With chlorovinyl ketones

Salts of 4-aminothiazoles react with chlorovinyl ketone (82) or with /3-diketones (83) at 140°C to yield the thiazoio[3.4-u]pyrimidine derivatives (84) (Scheme 58) (240). 

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). 

O-Acylation of 2-nitropropane occurs on reaction with either ketene or acetic anhydride (61) in the presence of dry sodium acetate at 70—80°C. Ketovinylation of 2-nitropropane at the 1-position occurs on treatment of sodium 2-propanenitronate with a chlorovinyl ketone (62). 

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)). 

To synthesize isomeric 3-substituted isoxazoles (301) the reaction of ethylene acetals of )3-ketoaldehydes (300) (readily available from -chlorovinyl ketones (57IZV949)) with hydroxylamine was employed. Owing to the comparative stability of the dioxolane group, this reaction gave exclusively 3-substituted isoxazoles (301) (60ZOB954). The use of noncy-clic, alkyl S-ketoacetals in this reaction resulted in a mixture of 3- and 5-substituted isoxazoles (55AG395). 

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). 

Since 1,5-enediones are usually obtained via pyrylium salts, syntheses of the type found in Section B, 2, a have a rather theroetical interest, save for a few special syntheses. There exist several direct syntheses of l,5-enediones, e.g., from j8-chlorovinyl ketones and j8-diketones or j8-keto esters special pathways to 1,5-enediones have also been described, namely, oxidation with lead tetraacetate or with periodic acid of cyclopentene-l,2-diols. ... 

Since -chlorovinyl ketones are reaction products of acetylenes with acid chlorides, the isolation of these lachrymatory and unstable intermediates is not necessary, as shown by Section II,D,2,d. 

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). 

Acetylene was passed into a stirred solution of 3.05 grams (0.44 mol) of lithium in 300 ml of liquid ammonia until the blue color exhibited by the mixture had disappeared. Ethyl /3-chlorovinyl ketone (47.4 grams 0.40 mol) dissolved in 50 ml dry ether was then added to the resulting solution of lithium acetylide over a period of 20 minutes, during which the color deepened through yellow to reddish-brown. The mixture was stirred under reflux maintained with a Dry Ice condenser for 2 hours. Thereafter, dry ether (200 ml) was added and the ammonia was permitted to evaporate with stirring overnight. 

Ethylcarbazole reacted at C-3 with tetracyanoethene in hot dimethyl-formamide generating 142. ° A series of aryl chlorovinyl ketones reacted with 9-methylcarbazole at the 3-position to give monosubstitution products 143 ulitizing aluminium chloride catalysis. ... 

Table 14 Mono- and Di-substituted 1-Azaquinolizinium Perchlorates (255) Obtained by [3 + 3] Reactions using a Dicarbonyl Derivative (253) or a /3-Chlorovinyl Ketone (254) with a 2-Aminopyridine (Scheme 124)...

The use of enones as precursors to heterophanes, e.g. (86), can be exemplified by the reaction of hydrazine with (87). Chlorovinyl ketone (88) is transformed into (86), (89) or (90), depending on the nucleophilic reagent used (70TL11, 76T1863). 

Pyridinophanes (96) can be constructed from bis-(/3-chlorovinyl ketonic) intermediates upon treatment with ammonia. Wolff-Kishner reduction of (96) gives the parent (3,5)pyridinophane (68HCA2027). Some /3-aminovinyl carbonyls have been condensed with cycloalkanones in the presence of triethylamine and piperidinium acetate to give the (2,3)pyridinophane series (97) (70TL3291). 

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13... 

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). 

Chlorovinyl ketones and related compounds also react with active methylene compounds to form pyran-2-ones, via the unsaturated keto acid derivative (61T63). 

Chlorovinyl ketones are potential 1,3-diketones and provide a useful extension to the above method. In the presence of Friedel-Crafts catalysts they react with ketones to give pyrylium salts which are unsubstituted in the 4-position. The example shown in Scheme 257 illustrates the synthesis of a more complex pyrylium salt (63ZC266). 

Enamines are also potential ketones and accordingly have been used as the ketonic component in this type of pyrylium synthesis (63AG(E)394). The initial adducts, which form pyrylium salts on treatment with perchloric acid, are similar to those derived from secondary amines and pyrylium salts. The significant feature of this variant is that it gives access to pyrylium compounds which are unsubstituted at the 4- and 6-positions but which carry substituents at C-2 and C-5. More conventional enamines, such as 1-piperidinocyclohexene, afford bicyclic pyrylium salts (652), whilst polycyclic salts (653) result if cyclic chlorovinyl ketones are used. 

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). 

Reactions of 2-aminopyridines with /i-chlorovinyl ketones were surveyed by Fischer.16 He established that in a nonacidic medium (acetone-methanol mixture) the pyridinium salts (7) are formed, which can then be cyclized by acids (acetic acid and 70% perchloric acid) to the 2-substituted pyrido[l,2- ]-pyrimidinium salts (10).1415 in acidic media, however, the 4-substituted pyrido[l,2-a]pyrimidinium salts (9) are formed via the enamine (8).616... 

One of the most important methods of pyrazole synthesis involves the reaction of 1,3-diketones with hydrazine derivatives. The method has wide scope, especially considering that the diketones may be replaced by acetals, hemiacetals, chlorovinyl ketones, tetrahalides, etc. Most accessible by this path is 3,5-dimethylpyrazole (10), obtained in 85% yield from acetylacetone and hydrazine hydrate.134-138... 

N. K. Kochetkov and A. N. Nesmeyanov showed that / -chlorovinyl ketones react with hydrazine in ethanolic solution to give high yields of 3-substituted pyrazoles.297 Unlike hydroxymethylene ketones, which by tautomerism give mixtures of isomeric pyrazoles, /3-chloro-vinyl ketones react with phenylhydrazine to give only one isomer, a point which was verified experimentally.340 This can only be explained... 

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... 

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). 

Condensation of thioamides or thiourea with, -unsaturated ketones is a general method for the construction of the 1,3-thiazine skeleton . -Chlorovinyl ketones 343 and the thioamide 344 in the presence of perchloric acid give intermediate thioimidium salts 345, which cyclize to yield 1,3-thiazinium salts 346 (Scheme 160) <1982T937>. 

The condensation of / -chlorovinyl ketones 237 with nitriles promoted by Lewis acids is known as a synthetic method of 3-azapyrylium salts 23858,131 (equation 68). 

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