Chloroacetone

This preparation illustrates the ready formation of the thiazole ring by the condensation of an ot-halogeno-ketone and a thioamide. Thus chloroacetone, which may conveniently be represented in the enol form (I), condenses with thiourea (II) to give 2-amino-4-methylthiazolc (III). 

Note. The chloroacetone, which should be freshly distilled (b.p. 119°), is lachrymatory, and therefore the distillation and the preparation should be performed in a fume-cupboard. 

Fit a 250 ml. three-necked flask with a stirrer, a reflux condenser and a dropping-funnel. (Alternatively, use a two-necked flask, with the dropping-funnel fitted by a grooved cork into the condenser.) Place 15 g. of powdered thiourea and 40 ml. of water in the flask and stir the mixture whilst 18 5 g. (16 ml.) of chloroacetone are added dropwise over a period of 20 minutes the thiourea will dissolve and the temperature of the mixture... 

Acetonylacetone is available commercially as a by-product of the manufacture of acetic acid from acetylene. It may be prepared by condensation of chloroacetone with ethyl sodioacetoacetate the resulting ethyl acetonylacetoacetate when heated with water under pressure at 160° undergoes ketonic scission to give acetonylacetone. 

Redistilled commercial chloroacetone, b.p. 118-120°, is used. The compound is lachrymatory. It is prepared inter alia by the chlorination of acetone in the cold. 

METHOD 8 Check this outi This uses benzene or 1,3-benzodioxole (forX) as the starting material [24]. This method is better suited for speed makers because the AICI3 catalyst can tear up that methylenedioxy ring structure of the X molecule precursor. Chloroacetone can be easily purchased. 

This is the infamous Friedel-Crafts method and works in a manner similar to the previously mentioned method where P2P was made by merging benzene and chloroacetone using AICI3. This method is for speed makers only and is not recommended for conversion of 1,3-benzodioxole. However, this should work in a limited way on catechol. The conversion factor is very low but that isn t a major concern of speed chemists because cheap old benzene is the precursor and all of that benzene that isn t converted can be run back through this simple little process over and over again. Before she knows it, the chemist will have amassed an enormous amount of allylbenzene [139, 140]. 

The maximum yield of 2-alkylseIenazole is 25%. In this way. 4-methylselenazole (7) was obtained starting from hydrogen cyanide, hydrogen selenide and chloroacetone. It is the only known selenazole not substituted in the 2-position. The yield relative to chloroacetone is very low (2.5%) (Scheme 2). 

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... 

Initially, 4-methylthiazole (7), R, = Me, Rj = H, was obtained in low yield (<40%) from chloroacetone (102,127). Kurkjy and Brown (364) using bromoacetone with dioxane as solvent increased the yield to 73%, whereas it only yields 39% in benzene (426). Kurkjy and Brown s method was extended later to 4-alkylthiazoles by Metzger and Carrega (455) with 75 to 90% yields. 4-Vinyl- and 4-isopropenylthiazoles (629), 4-adamanthylthiazole and derivatives (705), 4-carboranylmethylthiazole (706), 4,5-dialkylthiazoles (156, 220, 426, 703, 810), 4,5-... 

The cyclization of pentaacetyl-o-gluconic thioamide with chloroacetone and of pentaacetyl-D-galactonic acid thioamide with phenacyl bromide give the corresponding 4-substituted 2-(D-galactopentaacetoxypentyl)-thiazoles (27) (660) but in low yield (23 to 27%) (Scheme 13). The products may be deacetylated in the usual way. These compounds are interesting from a pharmacological point of view. 

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). 

Various 4-, 5-, or 4,5-disubstituted 2-aryIamino thiazoles (124), R, = QH4R with R = 0-, m-, or p-Me, HO C, Cl, Br, H N, NHAc, NR2, OH, OR, or OjN, were obtained by condensing the corresponding N-arylthiourea with chloroacetone (81, 86, 423), dichloroacetone (510, 618), phenacyichloride or its p-substituted methyl, f-butyl, n-dodecyl or undecyl (653), or 2-chlorocyclohexanone (653) (Method A) or with 2-butanone (423), acetophenone or its p-substituted derivatives (399, 439), ethyl acetate (400), ethyl acetyl propionate (621), a- or 3-unsaturated ketones (691), benzylidene acetone, furfurylidene acetone, and mesityl oxide in the presence of Btj or Ij as condensing agent (Method B) (Table 11-17). 

