Triethyl-ortho formate

N,N -Disubstituted formamidines, N-substituted from triethyl ortho formate and pnmary amines, 46, 41... 

The ring system in 541 was synthesized (76JHC1249) by interaction of 4-hydrazino-7-phenylpyrazolo[l,5-a][l,3,5]triazine 540 and ethyl pyruvate. The hydrazino derivative 540 was prepared on cyclocondensation of 5-amino-l-thioamido-3-phenylpyrazole 537 with triethyl ortho-formate to give the pyrazolotriazinethione 538 followed by methylation to give 539 and hydrazinolysis to give 540. 

An alternate route to fuse an imidazole to a pyrrolo-benzothiadiazepine includes side-chain nitro reduction and manganese oxide oxidation of the dihydroimidazole derived from amine 342 and triethyl ortho formate (Scheme 72, Section 4.2 (1994JHC1033)). 

A general route to meso-ionic l,3-diazol-4-ones (91) involves the reaction of amino amides (R NHCOCHjNHR ) either with triethyl ortho formate or with JV-phenylbenzimidoyl chloride. 

Cyclohexanone diethyl ketal was prepared according to a procedure by Howard and Lorette see Org. Synth., Collect. Vol. V 1973, 292 bp 80-83°C, 18 mm. The checkers prepared it by keeping cyclohexanone (50 g), triethyl ortho-formate (75 g) and concentrated hydrochloric acid (0.2 mL) in absolute ethanol (30 mL) for 10 hr at room temperature, followed by treatment with sodium hydroxide until the solution is basic. 

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 ortho formic acid esters trimethyl ortho formate HC(OCH3)3 or triethyl ortho formate 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 9.13). ft corresponds nearly step by step to the mechanism of hydrolysis of 0,0-acetals, which was detailed in Figure 9.12. The fact that the individual steps are analogous becomes very clear (see Figure 9.13) when one takes successive looks at... 

The method has been applied by the submitters2 to the preparation of cyclohexylmethylpropiolaldehyde diethyl acetal (54% yield) from cyclohexylmethylacetylene and triethyl ortho-formate of phenylethynyl -butyl dimethyl ketal (40% yield) from phenylacetylene and trimethyl tt-orthovalerate and of phenylethynyl methyl diethyl ketal (34% yield) from phenylacetylene and triethyl orthoacetate. w-Butylpropiolaldehyde diethyl acetal was isolated in 32% yield by heating an equimolar mixture of 1-hexyne and triethyl orthoformate containing catalytic amounts of a zinc chloride-zinc iodide catalyst under autogenous pressure at 190° for 3 hours. 

The cyclization of 4-hydrazinothieno[2,3-d]pyrimidine 58 with triethyl ortho formate gave the l,2,4-triazolo[4,3-c ]thieno[3,2-e]pyrimidine 59, whereas its cyclization with formic acid gave the isomeric l,2.4-triazolo[l,5-c]thieno[3,2-e]pyrimidine 60 (81JHC43). It was reported later (85JHC831) that the triazolothienopyrimidines formed by the cyclization of 4-hy-drazino-2-phenylthieno [2,3-rf]pyrimidine with triethyl ortho formate or formic acid have the l,2,4-triazolo[4,3-c]thieno[3,2-e]pyrimidine structure because of their failure to isomerize under acid catalysis, but under basic conditions isomerization yielded the 5-phenyl-l,2,4-triazolo[l,5-c]-thieno[3,2-e]pyrimidine (85JHC831). Proton magnetic resonance spectroscopy showed that the triazole proton of triazolo[4,3-c] isomers are more... 

Imidazo[4,5- ]pyridines 117 <2003BML2485>, 118 <2004BML3165>, 119 <2005BML2129>, and 120 <2003BML289> have been prepared from the corresponding diaminopyridine and the appropriate trialkyl ortho-formate or, in the case of 120, triethyl orthopropionate. However, in each case, the authors fail to report product yields. 

