Cyanoethylation, with acrylonitrile

Cinnolin-3(2//)-one (7) is methylated with diazomethane or methyl sulfate to give 2-methylcinnolin-3(2H)-one. In a similar manner, benzylation with benzyl chloride, cyanoethylation with acrylonitrile in the presence of benzyltrimethylammonium hydroxide and glucosidation with tetra-O-acetyl-a-o-glucopyranosyl bromide in the presence of a base affords the corresponding 2-substituted cinnolin-3(2//)-ones. However, glucosidation of the silver salt of cinnolin-3(2//)-one produces the corresponding O-substituted compound. 

Methylpseudouridine (m vj/) has been synthesised and incorporated into RNA where it was found to be slightly destabilising compared to pseudouridine.Psuedouridine can be selectively cyanoethylated with acrylonitrile, aiding its detection in tRNA by MALDI mass spectrometry. The presence of pseudouridine in RNA has also been detected by NMR using chemical exchange spectroscopy as pseudouridine has an additional Another... 

Synthesis of cyanoethylated ACEC XLVI (Scheme 61) involves the preparation of the monoglycidyl ether of the diol followed by cyanoethylation with acrylonitrile in the presence of 40% NaOH as catalyst (87% yield) and epoxidation with 45% aqueous PAA (89% yield). The diepoxide contains 9.93% oxirane oxygen (calculated 12.0%). 

It will be noticed that reaction at the pyrrole nitrogen atom usually involves either the use of potassium pyrrole or of alkaline conditions. It is not surprising, therefore, that in the presence of trimethylbenzylammonium hydroxide, pyrrole undergoes N-cyanoethylation with acrylonitrile e and that the sodium salt of 2-nitropyrrole behaves in the same way293. Related reactions are the formation of 1-pyridylethylpyrrole from the sodium pyrrole and 2-vinylpyridinei37 and of 1-vinylpyrrole from acetylene and potassium pyrrole. ... 

Ghloropyrrolo [2,3-d] pyrimidine and ethyl acrylate added to a soln. of Na in abs. ethanol, and refluxed 3 hrs. under anhydrous conditions ethyl 4-chloro-pyrrolo[2,3-d]pyrimidine-7-propionate. Y 92%. F. e., also N-cyanoethylation with acrylonitrile, s. R. A. West, J. Org. Ghem. 28, 1991 (1963). 

Acrylonitrile reacts with the sodium salt of 4.5-dimethvl-A-4-thiazoline-2-thione (73J (R4 = R5 = Me) to yield 3-(2-cyanoethyl)-4.5-dimethyl-A-4-thiazoline-2-thione (74) (R4 = R, = Me) (Scheme 35 (160). Humphlett s studies of this reaction showed that the size of the R4 substituent is a determinant factor for the S versus N ratio (161. 162). If R4 == H, 100% of the N-substituted product (74) is obtained this drops to 50% when R4 = methyl, and only the S-substituted product (75) is obtained when R4 = phenyl. The same trend is observed with various CH2 = CH-X (X = C00CH3. COCH3) reagents (149). The S/N ratio also depends on the electrophilic center for CH2 = CH-X systems thus S-reaction occurs predominantly with acrylonitrile, whereas N-substitution predominates with methvlvinvlketone (149). 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

Cyanoethylation. One of the eadiest examples of etherification of ceUulose by an unsaturated compound through vinyl addition is the cyanoethylation of cotton (58). This base-cataly2ed reaction with acrylonitrile [107-13-1/, a Michael addition, proceeds as foUows ... 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

A major type of reaction in this class is the cyclization of 4-amino- or 4-halo-pyrimidines carrying 5-cyanoethyl or 5-ethoxycarbonylethyl groups, which cyclize to 7-amino or 7-oxo derivatives of 5,6-dihydropyrido[2,3- f]pyrimidine, e.g. (131)->(63). The intermediates may sometimes be prepared by reaction of 4(6)-aminopyrimidines with acrylonitrile, or even via a pyrimidine ring synthesis from an amidine and a cyanoacetic ester or malononitrile derivative, e.g. (132) -> (133) (7lJOC2 85, 72BCJ1127). 

Cyanoethylation of pteridinones with acrylonitrile in pyridine/water provides a parallel to the alkaline alkylations, with substitution at the nitrogen atoms of the lactam groups (62JOC1366, 61JOC2364). 

The side-chain cyanoethylation of alkyl thienyl ketones with acrylonitrile has been studied " and used for the preparation of 8-oxonitriles and S-oxoacids. Aminomethylation (Mannich reaction) of 2-acetylthiophene followed by steam distillation yielded 50% of 2-thienyl vinyl ketone, and has also been used for the synthesis of compounds of biological interest. ... 

