Org.
`
`1903
`
`The Ally1 Ether as a Protecting Group in Carbohydrate Chemistry.
`Part I1 la
`By Roy Gigg and C. D. Warren, National Institute for Medical Research, Mill Hill, London N.W.7
`Mercuric chloride in the presence of mercuric oxide was used to hydrolyse prop-1 -enyl ethers of carbohydrates.
`Under these non-acidic conditions, 4.6-U-benzylidene-D-galactose and 2,3-di-U-benzyl-4,6-U-benzylidene-D-
`galactose were prepared from the corresponding prop-1 -enyl glycosides and a mixture of the anomers of methyl
`2,3,6-tri-U-benzyl-D-glucofuranoside was prepared from the corresponding 5-U-prop-1 '-enyl ether. Acid-
`catalysed cyclisation of prop-1 '-enyl 4.6-U-benzylidene-a-D-galactopyranoside gave 4.6-U-benzylidene-l.2-U-
`propylidene-D-galactose which was converted into 1.2-U-propylidene-D-galactose. Preferential rearrangement
`of the 2-U-ally1 group in methyl 2.3-di-U-allyl-4.6-U-benzylidene- a-D-glucopyranoside gave methyl 3-O-allyl-
`4,6-0-benzylidene-2-U-prop-l'-enyl-cr-D-glucopyranoside which was converted into 4.6-U-benzylidene-2-0-
`methyl-a-D-glucopyranoside. The rearrangement of an allyl group to a prop-1 -enyl group in a carbohydrate
`derivative containing a benzamido-group occurred without hydrolysis of the amide linkage. The elimination of
`butadiene from 3-methylallyl (crotyl) ethers by the action of potassium t-butoxide in dimethyl sulphoxide suggests
`that the crotyl ether may provide a useful protecting group in carbohydrate chemistry. The action of potassium
`t-butoxide in dimethyl sulphoxide on an oxazoline derived from D-glucosamine produced a rearrangement to give
`an oxazole. The monoprop-I '-enyl ethers of 1.2-diols give 2'-chloromercuripropylidene acetals when treated with
`mercuric chloride in the presence of mercuric oxide. Reduction of these acetals with sodium borohydride re-
`generates monoprop-1 '-enyl ethers of the glycol.
`
`WE have previously described the application of the
`allyl ether as a protecting group in carbohydrate chem-
`istry and other workers have also used the method.
`We now report procedures for extending the use of this
`protecting group.
`The allyl group is conveniently removed by isomeris-
`ation 3 to the cis-prop-l-enyl group and subsequent acid
`hydrolysis, but in the case of carbohydrate derivatives
`containing other acid-labile groupings we have used la
`( a ) Part I , J. Gigg and R. Gigg, J . Chem. SOC. ( C ) , 1966, 82;
`(b) J. Cunningham, R. Gigg, and C. D. Warren, Tetrahedron
`Letters, 1964, 1191; (c) R. Gigg and C. D. Warren, J . Chem.
`SOC., 1965, 2205; ( d ) R. Gigg and C. D. Warren, Tetrahedron
`Letters, 1966, 2415.
`2 A. L. Bullock, V. 0. Cirino, and S. P. Rowland, Canad. J .
`Chem., 1967, 45, 255; S. J. Angyal and T. S. Stewart, Austral.
`J . Chem., 1966, 19, 1683; D. E. Hoiness, C. P. Wade, and S. P.
`Rowland, Abst. ,151st Meeting Amer. Clzem. SOC., 1966, ~ 2 1 .
`( a ) T. J. Prosser, J . Anzer. Chem. SOC., 1961, 83, 1701; (b)
`C. C. Price and W. H. Snyder, J . Amer. Chem. SOC., 1961, 83,
`1773.
`
`ozonolysis followed by alkaline hydrolysis or oxidation
`with alkaline permanganate for the selective removal
`of the prop-l-enyl group. As both of these methods
`suffer from disadvantages, a convenient non-acidicmethod
`was required and the reaction of mercuric chloride with
`the prop- 1 -en yl group was therefore investigated.
`The reaction of ionised mercuric salts (e.g., mercuric.
`acetate) with isolated ethylenic bonds is well docu-
`mented4 and they are also known to react with the
`double bonds of enol ether^.^,^ However, mercuric
`4 J. Chatt, Chem. Rev., 1951, 48, 7; A. Pol& and J. L.
`Jungnickel, Org. Analysis, 1956, 3, 301.
`A. N. Nesmeyanov, I. F. Lutsenko, and N. I. Vereshchagina,
`Bull. Acad. Sci. U.R.S.S., Classe sci. chim., 1947, 63 (Chem. Abs.,
`1948, 42, 4148); A. N. Nesmeyanov, I. F. Lutsenko, and
`R. M. Khomutov, Izvest. A kad. N a u k S.S.S.R., Otdel. khim. N a u k ,
`1957, 942 (Chem. Abs., 1958, 52, 4476).
