Henry B. Sinclair

Displacement of carbohydrate sulfonates with halide ions of toluene-solubilized halides

Abstract Hexamethylphosphoramide was found to solubilize lithium halides in toluene. Nucleophilic displacement of carbohydrate with these toluene-solubilized halide ions produced in excellent yield and short reaction times the corresponding deoxyhalocarbohydrate. With iodide, bromide, and chloride ions a primary methanesulfonate needed respectively 0.25, 1, and 4h for the displacement. Isolated yields exceeded 70%. Displacement of secondary sulfonates was shown to occur with the solubilized halide ions.

Synthesis of a derivative of 1-deoxy-d-erythro-2,3-hexodiulose and its conversion into nonenzymic browning products

Abstract A new synthesis of 1-deoxy-4,5- O -isopropylidene- d - erythro -2,3-hexodiulose ( 5 ), a stable derivative of the elusive 1-deoxy- d - erythro -2,3-hexodiulose ( 6 ), starting from 3,6-anhydro-4,5- O -isopropylidene- d -mannitol ( 1 ) is described. Acid hydrolysis of 5 produced 6 , which without isolation was treated with piperidine acetate to yield piperidino-hexose-reductone ( 7 ) and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one ( 8 ). A third component in the reaction mixture has been tentatively assigned from mass-spectroscopic data the structure 4-hydroxy-2-hydroxymethyl-5-methyl-3(2 H )-furanone ( 9 ).

Two methyl anhydro-d-fructopyranosides prepared from d-mannitol

Abstract d -Mannitol ( 1 ) was converted into 1,5-anhydro- d -mannitol, which was treated consecutively with p -toluenesulfonyl chloride (1 mol. equiv.) and benzoyl chloride (3 mol. equiv.), to produce 1,5-anhydro-2,3,4-tri- O -benzoyl-6- O - p -tolylsulfonyl- d -mannitol. 1,5-Anhydro-2,3,4-tri- O -benzoyl-6-deoxy-6-iodo- d -mannitol ( 4 ) was prepared by displacing the p -tolylsulfonyl group by reaction with sodium iodide. 1,5-Diazabicyclo[5.4.0]undec-5-ene eliminated hydrogen iodide from 4 , to yield 1,5-anhydro-2,3,4-tri- O -benzoyl-6-deoxy- d - lyxo -hex-5-enitol ( 5 ). Addition of bromine to a methanolic solution in 5 in the presence of potassium carbonate resulted in a separable mixture of methyl 1-bromo-1-deoxy-α- d -fructopyranoside ( 6 ) and methyl 1-bromo-1-deoxy-β- d -fructopyranoside ( 8 ). Dilute alkali converted 6 into methyl 1,3-anhydro-α- d -fructopyranoside, identified as its 4,5-diacetate. Dilute alkali converted 8 into methyl 1,4-anhydro-β- d -fructopyranoside.

Preparation and Characterization of 1,3:4,6-di-O-chloroethylidenegalactitol

Abstract When galactitol was allowed to react with chloroacetaldehyde diethyl acetal in concentrated hydrochloric acid, a di- O -chloroethylidenegalactiol was isolated. This product, on treatment with excess p -toluenesulfonyl chloride in pyridine, gave an extremely acid-stable di- O -chloroethylidene-di- O - p -tolylsulfonylgalactitol, which on acetolysis in boiling acetic anhydride-acetic acid containing sulfuric acid, was cleaved to give 1,3,4,6-tetra- O -acetyl-2,5-di- O - p -tolylsulfonylgalactitol in moderate yield. The identification of this tetra- O -acetyl-di- O - p -tolylsulfonylgalactitol supports the structure of 1,3:4,6-di- O -chloroethylidenegalactitol for the original diacetal.

Preferential sulfonylation of methyl 2,6-di-O-mesyl-α-D-glucopyranoside

Abstract When equimolar ratios of mesyl chloride and methyl 2,6-di- O -mesyl-α- D -glucopyranoside were allowed to react in pyridine and the product resolved by preparative t.l.c., the 2,6-di-, 2,3,6-tri-, 2,4,6-tri-, and 2,3,4,6-tetra-mesyl esters were obtained in (0.5–0.6):1:(4–5):(1-2-1.4) molar ratio. Benzoylation of either the isolated 2,4,6-tri- O -mesyl ester or, more conveniently, the mixture from monomesylation gave the crystalline methyl 3- O -benzoyl-2,4,6-tri O -mesyl-α- D -glucopyranoside ( 8 ). As both of these trimesyl esters ( 7 and 8 ) are unreported, isolation of the benzoate established the 2,4,6-ester arrangement, and the 2,3,6-triester was prepared by standard methods. Treating methyl α- D -glucopyranoside with 3 molar equivalents of mesyl chloride and, subsequently, with 1 molar equivalent of benzoyl chloride, proved a convenient method for preparing the 3- O -benzoyl derivative in moderate yield. Monotosylation of methyl 2,6-di- O mesyl-α- D -glucopyranoside was not so definitive as mesylation, but a molar ratio of 1:2.8 for the 3- O -tosyl:4- O -tosyl product was derived from n.m.r. data. This work, when combined with literature reports, establishes that, in methyl α- D -glucopyranoside, the reactivity toward sulfonylation is 6-OH>2-OH>4-OH>3-OH.

The action of alkali on di-O-(2-bromoethylidene)-D-mannitols: formation of an unusually acid-stable acetal linkage

Abstract When cis,trans -1,2:5,6-di- O -(2-bromoethylidene)- d -mannitol and cis,cis -1,2:5,6-di- O -(2-bromoethylidene)- d -mannitol were treated with dilute, boiling sodium hydroxide, 5,6- O -( S )-(2-bromoethylidene)-3:1,2- O -[( R )-1-ethanyl-2-ylidene]- d -mannitol ( 3 ) and 3:1,2;4:5,6-di- O -[( R )-1-ethanyl-2-ylidene]- d -mannitol ( 10 ) were produced; the structures were established by a combination of chemical transformations, 1 H-n.m.r. spectroscopy, and mass spectrometry. The bicyclo ether-acetal linkage in 3 and 10 proved unusually resistant to hydrolysis by acid.