Esters ortho

Ortho esters are acid derivatives in which the carboxyl carbon is sp -hybridized however, most cannot be made from carboxylic acids. They are usually made by a two-stage alcoholysis of nitriles. Treatment of a nitrile with anhydrous hydrogen chloride in an alcohol gives the hydrochloride of an imidic ester. Treatment with an alcohol in a separate step (Eq. 6.17) [29] leads to the ortho ester. 

The orthoformates [30] and orthobenzoates [31] are made from chloroform or trichloromethyl compounds by reaction with sodium alkoxides. 

A new series of crystalline orthobenzoates has been synthesized, and the ease of preparation, as well as their crystallinity, makes them very useful for identification reactions. - The corresponding ortho acetates had been prepared by Pacsu, and their structure was discussed in this Series.  

When the ortho ester (7) is treated with benzyl alcohol and fused zinc bromide, benzyl 1,3,4,6-tetra-O-benzoyl-a-D-fructofuranoside (10) is formed this is readily saponified to the free fructoside (11). 

These experimental facts are illustrated in formulas (6) to (11) and, according to the opposite-face concept of the Walden inversion, discussed by Isbell and Frush, several structural assignments can be made. - The formation of an a-D-fructoside and the 2,3,6-tri-(ortho ester) corroborates 

A new conclusion emerges from these facts compounds (g) and (d) are possible intermediary products. But, substance (g) has never been isolated, and treatment of (a) and (g) together results in a greater proportion of 

An entirely different ester is D-fructosyl phosphate, both ring forms of which, (14) and (15), were synthesized, isolated, and identified. Important as a possible intermediate in the biochemical synthesis and breakdown of the fructans, the pyridine salt of the 1-phosphate (12) was treated with dicyclohexylcarbodiimide, to form the cyclic 1,2-ester (13), which is very labile and is hydrolyzed to a mixture of both forms, (14) and (15), of the 2-phosphoric ester. This cycUzation mechanism was first mentioned by Khorana and coworkers, and later confirmed. Separation was effected 

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The allylic geminal diacetate 141 undergoes the monoallylation of malonates to give 142 and the two regioisomers 143 and 144[93,94]. The dimethylacetal 145 or ortho esters of aromatic and a,/3-unsaturated carbonyl compounds react with trimethylsilyl cyanide to give the methyl ether of cyanohydrin[95]. 

Acylated Corticoids. The corticoid side-chain of (30) was converted iato the cycHc ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR )2 iu benzene solution ia the presence of i ra-toluenesulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) ia nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively iato prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The iatermediate ortho esters also are active. Thus, 17a,21-(l -methoxy)-pentyhdenedioxy-l,4-pregnadiene-liP-ol-3,20-dione [(96), R = CH3, R = C Hg] is at least 70 times more potent than prednisolone (89). The above conversions... 

An alternative synthesis converts monohromopentaerythritol to the ortho ester, followed by reaction with cuprous acrylate. 

Pentaerythritol in rosin ester form is used in hot-melt adhesive formulations, especially ethylene—vinyl acetate (EVA) copolymers, as a tackifier. Polyethers of pentaerythritol or trim ethyl ol eth an e are also used in EVA and polyurethane adhesives, which exhibit excellent bond strength and water resistance. The adhesives maybe available as EVA melts or dispersions (90,91) or as thixotropic, one-package, curable polyurethanes (92). Pentaerythritol spko ortho esters have been used in epoxy resin adhesives (93). The EVA adhesives are especially suitable for cellulose (paper, etc) bonding. 

Fig. 1. Proposed ortho-ester configuration for ring C of the oligosaccharide antibiotics.

PINNER Imlno Ether Synthesis Synthesis of imlno ethers, amidines and ortho esters from nitnles. 

Mono MOM derivatives of diols can be prepared from the ortho esters by diiso-butylaluminum hydride reduction (46-98% yield). In general, the most hindered alcohol is protected. ... 

The mixed ortho ester formed from tri(2-chloroethyl) orthoformate (100°, 10 min-2 h, 16% yield) is more stable to acid than is the unsubstituted derivative, but can be cleaved with 80% AcOH (20°, 1 h). ... 

A variety of cyclic ortho esters,including cyclic orthoformates, have been developed to protect czs-1,2-diols. Cyclic ortho esters are more readily cleaved by acidic hydrolysis (e.g., by a phosphate buffer, pH 4.5-7.5, or by 0.005-0.05 M HCl) than are acetonides. Careful hydrolysis or reduction can be used to prepare selectively monoprotected diol derivatives. 

The following ortho esters have been prepared to protect the diols of nucleosides. They are readily hydrolyzed with mild acjd to afford monoester derivatives, generally as a mixture of positional isomers. 

With this ortho ester good selectivity for the axial alcohol is achieved in the acidic hydrolysis of a pyranoside derivative." ... 

This ortho ester does not form a monoester upon deprotection as do acyclic ortho esters, thus avoiding a hydrolysis step. ... 

Ortho esters are among the few derivatives that can be prepared from acids and esters that protect the carbonyl against nucleophilic attack by hydroxide or other... 

Strong nucleophiles such as Grignard reagents. In general, ortho esters are difficult to prepare directly from acids and are therefore more often prepared from the nitrile. Simple ortho esters derived from normal alcohols are the least stable in terms of acid stability and stability toward Grignard reagents, but as the ortho ester becomes more constrained its stability increases. 

This is one of the few methods available for the direct and efficient conversipn of an acid, via the acid chloride, to an ortho ester. 

Oxygen ortho esters are readily cleaved by mild aqueous acid (TsOH Pyr, H20 NaHS04, 5 1 DME, H2O, 0°, 20 min ) to form esters that are then hydrolyzed with aqueous base to give the acid. Note that a trimethyl ortho ester is readily hydrolyzed in the presence of an acid-sensitive ethoxyethyl acetal. The order of acid stability is... 

The synthesis and interconvereion of simple ortho esters has been reviewed R. H. DeWolfe, Synthesis, 153 (1974). 

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