`6 ( a ) J. B. Johnson and J. P. Fletcher, Analyt. Chem., 1959,
`31, 1563; (b) G. R. Inglis, J. C. P. Schwarz, and L. McLaren,
`J . Chem. SOC., 1962, 1014; (c) P. T. Manolopoulos, M. Mednick,
`and N. N. Lichtin, J . Amer. Chem. SOC., 1962, 84, 2203.
`
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`

`1904
`
`to be unreactive towards isolated
`chloride is reported
`double bonds. A very slow reaction of allyl ethers
`with mercuric chloride in the presence of mercuric
`oxide was observed in the present work. The very
`rapid reaction between mercuric chloride and vinyl
`ethers was probably first observed by Feulgen and his
`co-workers during histochemical studies on the plasma-
`logens. Although at that time Feulgen was unaware of
`the nature of the reaction, subsequent work has shown
`that the plasmalogens contain a vinyl ether linkage
`and the reaction has been rationalised as the hydrolysis
`(1) of a vinyl ether by mercuric chloride to give a chloro-
`mercurialdehyde.8
`R1-O-CH=CH-R2 + HgCl, + H,O -+
`RlOH + OHC-CH(HgC1)R2 + HC1
`(1)
`The very rapid rate of reaction of mercuric chloride
`with vinyl ethers and the very slow rate of reaction with
`isolated double bonds suggested that it would be a
`more useful reagent than mercuric acetate for our
`purposes and we reported9 the application of
`this
`method for the removal of the prop-l-enyl group from
`carbohydrate derivatives containing other acid-labile
`groupings. The hydrogen chloride liberated in the
`reaction was conveniently removed by yellow mercuric
`oxide. Excess of mercuric chloride was removed at the
`end of the reaction by washing a solution of the product
`in an organic solvent with aqueous potassium iodide.
`The chloromercuripropionaldehyde formed was degraded
`by this treatment producing some metallic mercury and
`a volatile unsaturated product which was not further
`investigated. 2-Chloromercuripropionaldehyde was iso-
`lated as an oil from the reaction between l-O-prop-
`1 '-enyl-2,3-O-isopropylideneglycerol10 and mercuric
`chloride. The product slowly crystallised and the solid
`had a similar m.p. to that reported l1 for this compound.
`Chloromercuriacetaldehyde was prepared from mercuric
`chloride and ethyl vinyl ether in the presence of mercuric
`oxide and this compound was also degraded by potas-
`sium iodide solution to metallic mercury. When a
`water-soluble product was obtained after the removal
`of the prop-l-enyl group the excess of mercuric chloride
`was removed by passage of hydrogen sulphide (with
`sodium hydrogen carbonate present to retain a neutral
`medium). The 2-chloromercuripropionaldehyde and
`chloromercuriacetaldehyde were also decomposed by this
`procedure.
`Initial experiments on the removal of the prop-l-enyl
`group were carried out on compounds containing other
`easily hydrolysable groupings and it was found that the
`labile isopropylidene groups in 1,2-O-isopropylidene-
`3-O-prop- 1 '-en ylglycerol lo and 1,2: 5,6-di-O-isopropyl-
`idene-3-0-prop-~'-enyl-~-g~ucofuranose
`la were stable to
`the conditions required for the removal of the prop-
`
`7 R. Feulgen and K. Voit, Pflugev's Arch. ges. Physiol., 1924,
`206, 389.
`8 W. T. Norton, Nature, 1959, 184, 1144.
`R. Gigg and C. D. Warren, Tetrahedron Lettevs, 1967, 1683.
`lo J. Cunningham and R. Gigg, J . Chem. SOC., 1965, 2968.
`
`J. Chem. SOC. (C), 1968
`1 -enyl groups by the mercuric chloride procedure.
`Of greater interest was the mercuric chloride hydrolysis
`of prop-l-enyl glycosides containing other acid-labile
`groupings since in this case neither acid hydrolysis nor
`oxidation with permanganate was applicable.
`Prop-1'-enyl 4,6-0-benzylidene-a-~-galactopyranoside
`(11) was prepared by the isomerisation of
`the ally1
`
`CH2.OH
`I
`
`(1-11) R = CH2Ph
`
`R2 = CH2-CH=CH2
`(I) R' = H ;
`R2 = CHyCH-CH,
`(11) R' = H ;
`(111) R' = R2 = H
`(IV) R' = CH2Ph;
`R2 = CH2--CH=CH2
`(I-) R1 = CH,Ph;
`R2 = CH=CH-CH,
`R2 = H
`(VI) R' = CH,Ph;
`
`CH2.OH
`
`;:fH
`
`(VIII) R = H
`(IX) R = AC
`
`O-CHEt
`(X) R = H
`(XI) R = CH2Ph
`
`CH2.OR
`(XII) R = CH2Ph
`
`CH~.OR'
`
`(XIII) R1 = CPh,;
`R2 = H
`(XI\') RL = CPh,;
`R2 = CH2-CH=CH2
`
`(Sly) R' = H ;
`R2 = CH2-CH=CH,
`(XVI) R' = CH2Ph;
`R2 = CH,CH=CI-T.,
`(SVII) R' = CH2Ph;
`R2 = CH=CH-CH,
`(XVIII) R' = CH,Ph; R2 = H
`(XIX) R2 = CH,Ph; R2 = Me
`glycoside (I) which was prepared from allyl ceD-galaCtO-
`pyranoside12 by the action of benzaldehyde in the
`presence of zinc chloride. Compound (11) was rapidly
`into 4,6-0-benzylidine-~-galactose (111) l3
`converted
`by the mercuric chloride procedure and a by-product
`which was considered to be the 2-chloromercuripropy1-
`idene acetal was also formed at the same time (see below).
