Isosorbide derivatives

Optically active polymerizable isosorbide derivatives, (II) and ( ), were prepared by Koyama et al. (3) and used in photoresist compositions. 

The molecular structures of the two diastereoisomers of the 5-0-acyl substituted isosorbide derivative 5-[l,4-dihydro-3-(methoxycarbonyl)-2,6-... 

In the field of plasticizers for PVC, some isosorbide esters give functional performance equivalent to some of the most widely criticized phthalates, such as DEHP. ° As phthalates are used in a wide number of applications (PVC plasticizer, cosmetics, inks, lubricants, etc.) there is significant potential for isosorbide derivatives as an alternative to phthalates. 

Isosorbide derivates are of considerable importance for the replacement of fossil resource-based products. Applications include building blocks for new polymers and functional materials, new organic solvents, for medical and pharmaceutical applications, as weU as fuels (36). The derivatization of isosorbide is somewhat problematic because of the different configurations of the 2- and 5-positions and thus of the different reactivity of the hydroxyl groups. 

It was demonstrated that the application of previously synthesized ethers of isosorbide was beneficial and allowed preparing polyethers in better yields than the polyethers obtained in direct reactions of isosorbide and dibromo- or dimesylalkenes. Recently, a novel group of polyamides were synthesized by the microwave-assisted polycondensation of an optically active isosorbide-derived diamine with different... 

Figure 28 Reaction of isosorbide with jo-fluoronitrobenzene and further reduction into isosorbide-derived diamine.

In 1989, Prakash and co-workers reported that (trifluoro-methyl)trimethylsilane can be activated by a Lewis base to form the trifluoromethyl anion in situ, which could subsequently add to both carbonyls and imines. More recently, it has been demonstrated that the asymmetric addition of the trifluoromethyl anion to imines can be directed by sulfinyl chiral auxiliaries, whereas the addition to ketones can be controlled through the use of menthol " and isosorbide ° derived chiral auxiliaries. 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

Some interesting facts have come to light from a study of the amino derivatives of isomannide, isosorbide and isoidide.62 The diamines of isomannide (LXXIV) and isosorbide (LXXV) were made by Montgomery and Wiggins by treating the corresponding ditosyl derivatives with... 

Since no other stereoisomer but that of iditol, mannitol or sorbitol can exist in the as-fused ring series of l,4 3,6-dianhydrohexitols and since amination experiments on the ditosyl derivatives of each isomer have given three different amino derivatives, it is reasonable to assume that the two diamines which have been isolated are of the same configuration as their parent dianhydrohexitols. These two diamines LXXIV and LXXV on treatment with nitrous acid suffered deamination as expected but instead of obtaining in one case isomannide and in the other isosorbide, only one dianhydrohexitol was isolated and that was dian-hydro-L-iditol. The deamination must of course lead to the transitory carbonium cation LXXVIII and this on hydroxylation can take on any of the configurations, L-iditol, D-mannitol or D-sorbitol. That it preferentially takes on the configuration of L-iditol indicates that this is in some ways a more stable structure than the others. This behavior is paralleled... 

The hexitol anhydrides also have medicinal uses.97 Carr and Krantz98 found that l,4 3,6-dianhydro-D-mannitol was quite non-toxic to man and was a valuable diuretic. The dinitrates of both isomannide and isosorbide" have possible uses as agents for lowering blood pressure, though Burn and Stephenson100 found that the D-sorbitol derivative was twice as active as the D-mannitol derivative in this respect. 2,5-Diam-ino-2,5-didesoxy-l,4 3,6-dianhydro-D-mannitol and -D-sorbitol have been prepared and their sulfanilamido derivatives obtained.101 These however showed no outstanding bacteriostatic activity. 

Some sugar-derived dmgs obtained by chemical means have also achieved some importance, for example, ranitidine (Zantac ), an inhibitor of gastric acid secretion—one of the top 30 drugs based on sales —isosorbide dinitrate, a coronary vasodilatator, or topiramate, a fructose-derived anticolvulsant drug with high antiepileptic efficacy. ... 

Sorbitol easily dehydrates into its 1 4-3 6-dianhydro derivative, isosorbide (III), in the presence of an acid catalyst such as sulfuric, hydrochloric, or toluenesul-fonic acid or a cation exchange resin in a one-step preparation in high yield (75-85%)(1) ... 

LAGA is a monocarbonyl derivative of isosorbide. In contrast to isosorbide, however it is not hydroscopic and easily opens its lactone ring with the formation of potential cross-linking sites. 

DLSA are rigid diols. They have the same skeleton as isosorbide and LAGA. For instance, 1,4 3,6-dilactone of mannosaccharic acid is a dicarbonyl derivative of iso-mannide and monocarbonyl derivative of the lactone of the anhydromannonic acid. Therefore, DLSA could find applications as diols and their polymers are expected to have similar properties to that of isosorbide and LAGA polymers. 

Isosorbide and isomannide are important by-products of the starch industry, arising from dehydration of D-sorbitol and D-mannitol. These commercial starting materials provide an easy and inexpensive access to optically pure functionalized tetrahydrofurans like 04,05-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-glucitol and 04,05-isopropylidene-l-iodo-3,6-anhydro-1-deoxy-Q-mannitol. This procedure describes a preparation of the former compound and the epoxide derived therefrom. 

The conformations of D-isosorbide (21), D-isomannide (22), and L-isoi-dide (23), and of their diacetyl and dimesyl derivatives, have been studied in... 

A g.l.c. method (OV-101) for determining isosorbide in foods, using its trimethylsilyl derivatives,72 has been reported. D-Isomannide and 2(5)-chloro-2(5)-deoxyisomannide can be separated from a series of other sugar derivatives of mannitol on an OV-101 column.35... 

Protonation occurs preferentially at the primary hydroxyl group. The first dehydration step can also take place between the 3- and 6-position, leading to the 3,6-monoanhydro derivative 41. The second water-elimination step from the 1,4-, as well as from the 3,6-, anhydro-D-glucitol, leads to the formation of D-isosorbide. However, kinetic studies showed94 that the proportion of the 3,6-anhydro isomer is low compared to that of the 1,4-anhydride. An investigation giving similar results is described in Ref. 95. 

A different approach was used by Kiessing and Chatteijee.147 Isosorbide 5-methanesulfonate (79) reacted with 4-chlorophenol, affording the Walden-inverted isoidide derivative 80, which was transformed into the appropriate nitrate 81 (see Scheme 15). 

Reaction of 91 with methacrylic acid gives rise to double unsaturated side-chain compounds (93) these were subjected to polymerization.185 Subjecting isosorbide to etherification with a, m-dihaloalkanes, mono- and dialkyl derivatives were obtained. These could not be transformed into polyethers. The use of tram-1,4-dichlorobutene lead to oligomers up to the... 

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