Photochemical reactions of carbohydrates

Carbohydrate Research

EIsevkr Publishing PrintcdinIldgium

1

Compan~.Amsterdam

PHOTOCHEMICAL

REACTIONS

II. l-m PHOTOCHEMISTRY

OF CARBOHYDRA’kES

OF 6-DEOXY-6-10~0-1

,~:~,~DI-O-ISOPROPYLIDENE-~-C-D-

GALACTOPYRANOSE W. W.

BINIUEY

The New York Sugar Trade Laboratory. 37 Warren Street, New York, N- Y. 10007 (U. S. A.) AND

R. W. BINKLEY

The Cleaeland State University, Cieuefand, Ohio 44115 ( W. S. A.) (Received January 30th, 1969)

ABSTRACT

Ultraviolet irradiation (Pyrex filter) of a methanol solution of 6-deoxy-6-iodo1,2:3,4-di-0-isopropylidene-a-D-galactopyranose (1) in the presence of sodium hydroxide led to rapid, almost quantitative conversion of 1 into 6-deoxy-1,2:3,4di-0-isopropylidene-z-n-galactopyranose (2). The yield of 2 was found to depend on the solvent and on the energy of the light used for irradiation. The direct irradiation of 1 in rert-butyl alcohol in the presence of sodium hydroxide gave 2 in only 36% yield, together with 6-deoxy-1,2:3,4-di-U-isopropylidene-L-arabino-hex-5-enopyranose (4) in 32% yield. A mechanism is proposed in which the initial step is the light-induced homolysis of the carbon-iodine bond in 1 to a radical species Q and an iodine atom. The products formed from 5 depend on the relative ease of abstraction of hydrogen from the solvent. INTRODUCTION

Although the naturally occurring carbohydrates are products of photochemical reactions, practical photochemical syntheses of carbohydrate substances in the laboratory are relatively rare I-’ . In consequence, and also because of our‘ interest in carbohydrates and in photochemistry, we have initiated a program for exploration of the possible utility of photochemical reactions in the study of sugars and sugar derivatives. The present paper describes, and discusses in detailj, the photochemistry of 6-deoxy-6-iodo-l,2:3,4-di-O-isopropylidene-~-~-galactopyranose (0 RESULTS

Direct ultraviolet irradiation (Le., without a filter; quartz Iamp duly) of 1 in methanolic sodium hydroxide under nitrogen for 2.0 h at 25” (see Expt. A, Table I) led to its complete distippearance, and, on removal of solvent, a milky white syrup Carbohyd. Res., 11 (1969) 1-S

W. W. BINKLEY, R. W. BINKLEY

2

was produced_ This syrup was divided into an ether-soluble and an ether-insoluble fraction. When the ether-insoluble fraction was dissolved in water and rendered neutral, addition of silver nitrate caused the formation of a precipitate having the pale-yellow color characteristic of silver iodide. Column chromatography, on Florisil, of the ether-soluble fraction afforded two photoproducts; the major product, TABLE.

I

PIIOTOCHEhfBTRY

Ekpt.

A R C D E

OF

~-DEOXY-~-IODO-~,~:~.~-DI-~-ISOPROP~IDENE~-D-GALACTOPYRANOSE

Solvent

Base aaWed

Methanol

Cyclohexane Cyclohexane rert-Butyl alcohol Benzene

(1)

