Aldehydes 2- benzothiazole synthesis

There are several new methodologies based on the Julia olefination reaction. For example, 2-(benzo[t/Jthiazol-2-ylsulfonyl)-j -methoxy-i -methylacetamide 178, prepared in two steps from 2-chloro-iV-methoxy-jV-methylacetamide, reacts with a variety of aldehydes in the presence of sodium hydride to furnish the ajl-unsaturated Weinreb amides 179 <06EJOC2851>. An efficient synthesis of fluorinated olefins 182 features the Julia olefination of aldehydes or ketones with a-fluoro l,3-benzothiazol-2-yl sulfones 181, readily available from l,3-benzothiazol-2-yl sulfones 180 via electrophilic fluorination <06OL1553>. A similar strategy has been applied to the synthesis of a-fluoro acrylates 185 <06OL4457>. 

The synthesis of cyclopropyl compounds containing the olefin replacement for the amide bond but without the additional primary chiral amino substituent were prepared by modified Julia olefination procedures. Addition of the benzothiazole sulfone 44 to aldehyde 39 gave trityl protected olefins in a 1 1 ratio. These... 

The modified Julia-Lythgoe alkenation known as Julia-Kocienski alkenation is one-step synthesis of alkenes from benzothiazol-2-yl sulfones (RCH2SO2BT) 4.59 and aldehydes, which is an alternative procedure that leads to the alkene in one step and offers very good -selectivity. 

A one-pot three-component reaction of 2-aminobenzimidazoles, aldehydes 71 and P-ketoesters 72 has been developed for the synthesis of 4//-pyrimido[2,l-6]benzothiazoles 75 <05BMCL5553>. The reaction presumably proceeds in two steps Knoevenagel condensation of 71 with 72 produces 3-benzylidene-2,4-pentanedione 73 Michael addition of 73 with 2-aminobenzothiazole then generates 74, which cyclizes to 75. 

Important variants for the synthesis of benzimidazoles allow the use of aldehydes, rather than acids ytterbium triflate (best for aliphatic aldehydes) or scandium triflate catalyse the condensation and the subsequent air oxidation of the dihydrobenzimidazole immediate product. Incorporating nitrobenzene in the reaction mixture as the oxidant can also be used. orf/to-Nitroanilines can be used by incorporating a reducing agent in the reaction mixture - e.g. hydrogen over palladium or sodium dithionite - for in situ generation of the orffto-phenylenediamine. 2-Aryl-benzothiazoles can be made from 2-aminobenzenethiol, aromatic aldehydes and air, in the presence of activated carbon. ... 

By analogy to the synthesis of benzoxazoles, benzothiazoles Eire obtained by cyclocondensation of o-aminothiophenols or their salts with carboxylic acids, their derivatives or with aldehydes [101] ... 

The synthesis of fluoroalkene derivatives has recently been disclosed using 2-(l-fluoroethyl)sulfonyl-l,3-benzothiazole in the presence of various aldehydes and ketones7 Either NaHMDS or t-BuOK could be used as a base. 

Variations of this reaction have been applied over the years, typically involving the condensation of 2-aminothiophenols with substituted carboxylic acids, acyl chlorides, aldehydes, and nitriles. Initially, the reaction involves the formation of an imine that cyclizes spontaneously and then oxidation to form benzothiazole. An application of this chemistry has been showcased in the synthesis of 2-(4-aminophenyl)benzothiazoles and the evaluation of their in vitro and in vivo activities against breast cancer cell lines, with compound a exhibiting the most potent growth inhibition. Unfortunately, there are limitations due to the difficulties met during the syntheses of readily oxidizable o-aminothiophenol-bearing substituents. 

In this reaction, initially, acetophenone 36 was converted to a-iodo acetophenone 39 by iodine, which was further transformed into phenyl glyoxal 40 by DMSO (dimethyl sulfoxide). The formed aldehyde then reacted with 2-aminothiophenol 37 to provide intermediate 41, which was further converted to 42 through an intramolecular 1,2-addition. Then, 42 underwent iodine-catalyzed oxidative dehydrogenation to afford the desired product 2-acyl benzothiazole 38 (Scheme 9.9). Very recently, the same authors reported the synthesis of 2,5-disubstituted oxazoles using a similar domino process [17]. 

Very recently, Mandal and coworkers reported that CuO nanoparticles supported on silica (Cu0-NPs/Si02) could be utilized as a heterogeneous and recyclable catalyst for the one-pot synthesis of benzimidazoles, benzothiazoles, and benzoxazoles (Scheme 4.46) (Inamdar et al., 2013). The Cu-NPs/Si02-catalyzed cyclization of o-phenylenediamines, o-aminothiophenols, and o-aminophenols with various aldehydes efficiently delivered the corresponding heterocycles. 

Li, Y. Wang, Y Wang, J. A simple iodine-promoted synthesis of 2-substituted benzothiazoles by condensation of aldehydes with 2-aminothiophenol. Chem. Lett. 2006,35,460-461. 

Lee and co-workers developed a copper-based catalytic system for the one-pot syntheses of benzothiazoles from 2-iodoanilines, aldehydes, and NaSH iiHaO (Scheme 2.144a). This one-pot reaction system represents a significant advantage in that it does not require the isolation of the intermediate prior to execution of C-S bond formation and in most instances does not require the preparation of the starting materials. As the authors stated, this was the first example of the employment of NaSH iiHaO as a sulfur source, not only in the synthesis of the benzothiazole, but also in transition-metal-catalyzed C-S bond formation. In addition, the... 

Benzothiazoles can be regarded for synthetic purposes as carbonyl equivalents, and the sequence shown in Scheme 5 illustrates the synthesis of aldehydes. Yields are almost quantitative throughout. ... 

Methods for derivatization of aldehydes and ketones using preformed Mannich reagents have been summarized.2-(Morpholinothio)benzothiazole (55) is a key reagent in a synthesis of 2-substituted cyclopentenones from the cyclo-pentanone (Scheme 47). 

By analogy to the standard synthesis of benzoxazoles (cf. p. 180), benzothiazoles are synthesized [360] by cyclocondensation of (2-amino)thiophenols with carboxylic acids or esters, with orthoesters in the presence of the acidic montmorillonite KSF clay catalyst, practicable also for the synthesis of benzoxazoles and benzimidazoles [361] or with aldehydes in the presence of an oxidant [362] ... 

Synthetic applications of benzothiazoles appear to be limited due to their hydrolytic stability. However, as shown in the following synthesis of cyclohexene-1-carbaldehyde (22) [368], the benzothiazole system can be modified by quaternization and reduction to a 2,3-dihydrobenzothiazole system 21, which (as aldehyde thioaminal) is acid-labile and thus can be readily cleaved by hydrolysis to the corresponding aldehyde 22. 

SCHEME 64 Synthesis of benzothiazoles by condensation of 2-aminothiophenol with aldehydes using 15 wt% Sn02/SiQ2 as catalyst. 

Synthesis of another series of novel a-aminophosphonates (48) involving the one-pot condensation reaction of substituted aromatic/ heterocyclic aldehydes (44), 2-amino-6-metho y-benzothiazole (47) and dibutyl/diphenyl phosphites (37) in toluene under microwave irradiation in the absence of any catalyst has also been accomplished by Janardhan Rao et al. (Scheme 22). The new compounds showed promising antimicrobial and anti-oxidant activities, depending on the nature of bioactive groups at the a-carbon. 

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