`Similarly the dibenzyl ether (V) was converted into the
`free sugar (VI) by these conditions without loss of the
`
`11 D. Y. CurtinandM. J. Hurwitz, J . Amer. Ghem. SOC., 1952,
`74, 5381.
`12 E. A. Talley, M. D. Vale, and E. E'anovsky, J . Amev. Chew.
`SOC., 1945, 67, 2037.
`l3 ( a ) J. Pacbk and M. tern?, Coll. Czech. Chew?. Comm., 1961,
`26, 2212; 1963, 28, 541; (b) E. G. Gros and V. Deulofeu, Cheni.
`and Ind., 1962, 1502.
`
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`

`' OR2
`
`R, = H
`(XX) R' =
`R2 = CH,CH=CH,
`(XXI) R' =
`R2 = CH=CH-CH,,
`(XXII) R' =
`CH2-CH=CH2; R2 = CH=CH-CH,
`(XXIII) R' =
`CH2CH=CH2; R2 = H
`(XXIV) R1 =
`CHXH-CH,; R2 = H
`(XXV) R' =
`
`(XXVI) R' = CH=CH-CH,; R2 = Me
`(XXVII) R' =
`H; R 2 = M e
`
`(XXVIII) R' = CH=CH-CH,; R2 = CH2-CH=CH,
`(XXIX) R'=
`H ; R2 = CH2-CH=CH,
`(XXX) R' =
`H; R2 = CH=CH-CH,
`Me; R2 = CH=CH-CH,
`(XXXI) R1 =
`(XXXII) R' = Me; R2 = I-I
`
`
`1905
`ment to a monoallyl monopropenyl derivative occurred
`fairly rapidly and the product was isolated at this stage.
`The subsequent discussion will show that the product
`was compound (XXIII). The prop-l-enyl group was
`removed from this compound by mercuric chloride with-
`out affecting the allyl group to give compound (XXIV)
`which was isomerised to compound (XXV) and methyl-
`ated to give compound (XXVI). Hydrolysis of the
`prop-l-enyl group in compound (XXVI) with mercuric
`
`Org .
`benzylidene group. The free sugar (VI) was reduced
`by sodium borohydride to give 2,3-di-O-benzyl-4,6-0-
`benzylidene-D-galactitol (VII) which was required as an
`intermediate for synthetic studies in connection with the
`sphingolipids. Acid hydrolysis and subsequent catalytic
`hydrogenation of compound (VII) gave galactitol.
`Monovinyl ethers of 1,2-diols are rapidly cyclised to
`acetals in the presence of acidic catalysts l4 and it was
`considered that the prop-l-enyl ethers of carbohydrates
`might be cyclised similarly in appropriate cases to give
`useful synthetic intermediates.
`In compound (11)
`the C(2) hydroxyl group is in a suitable position for
`acetal formation and this compound was cyclised to
`the acetal (VIII) by heating in ethyl acetate with an
`acid catalyst. Catalytic hydrogenation of compound
`(VIII) gave crystalline 1 ,2-0-propylidene-D-galactose
`(X) which was characterised by conversion into the tri-
`O-benzyl ether (XI) followed by acid hydrolysis and
`sodium borohydride reduction
`to give 3,4,6-tri-O-
`benzyl-D-galactitol (XII) which was identical with
`the material which has been prepared and characterised
`previous1y.l"
`the anomers of methyl 2,3,6-tri-0-
`A mixture of
`benzyl-D-glucofuranoside (XVIII) was required as an
`intermediate for synthetic studies in connection with the
`sphingolipids and a route to this compound by use of the
`allyl ether was investigated. The triphenylmethyl ether
`(XIII) was converted into the allyl ether (XIV) and
`the product was hydrolysed with methanolic hydrogen
`chloride to give a mixture of the anomers of methyl
`N-- Ph
`5-0-allyl-3-O-benzyl-~-glucofuranoside (XV) . After
`NH-COPh
`benzylation and removal of the allyl group by isomeris-
`(XXXVI) R = CH,CH=CH,
`(XXXIII) R = H
`(XXXVII) R = CH=CH-CH,
`(XXXIV) R = CH,Ph
`ation and mercuric chloride hydrolysis the required
`(XXXV) R = CH2CH=CH2 (XXXVIII) R = H
`compound (XVIII) was obtained in good yield as a
`syrup. This compound was characterised by methyl-
`chloride gave methyl 4,6-0-benzylidene-2-O-methyl-a-~-
`ation, followed by catalytic hydrogenation and acid
`glucopyranoside (XXVII) with the same m.p. as re-
`hydrolysis to give the known 5-O-methyl-~-glucofuran-
`ported previously 18 for this compound. Allylation of the
`ose which was converted into the crystalline 3,6-di-0-
`prop-l-enyl ether (XXV) gave the isomeric allyl prop-
`acetyld-O-methyl-lJ2 J-O-isopropylidene-~-glucofuran-
`l-enyl ether (XXVIII) which was hydrolysed with
`ose.I6
`mercuric chloride to give the 2-0-ally1 ether (XXIX).