Irradiation time, h

2

Yield of products, % 4

sodiumhydroxide sodium hydroxide triethylamine sodium hydroxide

2.0 2.0 2.0 3.0

83 54 48 36

none none none 32

sodium hydroxide

6.0

none

none

isolated in 83% yield, was identified as 6-deoxy-1,2:3,4-di-0-isopropylidene-a-Dgalactopyranose (2) by d irect comparison with an independently synthesized sample4. The minor photoproduct (3), isolated in 11% yield, had an i.r. spectrum almost identical with that of 2, but, in contrast to 2, compound 3 was significantly less volatile and was much less mobile both on column and thin-layer chromatograms. Deacetalated 3 was markedly less mobile on paper than 6-deoxy-D-galactose (deacetalated 2). Compound 3 has not yet been definitely identified; however, reasoning based on the available data allows a tentative assignment of structure to this compound (see DISCUSSION). This photochemical conversion has also heen achieved in cyclohexane in the presence of (a) sodium hydroxide (see Expt. B, Tab_le I) and (6) trimethylamine (see Expt. C, Table I). In each case, however, the yield of product was less than from the irradiation in methanol. No reaction occurred on irradiation of a solution in benzene (see Expt. E, Table I). A distinct change in the course of the reaction occurred when the irradiation of 1 was conducted in terr-butyl alcohol, a solvent that is a poor hydrogen-donor5*6’. In this case (see Expt. D, Table I), column chromatography of the irradiation products gave compound 2 (36%) and a second product (in 32% yield) which was found to be 6-deoxy-l,2:3,4-di-O-isopropylidene-L-arabino-hex-5-enopyranose7 (4), identical by mixed m.p. and i.r. spectrum with an independently synthesized sample of 4. In Table II are given the yields of 6-deoxy-1,2:3,4-di-O-isopropylidene-a-Dgalactopyranose (2) resulting from irradiation (of 1 in methanol) without a filter (quartz lamp only) and from those in which each of two different filters was placed between the light source and the reaction vessel. Carbohyd. Res.,

11 (1969) l-8

PHOTOCHEMICAL TABLE

REACTIONS.

3

II

II

DEPENDENCE

OF

YIELD

OF PRODUCT

ON

EXCITATION

WAVELENGTH

EMPLOYED,

6-DEOXY-6-IODO-~,~:~,~DI-~-ISOPROPYLIDENEQ-D-GALACTOPYRANOSE

FOR

THE

IRRADIATION

OF

(1)

Erpt.

Irradiation time, h

Filter

Yield of 2. %

F G H

2.0 6.0 2.0

Vycof Pyrexb quartz’

78 97 83

nRemoves light of 1< 205 run. bRemoves light of A < 280 m-n. =Quart.z is transparent above 200 nm (% transmittance = 73 at 200 nm). DISCUSSION

The results presented in the previous section clearly show that the irradiation of 6-deoxy-6-iodo-l,2:3,4-di-O-isopropylidene-cc-D-galactopyranose (1) under the proper conditions provides an excellent means for replacement of the iodine atom by a hydrogen atom. This photochemical reaction represents, as a synthetic process, a potentially attractive alternative to the well-known reductive procedure for accomplishing such a substitution’, and may, therefore, be considered as one step in the general process for conversion of sugars into their deoxy derivatives. Although the possible synthetic utility of this reaction is clear, it is equally apparent from an inspection of Tables I and II that care must be taken in the selection both of the solvent and the energy of the light used in irradiation if the identity and yield of the photoproducts are to be controlled. The data shown in Table I describe the dependence of the photochemistry of 6-deoxy-6-iodo-l,2:3,4-di-O-isopropylidene-a-D-galactopyranose (1)on the solvent used in the irradiation. The formation of 6-deoxy-1,2:3,4-di-O-isopropylidene-a-Dgalactopyranose (2) is greatest in methanol, somewhat less in cyclohexane, and completely nonexistent in benzene. In rert-butyl alcohol, the formation of 2 is accompanied by a reaction that produces 6-deoxy-1,2:3,4-di-O-isopropylidene-rarabino-hex-5-enopyranose (4). Although complete understanding of the effect of the solvent on the photochemistry of 1 has not been achieved some insight into the usual changes brought about by use of different solvents can be obtained by considering the most probable mechanism for this reactions and the effect of the solvent on molecules reacting via this proposed pathway. In Scheme I is shown a proposed mechanism for the photochemical reactions observed on excitation of 1 in various solvents. The initial step in the process shown, regardless of the reaction solvent, is the light-induced homolysis of a carbon-iodine bond’ to give the radical species 5, as well as an iodine atom. Unlike the first step, the second step in the reaction sequence is critically dependent on the nature of the solvent. In methanol, an effective hydrogen-donor6’, the free radical 5 abstracts a hydrogen atom from the solvent, to produce 6-deoxy-1,2:3,4-di-O-isopropylidenea-D-galactopyranose (2), together with a hydroxymethyl radical. In tefz-butyl alcohol, Carbahyd. Res., 11 (1969) 1-8

