Isohexide preparation

Some special esters of isohexides (prepared conventionally, however) have been described, including diesters of several long-chain fatty acids121,122 and dicarboxylic acids,123 isomannide-mono-oleate,124 isosorbide dinicotin-ate,125 and perfluorinated long-chain fatty acid diesters of isosorbide and isomannide.126 Bis(chloroformate)s of isosorbide and isomannide, and the... 

As a consequence, in most cases, the preparation of dialkyl isohexides is described in the literature. Some mono ethers have also been prepared, bearing different acyl groups on the second hydroxyl group of the ring system. Only very few examples of monoalkyl derivatives lacking further substituents are known. 

Epoxides 72 may also act as starting materials for hybrid structures 77 containing an isohexide and a glyceryl moiety, with nitric ester functions at different positions.172 Additional monoethers of isosorbide 2- and 5-nitrate 78 were synthesized by reaction of the free hydroxyl group with any of several alkyl iodides in the presence of freshly prepared silver oxide. The yields were low, as usual.146 Amongst a larger series of different alcohol... 

Etherification of isohexides with substituted-benzyl chloride in aqueous sodium hydroxide, or by means of sodium hydride in dimethyl sulfoxide, yields mixtures of mono- and bis-ethers, which can be conventionally separated by distillation or by column chromatography.176 The preparation of some phenyl ethers was also described, using the tosylate-phenoxide exchange reaction. Monoethers (88) synthesized in this way were transformed into carbamates (89) by reaction with sodium cyanide-trifluoroacetic acid (see Scheme 18). 

Mesylates and tosylates of isosorbide and isomannide undergo nucleophilic displacement with a number of primary and secondary amines, as described in a pharmaceutically oriented publication.131 Several patents describe the preparation of numerous aminodeoxyisohexide derivatives bearing an additional nitric ester group at the 2 or 5 position of the isohexide ring-system.142 144 207 Among these, purines and purine-alkylamines were... 

With this intent, the acetates (R = COCH3, 78a), carbamates (R = CONH2, 78b), sulfamates (R = S02NH2, 78c), and ethyl ethers (R = C2H5,78d) of isosorbide 2- and 5-nitrate were investigated, and found to be similar in activity to the parent compounds.146 Several isohexide nitrates further substituted by purine bases 154 were prepared as potential cardiovascular agents.143... 

Among 138 examples of various sulfamoyl compounds, three isohexide derivatives were mentioned. Their preparation started from corresponding free hydroxyl compounds by reaction with sulfamoyl chloride, which itself had been generated in situ from chlorosulfonyl isocyanate. They were claimed for treatment of chronic arthritis and osteoporosis.221 ... 

Difunctionalized phenolic compounds of the general formula 171 were used to prepare, from isohexides and phosgene, polycarbonates having enhanced stability against electric-current leakages.264... 

Polyesters synthesized from terephthaloyl chloride and isohexides were prepared, and characterized by differential scanning calorimetry, n.m.r. spectroscopy, and viscosity measurement.25,128 Another polyester, prepared by copolymerization of (2-hydroxyethyl)methacrylate with isoman-nide dimethacrylate (172), forms a hydrogel when allowed to swell in isotonic sodium chloride solution. This gel has useful properties for manufacturing contact-lens material.265... 

The first papers on isohexide based semi-aromatic homo-polyesters were published by Thiem et al. in 1984 [10,11]. They prepared polyesters from all three isohexides by melt condensation with terephthaloyl chloride at elevated temperatures (Figure 9.3). Colourless, brittle oligomers were obtained with Mn 3000-8000. These materials exhibited very high TgS - that is. 

Storbeck and Ballauff prepared polyesters from isohexides and terephthaloyl dichloride by solution polymerization in pyridine, giving colourless, fibrous materials [13]. Isomannide and isoidide yielded semi-crystalline materials however, crystallinity could not be recovered after annealing since their glass transition temperature and melting temperature are too close to each other for them to be crystallized from the melt. Thermogravimetric analysis (TGA) of poly(isosorbide terephthalate) (PIT) showed thermal stability up to 360 °C under a nitrogen atmosphere. 

Homo-polyesters of isohexides and linear aliphatic diacids have been reported by various groups (see Table 9.5). Braun et al. reported the synthesis of polyesters from isosorbide or isomannide with a variety of linear aliphatic acid dichlorides (C4-C16) via melt condensation, giving relatively high molecular weight polymers [12]. Comparable polyesters from all three isohexides were prepared by Okada [36-38], Noordover et al. also described the synthesis... 

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