Orthoformic acid derivatives formation

A patent procedure for formation of compounds 19 from simple tartaric acid derivatives has appeared <06USP047129> and various new routes to chiral dioxolanones include synthesis of dioxolan-2-ones either by transition metal-mediated asymmetric synthesis <06T1864> or enzyme-mediated kinetic resolution <06H(68)1329> and a new synthesis of the chiral dioxolan-4-ones 21 from lactic or mandelic acid involving initial formation of intermediates 20 with trimethyl orthoformate in cyclohexane followed by reaction with pivalaldehyde <06S3915>. 

The formation of porphyrins from 1,19-dideoxybi)enes-/r can be achieved starting either from the 1-methyl derivatives or from l,19-dideoxybilene-Z>-l,19-dicarboxylic acid esters. In the first case the desired methine bridge of the porphyrin stems from the 1-methyl group whereas in the latter case orthoformates have to be added in the condensation step as a precursor for the methine unit. The 1-methyl- and also 1,19-dimethyl-l,19-dideoxybilene- > salts can be cy-clized to the corresponding porphyrins with copper(II) acetate in methanol.56 However, when the bilenes contain /i-acceptor substituents, the yields of porphyrins obtained by this method are very low.57... 

Acetalization with Trialkyl Orthoformates. In an acetal exchange reaction, trialkyl orthoformates will convert carbonyl groups to their corresponding acetal derivatives without concomitant formation of water. Weak acids such as NH4NO3 or amberlyst-15 (a sulfonic acid resin) catalyze the acetalization. ... 

Methyl-8-azapurin-6-one was finally obtained from 76a by a most unusual combination of reagents, namely, triethyl orthoformate and 10 N hydrochloric acid, with which it was refluxed for 1 h (yield, 86%) 76b similarly gave the 9-benzyl derivative (80% yield). The stability of the orthoester in 10 Wacid was attributed to formation of the diethoxycarbe-nium ion (78), which apparently synthesized the acetal 79 from 76a the desired product was formed from this by loss of two molecules of ethanol. 

Cyclopropylamines react with aldehydes to yield the corresponding imines in fair yield.Cyclopropane-1,2-diamine reacted with two equivalents of benzaldehyde to give corresponding diimine 1 in 58% yield. Imine formation is also involved as the key step in multistep reactions leading to a variety of complex compounds. For example, 4-[2,2-bis(benzyloxymethyl)cyclopropylamino]-6-chloro-5-formamidopyrimidine (2) reacted with triethyl orthoformate in the presence of hydrochloric acid to give purine derivative 3 in 58% yield. An analogous reaction took place when 1-azido-l-vinylcyclopropane was treated successively with triphenylphosphane and benzaldehyde to give iV-benzylidene-l-vinyl-cyclopropylamine in almost quantitative yield. 

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

Although esters of (oxomethyl)phosphonic acid have proved to be so elusive, derived acetals (495 R = H, X = O) have been prepared with relatively little difficulty from the acid-catalysed interaction of dialkyl hydrogenphosphonates and orthoformic esters ", and from mixtures of phosphorus(III) chlorides and orthoformic esters when heated in sealed tubes the reaction is included here since the ultimate stage is presumably of the Michaelis-Arbuzov type. The current view (Scheme 48) appears to be that the phos-phorus(III) chloride reacts with triethyl orthoformate in a stepwise fashion where appropriate, and with the formation, in the penultimate step, of a phosphorus(III) triester and ClCH(OEt)2. Such reactions were observed in a highly detailed study, by P NMR spectroscopy, of the very slow reaction, even at 150 °C, between triethyl orthoformate and the chloride 496, from which the phosphinic ester 497 was isolated the reaction between the chloride 498 and triethyl orthoformate was much faster, but even so, took place over an... 

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