W. W. BINKJXY,

4

R. W.

BINKLJZY

0-CMe2 5

1

nydmgen

abstraction from

/ solvent

-k

0-CMe,

4

.

HI

2

where abstraction of a hydrogen atom is more difficult’* 6a, hydrogen transfer from 5 to an iodine atom, to produce a molecule of 6-deoxy-1,2:3,4-di-O-isopropylidener..-arabino-hex+enopyranose (4), is able to compete effectively with the reaction giving 2. In benzene, which is an exceedingly poor hydrogen-donor, hydrogen abstraction leading to 2 is, reasonably, not observed. The apparent failure, in benzene, of the iodine atom to effect the abstraction of a hydrogen atom from radical 5 (to give 4) is more difficult to rationalize; however, even though the explanation for this behavior still remains obscure, it is clear that any radicals formed by homolysis of a carboniodine bond in benzene tend to recombine. It seems unlikely that 1 is unreactive in benzene due merely to the failure of the carbon-iodine bond to undergo photochemical fragmentation. The energy of the light used for exciting 6-deoxy-6-iodo-1,2:3,4di-O-isopropylidene-a-D-galactopyranose (1)also plays an important role in its photochemistry (see Table II). When the protons of higher energy are prevented from reaching the reaction mixture by the presence of a Pyrex filter, the-yield of 6-deoxy-1,2:3,4-di-0isopropyhdene-rr-D-gdactopyranose (2) becomes almost quantitative. The exclusion of photons of very high energy also has the effect of terminating the photochemical side-reaction that results in the formation of compound 3. Although the structure of the minor product 3 from the irradiation of 1 has not yet been determined, the information available about this compound does allow some statement concerning its molecular framework. The i.r. spectrum of 3 is almost superposable upon that of 6-deoxy-1,2:3,4-di-0-isopropylidene-cr-D-galactopyr~ose

(2), indicating a very strong similarity in structure between 2 and 3. Several additional observations are potential sources of further information about the structure of 3: (a) 3 does not distil at 130” (bath temp.)/O.2 torr, whereas 2 readily distils at 59-61” under the same pressure; (b) on t.1.c. of 2 and 3 on silica gel, 2 has a much greater mobiiity than 3; (c) the R, values, on paper, of the deacetalated products from 2 and 3 aiso show the product from 3 to be less mobiie than that from 2. In comparing two molecules, lower chromatographic mobility and higher b-p. Carbolzyd. Res., I1 (1969) 1-8

PHOTOCHEMICAL

REACTIONS.

5

II

are usually associated either with an increased polarity within the molecule or an increased molecular weight, or both. The fact that the i.r. spectra of 2 and 3 are so similar favors the supposition that 3 is a species having a molecular weight higher than that of 2, but suggests that 3 does not contain new, more-poIar bonding, because increased polarity in the bonding in 3 (as compared to 2) would produce corresponding changes in the infrared absorptions. Although, according to this reasoning, 3 should have a higher molecular weight than 2, this increased molecular weight is clearly not a resuIt of the incorporation of a molecule of the solvent into the starting material (or other reactive species) during photochemical reaction, as the same properties for the material designated 3 were found for the product5 formed in irradiations both in methanol and in cyclohexane. On the basis of these considerations and the fact that free-radical species are known to attack alkyl halides with expulsion of a halogen atom6b, we tentatively propose for the structure of compound 3 that shown in the following reaction depicting a probable process for the formation of 3.

