Methyl 4-chloroacetoacetate

Miscellaneous Fused Selenophens.—Selenolo[2,3-6]thiophen (691) has been prepared by metalation of thiophen>3-aldehyde diethyl acetal with butyl-lithium followed by reaction with selenium and methyl chloroacetoacetate. The intermediate (692) was, without isolation, hydrolysed and ring-closed to (693), which upon decarboxylation gave (691). Another isomeric... 

Ethyl-cf-chloroacetoacetate gives 5-carbethoxy-4-methyl-2-thiazole thiol (387), while 3-chloro-2,4-pentanedione affords the 2-mercapto-4-methyl-5-thiazolylmethylketone in good yield (74%) (387). 

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. 

Batchwise operated multipurpose plants are per defmitionem the vehicle for the production of fine chemicals. There are, however, a few examples of fine chemicals produced ia dedicated, coatiauous plants. These can be advantageous if the raw materials or products are gaseous or Hquid rather than soHd, if the reaction is strongly exothermic or endothermic or otherwise hazardous, and if the requirement for the product warrants a continued capacity utilization. Some fine chemicals produced by continuous processes are methyl 4-chloroacetoacetate [32807-28-6] C H CIO [32807-28-6], and malononittile [109-77-3] C2H2N2, made by Lonza dimethyl acetonedicarboxylate [1830-54-2] made by Ube and L-2-chloropropionic acid [107-94-8] C2H C102, produced by Zeneca. 

The same substrate (25) aud ethyl 2-chloroacetoacetate gave an analogous product, ethyl 3-hydroxy-3-methyl-3,4-dihydro-2//-1,4-thiazino[2,3-h]qui-noxahne-2-carboxylate (27) (KOH, EtOH, 20°C, 3 h 58%), which underwent dehydration to ethyl 3-methyl-2H-1,4-thiazino[2,3-h]quinoxaline-2-carboxy-late (28) (HCl gas, EtOH, 20°C, 15 h 60% analogs likewise). ... 

Because free or esterified imidazole(4,5)-acetates 745 are currently accessible only via a rather tedious multistep synthesis via (4,5)hydroxymethylimidazole [224— 226], it seemed obvious to react amidines such as isobutyraminidine-HCl 742 with commercially available methyl or ethyl 4-chloroacetoacetates 743a, b to obtain 745 directly in one step. Because of the low reactivity of the 4-chlorine in 743, however, reaction of 743, e.g. with isobutyramidine-HCl 742 in the presence of sodium methylate in methanol, affords exclusively 2-isopropyl-6-chloromethyl-pyri-midin-4-one 744 [227], whereas treatment of 743b with NaOEt in EtOH gives, in the absence of amidines, 2,5-bis(ethoxycarbonyl)cyclohexane-l,4-dione in nearly quantitative yield [228, 229]. 

In a typical example of aliphatic cyclizations, already discussed in Section 5.2, the enamine 675 is alkylated by silylated methyl 4-chloroacetoacetate 747 a [2] to give, via 760 and subsequent ehmination of pyrrolidine, the unsaturated bicycHc /9-ke-toester 761 in, as yet, only 30-40% yield [1]. Analogously, the bicycHc system 1408 with an additional 6-keto group is silylated to 1409 and cyclized via 1410, in an overall yield of 42%, to the tricyclic capnellene intermediate 1411 [3] (Scheme 9.1). An alternative synthesis of bicyclic compounds Hke 761 is given elsewhere [3 a]. 

As already discussed in Section 5.5.2, amidine hydrochlorides 743 react with O-silylated methyl (or ethyl) 4-chloroacetoacetate 746, in which the 4-chlorine atom... 

Reduction of 4-chloroacetoacetate methyl ester usually proceeds stereo-specifically. This activity is widely distributed in yeasts, molds and bacteria,... 

Mercaptoketones, condensation, with nitriles (or a-meicapto acids), 158 2-Mercapto-4-methyl-5-carbethoxythiazole, from ammonium dithiocarbamate and a-chloroacetoacetate, 264 2-Mercapto-4-methylthiazole, from chlor-aoetone yield of, 264... 

