4- Bromothiophene-3-carbaldehydes

Knoevenagel condensation between the quinolone-ester 499 and 3-bromothiophene-2-carbaldehyde followed by thermolysis gives the thienoquinolizine 500. The thermolysis also results in partial loss of the ester group (Equation 219) <1998T2785>. 

The presence of electron withdrawing substituents on the ring does not alter the reactivity of the halogenated substrates. 5-Bromothiophene-2-carbaldehyde (106) gave the phenyl derivative 107 in 54% yield. 3,5-Dibromothiophene-2-carbaldehyde (108) gave 5-phenyl-3-bromothiophene-2-carbaldehyde (109) in 43% yield, but 5-bromothiophene-2-carbonitrile (110) gave no reaction (89JPP(A)(47)191). 

Starting with 3-bromothiophene-2-carbaldehyde (X) the following sequence of reactions carried out ... 

The stepwise lithium exchange of 2,3-dibromothiophene referred to in CHEC-I <84CHEC-l(4)74l> has been used to generate a 1-alkenylthieno [2,3-c]furan <88TL1137>. The 2-lithio-3-bromothiophene is first reacted with DMF to get the 2-carbaldehyde then the 3-lithio compound is reacted with a co-unsaturated aldehyde. The product is converted to the required thieno [2,3-c]furan by standard reactions. 

Bromothiophene-2-carbaldehyde 13a served also as the starting compound in the synthesis of thieno[3,2- r]thiophene 23 containing the mercaptopropyl substituent (93TL5653). 

The multistep synthesis involving aldol condensation of thiophene-3-carbaldehyde 38 with malonic acid or the Heck reaction using 3-bromothiophene 30 or 4-bromothiophene-2-carboxylate produced thieno[3, 2 4,5]thieno[2,3-c]quinolones 82, which exhibit high antitumour activity (2002CPB656). 

Scheme 1 Synthesis of thieno[3,2-6]thiophene (1) via 3-bromothiophene-2-carbaldehyde (6) [15], and preparatirai of 2,6-diester 10 [16]...

The report in 1971 by MacDowell and Wisowaty on the S5mthesis of BDT unit started from thiophene derivatives [11,16], which was further improved by Beimling et al. in 1986 (Scheme 3.2) [12, 17]. Instead of using 3-thiophenecarboxaldehyde and 2,3-dibromothio-phene as starting materials in the original report, the improved method started with only 3-bromothiophene. It was first converted to 3-bromothiophene-2-carbaldehyde, which was then treated with 3-thienyllithium to afford compound 1. The newly formed hydroxyl group was reduced off to afford compound 2. The bromine on the 3 position of compound 2 was lithiated and quenched by N,N-dimethylformamide (DMF) to yield compound 3, which imder-went a cyclization in 48% hydrobromic acid solution to complete the synthesis of BDT monomer 4 with high yield. 

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