EXPERIMENTAL

General procedures. In each reaction, a solution of compound 1 was irradiated at 25”, with constant stirring, with the light from a loo-watt, Hanovia, high-pressure, quartz, mercury-vapor lamp which had been lowered into a watercooled, quartz immersion-well. Prepurified nitrogen was passed through the solution for 1 h prior to irradiation, and a slow stream of nitrogen was continued during photolysis. The solvent was removed from each irradiation mixture by distillation ilz vacua below 30”, before column chromatography. T.1.c. was performed on silica gel (- 100 pm thick) on polyester sheets (Eastman Kodak Co., Rochester, N-Y.) with 1OO:l (v/v) benzene-tert-butyl alcohol as the developer and l-naphtholphosphoric acid as the indicator lo. A. Direct irradiation in methanol in the presence of sodium hydroxide. - In a typical experiment, 1.000 g (2.78 mmoles) of compound 1 in 300 ml of methanol containing 390 mg of sodium hydroxide was irradiated for 2.0 h. No filter was used. T.1.c. of the crude reaction-mixture revealed, after treatment with l-naphtholphosphoric acid, the presence of two products. The more mobile of these (RF 0.44) was salmon pink in color; the second product (RF 0.22) was blue-gray. After removal of solvent, 655 mg of ether-soluble, residual syrup was chromatographed on a column (2.5 x 80 cm) of Fiorisil, packed as a slurry in I :9 ether-hexane. The column was developed with the following solvents: 200 ml of hexane, 200 ml Carbohyd.

Res., 11 (1969) l-8

6

W. W. BINKLEY, R. W. BINKLEY

of I:99 ether-hexane, 100 ml of I:49 ether-hexane, 100 ml of 1:24 ether-hexane, 200 ml of 1:12 ether-hexane, and 600 ml of I:6 ether-hexane. The effluent was collected in IOO-ml fractions. Fractions 4-9 gave 551 mg of a clear syrup, and fractions 11-12, 80 mg of another clear syrup. The major product had b.p. 59-61”/0.2 torr; [a];’ -62” (a supercooled melt; neat); rz;” 1.45053; jz~~~133.35, 3.44, 6.93, 7.27, 9.24, and 10.01 pm; R, 0.44 (I:100 tert-butyl alcohol-benzene). These constants are identical with those for a synthetic sample of 6-deoxy-l,2:3,4di-O-isopropylidene-a-D-galactopyranose4 (2). Anal. Calc. for C,,H,,O,: C, 59.00; H, 8.25. Found: C, 58.78; H, 8.21. A portion (390 mg) of the major product was deacetalated by refluxing a solution in I % aqueous sulfuric acid (16 g), followed by neutralization of the acid with barium carbonate, filtration, evaporation of the filtrate, and crystallization of the residue from ethyl alcohol (95%), to yield 147 mg of impure crystals. Recrystallization from the same solvent afforded elongated plates, m.p. 139-142”, [a];’ +76.6” (c 1, water), identical by mixed m.p. and paper chromatography with an authentic sampie of 6-deoxy-?-D-galactopyranose4. Hence, the major product from the irradiation of 6-deoxy-6-iodo-1,2:3,4-diO-isopropylidene-a-D-galactopyranose (1) is 6-deoxy-I ,2:3,4-di-O-isopropylidene-aD-galactopyranose (2), formed in 83% yield. The minor product from the irradiation of 1 did not distil at 130” (bath)/0.2 torr, and had an i-r. spectrum essentially identical with that of 2. Deacetalation with aqueous sulfuric acid (1%) yielded a syrup of Rf- 0.16 on paper (with 2:2:1 butyl alcohol+thyl alcohol-water as developer, and detection with p-anisidine hydrochloride to give a dark-green spot); 6-deoxy-a-D-galactose had R, 0.56 and gave a green-brown spot. On the basis of these data and the mechanistic consideration described in the DISCUSSION, the structure 3 is tentatively assigned to the minor photoproduct from the irradiation of 1. B. Direct irradiation in cyclohexane in the presence of sodium hydroxide. Irradiation of a solution of 360 mg (1 .OOmmole) of 1 in 300 ml of cyclohexane containing 190 mg of sodium hydroxide for 2.0 h, followed by evaporation, gave a milky syrup. The ether-soluble portion of the reaction mixture was chromatographed on a column (2.5 x 80 cm) of Florisil, packed as a slurry in 1:9 ether-hexane. The column was developed with the following solvents: 100 ml of hexane, 100 ml of I:99 ether-hexane, 100 ml of l:49 ether-hexane, 100 ml of l:24 ether-hexane, 100 ml of .I:12 ether-hexane, and 500 ml of I :6 ether-hexane. The effluent was collected in lOO-ml fractions. Fractions 4-8 gave 128 mg (54%) of a clear syrup, identical in i.r. spectrum and t.1.c. mobility with 6-deoxy-l,2:3,4-di-O-isopropylidene-a-D-galactopyranose (2). Fraction 9 afforded 17 mg of a clear syrup identical in i.r. spectrum and t.1.c. mobility with the minor product, from the irradiation in methanol, that had tentatively been identified as 3. C. Direct irrudiation in cyciohesane in the presence of triethylanline. - Irradi-

