Ortho-formate

HOUBEN - HOESCH Phenol Acylation Synthesis ol ketones (or aldehydes) by acylation ol phenols with nitriles (or ortho formates)... 

Diethylamino-4-methylselenazole on warming with ethyl ortho-formate in the presence of anhydrous zinc chloride gives an intense violet coloration. ... 

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

The final acetal is made by the usual acid-catalysed method, using the ortho-formate IIC(0Et)2 as a dehydrating agent. ... 

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. 

The conversion of a Grignard or an organolithium reagent to an aldehyde has been accomplished by a variety of reagents. The methods include such reagents as N-ethoxymethyleneaniline 2 ethyl ortho-formate 2" p-dimethylaminobenzaldehyde 25 dimethyl formamide 3 a... 

Fusion of the imidazole ring to pyrrolo-benzothiadiazepine 340 can be achieved by straightforward TosMIC cycloaddition approach (Scheme 72, Section 4.2 (1994JHC1033)). An alternative sequence starts with the addition of nitromethane to the C-N double bond on the thiadiazepine ring, nitro group reduction and manganese oxide oxidation of the intermediate dihydroimidazole derived from amine 342 and tiiethyl ortho formate. 

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. 

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. 

An intEiesting variant on the Wilgerodt reaction offers a simple three-step procedure that avoids the wastage involved in the schemes above, which require the incorporation of an extra carbon atom that must later be eliminated. The sequence starts with the acylation of isobutylbenzene (49-1) with propionyl chloride to give propiophenone (49-2). Reaction of that with thallium 111 nitrate and methyl ortho-formate in methanol leads in high yield to the methyl ester (49-3) of ibuprofen [50]. This would be the method of choice for preparing the dmg but for two unfortunate facts the extreme toxicity of thallium and the very high sensitivity of analytical methods for the detection of metals. It proved to be virtually impossible, in practice, to produce samples that showed zero residues of thallium. 

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. 

The procedure given for the preparation of phenylpropargyl aldehyde is a modification of Claisen s directions3 in part due to Kalff.4 The monobromocinnamic aldehyde was described by Zincke.5 Other methods of possible preparative value for the acetal are the interaction of sodium phenylacetylene,6 9 or the Grignard reagent from phenylacetylene,10 11 and ethyl ortho-formate. 

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 esterification of carboxylic acids with DMF acetal (Formula A in Figure 9.16) proceeds in line with the esterification of carboxylic acids with ortho formates (Formula A in Figure 9.15). The reaction conditions are even milder since no acid needs to be added. This is due to the fact that all cationic intermediates of an esterification according to Figure 9.16 are iminium ions in which the positive charge is better stabilized than by the cationic intermediates of esterifications shown in Figure 9.15, because they are carboxonium ions. 

Laschat and coworkers described an interesting domino Michael addition/elec-trophilic-trapping process leading to 2-191 as a single diastereomer in 53% yield, which was further transformed into enantiopure cylindramide (2-192) (Scheme 2.45) [110]. During the course of the process, substrate 2-190 was reacted with a TMS-protected propynyl cuprate and subsequently with ortho formate and BF3-OEt2. 

A very important and versatile method en route to a NHC is the ring closure reaction with ortho-formate [18,34,36,43] (see Figure 1.7). Here a suitable diamine is reacted with a triester of formic acid resulting in a N=CH-N group that can be deprotonated to form a carbene. 

The procedure has been extended to the formation of difunctional compounds like 3-methyl-3-butenal diethyl acetal (24%), 1,1-diethoxy-2-butyne (80%), and /3-ethoxyethyl methyl ketone diethyl ketal (92%). A somewhat related reaction is the formation of diethyl acetals of a-formyl esters by treatment of a-bromo esters with zinc and ethyl ortho formate (45 60%). ... 

The synthesis of chroman 15 involves an acid-catalyzed condensation of trimethyl hydroquinone (14) with methyl vinyl ketone (9), but unfortunately the mechanism is not clarified in detail and the role of the ortho formate is also not clear. Scott et al. assumed that the reaction proceeds via the intermediates 27 and 28. ... 

The equilibrium between a ketone and an alcohol on the one hand and the dimethyl acetal on the. ther is unfavourable and must be driven over by devices such as this. The ortho formate is even ore unstable than the acetal three C-O bonds instead of two at the same carbon atom) and the ener even more stable, because of conjugation, than the ketone. There are various mechanisms you -right have drawn, which differ only in details such as the order of the steps. Here is one such. 

Orthoformates have been reacted with secondary aliphatic aminesj- A -alkylanilines, 1,3.5-triaminocyclohexanes and cyclic triamines to afford trisaminomethane derivatives, e.g. (535) and (536) (Scheme 97), usually in unsatisfactory yields. Better results have been reported when ortho-formates were replaced by amide acetals. - ... 

Methyl-2-furoic acid has been prepared by the oxidation of 3-methyl-2-furaldehyde4 and by the degradation of 3-methyl-2-isovalerylfuran (Elsholtzia ketone).6 3-Methylfuran has been prepared by the present method 6 and more recently by a three-step method starting with methallyl chloride and ethyl ortho-formate.7 Circuitous routes from citric acid 8 and malic acid 9 have also been used. 

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 most general and probably the best method for synthesizing 9-aminopurines makes use of the cyclization of suitable 5-amino-6-hydrazi-nopyrimidines. As cyclizing agents, formic acid or ortho-formates are often used the best mixture is of ort/io-formate and acetic anhydride. The cyclization process is often accompanied by side reactions [Eq. (27)]. 

Micelles concentrate reactants from the surrounding medium and provide microenvironments favorable to reaction. Rate enhancement arises from electrostatic and hydrophobic interactions between reactants and micelles. Rates may be strongly dependent on the struture of the reactant. For example, the hydrolysis of methyl ort/iobenzoate is catalyzed by micellar sodium dodecylsulfate, whereas the hydrolysis of methyl ortho-formate (which has less hydrophobic character and less affinity for the micelle core) is not ". The more pronounced the hydrophobic nature of the reactant, the more rapid is the micellar catalysis. ... 

Angustmycin A (decoyinine, 68, R = adenin-9-yl, R = CH2OH) has been prepared from psicofuranine (71a) by way of the 1, 3, -ortho-formate. Standard elimination, and removal of the ester by partial hydrolysis with acid, gave a product which was identical with the natural antibiotic. In the course of the work, compound 68 (R = adeni-nyl, R = H) was again prepared.1298... 

Synthesis of ketones (or aldehydes) by Lewis acid catalyzed acylation of phenols with nitriles or ortho formates (see 1st edition). 

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... 

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