Bromothiazole

It has been demonstrated in the literature that the halogen-metal exchange of 2,4-dibromothiazole occurs predominantly at the C(2) position. 2-Stannyl-4-bromothiazole can be prepared using this strategy [32],... 

The preparation of stannylthiazoles via ditin chemistry has not been widely utilized. In one case, the synthesis of 4-tributylstannylthiazole 43 started with selective halogen-metal exchange at C(2) by treating 2,4-dibromothiazole with n-BuLi [33]. Trapping the resulting 2-lithio-4-bromothiazole with propanal and subsequent Jones oxidation secured 4-bromothiazole 42. The Pd-catalyzed reaction of 42 with hexamethyldistannane in the presence of PdCWPhjP provided 4-tributylstannylthiazole 43. 

In 1987, Yamanaka s group described a Pd-catalyzed reaction of halothiazoles with terminal acetylenes [51]. While the yield for the Sonogashira reaction of 2-bromo-4-phenylthiazole (89) with phenylacetylene to afford 90 was moderate (36% after desilylation), the coupling of 4-bromothiazole and 5-bromo-4-methylthiazole with phenylacetylene gave the desired internal acetylenes 91 and 92 in 71% and 65% yield, respectively. 

For the Heck reactions involving halothiazoles, 2-bromo- and 4-bromothiazoles tend to give resinous products, whereas some 5-bromothiazoles may form the desired Heck adduct with... 

A selective exchange reaction was observed on 2,4-dibromothiazoles allowing the synthesis of substituted 4-bromothiazoles . The use of functionalized organomagnesinm compounds as intermediates for the synthesis of polyfunctionalized heterocycles has been reviewed recently . 

Bromoethynes, in iron cluster compounds, 6, 296 4-Bromothiazoles, synthesis, 9, 38-39 Br0nsted acids, in fluoride abstraction, 1, 735 Buckyferrocenes, synthesis, 6, 187 Butadienes... 

The synthesis starts with 2,4-dibromothiazole (40), a regioselective Pd(0)-catalysed cross coupling step introduces a substituent at the 2-position. Alkyl or aryl zinc halides were employed as the nucleophiles to give 41. The 4-bromothiazole derivative 41 was then converted into a carbon nucleophile either as a zinc derivative (Negishi conditions) or as a tin derivative (Stille conditions) which then underwent a second cross coupling reaction with 2,4-dibromothiazole (40) to give exclusively 2 ,4-disubstituted 2,4 -bithiazoles 42. 

For the Heck reactions involving halothiazoles, 2-bromo- and 4-bromothiazoles tend to give resinous products, whereas some 5-bromothiazoles may form the desired Heck adduct with appropriate olefins. With respect to the heteroaryl Heck reaction using a thiazole as a coupling partner, the addition occurs regioselectively at the electron-rich C(5) position, whereas it occurs at C(2) for benzothiazole. 

For halothiazoles the conditions for selective deprotonations at the thiazole nucleus are quite variable depending on both the kind and position of the halogen atom (see Section 3.06.7.9.2). Thus, butyllithium deprotonates selectively 2-chlorothiazole at C-5 <90JCS(Pi)329> and 4-bromothiazole at the C-2 <92JCS(P1)215>. The same reaction cannot be carried out with 2-bromothiazole due to the halogen-lithium exchange much faster than with 2-chlorothiazole. Deprotonation at C-5 in 2-bromothiazole must be done with LDA <88CJC1617>. In a similar way 2,4-dihalothiazoles yield the... 

Easy access to a series of 5-substituted 4-bromo-2-thiazolamine derivatives 116 is based on the halogen dance (HD) reaction <05JOC567>. Treatment of 4-bromothiazole 113 with... 

An operationally simple halogenation of 4,5-dimethyl-2-arylthiazoles provides a regioselective approach to bromo- or chloro-methyl substituted thiazoles <04TL69>. Thus, treatment of 117 and its hydrochloride salt with NBS and NCS affords 4-bromothiazole 118 and 4-chlorothiazole 119, respectively, with >99% regioselectivity. The remarkable regioselectivity observed may arise from a Pummerer-type rearrangement mechanism via 120. 

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