PHOTOCHESfICAL

REACTIONS.

7

II

ation of a solution of 360 mg (1 .OOmmole) of 1 in 300 ml of cyclohexane containing 1.0 ml of triethylamine for 2.0 h, followed by evaporation, gave a yellow syrup. Column chromatography of the ether-soluble portion of the reaction mixture was effected on Florisil, exactly as described in section C. Fractions 4-8 afforded 120 mg (48%) of a clear syrup identical in i.r. spectrum and t.1.c. mobility with 2. A yellow solid that was isolated was identical (i-r. spectrum and mixed m-p.) with an authentic sample of triethylammonium iodide. D. Direct irradiation in tert-butyl alcohol in the presence of sodium hydroxide. A solution of compound 1 (360 mg, 1.00 mmole) and sodium hydroxide (190 mg, 2.3 mmoles) in 300 ml of tert-butyl alcohol was irradiated for 3.0 h as described under General Procedures. TLC. of the crude reaction mixture, followed by spraying with I-naphthol-phosphoric acid, indicated the presence of four compounds. The most mobile component had R, 0.79 and was pink, suggesting that it was unreacted 1. A bright-blue spot (RF 0.62) followed the pink one. The next spot was salmon pink and had RP 0.44, indicating that this compound was 6-deoxy-1,2:3,4_di-O-isopropylidene-cr-D-galactopyranose (2). Finally, the chromatogram showed a blue-gray spot near the origin. After removal of solvent, 204 mg of the ether-soluble, residual syrup was chromatographed on a column (2.5 x 80 cm) of Florisil, packed as a slurry in l:9 ether-hexane. The column was developed with the following solvents: 400 ml of hexane, 400 ml of I:99

