Glucal chlorination

On treatment of tri-O-acetyl-D-glucal with chlorine and silver fluoride,198 all four possible isomers were formed tri-0-acetyl-2-chloro-2-deoxy-a-D-mannopyranosyl fluoride (16%), tri-0-acetyl-2-chloro-2-deoxy-/3-D-mannopyranosyl fluoride (16%), tri-0-acetyl-2-chloro-2-deoxy-a-D-glucopyranosyl fluoride (6%), and tri-O-acetyl-2-chloro-2-deoxy-/3-D-glucopyranosyl fluoride (62%). These product ratios differ significantly from those of the corresponding bromofluorination and iodofluorination reactions of tri-O -ace tyl-D-glucal,43,53 and this behavior has been discussed198 in terms of the differences observed between the addition of bromine (or iodine) and chlorine to tri-O-acetyl-D-glu-cal, and the nature of the chlorination reaction itself. 

Tri-0-acetyl-l,5-anhydro-2-deoxy-D-arabino-hex-l-enitol (tri-O-acetyl-D-glucal) was the starting point for the synthesis of 1,5-anhy-dro-2-chloro-2-deoxy-D-glucitol or -D-mannitol by way of the 1,2-dichloride (22), which was reduced32 by means of lithium aluminum hydride to the 2-chloro-2-deoxy derivative (23). That the chlorine... 

Other methods of introducing amino substituents at C-2 by glycal additions include the use of the (saltmen)Mn(N) complex and trifluoroacetic anhydride,51 and the photochemical addition of Ar-chloro-chloroacetamide.52 In both cases tri-O-acetyl-D-glucal gives 2-amino-2-deoxy-D-glucose adducts, in the former case with the hydroxyl group at C-l, and in the latter with chlorine which can be displaced by alkoxy at that position. 

Besides the D-glucose derivative just described, three other crystalline dichlorides have been prepared from 2-hydroxyglycals, namely, the dichlorides from 2,3,4,6-tetra-0-benzoyl-(2-hydroxy-D-glucal)10 (yield, 22%), 2,3,6,2, 3, 4, 6,-hepta-0-acetyl-(2-hydroxycellobial)IS (yield, 30%), and 2,3,4-tri-0-benzoyl-(2-hydroxy-D-xylal)12 (yield, 17%). The 2,3,4,6-tetra-0-benzoyl-l,2-dichloro-l-deoxy-D-hexose prepared from the first of these by short chlorination in benzene reacted with sodium acetate in hot, glacial acetic acid. The crystalline product was assigned the structure of l-0-acetyl-3,4,6-tri-0-benzoyl-D-glucosone10 since it is not converted to kojic acid by pyridine-acetic anhydride (see below). A benzoyl group has been lost. 

Osone hydrates have been prepared from 2,3,4,6-tetra-0-acetyl-(2-hydroxy-D-glucal)1 and from the corresponding derivatives of 2-hydroxy-D-galactal,9 2-hydroxyceIlobial13 and 2-hydroxygentiobial.13 Hydrolysis of the dichloride may be effected simply by the addition of a little water to its solution in ether or benzene, but more often silver carbonate or sodium bicarbonate is added to neutralize the hydrogen chloride produced. Sodium and potassium carbonate are too alkaline and result in yellowing of the reaction mixture. A yield of 90% of the theoretical amount of osone hydrate was obtained from the crystalline dichloride derived from D-glu-cose. However, the crystalline dichloride derived from cellobiose resisted hydrolysis (see the previous Section). Nevertheless, the cellobiosone hydrate was prepared from the sirupy mother liquor. In any case, yields on the basis of the entire, chlorinated substances were low.1613... 

In a previous Section it was noted that the hydrolysis product from chlorinated 2,3,4,6-tetra-0-benzoyl-(2-hydroxy-D-glucal) and several substances derived therefrom also underwent conversion to di-O-benzoylkojic acid. 

Unidentified chlorination product of 2,3,4,6-tetra-0-acetyl-(2-hydroxy-D-glucal) 136... 

