Methanol nitriles

Analytical Procedures. Standard methods for analysis of food-grade adipic acid are described ia the Food Chemicals Codex (see Refs, ia Table 8). Classical methods are used for assay (titration), trace metals (As, heavy metals as Pb), and total ash. Water is determined by Kad-Fisher titration of a methanol solution of the acid. Determination of color ia methanol solution (APHA, Hazen equivalent, max. 10), as well as iron and other metals, are also described elsewhere (175). Other analyses frequendy are required for resia-grade acid. For example, hydrolyzable nitrogen (NH, amides, nitriles, etc) is determined by distillation of ammonia from an alkaline solution. Reducible nitrogen (nitrates and nitroorganics) may then be determined by adding DeVarda s alloy and continuing the distillation. Hydrocarbon oil contaminants may be determined by ir analysis of halocarbon extracts of alkaline solutions of the acid. 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

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). 

However, when the addition is performed 111 a nucleopliilic solvent such as methanol, cleavage of the imine linkage occurs to give difliioroamino compounds [78] (equation 12) W, At-Difluorotrifluoromethylamine can be prepared from or from thiocyanates, as shown in equation 13 [79, 80] Another way to produce difluoroamino compounds is the addition of fluorine to nitriles by means of AgFj [Sf ] or C0F3 [S/]... 

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. 

By selection of conditions and catalyst, the intermediate hydroxyimine (11) can be directed to either (he hydroxy ketone (10) or amino alcohol (12), Over platinum oxide in methanol-acetic acid-water the amino alcohol forms, whereas over alkali-free Ra-Ni in methanol-water or over 10% Pd-on-C in methanol-water containing boric acid, the hydroxy ketones form in excellent yield. Nitrile oxide cycloadditions have been applied to five-membered ring syntheses (.50). 

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. 

Interestingly, when R1 and R2 are hydrogens, the -configurated amino nitriles 1 arc obtained, whereas one or two methoxy substituents on the aromatic ring leads to (S)-diastereomers. This surprising effect is caused by the preferential crystallization of the (R)- or the (.S )-diastereomers, respectively. If the pure diastereomers of 1 are dissolved in methanol, equilibration occurs. On concentration, the optically pure diastereomer again crystallizes from the solution45. 

Usually, the reaction is carried out at 60 °C in methanol. After addition of acetic acid and on cooling, the diastereomerically pure amino nitrile crystallizes from the reaction mixture. If crystallization docs not occur, the mixture is stirred in the open vessel until precipitation of the pure diastereomer takes place. 

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]... 

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

The reaction of the a-bromo aldoxime 52e (R = R = Me) with unsaturated alcohols has been extended to the heterocyclic systems furfuryl alcohols and 2-thiophene methanol [29b]. The furanyl and thiophenyl oximes 63a-c were treated with NaOCl and the resulting heterocyclic nitrile oxides were found to undergo spontaneous intramolecular dipolar cycloaddition to produce the unsaturated tricyclic isoxazolines 64a-c in high yield (Eq. 5). In these cases, the heterocyclic ring acts as the dipolarophile with one of the double bonds adding to the nitrile oxide [30]. 

The microgels could be conveniently isolated by precipitation as white powders, readily redispersable in many different organic solvents such as dialkylamides, nitriles, dichloromethane, acetone and THF. Further to this, the DMAA-based microgels exhibited a rather amphiphilic character and were also soluble in water and in alcohols such as methanol or ethanol in contrast, their counterparts based on MMA turned out to be more lipophilic and therefore insoluble in water and alcohols but soluble in organic solvents of low polarity such as toluene. 

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