog in chloroform-d, Defayet3 reported 5 4.78 (doublet, J,,, 8 Hz, H-l), T 6.79 (quartet, J2,3 4.5 Hz, H-2). ACKNOWLEDGMENTS
The authors thank R. H. Bell and J. H. Lauterbach for n.m.r. spectral measurements and the Parke-Davis Company for laboratory facilities (for L.G.M.) during part of this investigation. REFERENCES 1 D. HORTON, LIGAYA G. MAGBANUA, AND J. M. J. TRONCHET, C!tem. Ind. (London), (1966) 1718. 2 P. A. S. SMITH AND D. R. BAER, Org. Reactions, 11 (1960) 157; A. STREITWIESER. JR., AND W. D. SCHAEFFER,J. Am. Chem. Sot., 79 (1957) 2888. 3 S. PEAT, Aduan. Carbohydrate Cbem ., 2 (1946) 37; F. SHAFIZADEH, ibid., 13 (1958) 43. 4 P.A.LEVENEANDF.B.LAFORGE. J.Biol.C~em..21(1915)345,351;P.A.L~vnv~,ibid.,36(1918) 89; A. B. GRANT, New Zealand J. Sri. Tecbnol., 37 (1956) 509. 5 B. C. BERA, A. B. FOSTER, AND M. STACEY, J. C/tern. Sot., (1956) 4531. 6 B. C. BERA, A. B. FOSTER, D. HORTON, AND KERSTIN D. PHILIPS, unpublished data. 7 F. TIEMANN AND R. HAARMAN, Bet., 19 (1886) 1257; E. FISCHER AND F. TIEMANN, ibid., 27 (1894) 138. 8 Y. MATSUSHIMA. B&I. Chem. Sot. Japan, 24 (1951) 144. 9 A. B. FOSTER, Cilem. Ind. (London), (1955) 627. 10 L. HOUGH AND M. I. TAHA, J. Cbem. Sot., (1957) 3564. 11 R. U. LEMIEUX AND J. D. STEVENS, Can. J. Chem., 44 (1966) 249. 12 M. RUDRU~I AND D. F. SHAW, J. Gem. Sot. (1965) 52. 13 D. HORTON, J. S. JE~ELL, AND KERXIN D. PHILIPS, J. Org. C/rem., 31 (1966) 3843,4022. 14 0. L. CHAphrAN AND R. W. KING, J. Am. Chem. Sot., 86 (1964) 1256. 15 B. CASU, M. REGGIANI, G. G. GALLO, AND A. VIGEVANI, Tetrahedron, 22 (1966) 3061. 16 H. S. EL KHADEM, D. HORTON, AND T. F. PAGE, JR., J. Org. Cbem., 33 (1968) 000. 17 R. U. LEMIEUX AND J. D. STEVENS, Can. J. Cbem., 43 (1965) 2059. 18 J. I. MUSHER AND E. J. COREY, Terrahedron, 18 (1962) 791. 19 C. V. HOLLAND, D. HORTON, MARTHA J. MILLER, AND N. S. BHACCA, J. Org. Chem., 32 (1967) 3077; compare D. HORTON, J. B. HUGHES, J. S. JEWELL, KERXIN D. PHILIPS, AND W. N. TURNER, ibid., 32 (1967) 1073. 20 D. HORTON AND J. S. JEWELL, J. Org. C’bem. 32 (1967) 1818; D. HORTON AND W. N. TURNER, Carbobyd. Res., 1 (1966) 444. 21 P. BRIGL AND R. SCHINLE, Ber., 65 (1932) 1890. 22 H. R. BOLLIGER AND M. D. SCHMIDT, Helu. Chim. Acra, 34 (1951) 1597. 23 J. DEFAYE, Bull. Sot. Chin France, (1967) 1101. Carbohyd. Res.. 6 (1968) 299-309