`Brimacombe and his co-workers recently described l7
`Isomerisation of compound (XXIX) followed by methyl-
`the rearrangement of methyl 2,3-di-O-ally1-4,6-O-benzyl-
`ation and removal of the prop-l-enyl group gave 4,6-0-
`idene-a-D-glucopyranoside (XXI) to the di-O-prop-
`benzylidene-3-0-methyl-a-~-glucopyranoside (XXXII)
`l-enyl ether (XXII). The yield of compound (XXII)
`with the same properties as those reported18b,l9 for
`reported was very low (ca. 4%) and we have therefore
`this material. Since the isomeric allyl ethers (XXIV)
`reinvestigated the rearrangement of compound (XXI) .
`and (XXIX) were resolved by t.1.c. and only compound
`At 100" the rearrangement to the di-0-prop-l-enyl
`(XXIV) was observed after the hydrolysis of the initial
`derivative (XXII) was complete within 40 min. as ob-
`product, this indicates that the initial product was not a
`served by t.1.c. and the product was readily hydrolysed
`mixture of compounds (XXIII) and (XXVIII).
`to methyl 4,6-O-benzylidene-a-~-glucopyranoside (XX)
`In order to use the allyl ether as a protecting group in
`by mercuric chloride. When compound (XXI) was
`the amino-sugar series it was necessary to show that the
`rearranged at 40°, t.1.c. showed that a partial rearrange-
`amido-group was stable to the strongly basic conditions
`of the isomerisation. For this purpose the allyl ether
`18 (a) E. J. Bourne, A. J. Huggard, and J. C. Tatlow, J . Chem.
`SOL, 1953, 735; (b) E. J. Bourne, M. Stacey, C. E. M. Tatlow,
`and J. C. Tatlow, J . Chem. Soc., 1951, 826.
`l9 (a) I<. S. Ennor and J. Honeyman, J . Chem. Soc., 1958,
`2586; (b) A. F. Krasso, E. Weiss, and T. Reichstein, Helv. Chim.
`A d a , 1963, 46, 2538; (c) H. R. Bollinger and D. A. Prins, Helv.
`Chirn. Acta, 1945, 28, 465.
`
`Me2C\' 'yHz
`
`0-
`
`l4 H. S. Hill and L. M. Pidgeon, J . Amer. Chem. SOC., 1928, 50,
`27 18.
`l5 R. E. Gramera, R. M. Bruce, S. Hirase, and R. L. Whistler,
`J . Org. Chem., 1963, 28, 1401.
`l6 (a) L. v. Vargha, Ber., 1936, 69, 2098; (b) 0. T. Schmidt,
`G. Zinke-Allmang, and U. Holzach, Chem. Bey., 1957, 90, 1331.
`l7 J. S. Brimacombe, B. D. Jones, M. Stacey, and J. J. Willard,
`Carbohydrate Res., 1966, 2, 167.
`
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`

`1906
`(XXXV) was hydrolysed by methanolic hydrogen
`chloride, under the very mild conditions described pre-
`viously,20a to give the methyl glycoside (XXXVI)
`and this compound was isomerised to the prop-l-enyl
`ether (XXXVII) without evidence of decomposition of
`the amide linkage. Hydrolysis of
`the prop-l-enyl
`group in compound (XXXVII) by mercuric chloride gave
`compound (XXXVIII) which was identical with the
`material obtained by the direct methanolysis of the
`oxazoline (XXXIII)
`Compound (XXXV) was
`treated with potassium t-butoxide in dimethyl sulphoxide
`
`. 2 0 a j b
`
`HO
`
`R1o$ORz
`
`(XXXIX) R1 = CH,-CH=CH2; RZ = H
`(XL) R' = CH=CH-CH,; R2 = H
`(XLI) R1 = CH=CH-CH3 ; R2 = AC
`(XLII) R1 = H ; R2 = AC
`(XLIII) R1 = R2 = H
`
`H
`OH C
`
`(XLV)
`
`, OCH2
`
`I Me2c'ob?
`
`J. Chem. SOC. (C), 1968
`material (XXXV) ; thus under the normal conditions
`of the rearrangement (100"/15 min.) it appeared that no
`reaction had occurred. The rearrangement of compound
`(XXXV) presumably occurs by removal of the proton
`at C(4) of the oxazoline ring, under the strongly basic
`conditions, with concomitant rupture of the 0-C bond
`of the furanose ring to give the oxazole (XXXIX).
