Halogenocarbonyl compounds

A variation of the general method for the synthesis of 2-amino-selenazoles is to avoid the use of the free a-halogenocarbonyl compound and in its place react the corresponding ketone and iodine with selenourea.This procedure is also taken from thiazole chemistry. By contrast with thiourea, the reaction with selenourea needs a longer reaction time and the work up of the reaction mixture is somewhat more difficult. Usually an excess of the ketone is used. In the preparation of 2-amino-4-( n-nitrophenyl)selenazole, a very high yield, calculated on the amount of iodine used, was obtained. To explain this peculiar result, the oxidative action of the nitro group was invoked. This liberates free iodine from some of the hydrogen iodide eliminated in the condensation reaction, and the free iodine then re-enters into the reaction. 

Reaction of A -substituted selenoureas with a-halogenocarbonyl compounds yields the corresponding 2-amino-selenazole substituted in... 

The free selenazole hydrazines are solids, sometimes well crystallized compounds. They show the typical properties of hydrazines. Thus they reduce Fehling s solution on warming and liberate silver, even in the cold, from ammoniacal silver nitrate solution. Further, they react with carbonyl compounds for example, benzylidene hydrazones are formed with benzaldehyde. These are identical with the hydrazones formed by direct condensation from benzaldehyde selenosemicarbazone and the corresponding a-halogenocarbonyl compound. 2-Hydrazino-4-phenylselenazole has also been reacted with acetophenone. The 2-a-methylbenzylidenehydrazone of 4-phenyl-selenazole (2, K = CJl, R" = H, R" = NH—N CMe-aH ) forms golden yellow plates mp 171°C. ... 

It is known that 3-aminobenzo[6]furan can be prepared from o-cyanophenols and a-halogenocarbonyl compounds with subsequent Thorpe cyclization (73JPR779). The extension of this synthesis to heteroatom substituted benzo[6]furans is straightforward (76JPR313). The reaction of potassium salts of 3-cyano-2-pyridones (e.g. 27) with a-halogenocarbonyl compounds (esters, ketones) yields 2-alkoxy-3-cyanopyridines which can be cyclized in the presence of sodium ethoxide to give 3-aminofuro[2,3-6]pyridines (Scheme 6). 

In spite of many previous studies on the mechanisms by which trialkyl phosphites interact with a -halogenocarbonyl compounds, the reactive intermediates which lead to ketophosphonate (Arbuzov reaction) and to vinyl phosphate (Perkow reaction) have in no cases been clearly identified. It is generally believed (JL), however, that the Arbuzov product 4 results from initial attack by phosphorus at the cf-carbon atom, whereas the Perkow product 7 is formed by initial attack at the carbonyl carbon atom, followed by migration of phosphorus from carbon to oxygen (Scheme 1). 

The most convenient method of making a-aminoaldehydes is by reduction of a-amino acid esters using sodium amalgam [5, 6] by what has come to be known as the Akabori method. Alternatively, an a-halogenocarbonyl compound can be converted via the Gabriel synthesis into the aminocarbonyl... 

The alternative 5-amino-1-substituted imidazoles are usually made by reactions between primary amines and alkyl 7/-cyanoalkylimidates (see Section 3.2). Other possibilities include ring closure of formylglycineamidines by heating them alone or with phosphoryl chloride (yields are usually low) (see Section 2.1.1), cyclization of or-cyanoalkylcyanamides (to form 5-amino-2-bromoimidazoles) (see Section 2.2), alkylation of arylamino-methylene cyanamides or cyanoimidothiocarbanates with or-halogenocarbonyl compounds (gives 4-acyl-5-aminoimidazoles) (see Section 2.3), and cycliza-tions of DAMN with amidrazones (to 1,5-diaminoimidazoles) (see Section 2.2.1). 

