Orthoformic acid derivatives orthoformate

Alkyl aryl ketones can be converted to arylacetic acid derivatives in an entirely different manner. The reaction consists of treatment of the substrate with silver nitrate and I2 or Br2, ° or with thallium nitrate, MeOH, and trimethyl orthoformate adsorbed on Montmorillonite K-10 clay, an acidic clay. ... 

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>. 

Quinolylaminomethylenemalonates (267) were prepared in the reactions of 2-aminoquinoline, ethyl orthoformate, and malonic acid derivatives (266) in the presence of A1C13 at 135-140°C for 30 min (74MIP1). 

For example, 4-(ethoxymethylene)-2-(l-naphthyl)-5(4//)-oxazolone 812, an intermediate for fluorescent 4-(A -substituted-aminomethylene)-2-(l-naphthyl)-5(4//)-oxazolones 813, was prepared from 1-naphthoylglycine and triethyl orthoformate.Reaction of 812 with amino acids gave the corresponding amino acid derivative 813 as a mixture of stereoisomers as shown in Scheme 7.249. 

Recent examples of the methods described in CHEC(1984) and CHEC-II(1996), and involving condensation of a substituted pyrimidine with a Ci unit, include the condensation of 3-amino-4-cyanopyrimidines with orthoformates <1995W095/19774> and a variety of carboxylic acid derivatives <1995EJM525, 1996JIC698, 1998JRM2880, 2002EJC995>. 

The condensation of 1,4-diamines with a variety of carboxylic acid derivatives, e.g. imidate esters, orthoformic esters, /V-ethoxycarbonylthioamides (77JOC2530), nitriles and ethoxyacetylene, produces the cyclic amidine linkage —N = C(R)NH— (67AHC(8)2l, p. 40). Cyclic ureas, —NHC(0)NH—, have been similarly produced using carbonyl chloride, A, A -carbonyldi imidazole, carbon monoxide, thiocarbonyl chloride or carbon disulfide (67AHC(8)21, p. 38). 

A 2- or 6-hydroxy-substituted purine can be prepared from the corresponding 4,5-diamino-pyrimidinol by cyclization with an acid, ester, ortho ester, or amide. If the ring closure is performed with reagents such as urea, alkyl chloroformates, urethanes, phosgene, and alkyl isocyanates, the 8-hydroxypurines are formed. Various xanthine and uric acid derivatives have been prepared by the condensation of 5,6-diaminopyrimidine-2,4-diols with formic acid. Purin-2-ol (1) was prepared by this route from 4,5-diaminopyrimidin-2-ol and ethyl orthoformate. ... 

Intramolecular Friedel-Crafts reaction Worthy of mention is the case of intramolecular Friedel-Crafts-type reaction affording 4(lH)-quinolone derivatives [443]. Thus, after extensive investigations, the authors prepared a solid-supported Meldrum s acid derivative by alkylation of a Merrifield resin with ethyl acetoacetate, decarboxylation, and subsequent ketalization of the resulting supported ketone with malonic acid (638). Treatment with triethyl orthoformate and various arylamines (639) afforded immobilized arylamino-methylene derivatives of Meldrum s acid (640). Upon thermal cyclization, these intermediates afforded 4(lH)-quinolone derivatives with simultaneous release from the resin (641). Highly pure final compounds were obtained in moderate to good yields. The resin was recovered in the form of the precursor of (638), i.e., the ketone (642), and thus could be potentially reused (Scheme 133). 

The formamides 16 are intermediates. Formamide (Bredereck variant of the Traube synthesis [149]), formamidine, orthoformic ester, diethoxymethyl acetate, Vilsmeier reagent (fi om DMF and POCI3) and dithioformic acid are used as formic acid derivatives. 4,5-Diaminopyrimidines can be obtained from 4-aminopyrimidines 17 by nitrosation with HNO2 followed by reduction of the nitroso compounds 18 ... 

As stated above, the synthesis of quinazoline derivatives can also be conducted in two stages, i.e., by the reaction of isatoic anhydrides with ammonia, amides, and various compounds containing the NH2 group followed by cyclization of the obtained anthranilic acid derivatives. Thus, the amino amides 157, formed during the action of aqueous ammonia on the anhydrides 61 (yields 61-73%), were brought into reaction with orthoformic ester, and this led to the quinazolinones 158 (yields 53-78%) [79],... 

Upon treatment with (la), orthoformate (95) is converted into cyclic carbonate (96) by an allylic transposition [153]. This transformation is initiated by activation of the C-OMe bond of the orthoformate moiety (Scheme 9.64). The triol acid derived from (96) is a potent vasodilator. 

Orthoesters are trivially named as derivatives of ortho acids such as triethyl orthoformate [122-51 -0] HC(OC2H )2, or named systematically as ethers, 1,1,1-triethoxymethane. 

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. 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylene-sulfonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > acetonide C (e.g., t.//s for 1,2-O-alkylidene-a-D-glucopyranoses of C5, C7, acetonide, and C derivatives are 8, 10, 20, and 124 h, respectively). The efficiency of cleavage seems to be dependent upon the electronic environment about the ketal. ... 

In general, the O-alkylation of benzoxepinones is accomplished via the anion. Alternatively, an acid-catalyzed process employing ortho esters may be used. For the acid-catalyzed formal O-alkylation of l-chloro-8-methoxydibenz[ft,/]oxepin-10(ll//)-ones with triethyl orthoformate rather drastic conditions are required (hot concentrated sulfuric acid) to give the 10-ethoxy derivative 12 in excellent yield.109... 

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... 

In contrast to the Vilsmeier formylation the formylation with trimethyl orthoformate in trifluoroacetic acid proceeds with high selectivity so that only the /3-monoformylated deuteroporphyrin derivatives 8 are formed without any methinc substituted or diformylated products.1073 6... 

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