Triethyl orthoformate reaction with diethyl

Preparation of tetraethyl monoortho-2-carbethoxy-succinate by the reaction of diethyl maleate with triethyl orthoformate [201]. 

Three separate methods were developed for the synthesis of 2,3 -bisindolylmethanes 177 <0451187>. These compounds were converted into indolo 3,2-i)lcarbazoles by an acid-catalyzed annelation reaction with triethyl orthoformate. A new synthesis of the structurally related indolo 3,2-a carbazoles involved the cyclocondensation of 2,3 -biindoles with dimethylaminoacetaldehyde diethyl acetal <04TL7273>. 

For the production of 8 - po-) -carotenal, a Cs-aldehyde, in form of its diethyl acetal, was required as the middle section of the carotene skeleton. This was obtained hy a horon trifluoride-catalysed condensation of ethyl 1 -propenyl ether with triethyl orthoformate. After partial hydrolysis and reaction with sodium acetyhde, the reaction with triethyl orthoformate was repeated. The yield over all steps was around 50 %. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Nitroacetaldehyde diethyl acetal is prepared by the reaction of nitromethane with triethyl orthoformate in the presence of ZnCl2 (Eq. 5.8).17 Jager and coworkers have used this reagent for the synthesis of amino sugars via nitro-aldol reaction.18 Preparation of this useful reagent is now described in volume 74 of Organic Synthesis.19... 

Guo et al. prepared N-(3-chloro-4-fluorophenyl)aminomethylenemalo-nate (256, R = 3-C1, R1 = 4-F, R2 = R3 = Et) in 60-70% yields when 3-chloro-4-fluoroaniline was reacted with triethyl orthoformate and diethyl malonate in the presence of a Lewis acid. From the reaction mixture, ethyl A-(3-chloro-4-fluorophenyl)-2-[(3-chloro-4-fluorophenyl)-aminomethylene]malonamate and A-(3-chloro-4-fluorophenyl)formanilide were also isolated as byproducts (88MI3). 

Triethyl orthoformate is often used in reactions with enolates and carbanions to form diethyl acetals that on treatment with dilute acid give the corresponding formyl derivatives. However, when indole is heated at 160 C with triethyl orthoformate the locus of reaction is at N-1 rather than at C-3, and 1-(diethoxymethyl)indole is formed (Scheme 7.6). The A -substituent is easily removed by acidic hydrolysis to reform indole. 

Granik et al. prepared pyrimido[l,6-enamino amide 487 with diethyl acetals of dimethylformamide or dimethylacetamide in refluxing ethanol (80KGS1120). Compound 488 (R = H) was also obtained from enamino amide 487 in 61% yield by reacting it with triethyl orthoformate in refluxing acetic anhydride. 

The reagent catalyzes the reaction of phenylacetylene with triethyl orthoformate to give phenylpropargylaldehyde diethyl acetal. A mixture of the reactants is... 

Tetrahydro-l//-pyrido[l,2-c]pyrimidines 189 and -1-one 190 were prepared from cyclic aminoazadienes 188 by reaction with aldehydes and triphosgene, respectively (92SL563). 4-Cyano-5,6,7,8-tetrahydro-3//-pyrido[l,2-c]pyrimidin-3-one and its 1-methyl and 5-dimethylaminomethylene derivatives were prepared in the reactions of 2-[cyano(aminocarbonyl)-methylenejpiperidine with triethyl orthoformate in acetic anhydride with N,N-dimethylacetamide diethyl acetal, or with N,A -dimethylformamide diethyl acetal (80KGS416, 80KGS1120 82KGS518). 

A more versatile synthesis of the pteridine ring from pyrimidine-4,5-diamine involves the initial formation of a Schiff base by reaction with an aldehyde followed by cyclization with triethyl orthoformate or dimethylformamide diethyl acetal. The general reaction is shown below, and is exemplified by the synthesis of 6-phenylpteridine-2,4(1 //,3//)-dione (2)." 7... 

Acetattzation. Diethyl acetals are formed from carbonyl compounds by functional group exchange with triethyl orthoformate (EtOH also present) under the influence of DDD." Benzylic activation. Hydride abstraction by DDQ from benzyl ethers, where the benzylic position is also activated by a nuclear substitutent (e.g., methoxy group), prepares such compounds to be attacked by nucleophiles. The reaction constitutes an important step in a synthesis of deoxyfrenolicin. ... 

