Mannitol 1,4:3,6-dianhydro

Sugihara and Schmidt49 reported the isolation of 2,5-anhydro-D-glucitol in crystalline form its preparation on a relatively large scale has been described in the patent literature,50 and consists in the thermal dehydration of D-mannitol. The process leads to the formation of 1,4-anhydro-D-mannitol, 1,5-anhydro-D-mannitol, 1,4 3,6-dianhydro-D-mannitol, and 2,5-anhydro-D-glucitol, which is isolated as the crystalline 1,3-O-isopropyIidene derivative (35). 

During gas-liquid chromatographic-mass spectrometric analysis of the acid-catalyzed dehydration reaction of D-mannitol, 1,4 3,6-dianhydro-2-chloro-2-deoxy-D-mannitol was found among the reaction products.35 Contrary to the postulated Sn2 mechanism, according to which 2,5-di-endo oriented leaving-groups are substituted by different nucleophiles, resulting... 

D-Mannitol, dianhydro-, mono-9-octadecenoate, (Z)- D-Mannitol, dianhydro-, monooleate. See Mannide monooleate... 

Synonyms Mannitan, Z-9-octadecenoate Definition Monoester of oleic acid and anhydrides derived from mannitol Empirical C24H440g Uses Emulsifier, surfactant in cosmetics Manuf/Distrib. Somerset Cosmetic Co. Variati D-Mannitol, 1,4-anhydro-, 6-dodecanoate. See Mannitan laurate D-Mannitol, dianhydro-, mono-9-octadecenoate, (Z)- D-Mannitol, dianhydro-, monooleate. See Mannide monooleate MAOH. See Methyl amyl alcohol Marble. See Calcium carbonate Mascagnite. See Ammonium sulfate Matting acid. See Sulfuric acid Maxatase. See Protease MC. See Methylcellulose MCC. See Microcrystalline cellulose... 

Loss of a second molecule of water occurs on heating (1) (106,107), (2), or (3) (108) with concentrated sulfuric or hydrochloric acid forming 1,4 3,6-dianhydro-D-glucitol (isosorbide) (5). Mannitol and iditol anhydrize under similar conditions to isomannide (6) and isoidide (7), respectively. In (6), both hydroxyl groups are oriented toward each other (endo) ia (7), both are oriented away from each other (exo) and ia isosorbide (5), one hydroxyl is endo and the other exo. XyUtol loses two moles of water to form l,3 2,5-dianhydrox5litol (109). 

Brigl and Griiner45 reported the isolation of three products when 1,6-di-O-benzoyl-D-mannitol (29) was heated in boiling 1,1,2,2-tet-rachloroethane in the presence of p-toluenesulfonic acid as the catalyst. These compounds were assigned mono- and di-anhydro structures, and were later shown by Hockett and coworkers46,47 to be 1,4-anhydro-D-mannitol dibenzoate (30), l,4 3,6-dianhydro-D-man-nitol dibenzoate (31), and 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol (32). The latter compound, which can be readily isolated from the... 

Intramolecular displacement of primary sulfonyloxy or halide groups in derivatives of D-mannitol can also be brought about under basic conditions, albeit in low yield. Treatment of l,6-di-0-(methyl-sulfonyl)-D-mannitol (78), or the corresponding dichloride derivative, with sodium methoxide gave 2,5 3,6-dianhydro-D-glucitol74 (79). Treatment of the latter with hydrochloric acid at 100° in a sealed tube gave the 6-chloro-6-deoxy derivative (80), which was converted into the known 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol45 47 (32). The sequence 78-80 is of interest in the context of C-/3-D-nucleoside precursors, but it suffers from the fact that yields are low. 

Dianhydro-n-mannitol or isomannide was first prepared many years ago by Fauconnier44 who obtained it by heating D-mannitol with hydrochloric acid. The dianhydrides of D-sorbitol and L-iditol were not prepared, however, until very recent times. Although isomannide is a crystalline substance forming well defined derivatives very little work has been carried out on it and its structure was not determined until 1945, but in that and the following years a flood of experiments having a... 

Wiggins45 synthesized 1,2,5,6-tetrachloro-tetradesoxy-D-mannitol by an unequivocal route and found it to be identical with the tetrachloro-tetradesoxy-D-mannitol actually obtained from isomannide. Thus isomannide must be l,4 3,6-dianhydro D-mannitol (LI). 