A photochemical reaction of indole with acrylonitrile gave an a-cyanoethylated indole (delocalization band in Scheme 10) [46]. This is a photochemical reaction in the delocalization band. 

On treatment with acrylonitrile in 2% aqueous sodium hydroxide at 0°, tetrahydropyran-2-yl /3-D-glucopyranoside gave the 2-, 3-, 4-, and 6-0-(2-cyanoethyl) ethers (together with some diethers) in yields that, on extrapolation to zero reaction, showed3 9 k2 k3 k4 k6 to be in the ratios of 3 1 2 8 these values represent equilibrium, not rate, constants. The tendency for substitution at 0-6 is a consequence of the greater stability of an ether derived from a primary (compared to a secondary) hydroxyl group, as a result of lower steric interactions in the former. 

Cyanoethylation of acrylonitrile with monohydric alcohols gives alkoxypropio-nitriles (Scheme 25). These nitriles can be converted into various types of carboxylic acids by hydrolysis, and they can be hydrogenated to give amines. Therefore, cyanoethylation of alcohols is an important reaction for the synthesis of drug intermediates and organic compounds of industrial interest. 

Sorm and Beranek39 used an intramolecular acylation in their synthesis of l-azoniumtricyclo[3.3.3.0]undecane (66). Condensation of nitromethane with acrylonitrile in the presence of an alkaline catalyst resulted in the formation of tris-(2-cyanoethyl)nitromethane (60), which afforded the triethyl ester 61 on hydrolysis followed by esterification. The ester was reduced catalytically to give a pyrrolidone (62). The derivative (62) gave rise to 8-(j8-carboethoxyethyl)-3,5-dioxo-pyrrolizidine (63) on heating. Reduction of 63 resulted in the formation of 8-(y-hydroxypropyl)pyrrolizidine (64). Replacement of the hydroxy group by bromine (65), followed by cyclization, afforded the tricyclic compound 66. 

Pyrazino[l, 2-a Jpyrimidines can also be prepared from piperazin-2-ones. Catalytic hydrogenation of 4-benzyl-l-(2-cyanoethyl)piperazin-2-one (279) over Raney nickel gives the cyclized product (280) in near quantitative yield. The cyanoethyl piperazine can be prepared from the corresponding piperazine (278) by reaction with acrylonitrile (73BCJ3612). 

Cyanoethyl derivatives can be prepared with acrylonitrile. Both mono-and disubstituted amino groups can be produced. Reaction at pH 9.2, 2°, with 0.4 M acrylonitrile for 7 days modified all lysine residues with no apparent change in any of the other amino acids (106). The lysine was almost entirely accounted for as dicarboxyethyllysine in acid hydrolysates of the derivative. The a-amino group had apparently also reacted. The fully substituted derivative had no RNA activity. The physical properties were very similar to those of native RNase-A. 

The same method of synthesis was used in the case of polysarcosine dimethylamide, the terminal base group of which reacts rapidly with acrylonitrile to give tertiary cyanoethylated base residues (24). Me-NH-CHj-CO (-N -C. H 2-CO)M-NMe ... 

In the simplest case, reaction of a primary monoamine via a two-fold Michael reaction with acrylonitrile (bis-cyanoethylation) led to the dinitrile (Fig. 1.1). Subsequent reduction of the two nitrile functions - by hydrogenation with sodium borohydride in the presence of cobalt(II) ions - afforded the corresponding terminal diamine. Repetition (iteration) of this synthetic sequence, consisting in Michael addition followed by reduction, provided the first - structurally variable - access to regularly branched, many-armed molecules. 

Irradiation of naphthols or their trimethylsilyl ethers with acrylonitrile gives the photocycloadduct, which is converted to cyanoethyl-substituted naphthols (30,31) by treatment with a base [111,119] (Scheme 13). 

Nucleophilic additions of alcohols to a,/ -unsaturated compounds have been performed on alkali metal oxides and hydroxides. Cyanoethylation of various alcohols with acrylonitrile to form 3-alkoxypropanenitriles has been carried out efficiently in the presence of these solid base catalysts at a temperature of 323 k.[68,69] In cyanoethylation of methanol, conversions of 98 % after 2 h in a batch reactor were obtained with MgO, CaO and SrO in contrast, with BaO the conversion was only 68 %. 

The cyanoethylation of polysaccharides has been studied extensively in starch and cellulose. The hydroxyl groups (typically the C-4) on the molecule react with acrylonitrile in the presence of alkali to form a cyanoethyl ester. O-Cyanoethylated cellulose is used in the paper industry to enhance the mechanical strength, heat resistance, and microbiological resistance of the paper. Cyanoethylated starch is used in the textile industry. 

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