ether-hexane,

400 ml of I:49

ether-hexane,

400 ml of 1:24

ether-hexane, 400 ml of I: 12 ether-hexane, 800 ml of I:6 ether-hexane, and 400 ml of 1:3 ether-hexane. The eihuent was collected in 20-ml fractions. Fractions 99-106 gave 35 mg of unreacted 1, identified by its i-r. spectrum and t.1.c. analysis. Fractions 130-156 afforded 75 mg (36%) of 6-deoxy-1,2:3,4-di-0isopropylidene+D-galactopyranose (2), identified by i.r. spectrum and t.1.c. analysis. Fractions 114-124 gave 72 mg (32%) of colorless crystals, m.p. 76-81”. Recrystallization from ethyl alcohol (95%) yielded pure compound, m-p. 85-86”, A:!:” 3.33, 6.04, and 7.26 jlrn, identical (mixed m.p., t.l.c., and i-r. spectrum) with a synthetic sample of 6-deoxy-l,2:3,4-di-U-isopropylidene-8-L-arabino-hex-5~nopyranose7 (4). E. Direct irradiation in benzene in the presence of sodium hydroxide. - Irradiation for 6.0 h of a solution of 360 mg (1.00 mmole) of 1 in benzene containing 190 mg (2.3 mmoles) of sodium hydroxide, as described under General Procedures, gave, on removal of solvent, a colorless solid. The ether-soluble portion of this material was identical, in i.r. spectrum, m-p., and mixed m.p., with the starting material (1). F. Irradiation (Vycor filter) in methanol in the presence of sodium hydroxide. The irradiation and isolation procedures were the same as those used in section A, except that a Vycor filter was placed between the light source and the reaction mixture. Fractions 4-8 gave 510 mg (78%) of a clear syrup identical in i.r. spectrum and t.1.c. mobility with 6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose (2). Curbohyd.Res., 11 (1969) l-8

W. W. BINKLEY,

8

R. W. BINKLEY

Fraction 9 afforded 18 mg of a clear syrup identical in i.r. spectrum and t.1.c. mobility with the minor product (3) from the direct irradiation of a solution in methanol (section A). G. Irradiation (Pyrex-filter) in methanol in the presence of sodium hydroxide. The irradiation and isolation procedures were the same as those used in section A, except that a Pyrex filter was placed between the light source and the reaction mixture. Fractions 4-9 gave 635 mg (97%) of a clear syrup identical in i.r. spectrum and t.1.c. mobility with 6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose (2). No other products were isolated. Test of the stabitity of 6-deoxy-6-iodo-I,2:3,4-di-O-isopropylidene-a-~-gaIactopyranose (1)under the conditions of reaction and isolation. - In order to test the stability of the starting material under the conditions of reaction and isoIation, compound 1 was treated exactly as described for direct irradiation in methanol in the presence of sodium hydroxide (section A), except that the light was not turned on. The isolation procedure was identical with that described in section A. Unreacted starting-material was isolated in quantitative yield. ACKNOWLEDGhiENT

R. IV. B. thanks the Research Corporation

for partial support of this work.

REFERENCES 1 D. HORTON AND W. N. TURNER, Chenr.I&. (London), (1964) 76; Curbohyd. Res., 1 (1966) 444; BELL, D. HORTON, AND D. HORTON AND J.S. JEWELL, J_ Org. Clzem.,31 (1966) 509; R.H.

CO~~IIII., (1969)323. (1968) 403. 3 Forapreliminary reportofthiswork,seeW.W. D. M. WILLIAMS, Gem.

2

P. M. COLLINS, Chem.

4 5 6

BINKLEYAND R. W.BINKLEY, Curbohyd. Res., 8 (1968) 370. K. FREUDENBERG AND K. RASCHIG,B~K, 60(1927)1633. S. G. COHEN AND H. M. CHAO, J. Amer. Cbem. Sm., 90 (1968) 165. W. A. mYOR, Free Radicals, McGraw-Hill Book Company, Inc.,New York, 1966,(a)p. 219,

COMntIitl.,

(b)p. 145.

7 K. FREUDENBERG AND K. RASCHIG, Ber-, 62(1929)373. 8 0. T. SCHMIDT, Methods Curbohyd. Chenz., 1 (1962) 193. 9 J. G. CALVERT AND J.N. Pm-s, JR.,Photochemistry, Wiley, New York, 1967, p. 524. 10 W. W. BI-NKLEY. Intern. Sugur J.. 68 (1966) 10. Curbohyd. Res.,

11 (1969) l-8