`This reaction is followed by a normal rearrangement of
`the allyl ether to give the prop-l-enyl ether (XL). The
`structure of
`the crystalline compound
`(XL) was
`established by conversion to a crystalline acetate
`(XLI) followed by hydrolysis of the prop-l-enyl group
`with mercuric chloride and basic hydrolysis of the acetate
`group to give the crystalline diol (XLIII). Oxidation
`of this diol with sodium metaperiodate gave crystalline
`4-formyl-2-phenyloxazole (XLV) with the properties
`reported previously.21 Basic hydrolysis of compound
`(XLV) gave benzamidomalondialdehyde as reported.21
`Hydrolysis of the diol (XLIII) or of the prop-l-enyl
`ether (XL) with acid gave the oxazole (XLIV) derived
`from 2-benzamido-2-deoxy-~-glucose. The lability of
`the proton in the 4-position of 2-phenyloxazolines in the
`presence of potassium t-butoxide in dimethyl sulphoxide
`suggests that isomerisations might occur in other
`carbohydrate derivatives containing this grouping under
`these conditions and this subject is being investigated
`further.
`Isomerisations at the 4-position of 2-phenyl-
`oxazolines under milder basic conditions have been
`observed with derivatives of 4-ethoxycarbonyl-2-phenyl-
`oxazoline. 22
`When compound (XL) was treated with mercuric
`chloride in an attempt to remove the prop-l-enyl group,
`the major product was the chloromercuripropylidene
`derivative (XLVI) and only a small amount of the diol
`(XLIII) was formed. Compound (XLVI) was converted
`into the crystalline iodomercuri-derivative (XLVII)
`after washing a solution of the product with potassium
`iodide solution, In an attempt to prepgre the propyl-
`idene acetal (XLVIII) , compound (XLVII) was reduced
`with sodium borohydride as described previously 6b923
`for the replacement of
`the chloromercuri-group by
`hydrogen. The product was mainly a monoprop-l-enyl
`ether of the diol (XLIII) which cochromatographed with
`compound (XL). However, only a small amount of
`the crystalline compound (XL) was obtained from
`the product and it is assumed that a mixture of the
`cis- and trans-isomers of compound (XL) was produced
`whereas in the isomerisation which produced com-
`pound (XL) from the allyl ether only the cis-isomer is
`produced.3 The mechanism of the action of sodium
`borohydride with the 2-iodomercuripropylidene deriv-
`ative is presumably similar to the action14*24 of alkali
`23 H. B. Henbest and B. Nicholls, J . Chem. SOC., 1959, 227;
`H. B. Henbest and R. S. McElhinney, J . Chem. SOC., 1959, 1834.
`24 (a) J. Wislicenus, Annalen, 1878, 192, 106; H. S. Hill, J .
`Amer. Chem. SOC., 1928, 50, 2725; J. F. Arens and D. A. van
`Dorp, Rec. Trav. chim., 1946, 65, 729; C. Piantadosi, A. F.
`Hirsch, C. L. Yarbro, and C. E. Anderson, J . Org. C h m . , 1963,
`28, 2425; (b) J. C. Craig and D. P. G. Hamon, ibid., 1965, 30,
`4168; (c) J. C. Craig, D. P. G. Hamon, H. W. Brewer, and H.
`Harle, ibid., 1965, 30, 907.
`
`.f OlCMe,
`
`CH2.0
`(XLVI) R = CH(HgC1)CH3
`(XLVII) R = CH(HgI)CH3
`(XLVIII) R = CH2CH3
`
`CH2.0.CH2-CH: CHMe
`I
`
`
`CHO \ CMe2
`
`CH2-O'
`(LIII)
`
`0 - C Me2
`(XLIX) R = CH2-C(Me)=CH2
`(L) R = CH=CMe2
`(LI) R = CH2-CH=CH2
`(LII) R = CH2-CH=CH-CH3
`to investigate the stability of the oxazoline ring in carbo-
`hydrate derivatives to the isomerisation conditions.
`At 20" a reaction to a more slowly moving compound
`(XXXIX) was observed by t.1.c. At 50" compound
`(XXXIX) was slowly converted into compound (XL)
`which had the same mobility on t.1.c. as the starting
`2o (a) S. Konstas, I. Photaki, and L. Zervas, Chem. Ber., 1959,
`92, 1288; (b) R. Gigg and C. D. Warren, J . Chem. SOC., 1965,
`1351; (c) B. Lindberg and H. Agback, Acta Chem. Scand., 1964,
`18, 185.
`21 J. W. Cornforth, E. Fawaz, L. J. Goldsworthy, and R.
`Robinson, J . Chem. SOC., 1949, 1549.
`22 D. F. Elliott, J . Chem. SOC., 1949, 589; 1950, 62; E. E.
`Hamel and E. P. Painter, J . Amer. Chem. SOC., 1953, 75, 1362;
`H. E. Carter, J. B. Harrison, and D. Shapiro, J . Amer. Chem.
`SOC., 1953, 75, 4705.
`
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`

`Org .
`In the
`metals on 2-halogenoalkylidene acetals of diols.