The N,N-disubstituted thioureas (135) condensed with a-halocarbonyl compounds give 2-disubstituted aminothiazoies (136) but in lower yields (30 to 70%) (Scheme 65 and Table 11-20) (518). For example, N,N-dialkylthioureas condensed with chloroacetaldehyde or dibromoether lead to Ar,At-dialkyl-2-aminothiazoles in 136, Ri=R2 = methyl (342, 404, 436, 637), ethyl (343, 436), n-propyl (518), n-butyl (518), ally] (518), and benzyl (26, 29). When chloroacetone and dichloroacetone are the carbonyl reactants the corresponding 4-methyl (518) and 4-chloromethyl derivatives (572) were obtained. 

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). 

Thus the condensation of dichloroether or chloroacetone fails to give the parent compound, 2-hydroxythiazole (158a), Rj = R2 = R3 = H (221). However, 2-hydroxythiazole can be obtained in 12% yield from chloro-acetaldehyde (386). The condensation of ammonium thiocarbamate with cf-chloroketones gives the corresponding 2-hydroxy derivatives in 25 to 70% yields (76, 221, 304, 412) (Table 11-24). These compounds condensed with ClP(S)(OEt)2 give the corresponding 2-thiazolyl-thiophosphates (791). 

Chloroacetone, phenacylbromide, a-bromoisobutyrophenone, 3-bromo-3-methyl-2-butanone, 1 -alkylsulfonyl-3-bromo-2-propanone, and ethyl-y-chloroacetoacetate give with ammonium dithiocarbamate the corresponding 4-hydroxythiazolidine-2-thiones (177), which have a characteristic absorption between 273 and 279 nm. Dehydration by heating with dilute HCl can be followed by ultraviolet spectroscopy because the products formed (175) absorb at 315 to 340 nm. 

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

Other applications of zirconium tetrafluoride are in molten salt reactor experiments as a catalyst for the fluorination of chloroacetone to chlorofluoroacetone (17,18) as a catalyst for olefin polymerization (19) as a catalyst for the conversion of a mixture of formaldehyde, acetaldehyde, and ammonia (in the ratio of 1 1 3 3) to pyridine (20) as an inhibitor for the combustion of NH CIO (21) in rechargeable electrochemical cells (22) and in dental applications (23) (see Dentalmaterials). 

Optically Active PO. The synthesis of optically pure PO has been accompHshed by microbial asymmetric reduction of chloroacetone [78-95-5] (90). (3)-2-Meth5loxirane [16088-62-3] (PO) can be prepared in 90% optical purity from ethyl (3)-lactate in 44% overall yield (91). This method gives good optical purity from inexpensive reagents without the need for chromatography or a fermentation step. (3)-PO is available from Aldrich Chemical Company, having a specific rotation [0 ] ° 7.2 (c = 1, CHCl ). 

Chloroacetone [78-95-5] M 92.5, b 119 /763mm, d 1.15. Dissolved in water and shaken repeatedly with small amounts of diethyl ether which extracts, preferentially, 1,1-dichloroacetone present as an impurity. The chloroacetone was then extracted from the aqueous phase using a large amount of diethyl ether, and distd at slightly reduced pressure. It was dried with CaCl2 and stored at Dry-ice temperature. Alternatively, it was stood with CaS04, distd and stored over CaS04. LACHRYMATORY. 

Charcoal screenings, wet Charcoal, wet Chlorine azide Chlorine dioxide Chloroacetaldehyde Chloroacetone (unstabilized) Chloroacetonitrile Chloroformates, n.o.s. Chloroprene, uninhibited Chlorosulphonic acid Coal briquettes, hot Coke, hot Copper acetylide... 

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%. 

In 1902 Feist first described the combination of chloroacetone (4) and diethyl 3-oxoglutarate (5) in the presence of ammonia to yield trisubstituted furan 6 ... 

---