Halogeno-ketones

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). 

Alkyl-/l -pyrrolines (8, n = 1) and 2-alkyl-/l -piperideines (8, n = 2) are readily formed by the methods used to prepare y- and S-amino ketones (3-6). The reaction of corresponding halogeno ketones with ammonia belongs to the classical reactions of this type. 

The chemistry of thiazoles is interesting in view of their propensity for biological activity. Eor that reason thiazoloquinolines have also been a widely studied group of compounds. A preferred route to thiazoles exploits a-halogeno ketones in a reaction with thioamides to give the fused 2-substituted thiazole derivatives. 

Cyclic 1,3-diketones have been converted into / -halogeno-ketones (118) by tri-phenylphosphine dihalides in benzene or acetonitrile,100 although this paper adds little to previous work101 in this field. The reactions of phosphorus pentachloride with acetals have been extended to mixed acetals, such as (119).102 Only one product... 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

Improved yields of epoxyphosphonates of type (48) are reported for a development of existing synthetic methods, involving mixing of stoicheiometric amounts of hydrogen phosphonate, a-halogeno-ketone, and alkoxide.42... 

Reactions of this type provide major routes to both the monocyclic system and to 1,5-benzothiazepines. In some cases the reactions are single-stage processes but in many cases the intermediate produced by the primary formation of the S—C bond can be isolated. Thus 2-aminoethanethiol reacts with a,/3-unsaturated or j3-halogeno ketones to give (408). Similarly reaction with a,/3-unsaturated acids, esters or acid chlorides and with 3-halogenopropionyl halides gives the 5-oxo derivative (409). 2-Aminoethanethiol also reacts with activated 2-chlorobenzophenones to give 1,4-benzothiazepines. 

Amino-l,3,4-oxadiazoles (205) on treatment with cr-halogeno-ketones gave intermediate quaternary salts 206 that did not cyclize directly to imidazo[2,l-6]oxadiazoles (208) with base. Hydrolysis of 206 with aqueous potassium carbonate caused ring-opening at C-2 with subsequent closure to the imidazolone 207. These latter compounds could be cyclized to 208 with phosphorus oxychloride.204c 21 246... 

A Tschitschibabin reaction in Scheme 7 with Y = NH B Tschitschibabin reaction in Scheme 7 with Y = S a a-halogeno ketone used b propargyl bromide used. 

Reaction of 4-cyano-l -oxo-2,3-dihydro-l H-pyrido [1,2-c] pyrimidine-3-thione 72 with halogeno ketones 73 afforded tricyclic derivatives 74 (08MI2). 

N—C—O + C—C. The construction of the oxazole ring by the condensation of a-halogeno ketones with primary amides (equation 122) is the Bliimlein-Lewy synthesis (1884/1888). The method succeeds best when the resulting oxazole contains one or more aryl substituents. The use of formamide leads to oxazoles with a free 2-position and in this case it is possible that the reaction proceeds as in equation (113). 2-Aminooxazoles are produced by the action of a-halogeno ketones on urea and its derivatives (equation 123) or on cyanamide (80ZOR2185). The mercury(II) sulfate-catalyzed condensation of alkynic alcohols or their esters with primary amides leads to trisubstituted oxazoles (equation 124). 

Thiiranes are assumed to be intermediates in the formation of l-oxa-6,6aA4-dithiapen-talenes from l,2-dithiole-3-thiones reacting either with diazo ketones or with a-halogeno ketones with subsequent desulfuration in basic medium (71AHC(13)161, pp. 177-179). 

A number of thiopyran-2-thiones have been alkylated with a-halogeno-ketones yielding thiopyrylium cations of the type 163 (74BSF1356 80BSF(2)427 84AP938 86MI3 87FES465],... 

Feist-Benary synthesis. Formation of furans from a-halogeno ketones or ethers and 1,3-dicarbo-nyl compounds in the presence of pyridine. With ammonia as condensing agent, pyrrole derivatives are always formed as secondary products. 

Tosylazo-enes (e.g. 435), derived from the a-halogeno-ketones, undergo alcoholysis to give enol ethers (436), probably via addition-elimination as illustrated. In the case of 21-substituted pregnan-20-ones (437 X = F or OMs),... 

A classical synthesis of alkyl- and arylpyrazines involves dimerization of a-amino carbonyl compounds, which may be produced by many methods such as reduction of a-oximino ketones, aminolysis of a-halogeno ketones (Section 6.0T11.2), oxidation of a-amino alcohols and reduction of a-amino acids . The condensation of 1,2-diamines with a-dicarbonyl compounds is available for the synthesis of particularly quinoxaline derivatives (Section 6.03.11.1). The synthetic methods which rely on self-condensation, however, provide only symmetrically substituted pyra-... 

The Perkow reaction has been used to generate a wide range of vinyl phosphates. Reaction of trialkyl phosphites with a-halogeno-ketones provide vinyl phosphates.1-5 Alkenes are produced via reduction of the dialkyl enol phosphate using either sodium or lithium in liquid ammonia. 

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