Chloroacetone, reaction

The direct alkylation of hydrogenphosphonic diesters with a diazoketone has been recorded alongside that with diazoalkanoic esters, and explored particularly with methyl 2-diazo-3-oxobutanoate but also for several chloroacetones. Reactions involving 1-chloro-3-diazo-2-propanone are effectively catalysed by [Cu(acac)2], but more heavily chlorinated substrates suffer stepwise dechlorination. Thus l,l,l-trichloro-3-diazo-propan-2-one initially yields the expected dialkyl (3,3,3-trichloro-2-oxopropyl)phospho-nate, but under the experimental conditions, dechlorination then proceeds to give the dialkyl (3,3-dichloro-2-oxopropyl)phosphonate only the monochloroketone undergoes a reaction in which the original halogen content is retained in the final product ... 

Hantzsch and Weber began their description with the compound which led them indirectly to the discovery of the thiazoles the a-thiocyanoacetone imine ( Rhodanpropimin ) of J. Tcherniac and C. H. Norton. C4H6N2S. obtained by reaction of ammonium thiocyanate with chloroacetone. After Tcherniac and Norton (18), the a thiocyanoacetone... 

For example, when an N-methylthioacetamide (96), R, = R — Me, was condensed with chloroacetone, a 2,3,4-trimethylthiazolium chloride was obtained in quantitative yield. The reaction is usually run in aqueous or alcoholic solution at room temperature. At low temperature, with N-phenylthioacetamide (96), Rj = Me, R2 = Ph and chloroacetone, an acyclic intermediate (98) was isolated and characterized (Scheme 43). It was easily converted to 2,4-dimethyl-3-phenylthiazolium chloride (97), R, = Rs = Me, Rj -Ph, by heating (99,102, 145). 

With R] different from R2 two isomeric compounds (138 and 139) are possible, depending on the direction of ring closure (86). However, only one form is generally obtained. Finally, the trisubstituted thioureas such as N,N,N -trimethylthiourea react with chloroacetone to give a thiazolium salt, in a reaction identical to that of the N-monosubstituted thioamides (Scheme 67). 

But the reaction with aliphatic a-halocarbonyl compounds is usually complex, and a variety of compounds can be formed depending on the reactants and the reaction conditions. With chloroacetone in neutral medium (alcohol) the acyclic intermediate (144) analogous to those obtained with thiourea and thioamides was isolated (Scheme 70). 

Hydroxy-4-methylthiazole has been prepared in 68% yield through the reaction of barium thiocyanate with chloroacetone (70). 

Although bromo derivatives have been used, the two most common ot-halocarbonyl compounds for this reaction are chloroacetaldehyde and chloroacetone. The dicarbonyl component is typically ethyl acetoacetate or one of its derivatives. A variety of bases including triethylamine and potassium hydroxide can promote the reaction however, the most popular base is pyridine. Conversion to the furan takes place either at room temperature or upon heating to 50°C with reaction times varying from four hours to five days and yields ranging from 30-86%. 

Syntheses of trisubstituted furans are much less common than the disubstituted derivatives only one 2,4-disubstituted 3-furoate has been prepared using the Feist-Benary reaction. Combination of chloroacetone (4) with ethyl acetoacetate (9) provides ethyl 2,4-dimethyl-3-furoate (28) in 54-57% yield. The procedure for this... 

By this process, 4-methylselenazole (2 R = CH3, R = R" = H) could be obtained by the reaction of hydrocyanic acid and hydrogen selenide with chloroacetone. This is the solitary selenazole unsubstituted in the 2-position that is known. The yield, however, was only 2.5% calculated on the chloroacetone used. 

Chloroacetic acid, reaction with salicyl-aldehyde, 46, 28 Chloroacetone, 46, 3 Chloroacetyl fluoride, 45, 6 o-Chloroacetyl isocyanate, 46,16 -Chloroaniline, reaction with carbon disulfide and aqueous ammonia,... 

Ethyl 2,4-diphenylbutanoate, 47, 72 Ethyl 2,3-diphenylpropionate, 47, 74 Ethyl isocyanide, 46, 76, 77 Ethylmagnesium bromide, use with ferric chloride in cyclization of di-chloroacetone -tolylmagnesium bromide adduct to l-/>-tolylcy-clopropanol, 47,108 Ethyl nit ropheny lace late, reaction... 