C5H7CI03 methyl 4-chloroacetoacetate 32807-28-6 416.65 35-937 2 4762 C5H8Br202 methyl 3-bromo-2-(bromomethyl)propionate 22262-60-8 481.90 42.148 2... 

Aryl-4-formylsydnone 4 -phenylthiosemicarbazones 183 were treated with ethyl 2-chloroacetoacetate and 2-bromoacetophenone in buffer systems of sodium acetate and acetic acid, to produce anti-oxidants 2-[(3-arylsyd-non-4-ylmethylene)-hydrazono]-4-methyl-3-phenyl-2,3-dihydrothiazole-5-carboxylic acid ethyl esters 184 and 3,4-diphenyl-2-[(3-arylsydnon-4-ylmethylene)hydrazono]-2,3-dihydrothiazoles 185 in good yields (Scheme 71) <2004BMC4633>. 

The reaction between diethyl phosphite and a-chloroketones can also be accomplished by fluoride ion-mediated deprotonation reaction in DMF (dry KF or KFTHjO as fluoride ion source), which constitutes anonbasic route to diethyl 1,2-epoxyalky Iphosphonates. Unfortunately, the application of this technique provides a mixture of 1,2-epoxyalkyIphosphonate (about 50%) and vinyl phosphate (about 30%) whatever the a-chloroketones. The reaction between 3-(co-bro-moacetyOcoumarin and diethyl or di- -butyl phosphite has been performed with 50% NaOH in CgHg under phase-transfer catalysis conditions with TEBA as catalyst. The only products of the reaction are the epoxyphosphonates isolated in 70% and 34% yields, respectively. In the presence of EtjN, diethyl phosphite reacts with 2-chloroacetoacetate to give diethyl 2-(ethoxycarbonyl)-l-methyl-l,2-epoxyethylphosphonate in 72% yield as a mixture of cis and trans isomers. ... 

Using ethyl a-chloroacetoacetate instead of ethyl acetoacetate as starting material, the chlorine analogue of E 838, 0,0-diethyl-0-(3-chloro-4-methyl-2-oxo-2H-l-benzopyranyI-7) phosphorothioate (coumaphos, 45), is formed (Schrader, 1951). 

Based on the research work of Stiles (1952), one of the most important phosphorus ester insecticides, 0,0-dimethyl-0-[(l-methyl-2-carbomethoxy)vinyl] phosphate (mevinphos, 73) was introduced in 1957 under the trade name Phosdrin . It is prepared by the Perkow reaction from trimethyl phosphite and methyl a-chloroacetoacetate. 

The ammonium formate in formic acid procedure has rendered possible the first preparation of isomeric 4,5-disubstituted oxazoles.03101 Bredereck, Gompper, and Reich101 have reported the anomalous behavior of certain long-chain a-bromo ketones a single a-bromo ketone on reaction with ammonium formate in formic acid gives a mixture of two isomeric oxazoles. Refluxing of a-bromo ketones or of a-chloro-/3-keto esters with ammonium acetate in acetic acid results in the formation of substituted 2-methyl-oxazoles.40 102 Ethyl a-chloroacetoacetate on heating with ammonium carbonate or formamide in formic acid yields 4-methyloxazole-5-carboxylic ester.40 103... 

Mevinphos (96, Phosdrin ) is prepared from methyl 3-chloroacetoacetate in reaction with trimethyl phosphite. Mevinphos (Phosdrin ) is a mixture of Z and E stereoisomers in which the Z isomer was found to be 100 times more active.54 In contrast to mevinphos, E and Z isomers of bromfenvinphos (92) and chlorfenvinphos (94) show no significant difference for a number of biological properties for insecticides.55 The less toxic Clodrin (98) is synthesized from the 1-phenylethoxy ester of 3-chloracetoacetate 97 which is used for control of ectoparasites in horses, cattle, sheep, and swine.54... 

Condensed Selenophens.—The reaction of phenylacetylenesulphonamide with selenium dioxide and hydrogen bromide gave 3-bromo-2-benzo[i>]selenophen-sulphonamide. Heating of (165) with selenium gave (201). " The reaction of 2,3-dimethylselenophen-5-thiol with methyl y-chloroacetoacetate, followed by cyclization with PPA and hydrolysis, gave 4,5-dimethyl-3-selenolo[2,3- >]-... 

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