Benzothiazoles carbonyl compounds

In the case of the benzothiazole system, both aldehydes and mixed ketones have been synthesized by reduction or alkylation of the appropriate carbonyl precursors. The carbonyl compounds are in turn prepared from the benzothiazole-2-anion either directly by reaction with esters or indirectly by reaction with aldehydes followed by PCC oxidation (Scheme 154) (85H2467 91BCJ3256). 

An extensive study on the use of benzothiazoles as carbonyl equivalents has been conducted (78TL5, 9). The 2-lithiobenzothiazole (576) readily adds to carbonyl compounds to furnish on dehydration of the carbinol a vinylbenzothiazole (578). The benzothiazole nucleus can then be unmasked by a sequence of reactions involving (a) Af-methylation with methyl fluorosulfonate, (b) addition of either hydride (NaBKU) or an organometallic (MeLi) to afford the iV-methylbenzothiazoline and (c) hydrolysis of the crude Af-methylbenzothiazo-line (e.g. AgN03). A representative example is shown in Scheme 126. 

A range of other base-solvent combinations were applied with various sulfones. Judka and Makosza have used t-BuOK, t-BuOLi and EtONa in THF or DMF. Reactions of ethyl (benzothiazol-2-yl-sulfonyl)acetate [108] with carbonyl compounds were conveniently carried out using DBU as a base in DCM at reflux (2 molar excess of the sulfone was used). Reaction of methyl tert-butyltetrazolyl sulfones [109] was executed by CS2CO3 in THF-DMF at reflux. 

Baudin, J. B., Hareau, G., Julia, S. A., Ruel, O. A direct synthesis of olefins by the reaction of carbonyl compounds with lithio derivatives of 2-[alkyl- or 2 -alkenyl- or benzylsulfonyl]benzothiazoles. Tetrahedron Lett. 1991, 32,1175-1178. 

The -oxidation of thiazoles to sulfoxides or sulfones has not been reported. Under base conditions both thiazoles and benzothiazoles are resistant to the action of PhI(OAc)2 <88IJC(B)929>. Raney Nickel promotes desulfuration of thiazoles, probably through an initial coordination of the sulfur at nickel, affording carbonyl compounds <84CHEC-I(4)240>. 

Aminobenzenethiol reacts readily with carbonyl compounds to give 1,3-benzothiazoles (63).106 Certain derivatives of this ring system have been found to undergo ring expansion under specific conditions to give benzothiazines. The first report in the literature of this type of reaction involved the treatment of benzothiazolium salt 64 with base the postulated mechanism12 is shown in Scheme 1. 

It has been found possible to construct the 1,4-benzothiazine ring by direct interaction of bis-(2-aminobenzene) disulfide (96) with carbonyl compounds.139,140 The reaction is most efficient when conducted under a nitrogen atmosphere with a 1 1 ratio of reactants otherwise, the principle products are benzothiazoles. While reduction of the benzothiazine 97 with sodium borohydride gives a stable dihydro derivative, the unsaturated benzothiazines themselves were prone to autoxidation, giving rise to benzothiazoles and benzothiazine sulfoxides.141... 

Similarly, MyllymSki et al. have employed this concept in the synthesis of aryl ketones via the reaction of the lithio benzothiazole with an aryl acid chloride to produce the desired ketone. A series of such carbonyl compounds was synthesized and evaluated as potential fatty acid amide hydrolase (FAAH) inhibitors. 

AlkylbenzimicJazoles show side-chain C-H acidity and reactivity like their benzox-azole and benzothiazole analogs. For instance, 2-methylbenzimidazole reacts at 0°C with 2 mol of nBuIi to give the dihthio compounds 5, which gives aza-aldol addition to carbonyl compounds ... 

Sylvestre Julia and co-workers discoveried in 1991 a direct synthesis of olefins by reaction of carbonyl compounds with lithio derivatives of 2-[alkyl- or (2 -alkenyl)- or benzyl-sulfonylj-benzothiazoles (BT, 5). Since the initial study of the reaction of metallated BT sulfone 5 with carbonyl compounds, the versatility of these derivatives has been fully demonstrated through their application in the total synthesis of a large number of nature products. Kocienski and co-workers found in 1998 that l-phenyl-17/-tetrazol-5-yl sulfone (PT, 6) is a better olefination partner comparing to BT sulfones. This allowed the one-port Julia-Lythgoe olefination to be employed more efficiently and broadly, especially in the synthesis of nature products. 

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