`latter reaction a mixture of cis- and trans-isomers of the
`two possible vinyl ethers is produced.rn3C The simple
`addition products of mercuric salts with olefins in alcohols
`can also be reduced with hydrazine or with sodium in
`ethanol to give some of the original olefin.%
`The 2-methylallyl ether (XLIX) of 1,2:5,6-di-O-iso-
`propyhdene-D-glucofuranose was prepared and the rates
`of isomerisation of this compound and of the allyl ether
`(LI) were compared. The allyl ether was isomerised
`about twenty times more quickly than compound
`(XLIX) which was converted into the crystalline ether
`(L) *
`We have shownlo that y-substituted allyl ethers are
`eliminated to give dienes by treatment with potassium
`t-butoxide in dimethyl sulphoxide and this has been
`confirmed by others.25 The action of these basic con-
`ditions on the 3-methylallyl (crotyl) ether (LII) 26 of
`1,2:5,6-di-O-isopropylidene-~-glucofuranose was investi-
`gated. At 50" elimination was complete in 1 hr. whilst
`at 20" elimination was complete in 30 hr. The same
`behaviour was observed with the crotyl ether (LIII)
`although a previous report 24b indicated that this com-
`pound was stable to these conditions. The ease of
`elimination of butadiene from the ether (LII) indicates
`that the crotyl ether should provide a further useful
`protecting group in the carbohydrate series and this
`subject is being investigated.
`
`C
`
`EXPERIMENTAL
`T.1.c. was as described previously.1° Light petroleum
`had b.p. 40-60" unless otherwise stated. Specific rotations
`were measured a t 22-24" on a Bendix Automatic Polari-
`meter. Solvents were evaporated under reduced pressure.
`Action of Mercuric Chloride-Mercuric Oxide on 3-0-Prop-
`
`1 ',enyl- 1,2: 5,6-di-O-isopro~ylidene-~-glucofuranose and 3-0-
`A llyl- 1,2: 5,6-di-O-isopropylidene-~-glucofuranose (General
`Procedure for the Hydrolysis of Prop-l-enyl Ethers by Mer-
`solution of mercuric chloride (900 mg.,
`curic Clzloride) .-A
`3.3 mmoles) in acetone-water (10: 1, 10 ml.) was added
`dropwise with stirring to a mixture of 3-O-prop-l'-enyl-
`1,2:5,6-di-O-isopropylidene-~-glucofuranose
`la (1 g., 3.3
`mmoles), yellow mercuric oxide (900 mg.), and acetone-
`water (10 : 1, 30 ml.) during 3 min. When the addition was
`complete, t.1.c. (ether-light petroleum, 3 : 1) showed com-
`plete conversion of the starting material (Rf 0.9) into the
`product (Rf 0.58) and 2-chloromercuripropionaldehyde
`(R, 0.1) (detected with the potassium permanganate
`spray lo). The mercuric oxide was removed by filtration
`through Celite, the acetone was evaporated, and ether was
`added to the residue. The ether layer was washed with a
`semisaturated aqueous solution of potassium iodide (10
`ml.), dried (K,CO,), and the solvent evaporated. Recrystall-
`isation of the residue from cyclohexane gave 1,2: 5,6-di-0-
`isopropylidene-D-glucofuranose (800 mg.), m.p. and mixed
`m.p. 108-110".
`In smaller scale reactions the mercuric
`oxide was not removed but the acetone was evaporated
`25 G. Kesslin and C. M. Orlando, J . Org. Chem., 1966, 31, 2682;
`G. M. Mkryan, N. A. Papazyan, and A. A. Pogosyan, Z h w . ovg.
`Khim., 1967, 3, 1160 (Chem. Abs., 1967, 67, 90,349).
`26 W. M. Corbett and J. E. McKay, J . Chem. SOC., 1961, 2930.
`
`1907
`
`and a mixture of the residue with ether was washed directly
`with potassium iodide solution which dissolved all of the
`mercury derivatives.
`When 3-O-allyl- 1,2: 5,6-di-O-isopropylidene-~-glucofuran-
`ose was subjected to the same treatment, t.1.c. (ether-
`light petroleum, 1 : 1) showed no reaction of the starting
`material (Rf 0.7) until 30 min. after the addition of the
`mercuric chloride whereupon a trace of product (Rf 0.1)
`was detected. After 60 hr. the starting material was
`completely converted into the product (Rf 0.1) which was
`not further investigated.
`Ally1 4,6-O-Benzylidene-a-~-galactopyranoside (I) (with
`J. GIGG) .-A mixture of allyl a-D-galactopyranoside l2
`(50 g.), anhydrous zinc chloride (50 g.), and benzaldehyde
`(100 ml.) was stirred a t room temperature for 3 hr. and then
`poured with stirring into a mixture of ice-water and light
`petroleum. The solid product was filtered off, washed with
`light petroleum, and dissolved in chloroform. The solution
`was dried (K,CO,), the solvent evaporated, and the crude
`product (70 g.) triturated with light petroleum to remove
`benzaldehyde. Recrystallisation from ethyl acetate-
`light petroleum gave the product, m.p. 115-117",
`[a],
`+121"
`(c 1.9 in CHC1,) [Found: C, 60.45; H, 6.5.
