Nitriles from formic acid

Several examples exist for the conversion of 5-aminothiazoles into the corresponding thiazolopyrimidines. Shaw and Butler report the formation of aminothiazole thiocarboxyamide 27 from the thioamide 26 and carbon disulphide using Cook and Heilbron s procedure. Methylation of 27 gave carboxythioimidate 28 which then reacted with sodium hydroxide to give amino-nitrile 29, and with formic acid and acetic anhydride to give the thiazolopyrimidine 30. 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

A related method for the synthesis of aldehydes from nitriles has also been studied.8 This method, which has been found to be extremely effective for the reduction of hindered nitriles to aldehydes, uses moist, preformed Raney nickel catalyst in formic acid. Compounds synthesized by this method are illustrated in Table II. 

Dihydrooxadiazoles 106 have been syntheised in moderate to high diastereomeric excess by the addition of aromatic nitrile oxides across the C=N bond of the hydrazones 105. The N-N bond can subsequently be cleaved with formic acid, and the chiral auxiliary recycled <99H(50)995>. The oxadiazolone 108 was produced (56%) from the oxime 107 by heating it with phenyl isocyanate <99SC3889>. ... 

In addition, minor variation of the catalyst in combination with immobilization on a resin support gave an analogous recyclable solid-supported organocatalyst. Varying the derivatization method by trapping the a-amino nitrile intermediate with formic acid and acetic anhydride gives the crystalline formamides 19 in excellent yield and with high enantioselectivity. These features of this catalytic process have been demonstrated by results from the synthesis of r-tert-leucine (Scheme 14.8) [49]. 

As the isonitriles are rapidly hydrolyzed to amines and formic acid, an extraction step with hydrochloric acid is normally sufficient in practice to remove these impurities from a desired nitrile product. 

In the aromatic series the direct conversion of acid amides into acid nitriles does not take place readily but the acid itself is made from the acid amide by the reverse process as indicated above, viz., by hydration to the ammonium salt of the acid, which then yields the acid. A related method, however, is used for preparing acids from anilides of formic acid. Aniline being an ammonia compound yields acid-amidelike products with aliphatic acids, e.g. acet anilide, CH3—CO—NH— CeHs (p. 556). Such a compound can not, however, lose water in the same way as the acid amide in the above reaction for the ammonia residue in an anilide contains only one hydrogen. Nevertheless anilides lose water but in a different way. In the case of the anilide of formic acid, i.e. formanilide, H—CO—NH—CeHs, the loss of water results in a compound in which the carbon and nitrogen remain linked to the benzene ring and an iso-cyanide or iso-nitrile is formed. The isonitrile is readily converted into the nitrile and the acid may then be obtained from that. 

Aldehydes from Nitriles with Raney Nickel Catalyst IN Formic Acid ... 

Sulfonyl halides (e.g. benzenesulfonyl chloride) form adducts (11) with acid amides in an equilibrium reaction. From these adducts or via adducts of this type 0-sulfonated lactim ethers, isonitriles, adenine, nitriles, amidines, amidinium salts and formic acid esters were prepared. The adducts from DMF and chlorosulfonamides (12) can be used to prepare amidines or amidrazones. A/-Chlorosulfonylcarboxylic acid amides yield nitriles on treatment with DMF or other tertiary amides, presumably via an acid amide sulfonyl chloride complex (13 equation 3). ... 

L.-M. Yang and co-workers designed and synthesized a new series of frans-stilbene benzenesulfonamide derivatives as potential antitumor agents.A common precursor diethylphosphonate was prepared from commercially available sulfanilamide in six steps. The aromatic nitrile-to-aldehyde reduction was affected by the modified Stephen reduction using Raney nickel alloy in aqueous formic acid. The corresponding aldehyde was obtained in high yield. 

The Taft analysis has the working disadvantage that it requires two measurements to define a a value, and it also suffers from the problem that the parameters of some substituents cannot be obtained either because the ester decomposes too quickly for measurements to be made or because it would not decompose by ester hydrolysis. Such restrictions apply to the halogen substituents, nitrile or the nitro group, which would require study of such compounds as Hal-CO-OR, NC-CO-OR and O2N-CO-OR. This problem can be solved by use of Taft analysis of esters of the type X-CH2-CO-OR instead of X-CO-OR. In this analysis the similarity coefficient, p, for the substituted acetic acid derivatives is attenuated by 0.41 from the set value of p = 2.48 for the formic acid derivatives (Equations 8 and 9). The a constants based on formic acid derivatives are recorded in Table 1 in Appendix 3. ... 

