Reaction with methyl formate

Catalytic reduction of folic acid to 5,6,7,8-tetrahydrofolic acid (225) proceeds fast in trifluoroacetic acid (66HCA875), but a modified method using chemical reductants leads with sodium dithionite to 7,8-dihydrofolic acid (224). Further treatment with sodium borohydride gives (225) which has been converted into 5-formyl-(6i ,S)-5,6,7,8-tetrahydro-L-folic acid (leucovorin) (226) by reaction with methyl formate (equation 70) (80HCA2554). 

Phosphorus pentachlonde, for conver sion of d l 10 camphorsulfomc acid to acid chloride, 46,14 reaction with methyl formate to yield dichloromethyl methyl ether, 47, 47... 

Good, D.A., Hanson,]., Francisco, ].S., Li, Z., andjeong, G.-R. Kinetics and reaction mechanism of hydroxyl radical reaction with methyl formate, J. Phys. Chem. A, 103(50) 10893-10898, 1999. 

Another aspect of the reactivity of the sulfur atom is illustrated by a reaction done on thianthrene. Indeed, 8 is not sufficiently nucleophilic to be alkylated by methods that work well with dialkyl and alkyl aryl sulfides, although Saeva was able to alkylate it by reaction with -cyanobenzyl bromide and silver triflate <1986T6123>. The sulfonium salt 52 bearing a methyl group can be obtain by an acid-promoted reaction with methyl formate (Equation 4) <1998JCX37522>. 

N-(1-Ethoxyvinyl)-4-pyridone, from ethoxyacetylene, 822 a-Ethylacetoacetanilide, reaction with methyl formate, 616... 

Even though form amide was synthesized as early as 1863 by W. A. Hoffmann from ethyl formate [109-94-4] and ammonia, it only became accessible on a large scale, and thus iadustrially important, after development of high pressure production technology. In the 1990s, form amide is mainly manufactured either by direct synthesis from carbon monoxide and ammonia, or more importandy ia a two-stage process by reaction of methyl formate (from carbon monoxide and methanol) with ammonia. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

The second group of reactions is called vicinal difunctionalization. They embrace the C2 and C3 positions of the furan ring simultaneously. Thus, complex 3 (X = O, R = R = R = H) reacts with benzaldehyde dimethyl acetal to give 4H-furanium cation (the product of electrophile addition at C4), which experiences further attack by the methoxide group with formation of the acetal 8 (950M2861). This reaction is possible in the presence of the Lewis acid (BF3—OEt2). Reaction with methyl vinyl ketone in methanol, when run in identical conditions. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Ab initio molecular orbital calculations are being used to study the reactions of anionic nucleophiles with carbonyl compounds in the gas phase. A rich variety of energy surfaces is found as shown here for reactions of hydroxide ion with methyl formate and formaldehyde, chloride ion with formyl and acetyl chloride, and fluoride ion with formyl fluoride. Extension of these investigations to determine the influence of solvation on the energy profiles is also underway the statistical mechanics approach is outlined and illustrated by results from Monte Carlo simulations for the addition of hydroxide ion to formaldehyde in water. 

When alkyl nitrates and in particular methyl and ethyl nitrates are added to acids (H2SO4, SnCl4, BF3) they give rise to a very violent reaction with the formation of large quantities of gas. The presence of impurities, nitrogen oxid, transition metal oxides increases the sensitivity of these mixtures to detonation. 

The ionic cycle is important under reaction conditions where iodide ion can exist, e.g., higher water levels (CH3OH + HI CH3I + H20) or with salt additives. However, while higher ionic iodide levels give an iridium species capable of very rapid reaction with methyl iodide, they also serve to inhibit the formation of an acyl species. The relatively slow conversion of [CH3Ir(CO)2I3] to an acyl species is almost certainly not... 

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