Orthoesters preparation

Schuerch2) reviewed the medical application of synthetic poly-saccharides. Capozza199 reported that the poly-orthoester prepared from 2-ethoxy-4-hydroxymethyl-l,3-diox-olane in the presence of add are useful as slow-release agents for drugs. Poly-2,6,7-trioxabicyclo[2.2.1]heptane VIII showed the same behavior200). 

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). 

Orthoesters (e.g., methyl orthoacetate) have also been prepared by acid-catalyzed exchange with trimethyl orthoesters, from 16a,17a-dihydroxy-pregnanes with or without a 21-hydroxyl substituent. 

Ketene di(2-melhoxyethyl) acetal has been obtained by the present method with the use of diethylene glycol dimethyl ether as solvent.3 Other methods for the preparation of ketene acetals include the dehydrohalogenation of a halo acetal with potassium t-butoxide 4 and the reaction of an a-bromo orthoester with metallic sodium.5... 

Imidazo[l,2-c/][l,2,4]triazines 488 were prepared (78USP4096257) from the reaction of 2-imidazocarboxylic acid hydrazide 487 with orthoesters. They inhibited cyclic-AMP phosphodiesterase in the mouse skin phosphodiesterase test and had antiasthina. 

Imidazo[l,5-t/)[l, 2,4]triazin-l(2//)-ones 504 were prepared (78-USP4115572 79JHC277 88USP4743586) by the cyclization of hydrazide 503 with triethyl orthoesters. l,2,3,4-Tetrahydro-2,4,4-trimethyl-8-nitroimidazo[ 1,5-t/J[ 1,2,4]triazin-1 -one 506 was isolated as a byproduct during the course of purification of hydrazide 505, whose structure was determined (91MI4) by crystal structure analysis. They had antiasthmatic... 

Dimethyl or diethyl acetals can be prepared by acid-catalyzed exchange with an acetal such as 2,2-dimethoxypropane or an orthoester.247... 

Various nonracemic allenylstannanes have been prepared from nonracemic propargylic mesylates and (Bu3Sn)2CuLi. The stereochemistry of the displacement was shown to be anti by correlation with an allenic stannane prepared through Claisen orthoester rearrangement of a propargylic alcohol of known configuration (Scheme 33)80. 

The application of these optimized conditions permitted Kochetkov et al. to prepare, among others, [1-cholcstcryl glucoside in 45% yield. However, with low reactive agly-cons (R OH) the yield was poor (10-20%) owing to the competing glycosylation of the extruded alcohol (ROH) from the initial orthoesters (Scheme 5.6). 

Wolfbeis investigated the reactions of amines and orthoesters with different CH-acid molecules (81CB3471). When the reactions of aniline, ethyl orthoformate, and dialkyl malonates (2 mol) were carried out at 130-140°C for 4 hr, phenylaminomethylenemalonamates (245) were obtained (81CB3471). Similar reactions with aliphatic amines were unsuccessful. Phenylaminomethylenemalonic acid could not be prepared in the reactions of aniline, methyl orthoformate or orthoacetate, and malonic acid. When these reactions were carried out in 2-propanol, only amidines (246) were obtained. 

The phosphazinium bromides (25), conveniently prepared from hydrazinotri-phenylphosphonium bromide and orthoesters, when treated with base (Scheme 6) give the thermally stable ylides as a mixture of syn- and a/ift-forms.28 These ylides are converted efficiently by various aromatic aldehydes into mixed azines. 

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... 

---