Chlorine can add to the double bond in triacetyl-D-glucal in a manner similar to that of bromine.311 The resulting dichlorides (XIV) have more tendency to crystallize than the dibromides. However, many of the... 

A method using silver(I) fluoride and chlorine is sufficiently mild for the isolation of the chlorine fluoride adducts in good yield, whereas the combination of IV-chlorosuccinimide and hydrogen fluoride gives no fluorinated products. The reaction of chlorine with a suspension of D-glucal triacetate and silver(I) fluoride in an acetonitrile/benzene solution is unusual in that it gives all four possible 3,4,6-tri-0-acetyl-2-chloro-2-deoxy-D-glycopyranosyl fluorides... 

Addition of dichlorocarbene, produced by treatment of ethyl tri-chloroacetate with sodium methoxide, to 3,4,6-tri-O-methyl-D-glucal gave, apparently, one product (gas-chromatographic analysis) in 82% yield. By stereochemical analogy with epoxidations, the product was considered to be l,5-anhydro-2-deoxy-l,2-C-(dichloromethylene)-3,4,6-tri-O-methyl-D-g/j/cero-D-ido-hexitol (21). Demethylation was brought about with boron trichloride at—70°, to give atriol from which a crystalline tribenzoate was obtained and reaction with lithium aluminum hydride caused reductive cleavage of the carbon-chlorine bonds.36 A similar addition was applied to 3,4-unsaturated furanosyl compound (see p. 247). 

Recent publications in this field have reported a thorough investigation of the addition of bromine and chlorine to tri-O-acetyl-n-glucal and -D-galactal, and the isolation, after thin-layer chromatographic separation, of the a-ji-gluco and a-D-manno products of chlorination of tri-O-acetyl-n-glucal. ... 

The adducts of tri-O-acetyl-n-glucal with bromine or chlorine react with aryl Grignard compounds, to give products which, by analogy with those... 

The chlorination of 2,3,4,6-tetra-0-benzoyl-2-hydroxy-D-glucal (138) has been mentioned in Chapter 7. Further work established that the 2-chloro-l,2-benz-oxonium salt formed on low-temperature (— 30 °C) chlorination of (138) is readily hydrolysed to the glycosulose (316), which readily eliminated benzoic acid to give the enolone (317 R = OBz) on heating with sodium hydrogencarbonate in wet toluene. The enolone (317 R = OBz) afforded a-haloenolones (317 R = Cl... 

Preparative TLC has afforded the two pure isomeric dichlorides obtained by addition of chlorine to tri-O-acetyl-D-glucal. The capacity of silica gel G plates is favorable for preparative purposes. The 250 [x thick layers (20 x 20 cm plate) permitted separation of 25 mg of the mixture of dichlorides with the solvent toluene-ether (67 + 33) [89]. Tate and Bishop [84] report the separation of up to 100 mg of the benzylated sugars on one plate. 

Methylenecyclohexane is an example of an alkene that adds an electrophile to give a stable cationic intermediate, and with tri-O-acetyl-o-glucal and tin(IV) bromide as catalyst it gives the diene indicated in Scheme 10 stereospecificaUy in 94% yield. On the other hand, reaction of methylenecyclobutane (EtAlCl2 as catalyst) results in the chlorinated adduct 46, since the ionic reaction intermediate favours addition rather than elimination [39]. 

An improved synthesis of the 2-acetamido-D-glucal derivative (216) has been described (Scheme 83). The chlorination of 2,3,4,6-tetra-0-benzoyl-2-hydroxy-D-glucal is discussed in Chapter 7. 

The stereoselectivity of formation of l,2-dideoxy-l,2-dihalogeno-a-D-gluco-pyranose derivatives when bromine and chlorine are added to 3,4,6-tri-O-acetyl-and 3,4,6-tri-O-benzyl-D-glucal has been shown to be influenced both by the substituents and the polarity of the solvent. Similar results were observed for halogenomethoxylations. 

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