Cyanomethyl ketones

It is sometimes impossible to isolate the resultant jS-ketonitrile derivatives as such as they are unstable and readily polymerize, e.g. cyano-acetone. They are therefore identified as their corresponding arylhydrazones. The simpler alkyl-w-cyanomethyl ketones are, however, much more stable and their production through the cleavage of 5-alkylisoxazoles has been suggested as a preparative synthetic method. ... 

Gastaldi synthesis. Formation of dicyanopyra-zines by cyclization of two molecules of an amino-cyanomethyl ketone, produced by treatment of an isonitrosomethyl ketone bisulfite compound with potassium cyanide, heating in hydrochloric acid, and oxidation. 

A general synthesis of 2,4-diaryl-5-cyano-l,3-thiazin-6-ones (253) is described in which dithi-azolium perchlorates (254) are condensed with cyanomethyl ketones such as l-(cyanoac tyl)-3,5-dimethylpyrazole (255) in the presence of a base, sodium acetate, at room temperature (Equation... 

The phase-transfer catalysed alkylation of S-cyanomethyl dithiocarbamates provides a high yielding and convenient route to aldehydes (from monoalkylation) and ketones (from dialkylation) [128]. The procedure has been used to produce a range of alicyclic and small-ring ketones (>85%). 

Fig. 12 Formation of A-(cyanomethyl)amides in the MCR between primary isocyano amides, aldehydes/ketones, and amines...

The synthetic utility of many of the substitution reactions described so far is limited because there are well-established thermal routes to the same products. However, a third group of photochemical nucleophilic substitutions involves aryl halides and nucleophiles based on sulfur, phosphorus or, of particular importance, carbon. Two examples are the reaction of bromobenzene with the anion of t-butyl methyl ketone 13.12), and the replacement of bromine by cyanomethyl in 2-bromopyridine (3.13). This type of reaction offers a clear advantage over lengthy thermal alternatives, and intramolecular versions have been used in the synthesis of indoles (e.g. 3.14) or benzofurans from o-iodoaniline or o-iodoanisole respectively. 

These are usually prepared by the following methods (a) the Willgerodt reaction on the corresponding methyl ketone,82,98,337,485, 557 (6) hydrolysis of the corresponding cyanomethyl compound,77,337, 485,499,517,521,568 cyclization reactions (Section IV, C) (for 3-acetic acids only),143,209,310,311,313,351 or (d) the Arndt-Eistert reaction on the corresponding carbonyl chloride, which may lead directly to the acetic acid 689 or its amide.337, 568... 

Ethyl-2-(sulfonylmethyl)- and 2-(cyanomethyl)-allyl carbonates133 as well as (methoxycarbo-nyl)methylallyl carbonates136 serve as substrates for the [3 + 2] cycloaddition. Oxidative addition into the allylic C—O bond of the carbonate, followed by decarboxylation, gives a 2-substituted allylpalladium al-koxide. The alkoxide then deprotonates the C—H a to the electron-withdrawing substituent at the 2-position of the allyl. This anion then undergoes a Michael addition to an a,(3-unsaturated ketone or ester, followed by intramolecular allylation of the anion of the Michael product (Scheme 2). 

Keywords 5-amino pyrimidin-4(3//)-one, cyanomethyl phenyl ketone, benzalde-hyde, microwave irradiation, dihydropyrido[2,3-r/]pyrimidin-4(3/7)-one... 

A related approach exploited a A-cyanomethyl group to serve in the dual role of a nitrogen protecting group and a latent precursor of the formaldehyde im-inium ion (e.g., 478), and this innovative modification in tactics resulted in a simplified route to the c/.v-3a-aryloctahydroindole 474 (203a,c). To this end, the amino ketone 482 was readily prepared in one step by the reaction of 1,2-bis(trimethylsilyloxy)cyclopentene with A -benzyl-A -cyanomethyl amine. When 482 was exposed to [l-(3,4-methylenedioxyphenyl)ethenyl]lithium, a mixture (1 14) of 483 and 484 was obtained. It is noteworthy that the stereochemical sense... 

The C-4 hydroxy group of Neu5Ac2en was oxidized to the ketone 18, resulting in a drop in potency by a factor of over 100.72 Cyanomethyl ether 19, a key intermediate towards the synthesis of the inhibitors 20 and 21, which intended to mimic Zanamivir at C-4, was evaluated against NA.74,75 These modifications were not particularly successful, as 19-21 showed only 7-30% inhibition of catalysis at 1.0 mM compared to Zanamivir, which inhibits NA activity by over 90%. 

Dialkyl allyl telluronium bromides and dibutyl ethoxycarbonylmethyl (cyanomethyl, benzoylmethyl) telluronium bromide generated dialkyl alkylidene telluriums on treatment with potassium terr-butoxide in tetrahydrofuran at low temperatures (s.p. 837). The tellurium ylides were not isolated but were trapped with aldehydes and ketones . 

As do otlier azides, vinyl azides undergo loss of molecular nitrogen and rearrangement in the presence of strong mineral acids. Such acid-catalysed decompositions have not been extensively studied. One example, however, is die addition of hydrochloric acid to a glacial acetic acid solution of -azidovinyl phenyl ketone (73, R = H), which led to the isolation of a high yield of cyanomethyl phenyl ketone (75, R = H) and a small amount of 5-phenylisoxazole (74, R = H) Thermolysis of this ketone gave very similar results (See... 

Kirilov, M., and Petrova. J., Reaction of esters of (cyanomethyl)phosphonic acid with aliphatic, alicyclic, and aromatic ketones, Dokl. Bolg. Akad. Nauk. 21,339,1968 Chem. Abstr, 69,77366f, 1968. 

Diazotization of appropriate 2-substituted arylammes and subsequent coupling with a-halo ketones 1 affords the hydrazonyl chloride 2. When 2 is treated with excess triethylamine in refluxing benzene, the 4,1,2-benzothiadiazines 4a-c and 6a, b are formed.114 The reaction proceeds via the intermediates 3 and 5. On heating 2 for 4-5 hours, the cyanomethyl group of 5 is split off and the 4,1,2-benzothiadiazines 6 a, b are formed. For further syntheses of 4,1,2-benzothiadiazines using this method, see refs 115 and 116. 

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