0-Chlorovinyl methyl ketone

Chlorovinyl methyl ketone, 32, 29 5-Chloro-2-vinylthiophene, 38, 89 3,4-SeC0-A6-CHOLESTEN-3,4-DIOIC ACID, 35, 38... 

This preparation works equally well for the isobutyl and isohexyl homologs. For /3-chlorovinyl methyl ketone, which is both a lachrymator and a vesicant, the initial rapid rate of absorption of acetylene begins only after 3-9 hours. 

When this procedure is used to make the dimethyl acetal of /S-ketobutyraldehyde, the methanol and /5-chlorovinyl methyl ketone must be mixed quickly and cooled well. If these two liquids are placed in the same flask without immediate cooling and mixing, the ketone may decompose rapidly with the evolution of heat and large amounts of hydrogen chloride. 

This nucleophilic reactivity of 2-aminothiazoles has been used to prepare biheterocyclic compounds. Thus 2-aminothiazole reacts with chlorovinyl methyl ketone yielding 5-methyl-thiazolo[3,2-a]pyrimidinium chloride (Scheme 109). In the presence of formaldehyde, aminothiazoles react with ends affording condensation products, through the intermediacy of Mannich bases (Scheme 110). In acidic medium and at higher temperatures, condensation of 4-aryl-2-aminothiazole with benzaldehyde takes place at the C-5 position (Scheme 111). The same orientation is observed when 2-amino-4-methylthiazole is alkylated by secondary or tertiary alcohols in 85% sulfuric acid (Scheme 112). 

AcCl/AlCU, CCI4, 0-5 °C), acetylene undergoes acetylation to afford -chlorovinyl methyl ketone in 62% yield and under similar conditions (AcSbFs, MeN02, —25 °C) 5-decyne undergoes acetylation to afford 6-acetyl-5-decanone in 73% yield. ... 

The chlorovinyl immonium salts (654), obtained through Vilsmeier formylation of methyl ketones, behave as 1,3-dicarbonyl compounds. In the presence of strong base they react with methyl ketones to form dienones (655). On treatment with a mixture of perchloric and acetic acids the pyrylium salt results (Scheme 259) (71JPR1110). In a similar reaction 2-naphthol is converted into the naphtho[2,1 -b]pyrylium salt (656) (79S241). 

Chlorovinyl ketones or chlorovinyl immonium salts also condense with aryl methyl ketones yielding pyrylium salts [5]. 

Variation of this principle of pyryhum synthesis is achieved by introducing related 1,3-biselectrophiles hke alkoxyvinyl or chlorovinyl ketones [3]. For instance, 2,6-disubstituted pyrylium salts 29 are obtained from two molecules of an aryl methyl ketone and orthoformate in the presence of strong acids (HCIO4, HBF4) ... 

With an activated C—C triple bond two successive additions can occur if the intermediate alkene is reactive enough. DMAD and 3,5-dimethylpyrazole give an initiaj fumarate (255) which reacts further at the other end to form regioselectively the succinates (256). On the other hand, methyl ethynyl ketone reacts twice at the same carbon atom with pyrazole to form 1,1-pyrazolylbutanone (258) (68ZC458). The probable intermediate, a pyrazolide vinylogue (257), can be prepared from methyl chlorovinyl ketone and pyrazole, in a reaction which is similar to acetylation (Section 4.04.2.1.3(x)). 

At higher temperatures the mixture of 10 and methyl vinyl ketone yields the 1,4-carbocyclic compound as described previously. Methyl isopropenyl ketone (5), ethyl acetylacrylate (d), 2-cyclohexenone (21), and 1-acetyl-1-cyclohexene (22) also undergo this type of cyclization reaction with enamines at higher temperatures. This cycloalkylation reaction occurs with enamines made of strongly basic amines such as pyrrolidine, but the less reactive morpholine enamine combines with methyl vinyl ketone to give only a simple alkylated product (7). Chlorovinyl ketones yield pyrans when allowed to react with the enamines of either alicyclic ketones or aldehydes (23). 

Presumably, jS-chloro ketones could also react similarly with methyl(ene) ketones. Another logical extension is the possibility of synthesizing pyrylium salts by dehydrogenative condensation of -chlorovinyl ketones with oleflns like styrene, in the presence of stannic chloride (the olefins so far tested, like isobutene, are not suitable structurally). 

Stereochemistry of this reaction is also quite interesting. Thus, both geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides (165-167) were synthesized from 2-cyclohexenone, methyl vinyl ketone and 2-heptanone respectively, and the corresponding magnesium alkylidene carbenoids were generated and treated with A-lithio aniline or A-lithio 1-aminonaphthalene. The results are summarized in Table 9. 

Pyrimido[2,l -a]isoquinolinium perchlorates (316) were obtained in the reactions of 1-aminoisoquinoline and /3-diketones in acetic acid at 260°C for 2 h in sealed tubes and with phenyl and methyl 2-chlorovinyl ketones in acetic acid at 100°C for 5-10 min, then treatment with perchloric acid (74KGS1148). 

According to Chuiguk and Oksanich13 the reaction of 2-aminopyridinium perchlorates and /i-chlorovinylaldehydes led exclusively to the 4-substituted products (9) whereas from 2-amino-6-methylpyridine no cyclic product was obtained. With //-chlorovinyl ketones both the 2- and 4-substituted pyrido-[l,2-u]pyrimidinium salts were detected by H NMR.3 2-Amino-6-methyl-pyridine gave rise only to the 2-substituted isomer (10). 

It is therefore not surprising that an alternative approach to the synthesis of benzodiazepines involves the reaction of /3-chlorovinylcarbonyl compounds with o-phenylenediamine. In the first example methyl 3-chlorovinyl ketone was used to obtain 5-methylbenzodiazepinium chloride (62 JPR163). An extensive investigation has been made of the use of /3-chlorovinylaldehydes for the preparation of 2,3-substituted benzodiazepines (64ZC458 67CB584). The preferred conditions for reaction were in... 

Pudovik, A.N., Nikitina. V.L, and Kurguzova, A.M., Reactions of organophosphorus compounds containing active methylene groups with methyl (l-chlorovinyl ketone and a-halo ethers, Zh. Obshch. Khim., 40, 291, 1970 J. Gen. Chem. USSR (Engl. Transl.), 40, 261, 1970. 

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