Methanol with nitrile

Reaction of Methanol with Nitriles. - As the source of HCHO, it is impossible to use the HCHO which is formed by oxidation of methanol because the reaction of HCHO with nitriles is not promoted by acid catalysts and, on the other hand, HCHO... 

Reaction of Methanol with Nitriles, Ketones, and Esters... 

Reactions of methanol with nitriles, ketones and esters to yield or,/5-unsaturated compounds were found by Ueda etal. These reactions proceed by the catalysts possessing both acidic and basic functions. The general formula of the reactions is... 

A mixture of 3-bromoadamantane-l-carboxylic acid (5.8 g), acetonitrile (45 ml) and concentrated sulphuric acid (9 ml) was refluxed for 20 h. After cooling, the mixture was poured into water (250 ml), and the resulting suspension concentrated in vacuo to remove most of the acetonitrile. Aqueous sodium hydroxide (33%) was added until the pH was 4.0 (about 24 ml). The precipitate was filtered off, washed with water, and dried to yield 4.4 g of the 3-acetaminoadamantane-l-carboxylic acid, melting point 254°-258°C (two recrystallizations from methanol-aceto nitrile). 

In a recently reported synthesis of pyridines, lithiated methoxyallenes react with nitriles in the presence of trifluoroacetic acid (Scheme 107) <2004CEJ4283>. The mechanism is postulated to proceed via initial protonation followed by nucleophilic addition of the trifluoroacetate ion with subsequent intramolecular acyl transfer and aldol condensation to give the pyridine. An additional pyridine formation starting from azaenyne allenes forms a-5-didehydro-3-picoline diradicals, which can be trapped by 1,4-cyclohexadiene, chloroform, and methanol to produce various pyridines <20040L2059>. 

MgO, modified with a metal ion, is useful for the formation of unsaturated compounds by the reaction of methanol with ketones, esters, and nitriles (equation 14). The reaction is initiated by dehydrogenation of methanol followed by aldol addition and subsequent dehydration. The dehydrogenation activity of MgO is enhanced by the addition of Cr +, Fe +, and Mn +. ... 

An attempt based on the same concept was made using MgO-supported metal catalysts by Kurokawa et al. The results are listed in Table 17. The best performance is observed with the Mn catalyst. The reaction of methanol with acetonitrile is performed in the presence of a large excess of methanol that is, with a nitrile/methanol molar ratio of 1/10. The yield of acrylonitrile reaches 27.0 mol% based on the charged acetonitrile (2.7 mol% based on methanol) at an acetonitrile conversion of 29.6 percent. On the other hand, over the MgO supported Mn-Ni binary catalyst, the main product is propionitrile in analogy with the Zn/Na-aluminosilicate. The one-pass yield of propionitrile reaches 11.2 mol% based on acetonitrile (1.12 mol% based on methanol). In the reaction with propionitrile over the Mn catalyst, the yield of methacrylonitrile reaches 30.5 mol% based on propionitrile (3.05 mol% based on methanol). A small amount of isobutylonitrile is also observed in the product. 

It is possible to use the methanol as the source of HCHO in the reaction of HCHO with nitriles. However, the obtained yields of condensation products are lower than those obtained by using HCHO. Moreover, the side reactions of methanol, which usually exist in excess with respect to the amount of nitrile, are not reported. Possibly, a large part of... 

Reaction of Methanol with Carbonyl Compounds. - Similar to the reaction of methanol with carboxylic acid, esters, or nitriles shown in Sections 5.2 and 6.2, attempts were made to use the HCHO which is formed by dehydrogenation of methanol. Ueda et al. performed the reaction of methanol with acetone over various transition metal catalysts supported on MgO using an acetone/methanol molar ratio of 1/10. The best performances are obtained with a catalyst containing 3.1 wt% of Fe. The main products are methyl vinyl ketone, methyl ethyl ketone, and 2-propanol. The yields are 7.1, 2.8, and 2.8 mol%, respectively, based on the charged acetone at the conversion of 20.1% selec-tivities are 34.8, 13.9, and 13.9 mol%, respectively, based on acetone. The yield of methyl vinyl ketone is much lower than that achieved in the reaction with HCHO. Unfortunately, there is no information about the reaction of methanol that exists in the feed ten times greater than acetone. It is considered that methyl ethyl ketone and 2-propanol are formed by hydrogenation of methyl vinyl ketone and acetone, respectively, with methanol. 

When trans-mesylate (lb) was reacted in methanol with sodium cyanide, the imino compound (1 ) was isolated in 51 % yield in addition to 8 % side product. Thus, under the given conditions, the nitrile presumably formed as an intermediate, very rapidly undergoes to ring closure. Treatment of the amidine ( 4) with aqueous hydrochloric acid afforded 3-epi-eburnamenine. 