`(C,,H,,O,),,H,O
`requires C, 60.5; H, 6 ~ 7 x 1 (Found, after
`drying at 100" under high vacuum for 3 hr. : C, 62.1 ; H,
`6.6. C16H200, requires C, 62.3; H, 6.5%).
`Prop- 1 '-enyl 4,6-O-Benzylidene-a-~-galactopyranoside (11)
`(with J. GIGG).-The allyl galactoside (I) (20 g.) was isomer-
`ised with potassium t-butoxide (20 g.) in dry dimethyl
`sulphoxide (100 ml.) a t 100" for 2 hr. whereupon t.1.c.
`(ethyl acetate) showed complete conversion of the starting
`material (Rf 0.7) into the product (Rf 0.8). After addition
`of water and extraction with ether, the product (19 g.)
`was recrystallised from ethyl acetate-light petroleum,
`and had m.p. 114-115", [a], +58" (G 1 in CHCl,) (Found:
`C, 58.9; H, 6.8. C16H200,,H20 requires C, 58-9; H, 6.8%).
`The diacetate was prepared by the action of acetic anhydride
`in pyridine and when recrystallised from ethyl acetate-
`light petroleum had m.p. 165", [a], +207" (c 1 in CHC1,)
`(Found: C, 61.0; H, 6.1. C,OH2408 requires C, 61-2;
`H, 6.2%).
`prop- 1 -
`1,2-O-~ro~y~idene-~-ga~acto~yranose
`(X) .-The
`enyl galactoside (11) (7.5 g.) was fused under high vacuum
`and dried for 5 hr. a t 120", then dissolved in dry ethyl
`acetate (50 ml.) and anhydrous toluene-9-sulphonic acid
`(50 mg.) was added. After heating under reflux for 3 hr.,
`t.1.c. (ether) showed conversion of the starting material
`(Rf 0.4) into a product (Rf 0.8). After neutralisation of the
`acid (K,CO,) and evaporation of the solvent the crude
`product was chromatographed on alumina and elution
`with ethyl acetate gave 4,6-O-benzylidene- 1,2-O-propyl-
`idene-D-galactopyranose (VIII) (4.3 g.) as a syrup which
`gave a non-crystalline acetate (IX), [a], -54"
`(c 0.4 in
`CHCl,) (Found: C, 61.4; H, 6-2. C18H220, requires C,
`61-7; H, 6.3%). Compound (VIII) (2 g.) was hydrogenated
`in glacial acetic acid a t atmospheric pressure in the presence
`of palladium-charcoal until uptake was complete. After
`evaporation of the solvent the residue was recrystallised
`from ethyl acetate to give 1,2-0-propylidene-~-galacto-
`pyranose (X) (0.8 g.) as needles, m.p. 115-116",
`[a],
`+93*2" (c 0.75 in MeOH) (Found: C, 49.0; H, 7.2.
`requires C, 49.1; H, 7.3%). Acetylation with
`C,H,,O,
`acetic anhydride and pyridine gave the triacetate as a
`syrup [a], +96.8" (c 0.6 in CHC1,) (Found: C, 52-1 ; H,
`6.4. C,,H,,O,
`requires C, 52.0; H, 6.4%).
`
`Published on 01 January 1968. Purchased by adrienne.stephens@knobbe.com on 31 July 2017.
`
`View Article Online
`
`

`

`J. Chem. SOC. (C), 1968
`
`3,4,6-Trz-O-benzyl-~-gaZactdol (XII) .-
`(chloroform-ethyl acetate, 1 : 2) showed complete conversion
`1,2-O-Propyl-
`idene-D-galactopyranose (X) (150 mg.) was benzylated with
`the starting material (RR~ 0.7) into 2,3-di-O-benzyl-
`of
`sodium hydride and benzyl chloride in refluxing benzene
`D-galactitol (Rf 0.2) which was obtained as a syrup after
`until t.1.c. (ether-light petroleum, 1 : I) showed complete
`neutralisation (BaCO,) and evaporation of the solution.
`conversion into the tri-O-benzyl ether (XI) (Rp 0.85).
`The syrup was dissolved in glacial acetic acid and hydrogen-
`The excess of sodium hydride was decomposed by the ad-
`ated at atmospheric pressure over palladium-charcoal
`dition of methanol and the benzene solution was washed
`until uptake was complete. The catalyst was filtered off
`with water and dried (MgSO,). Evaporation of the solvents
`and washed with water. Evaporation of the filtrate gave a
`gave compound (XI) as a syrup which was hydrolysed in
`solid residue which was recrystallised from glacial acetic
`dioxan-N-sulphuric acid (5 : 1) until t.1.c. showed that
`acid to give galactitol, m.p. and mixed m.p. 186-188"
`hydrolysis to the free sugar was complete (Rp 0.4 in ether).
`(lit.,27 m.p. 185-186").