Having established that 1 catalyzes the hydrolysis of orthoformates in basic solution, the reaction mechanism was probed. Mechanistic studies were performed using triethyl orthoformate (70) as the substrate at pH 11.0 and 50 °C. First-order substrate consumption was observed under stoichiometric conditions. Working under saturation conditions (pseudo-0 order in substrate), kinetic studies revealed that the reaction is also first order in [H+] and in [1]. When combined, these mechanistic studies establish that the rate law for this catalytic hydrolysis of ortho-formates by host 1 obeys the overall termolecular rate law rate = k[H+][Substrate][l], which reduces to rate = k [H ][l] at saturation. 

An example of the formation of an ester of an -4,5-alkenoic acid 164 comes in a synthesis of chrysanthemic acid by Ficini and her group.31 Reduction gives the allylic alcohol 163 and [3,3] Claisen rearrangement with triethyl ortho-acetate gives the product 164 in one step. 

C.HisOj]- (CH3CH20)2CH0CHCH3 Reaction of TBO- with triethyl-ort/io-formate/ T riethyl-ortho-formate EPR/ 233 H(a) 1.564 2.275 H(y) 0.067 69Hud6... 

Having a cyano group and an amino group ortho to each other on a ring is another system that has led to the formation of fused pyrimidine ring systems. In this case, an aminopyrimidine is the result. Compound 42 in Scheme 5 is one such structure. Treatment of 42a with formamide leads to the amino derivative 43 <1999PS(155)175>. Alternatively 42b provides 44 after treatment with triethyl orthoformate followed by hydrazine <1999PS(155)175>. 

Methylene groups of pyrylium cations also react under mild conditions with nitrosoben-zenes in the presence of acetic anhydride and an alkali metal salt, which plays an essential role in the formation of Schiff s bases (116). The latter are hydrolyzed to the carbonyl compound (117) (71BSF3603). It is possible to form potential dyes by treatment of pyrylium salts with ortho esters such as triethyl orthoformate. The reactants are heated together in acetic anhydride or pyridine and trimethine dyes of type (118) and (119) are formed (70JHC1395, 71JOC600, 59CB2309). 

Cyclization of 2-aminobenzamides or 2-aminothiobenzamides 3 with ortho esters to form 2-substituted quinazolin-4(3f/)-ones or quinazoline-4(3//)-thiones 5 is a general although little studied cyclization process which can be applied also to hetarenic 2-aminocarboxamides. The isolation of intermediate 4 (R = H = Me X = CH = CH Y = O) from the reaction of 2-aminobenzamide with triethyl orthoacetate and the demonstration of its facile cyclization to 2-methylquinazolin-4(3//)-one on heating in ethanolic solution strongly supports the intermediacy of compounds of type 4 in the formation of 5. ° ... 

Much of the work on deoxygenation of aromatic nitro and nitroso compounds by tervalent phosphorus reagents has been reviewed.3 Triethyl phosphite has been used frequently, but diethyl methylphosphonite was found to be superior for the deoxygenation of nitro compounds.3,263 The isolation of azepines from such reactions (Scheme 42) indicated the initial formation of arylnitrenes. However, a marked influence of the nucleophile upon the direction of the apparent migration of the nitrene—away or toward an ortho substituent—was noted (Scheme 42).264 Evidence that the same intermediates are involved in the azepine forming reactions from phenyl azides and nitro-benzenes was obtained by a careful examination of the azepines formed from meta-substituted derivatives (Scheme 43). The ratios of the azepines 216 and... 

Thus, chalcone (26), available via aldol condensation between the appropriate benzaldehyde and acetophenone, was transformed into the 1,3-diarylpropene (27) via a two-step sequence involving ethyl chloroformate and NaBH4, followed by protection of the phenolic hydroxy group as the TBDMS ether. Asymmetric dihydroxylation of olefin (2 7) with AD-mix-a gave an intermediate diol, which was converted into ortho-ester (28) with triethyl orthoformate in the presence of catalytic pyridinium -toluenesulfonate (PPTS), followed by deprotection of the TBDMS ether with TBAF in THE. Treatment of ortho-ester (28) with triethyl orthoformate and PPTS gave an intermediate (27( ,35)- w j -flavan-3-ol formate ester. De-esterification with K2CO3 in THF/methanol and oxidation of the... 

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