Formic acid nitriles

Ameisensaure, /. formic acid, -nitril, n. formo-nitrile (HCN). -salz, n. salt of formic acid, formate, -sulfonsiure, /. eulfoformic acid. Ameisen-spiritus, m. = Ajneisengeist. -wein-ather, m. ethyl formate. 

Nitrile of Formic Acid Nitrile of Acetic Acid Imide of Carbonic Acid Amide of Carbonic Acid Amide of Imide of Carbonic Acid... 

Hydrogen cyanide, as the nitrile of formic acid [64-18-6] CH2O2, undergoes many of the typical nitrile reactions. For example, it can be hydrolyzed to formic acid by aqueous sulfuric acid (4) it can be hydrogenated to methylamine [74-89-5], CH N (5) and it can be converted to phenylformamidine [618-39-3], CyHgN2, using aniline and hydrogen chloride (6). 

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 removal of the carbohydrate auxiliary group and the hydrolysis of the amino nitriles is achieved by acidolytic cleavage of the hemiaminal /V-glycosidic bond and the concomitant acid-catalyzed solvolysis of the nitrile using either hydrogen chloride in formic acid or hydrogen bromide in acetic acid56 57. 

The reaction proceeds via die hydrolysis of nitrile groups to an amide. The amides may also be A-formyl amines, which react with acid groups whereby volatile formic acid is shipped10 ... 

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>. 

Ammonium cerium(IV) nitrate on reaction with acetone or acetophenone generates acetyl- or benzoylformonitrile oxides, respectively (99). These nitrile oxides dimerize to furoxans and give, in the presence of alkenes and alkynes, 3-acetyl- or 3-benzoyl-4,5-dihydroisoxazoles and 3-acetyl- or 3-benzoylisoxazoles, respectively the yield of the isoxazole derivatives was improved on using ammonium cerium(III) nitrate tetrahydrate-formic acid (99). 

This reduction has also been achieved by treating the nitrile with sodium hypophosphite (NaH2P02 ) and Raney nickel in aqueous acetic acid - pyridine or formic acid. 

NAPHTHALENETHIOL, 51, 759 o-Tolualdehyde, by reduction of o-tolu-nitrile with Raney nickel alloy in formic acid, 51,25 p-Toluenesulfonyl azide, with 2-(hy-... 

An alternative method for the conversion of aromatic nitriles to aldehydes is their heating with Raney nickel and sodium hypophosphite in water-acetic acid-pyridine (1 1 2) at 40-45° for 1-1.5 hours (yields 40-90%) [1154], or heating with Raney nickel and formic acid at 75-80° for 30 minutes (yields 35-83%) [7/55], or even their refluxing for 30 minutes with Raney nickel alloy in 75% aqueous formic acid (yields 44-100%) [1156]. 

Substituted 1,2,4-oxadiazoles were prepared by addition of nitrile oxides to imines or hydrazones. It has been reported that interaction of hydroximoyl chlorides 262 with chiral hydrazones 263 in the presence of EtsN leads to intermediates 264 with diastereoselectivity up to 97%. A subsequent N-N bond cleavage to remove chiral auxiliary by formic acid leads to 1,2,4-oxadiazolines 265 with ee up to 91% (equation 113). ... 

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>. ... 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

LiAIH(OEt)3,345 DIBALH,346 and NaAIH4.347 The metal hydride method is useful for aliphatic and aromatic nitriles. Reduction to the aldehyde has also been accomplished by treatment of the nitrile with sodium hypophosphate and Raney nickel in aqueous acetic acid-pyridine or formic acid,348 and with zinc and a Cob(I)alamin catalyst in aqueous acetic... 

Not only do oximes undergo the Beckmann rearrangement, but so also do esters of oximes with many acids, organic and inorganic. A side reaction with many substrates is the formation of nitriles (the abnormal Beckmann rearrangement, 7-38). Cyclic ketones can be converted directly to lactams in one laboratory step by treatment with NH2OSO2OH and formic acid (6-20 takes place first, then the Beckmann rearrangement).247... 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

Many methods for the dehydration of primary amides to nitriles involve the use of strong acids and/or other reagents which are incompatible with sensitive functionality. French workers have recently described an unusual, mild, efficient (64-92%) and fairly general procedure for the RCONH2 —> RCN transformation which simply involves heating a mixture of the amide, an aldehyde and formic acid under reflux in acetonitrile for 12 hours. The following observations were made ... 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

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. 

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