Halo carbonyl compounds 390 Synthesis

Synthesis Since a-halo-carbonyl compounds are very reactive electrophiles, we can use a short cut ... 

Reaction of /V,/V-unsubstituted selenoureas 332 with methyl vinyl ketone in the presence of ferric chloride in refluxing ethanol gives 2-amino-5-(l -ethoxy)-1,3-selenazoles 335 <06H(68)2145>. This approach obviates the use of lachrymatory halo carbonyl compounds frequently utilized in the synthesis of 1,3-selenazoles. 

A lot of methods are available for the synthesis of this heterocycle, and most of them rely on the formation of the five-membered ring. In this section, only the methodologies of reasonable scope will be reported. The most classical method involves the cyclocondensation of 2-aminopyridine with an a-halo carbonyl compound. Due to the broad availability of the required substrates and the efficiency of this cyclocondensation, it continues to be the method of choice to prepare this heterocycle. New examples highlighting the generality of this reaction are collected in Table 14. 

This synthesis, originally devised by Tschitschibabin,8 is still the most widely used because it can easily be modified to yield substituted indolizines. The synthesis involves the quaternization of a 2-substituted pyridine, normally using an a-halo carbonyl compound, followed by intramolecular cyclization of the quaternary salt with a mild base, usually aqueous sodium bicarbonate (Scheme 1). 

When the Wittig reaction was introduced (Chapter 14) we saw it simply as an alkene synthesis. Now if we look at one group of Wittig reagents, those derived from a-halo-carbonyl compounds, we can see that they behave as specific enol equivalents in making unsaturated carbonyl compounds. 

The reaction of -halo carbonyl compounds with primary amides is appropriate for oxazoles containing one or more aryl groups . Ureas form 2-aminooxazoles. Formamide can be used resulting in a free 2-position in the oxazole. A convenient synthesis of 5-substituted-4-cyanooxazoles 223 is based on the condensation of -hydroxy—cyanoenamines 222 with trimethyl orthoformate (Scheme 109). The cyanoenamine intermediates 222 are derived from Lewis acid-catalyzed Passerini reactions between /-butyl isonitrile and aldehydes <2002S1969>. 

Scheme 1 One-pot synthesis of lmldazo[l,5-b][l,2,4]triazoles 8 from of a,a-dlsubstltuted a-halo carbonyl compounds 1 with potassium thiocyanate in acetic acid and monosubstituted hydrazines 3.

The halogen-magnesium exchange of a-halo carbonyl compounds has been reported to afford magnesium enolates which react with aldehydes to yield aldol products [107, 108]. The application of this reaction to the synthesis of penicillin derivatives has been reported (Scheme 3.94) [109-111]. 

Tripett, S., New synthesis of acetylenes. Part 2. Reaction of triphenylphosphine with a-halo carbonyl compounds, J. Chem. Soc., 2337. 1962. 

Carbon monoxide Ketone synthesis using cyanide ion Reactions with a-halo-carbonyl compounds Polyene Cyclisations Looking Forwards... 

The known preparative methods for the synthesis of imidazo[l,2-a]pyrazines prior to 1983 have been reviewed extensively <84CHEC-1(5)607>. This section will review new methods of syntheses published since 1983. The most common syntheses of this ring system involve closure of the imidazole ring by cyclization of an appropriately substituted aminopyrazine using a variety of reagents, or by the reaction of bifunctional agents (such as a-ketoacids, a-ketoaldehydes, a-halo-carbonyl compounds), with 2-aminopyrazines. 

Wender and White published a very simple indole ring synthesis that involves the generation of a bis-lithio anion 1 and its reaction with an a-halo carbonyl compound 2, followed by acid- or base-catalyzed dehydration [1,2], The overall transformation is shown in Scheme 1, along with three examples. This chemistry illustrates yet another indole ring synthesis that uses a-halo carbonyl compounds [3]. We will encounter these compounds again with the venerable Bischler indole synthesis in Chapter 23. A summary of several Wender indole ring syntheses is tabulated in Table 1 [1, 2, 4-7], Entry 5 features a directed lithiation method to the bis-lithio nucleophile [5], a modification also described by Wender and White [2], Sainsbury and... 

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