Isoxazoles display a range of biological activities, such as anti-inflammatory, antimicrobial, anticancer, and antinociceptive, that justify a constant effort in the development of new synthetic strategies. New syntheses of isoxazoles 1 and isQxazolines 2 via 1,3-dipolar cycloaddition (1,3-DC) of alkynes and alkenes with nitrile oxides were described (130L4010). The 1,3-dipoles were generated by oxidation of aldoximes catalyzed with hypervalent iodine species formed in situ from catalytic iodoarene and oxone as a terminal oxidant, in the presence of hexafluoroisopropanol (HFIP) in aqueous methanol solution. 

DL-Serine is synthesized in 51% over-all yield by Redemann and Icke s (661) modification of the method of Dunn et al. (212). Ethoxy-acetaldehyde (A) is prepared in aqueous solution by oxidizing ethylene glycol monoethyl ether (ethyl cellosolve) with copper chromite catalyst at 310-330°C. DL-Serine is prepared by reaction of NaCN, NH Cl and NH, in methanol with (A) and hydrolysis of the intermediate ethoxy nitrile with HBr. Other methods for the preparation of ethoxyacet-aldehyde have been described by the authors referred to by Dunn (203, p. 21) and by other workers (196-198, 412, 226). This synthesis... 

Instmmental methods of analysis provide information about the specific composition and purity of the amines. QuaUtative information about the identity of the product (functional groups present) and quantitative analysis (amount of various components such as nitrile, amide, acid, and deterruination of unsaturation) can be obtained by infrared analysis. Gas chromatography (gc), with a Hquid phase of either Apiezon grease or Carbowax, and high performance Hquid chromatography (hplc), using siHca columns and solvent systems such as isooctane, methyl tert-huty ether, tetrahydrofuran, and methanol, are used for quantitative analysis of fatty amine mixtures. Nuclear magnetic resonance spectroscopy (nmr), both proton ( H) and carbon-13 ( C), which can be used for quaHtative and quantitative analysis, is an important method used to analyze fatty amines (8,81). 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

A solution of 3 g of the nitrile, water (5 moles per mole of nitrile), and 20 g of boron trifluoride-acetic acid complex is heated (mantle or oil bath) at 115-120° for 10 minutes. The solution is cooled in an ice bath with stirring and is carefully made alkaline by the slow addition of 6 A sodium hydroxide (about 100 ml). The mixture is then extracted three times with 100-ml portions of 1 1 ether-ethyl acetate, the extracts are dried over anhydrous sodium sulfate, and the solvent is evaporated on a rotary evaporator to yield the desired amide. The product may be recrystallized from water or aqueous methanol. Examples are given in Table 7.1. 

After chilling to -t-12°C, additional methanol (35 ml) and a concentrated aqueous ammoniurt hydroxide solution (1.4M) (100 ml) are added and stirring is continued for 2 hours at a temperature maintained at from -t-5° to -H5°C. The organic layer is separated and solvent is stripped from the aqueous layer at water aspirator pressure at a temperature below 40°C. The residue is extracted several times with chloroform and the chloroform extracts are combined with the separated oil. Chloroform is removed at water aspirator pressure at a temperature below 35°C to leave crude q-amino- -methylmercaptobutyronitrile (methionine nitrile) in 88% yield (68 g) as a clear, somewhat viscous oil. 

The methionine nitrile (20 g) is dissolved in a solution prepared from 50 ml of aqueous 5N sodium hydroxide solution and 65 ml of ethanol. The solution is then refluxed for 24 hours ammonia is evolved. The solution is treated with activated carbon, filtered, acidified with glacial acetic acid (17 ml), chilled to -10°C and filtered to give crude product. This crude product is then slurried with a solution made up of 20 ml of water and 20 ml of methanol, filtered at -5° to -H0°C and dried to give dl-methionine as white platelets. 

The synthesis of pyrido[2,3-d]pyrimidin-7(8H)-ones has also been achieved by a microwave-assisted MCR [87-89] that is based on the Victory reaction of 6-oxotetrahydropyridine-3-carbonitrile 57, obtained by reaction of an Q ,/3-unsaturated ester 56 and malonitrile 47 (Z = CN). The one-pot cyclo condensation of 56, amidines 58 and methylene active nitriles 47, either malonitrile or ethyl cyanoacetate, at 100 °C for benzamidine or 140 °C for reactions with guanidine, in methanol in the presence of a catalytic amount of sodium methoxide gave 4-oxo-60 or 4-aminopyridopyrimidines 59, respectively, in only 10 min in a single-mode microwave reactor [87,88]... 

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