When cyanoimidothiocarbamates react with or-halogenocarbonyl compounds, the products cyclize in base to form 1-substituted 2-alkylthio-5-amino-imidazoles (see Section 2.3, Scheme 2.3.1 and Table 2.3.1), while similar condensations of IV-cyanoiminodithiocarbamates with sarcosine nitrile salts, sarcosine ester salts or methylaminoacetophenone lead to analogous products, often in quite high yields (see Scheme 2.3.2). 

Ketones.- A new synthesis of cyclopentadienes by the reactions of allylidenetriphenylphosphonium ylides (40) with a-halogenocarbonyl compounds has been reported.33 Wittig reactions of the ylide derived from the phosphonium salt (41) provide the hydrazones (42).34 This reaction combined with hydrolysis of (42) constitutes a method for the n-i-2 homologation of ketones and aldehydes (Scheme 8). 

A series of oxatellurolanes-1,2 69 with various halogen atoms attached to the tetracoordinated tellurium center was prepared in 53-86% yields by the reaction of dehalogenation of a-halogenocarbonyl compounds (oj-chloro-, bromo- and iodo-acetophenones, diethylbromo- and diethyldibromomalonates) by 3-organ-yltelluropropanoles-1 70 (97H(45)575) (Scheme 40). 

The suggested mechanism for the formation of heterocycles 69 involves addition of dicoordinated tellurium center to a halogen of the a-halogenocarbonyl compound followed by deprotonation of the adduct and intramolecular cyclization to 69 (Scheme 41). 

The first syntheses of /-aminothiazoles were based on cyclization. As starting compounds, one could use thiosemicarbazide, thiocarbohydrazide, dithiocarbohydrazide and their derivatives interacting with a-halogenocarbonyl compounds. Thus, McLean and Wilson carried out the reaction of thiosemicarbazide with chloroacetone and described the compound thus obtained as 1,3,4-thiadiazine 243 (37JCS556). However, Beyer and co-workers showed that the course of this reaction is hard to define... 

Aminothiazoline-2-thiones are synthesized from potassium dithio-carbazate (54AK249 S7H1323) or potassium benzoyldithiocarbazate 67AG618) obtained in situ by the action of carbon disulfide on hydrazine or benzoylhydrazine. The alkylation of potassium salts by a-halogenocarbonyl compounds leads to intermediates 248 or 250, which are cyclized to the corresponding 3-aminothiazoline-2-thiones (249) and (252) in acidic medium. The product 252 was first mistakenly described as a thiadiazine (251) (57YZ771), but the structure was corrected in favor of... 

Almost all such cyclizations were carried out with a-thio derivatives of 4-amino- -triazole and 1-aminoimidazole. As cyclizing agents, two groups of compounds were mainly used (1) carboxylic acids and their derivatives, and (2) a-halogenocarbonyl compounds. In the former case, annelation... 

Some general reactions of the azinium salts (198) produced by reacting a-halogenocarbonyl compounds (197) with a-methylazines (196) are shown in Scheme 46. They cyclize in the presence of base to give pyrroloazines (199) or alternatively condense with a-diketones to give pyridoazinium salts (200) (the Westphal synthesis). 

In a number of fragmentations, the electrofugal group is generated only after an initial addition of a nucleophilic species. Typical of this class of fragmentation are the reactions of /3-halogenocarbonyl compounds, e.g. ... 

Excess ethyl a-bromoacetate followed by excess triethylamine added to a soln. of methyl 3-morpholinodithioacrylate in acetone 2-methylthio-5-carbethoxythio-phene. Y almost 100%. - The reaction is a general one with a-halogenocarbonyl compounds. F. e. s. E. J. Smutny, Am. Soc. 91, 208 (1969). 

Bing closures of halogenocarbonyl compounds activated by Lewis acids 3,5-Diazapyrylium salts from carboxylic acid chlorides and nitriles... 

Syntheses of Thiophens by Ring-closure Reactions.—The base-catalysed reaction between 3-amino-substituted dithioacrylate esters or amides (1), which are easily available from trithione, and a-halogenocarbonyl compounds yields 2,5-disubstituted thiophens (2). The same is true for... 

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