Oxadiazoles can be sucessfully obtained from amidoximes and diethyl carbonate/ f-BuOK °, triethyl orthoformate/BFs OEtg or by reaction of hydroximoyl chlorides with nitriles . ... 

Organoaluminum compounds, reaction with imino carbocations, 66, 189 Orthoester Claisen rearrangement, 66, 22 Orthoformic acid, triethyl ester, 65, 146 Oxalic acid, diethyl ester, 65, 146... 

One can also acetalize carbonyl compounds completely without using the alcohol in excess. This is the case when one prepares dimethyl or diethyl acetals from carbonyl compounds with the help of the orthoformic acid esters trimethyl orthoformate HC(OCH3)3 or triethyl orthoformate HC(OC2H5)3, respectively. In order to understand these reactions, one must first clearly understand the mechanism for the hydrolysis of an orthoester to a normal ester (Figure 7.16). It corresponds step by step to the mechanism of hydrolysis of <9,<9-acctals, which was detailed in Figure 7.15. The fact that the individual steps are really strictly analogous becomes very clear when one takes successive looks at... 

Diethyl acetals and ketals. Claisen showed that triethyl orthoformate reacts with aldehydes and ketones to form diethyl acetals and diethyl ketals. The reaction... 

Reaction with reactive-methylene compounds. Claisen" developed a method for the preparation of diethyl ethoxymethylenemalonate by heating a mixture of triethyl orthoformate, malonic ester, and acetic anhydride with a catalytic amount of zinc chloride. The yield cited is that obtained in a standardized procedure."... 

The reactions of l-aminocarbonylmethylene-3,4-dihydro- and 1,2,3,4-tetrahydroisoquinolines with N,A -dimethylcarboxamide diethyl acetals, triethyl orthoformate, and diethyl carbonate yielded 6,7-dihydro-2//-pyrimido[6,l-a]isoquinolin-2-ones [81KFZ(5)44 82KGS1095 84JMC1470] and 9,10-dimethoxy-3,4,6,7-tetrahydro-2//-pyrimido[6,l-fl]isoquinoline-... 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

The reactions of l-aminocarbonylmethylene-3,4-dihydro- and 1,2,3,4-tetrahydroisoquinolines with lV,lV-dimethylcarboxamide diethyl acetals, triethyl orthoformate, and diethyl carbonate yielded 6,7-dihydro-2//-pyrimido[6,l-a]isoquinolin-2-ones [81KFZ(5)44 82KGS1095 84JMC1470] and 9,10-dimethoxy-3,4,6,7-tetrahydro-2//-pyrimido[6,l-n]isoquinoline-2,4-dione (84JMC1470), respectively. A mixture of l-ethoxycarbonyl-9,10-dimethoxy-3,4,6,7-tetrahydro-27/-pyrimido[6,l-fl]isoquinoline-2,4-dione and l-[cyano(ethoxycarbonyl)methylene]-l,2,3,4-tetrahydroisoquinoline was obtained when 6,7-dimethoxy-l-aminocarbonylmethylene-l,2,3,4-tetrahydroisoquinoline was reacted with ethyl chloroformate in methylene chloride in the presence of pyridine (84JMC1470). 

The strategy for the synthesis of phosphinate 54a or 54b involves the activation of the phosphoms atom into the P reactant, followed by successive reactions with a Michael acceptor (ethyl acrylate or diethyl maleate), dibromoethane, and an esterification using triethyl orthoformate. The incorporation of the amino acid group accomplished by nucleophilic substitution of the anion of the diethylaceta-midomalonate yielded the branched phosphinates in 50-77% yield. The final deprotected compounds were obtained in 11-21% yield after acidic deprotection and decarboxylation and they were purified by ion exchange chromatography. Compound 54b was synthesized by alkylation of the phosphonite intermediate with acetamidoacrylic acid, followed by acidic deprotection and ion exchange chromatography purification (Scheme 8). 

Active Methylene Compounds. Triethyl orthoformate can formylate diethyl malonate under slightly acidic conditions. With less activated compounds it can be induced to undergo a Mannich reaction, and can also formylate a cyclohexanone enolate anion (eq 9). ... 

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