Orthoesters, and

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

With l,3-dimethyl-2,l-benzisoxazolium salts, however, considerable reactivity has been reported. Condensation occurs readily with aldehydes, ketones, orthoesters and diazonium salts to yield styryl, cyanine and azo compounds, respectively (78JOC1233). In the presence of triethylamine, dimerization was observed, and the reactions of the cation were considered to involve the intermediacy of the anhydro base (77JOC3929). 

Deep fluorinalion of alkanes, ethers, acid fmlides, esters, alkyl chlorides, most ketones, ketals, orthoesters, and combinations of these functional groups produces principally the perfluonnated analogues (Table 2) Chlorine substituents (or chloro groups) usually survive fluorination... 

Choi, N. S., and Heller, J., Structured orthoesters and orthocarbonate drug delivery devices, U.S. Patent 4,131,648, December 26, 1978. 

It is for this reason that orthoesters and acetals are (comparatively) stable in the absence of an acid. Alternatively, one can have an uncatalyzed mechanism involving preliminary tautomerization to a zwitterion, but the thermodynamic cost of this imposes a considerable barrier to reaction. 

Alkyl and aryl thiohydrazide derivatives react with orthoesters and trihalomethyls to afford 1,3,4-thiadiazoles. The reactions proceed via a thiosemicarbazone intermediate which cyclizes to eliminate either alcohol or hydrogen chloride. Treatment of the iV-thiohydrazide pyrazole 143 with triethyl orthoformate in acetic acid at reflux gave the 5-acetamido-l,3,4-thiadiazol-2-ylpyrazole 144 (Equation 51), and in the absence of acetic acid the 5-amino-l,3,4-thiadiazol-2-ylpyrazole 145 in 76% yield <2000JCM544>. 

Often these intermediates are generated in situ from orthoesters and propargylic alcohols [551] or propargyl esters such as 167 (Scheme 1.74) [552],... 

In the presence of orthoester and perchloric acid, 3-acetyltropolone (74) with benzaldehydes affords pyranones 76 directly (90JHC891). The reaction is considered to pass through a carbocation (from 74 and orthoester) which is stabilized by electron-donating substituents in the benzaldehyde (Ar). Therefore, the one-step synthesis might be limited to methoxy- and hydro-xybenzaldehydes. These synthons are also used to prepare corresponding... 

Extended application of the procedure by the Russian group has led to the synthesis of difunctional monomers having an orthoester and a potential alcoholic group within the same molecule, and their polymerisation to synthetic polysaccharides of regular structure (e.g. Scheme 10)... 

The reactivity of the methoxyethy1idene derivatives with nucleophiles other than water has been examined. It has been already found (13) that they may be readily opened by halogenating reagents ( N -b romo succ i n i-mide for instance) to give a or 3-ha 1 oacetates (respectively from five- or six-membered-ring orthoesters), and this reaction may be compare with the familiar Hanessian procedure for conversion of henzylidene acetals iiito bro-mo-deoXybenzoates (68). ... 

Orthoesters and related species as precursors 49 Amide acetals as precursors 55 Ketene acetals as precursors 57 Oxocarbocations as precursors 59... 

The effect of substituents on h+ for the C— bond cleavage of orthoesters and hemiorthoesters derived from benzoic acid... 

This variation in the relative rates of C— bond cleavage of analogous orthoesters and hemiorthoesters (and of acetals and hemiacetals) is of course a reflection of the different effect of substituents on the rates of these two classes of reaction. As discussed above, substituents capable of stabilizing carbocations have a greater effect on the rates of C— bond cleavage of orthoesters (and acetals) than of hemiorthoesters (and hemiacetals). 

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