The dimethyl derivative of isomannide was synthesized by Wiggins as follows. l,6-Dichloro-l,6-didesoxy-3,4-isopropylidene-D-mannitol was converted i nto 1,6-dichloro-l, 6-didesoxy-2,5-dimethyl-3,4-isopr opylidene-D-mannitol (LVI). This on mild acid hydrolysis gave 1,6-dichloro-l,6-didesoxy-2,5-dimethyl-D-mannitol (LVII) which with cold sodium methoxide furnished 2,5-dimethyl-l,4 3,6-dianhydro-D-mannitol (LVIII), identical with the product of methylation of isomannide itself. Further... 

Overend, Montgomery and Wiggins60 noted an interesting reaction between isomannide and phosphorus tribromide. None of the expected 2,5-dibromo-2,5-didesoxy-l,4 3,6-dianhydro-D-mannitol (LIX) was isolated instead, ring scission took place and l,6-dibromo-l,6-didesoxy-D-mannitol (LX) was formed. Since no such ring scission occurs with hydrobromic acid under similar conditions it was probable that the phosphorus tribromide itself had effected the ring breakdown by direct attack on the oxide rings. 

Dianhydro-D-sorbitol (L-gulitol). 4. 2,5 Imino-2,5-didesoxy-l,4 3,6-dianhy-dro-D-mannitol. 

The stereochemistry of the hexitols affects the manner of ring fusion, as is seen in Figs. 3 and 4. In mannitol, sorbitol (gulitol) and iditol, the l,4 3,6-dianhydro rings are m-oriented, whereas in the dulcitol, allitol and altritol (talitol) series the 1,4 3,6-rings are trans-oriented. This makes the ring system in this latter series almost planar although in the case of dianhydrodulcitol and allitol there is considerable strain in the molecules. 

The most interesting ethylene oxide derivative of the hexitols encountered hitherto is 1,2 5,6-dianhydro-D-mannitol. This was obtained in the form of its 3,4-isopropylidene (LXXXVIII) and 3,4-ethylidene (LXXXIX) derivatives.72 The isopropylidene compound was synthesized from l,6-dichloro-l,6-didesoxy-D-mannitol through its conversion first into l,6-dichloro-l,6-didesoxy-3,4-isopropylidene-D-mannitol. This,... 

The acetates of the l,4 3,6-dianhydrohexitols may also be useful as plasticizers both 2,5-diacetyl-l,4 3,6-dianhydro-D-mannitol and the analogous D-sorbitol derivative have been described.97... 

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. 

One would also think that saccharides are more attractive starting raw materials for direct preparation of epoxy resins than hydrocarbons since they already possess oxygen atoms needed for the epoxy rings. Such diepoxy derivatives of hexitols are known compounds, for instance 1,2 5,6-dianhydro-3,4-0-isopropylidene-D-mannitol (XIX). Their preparation, however is difficult and requires 15 to 18 steps which proceed in very low overall yield (17-19). 

As a first step in this direction, we have been able to prepare 1,2 5,6-dianhydro-3,4-0-isopropylidene-D-mannitol as a model diepoxy hexitol derivative in four steps with overall 50% yield according to the following scheme ... 

Finally, epoxy ring formation has been carried out in methanol at room temperature with sodium methoxide as a catalyst (24). 1,2 5,6-Dianhydro-3,4-0-isopropylidene-D-mannitol (XIX) has been obtained in near quantitative yield. 

Closely related to the synthetic work reported in the previous section is the incorporation (131) of a 2,5-anhydro-3,4Hdi-0-methyl-D-mannitol residue (Figure 15) into the 18-crown-6 derivative d-91. Other derivatives of D-mannitol that have been built into crown ether receptors include l,4 3,6-dianhydro-D-maiuiitol (132), l,3 4,6-di-0-methylene-D-marmitol (13 134), and 1,3 4,6-di-O-benzylidene-D-mannitol (134). Examples of chiral crown compounds containing these residues include dd-92, dd-93, d-94, and d-95. Although not derived from carbohydrates—but rather (135) from the terpene, (-t-)-pulegone—... 

A development of some promise lies in the dehydration of mannitol and sorbitol to give anhydro compounds. Mannitol can be dehydrated to give 1,4-anhydro-mannitol (XIII) (mannitan) and isomannide, shown to be 1,4 3,6-dianhydro-mannitol (XIV) by Wiggins. Similarly,... 

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