Some observations are important for improvement of the yield and for the elucidation of the mechanism of the Meerwein reaction. Catalysts are necessary for the process. Cupric chloride is used in almost all cases. The best arylation yields are obtained with low CuCl2 concentrations (Dickerman et al., 1969). One effect of CuCl2 was detected by Meerwein et al. (1939) in their work in water-acetone systems. They found that in solutions of arenediazonium chloride and sodium acetate in aqueous acetone, but in the absence of an alkene, the amount of chloroacetone formed was only one-third of that obtained in the presence of CuCl2. They concluded that chloroacetone is formed according to Scheme 10-50. The formation of chloroacetone with CuCl2 in the absence of a diazonium salt (Scheme 10-51) was investigated by Kochi (1955 a, 1955 b). Some Cu11 ion is reduced by acetone to Cu1 ion, which provides the electron for the transfer to the diazonium ion (see below). 

The chain process of the Meerwein reaction can be visualized as shown in Scheme 10-57. There are at least two likely termination reactions for the chain process, namely the addition of a chlorine atom from CuCl2 to the aryl radical (Scheme 10-58) or reaction of the aryl radical with a hydrogen atom of acetone, followed by the formation of chloroacetone (Scheme 10-59). 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

Electrophilic substitution provides a third and best synthesis. The p-chlorobenzoy1 group can be added in a Priedel-Crafts reaction, leaving (16) which can be disconnected to (15) and chloroacetone. 

Feist-Benary cyclo-condensation of (2,4-dioxobutylidene)-phosphoranes with a-chloroacetone gave rise to substituted furfuryl phosphonium salts, which underwent subsequent Wittig reactions to afford alkenylfurans in good yields as can be seen below <06JOC8045>. 

The reaction of commercially available 2-amino-5-methyl-l,3,4-thiadiazole 451 (R Me) with chloroacetone followed by treatment with 1M HBr provides 2,6-dimethylimidazo[2,l- ][l,3,4]thiadiazole 161 (Equation 103) (Table 59) <2000AF550>. 

Hansa yellow org chem Group of organic azo pigments with strong tinting power, but poor opacity in paints used where nontoxIcIty Is Important. han-sa yel o ) Hantzsch synthesis org chem The reaction whereby a pyrrole compound is formed when a p-ketoester, chloroacetone, and a primary amine condense. hansh, sin-tha-sas ... 

Coumarinyl-substituted thiazolo[3,2-h][l,2,4]triazoles have also been reported. They are available in one step by reaction of 5-aryl-3-mercapto[l,2, 4]triazoles with 3-bromoacetylcoumarin (ethanol, reflux, 8 h yield 44-65%) (81AP435) or in a two-step reaction from the corresponding S-alkylated intermediates with PPA [93MI2 94IJC(B)579]. 2-Aminothiazolo[3,2-h][l,2,4]triazoles are also available from 3-mercaptotriazoles. Treatment of 5-amino-3-mercaptotriazole with chloroacetone (DMF, K2CO3) and subsequent acid-catalyzed cyclization yields 146 [90JAP(K)02/142797]. 

Triphenylphosphine dichloride exhibits similar reactivity and has been used to prepare chlorides.18 The most convenient methods for converting alcohols to chlorides are based on in situ generation of chlorophosphonium ions19 by reaction of triphenylphosphine with various chlorine compounds such as carbon tetrachloride20 and hexa-chloroacetone.21... 

Reactions of the salts 79-81 with chloroacetonitrile, methyl chloroacetate, chloroacetone, or substituted phenacyl bromide yield different products the thiazoles 90 are formed in excellent yield from the reaction with 79 (Equation 1) and when salts 80 and 81 are treated with phenacyl bromide, thiazolopyridine 91 and benzoxazine derivative 92 are formed, respectively <2004H(63)2319>. 

The earlier work on chloroacetone (18,19) already indicated that trialkyl amines were superior to other bases for this reaction. Therefore the decision to use trialkyl amines to scavenge HCl was already determined by the literature precedent. However, when compared to the tributyl amine, smaller amines might be preferred since they could boost the reactor productivity by reducing the volume. Unfortunately, for unknown reasons, the process did not work as well with the simpler amines. Both tripropyl amine and triethyl amine displayed both lower rates and lower selectivity for methyl pivaloyl acetate. (See Table 6.)... 

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