`Methyl 4,6-O-BenzyZzdene-2,3-d~-O-pvop-l'-enyl-a-~-gluco-
`The acid was neutralised (BaCO,), the solvent evaporated,
`pyranoside (XXII).-The di-O-ally1 ether (XXI) 17 (2 g.)
`and the crude product was chromatographed on neutral
`alumina. After removal of impurities by elution with
`was treated with potassium t-butoxide (2 g.) in dimethyl
`(10 : 1) the 3,4,6-tri-O-benzyl-~-galacto-
`ether-methanol
`sulphoxide (50 ml.) a t 100" for 40 rnin. whereupon t.1.c.
`pyranose la (200 mg.) was obtained as a syrup by elution
`(ether-light petroleum, 1 : 2) showed conversion of
`the
`starting material (Rf 0.4) into the di-O-prop-l-enyl ether
`with methanol. This was reduced with sodium borohydride
`in ethanol at room temperature for 8 hr. Glacial acetic
`(Rf 0.6). After dilution with water and extraction with
`acid was added and the solvent was evaporated. Several
`ether the product was recrystallised from light petroleum
`portions of methanol were evaporated from the residue to
`to give needles (1.35 g.), m.p. 99-loo",
`[a], +90" (e 1 in
`remove boric acid and water was added to the residue and
`CHC1,) (Found: C, 66-0; H, 6.95. Calc. for C2,H2,06
`the product filtered off. Recrystallisation from ethyl
`C, 66.3; H, 7.2%) [lit.,17 m.p. 94-95, [a],23 +41° f 5"
`acetate-light petroleum gave 3,4,6-tri-O-benzyl-~-galactitol
`(e 0.024 in CHCl,)]. The prop-l-enyl groups were removed
`(120 ing.), m.p. and mixed m.p. with material prepared
`with mercuric chloride and the product isolated as described
`(Found: C, 71.5; H, 7.0. Calc. for
`above to give methyl 4,6-O-benzylidene-a-~-glucopyrano-
`previously la 98-100"
`C27H3206 C, 71-6; H, 7-17;).
`side (80%), m.p. and mixed m.p. 158-159".
`Ally1 2,3-Di-O-benzy1-4,6-0-beiazylidene-u-~-gaEactopyrano-
`Met?iyl 3-0-Allyl-4,6-O-beu2zylzdine-a-~-glucopy~anoside
`side (IV).-Compound
`(I) (3 g.) was benzylated with
`(XXIV).-The di-O-ally1 ether (XXI) (1 g.) in dimethyl
`powdered sodium hydroxide and benzyl chloride until
`sulphoxide (10 ml.) with potassium t-butoxide (0.5 g.) was
`t.1.c. (ether-light petroleum, 1 : 1) showed complete con-
`kept a t 40" and the reaction followed by t.1.c. (ether-
`version into the di-O-benzyl ether (Rf 0.6). After washing
`light petroleum, 1 : 1). After 30 min. there was a major
`with water and drying and evaporation of the solvent,
`product ( R f 0.55) together with traces of starting material
`the residue was recrystallised from light petroleum (b.p.
`( R f 0.4) and di-O-prop-l-enyl ether (Rf 0.6). Water was
`to give the product (IV) (3-8 8.) as plates, 1n.p.
`80-100°)
`added and the product (0.95 g.) was extracted with ether
`[a], 3-82-4" (c 1 in CHCl,) (Found: C, 73.9;
`123-125",
`and treated with mercuric chloride as described above.
`H, 6-6. C,,,H,,06
`requires C, 73-75; H, 6.6%).
`T.1.c. (ether) showed complete removal of the prop- l-enyl
`Prop-1'-enyl 2,3-Di-O-benzy1-4,6-O-benzylidene-a-~-galac-
`groups to give a major product (I?, 0.7) and traces (Rf
`topyranoside (V) .-Compound
`(IV) (3 g.) was isomerised
`0.2 and 0.95). Chromatography on alumina and elution
`with potassium t-butoxide in dimethyl sulphoxide as de-
`with ether removed the material Iif 0.95 (compound XXI)
`scribed previously la until t.1.c. (ether-light petroleum, 1 : 1)
`and further elution with ether-methanol (50 : 1) gave the
`major product (Rf 0-7) (0.54 g.). This compound was
`showed complete conversion of the starting material (Rf
`0.6) into the product (Rf 0.7). After dilution with water
`recrystallised from methanol to give cowpound (XXIV),
`and extraction with ether the product (2.5 g.) was recrystall-
`[u], +104O (c 0.7 in CHC1,) (Found: C,
`m.p. 154-155",
`ised from light petroleum (b.p. 60-80°) and had m.p.
`63-3; H, 6.7. C1,H2,06 requires C, 63.3; H, 6.9%).
`[u], +81" (c 1 in CHC1,) (Found: C, 73.7; H,
`122-124",
`Compound (XXIV) (1.5 g.) was isomerised as described
`6-4. C3,H3,06 requires C, 73.75; H, 6.6%).
`previously
`and the product was recrystallised from
`(VI) .
`2,3-