Amides from nitriles.1 Nitriles are converted into amides in high yield when heated at 250° (2 hours) with an equimolar amount of 100% formic acid in a pressure vessel which is preferentially cased with tantalum or silver. 

Because the yields of diesters (III.30) and (III.44) from nitriles (III.35) and (III.36) were only 15%, an alternative route was sought [32a]. Nitrile (III.38) was converted to aldehyde (III.39) by treatment with formic acid and Raney Ni, and the aldehyde was reduced with NaBH4 and converted directly to 2,4-diamino-6-bromomethyl-5-methylpyrido [1,3-d] -pyrimidine (III.40) by bromination with dibromotriphenylphosphorane in N,7V-dimethylacetamide (DMA). Coupling of (III.40) to dimethyl A-[4-(N-methylamino)benzoyl]-L-glutamate and diethyl A-[4-(A-ethylamino)benzoyl]-L-glutamate afforded the diesters (III.45) and (III.46), respectively. While the yield of (III.45) from (III.40) was 27%, that of (III.46) was unfortunately only 8%. Hydrolysis of the diesters gave the acids (III.42) and (III.43). 

MJnsaturated acids are rarely formed from -hydroxy acids by means of dehydrating agents, which, instead, afford lactides and anhydrides or, with loss of formic acid, aldehydes. However,, / -unsaturated nitriles can be obtained from a-hydroxy nitriles (cyanohydrins) by means of thionyl chloride45 or phosphorus(v) oxide,46 and are readily hydrolysed to the corresponding <%,/ -unsaturated acids. 

Haloformamidines are derivatives of formic acid the name haloforma-midines is used by Chemical Abstracts, which numbers the center carbon atom 1, and lists the nitrogens as N and N. However, this class of compounds is more closely related to carbamic acid, as evidenced by its synthesis from urea (carbamic acid amide) and cyanamide (carbamic acid nitrile). In a recent article ( ) concerned with the synthesis and reactions of substituted chloroformamidine hydrochlorides, the term carbamido chlorides was used. Since chloroformamidine hydrochlorides I are the amido chlorides of carbamide, this generic name is not unreasonable. There is no evidence for the isomeric geminate chloride structure II, and the polar character of I is evidenced by the relatively high melting points of chloroformamidine hydrochlorides, and by their insolubility in nonpolar solvents ( ). 

Nitrile benzoyl cyanide. C.H5ON. HfW, 131. M.p. 32-3°. B.p. 206-8°. NHj —> benz-amide. Alkalis—> benzoic acid + formic acid.. 45nide 0, 0. MW, 149. M.p. 91 Oxime a-isonitrosophenylacetic acid. Two forms, a-. Prisms from EtjO. M.p. 127°. Very unstable, p-. Needles from HjO. M.p. 145° decomp. Bess sol. than a-form. 

From o-Aminobenzenethiols (Type A S—C H4—N + C).—An improvement on the standard procedures (milder conditions) is the use of DMF dimethyl acetal instead of formic acid or alkyl orthoformates. A 64% yield of benzothiazolin-2-one is obtained when o-aminobenzenethiol is treated sequentially with carbon monoxide and oxygen in the presence of triethylamine and selenium in DMF. o-Aminobenzenethiol forms substituted vinylamine adducts with acetylenic nitriles RC=CCN. These cyclize in the presence of sodium ethoxide, and the products lose acetonitrile on distillation at atmospheric pressure to give 2-sub-... 

Almost all recorded purine syntheses from imidazoles involve the cyclization of 5(4)-aminoimidazole-4(5)-carboxylic acid derivatives especially the carboxamides, thiocar-boxamides, carboxamidines, carboxamidoximes, nitriles and esters. The intermediates used for completion of the purine ring are much the same as have been used for Traube cyclization of diaminopyrimidines (Section 4.09.7.3), especially formic and carbonic acid derivatives, and cyclization generally occurs-under much milder conditions. This feature has been of special value in the synthesis of purine nucleosides from imidazole nucleoside precursors. The resultant purine will have variable substituents at C-2 and C-6 and it is convenient to discuss and classify the various preparations largely in terms of the introduced 2-substituents. The C-6 substituents largely reflect the type of carboxylic acid moiety used and do not vary very much between amino, oxo and thioxo. 

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