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Chapter 2
Synthesis of substituted pyrimidines via Wittig
2.7 Results and discussion
Scheme:-1 Synthesis of pyrimidine derivatives via Wittig reaction in aqueous
media.
F
F
F
O
Cl
N
N
O
DIBAL
Toluene
Cl
N
N
OH
1) PBr 3 /MDC
2) TPP/Toluene
Cl
N
N
P
Br
ASM-3e INT-01 INT-02
R-CHO
STPP
Water
F
Wittig reaction
N
R
Cl
N
AW-01 to AW-20
The synthetic route for the targeted compounds (AW-01 to AW-20) is shown
in Scheme 1. Compound ASM-03e was prepared by following the methods described
in chapter-1. The reaction of ASM-03e with diisobutylaluminium hydride (DIBAL) in
toluene at 0 o C for 3 h. afforded (2-chloro-4-(4-fluorophenyl)-6-isopropyl pyrimidin-
5-yl)methanol (INT-01) in good yield. INT-01 was then treated with phosphorous
tribromide in MDC at 0-5 o C for 2-3 h. The crude oily residue was reacted with
triphenyl phosphine in toluene at reflux temperature for 3-4 h. to afford triphenyl[2-
chloro-{4-(4-flourophenyl)-6-isopropyl-pyrimidin-5-ylmethyl}phosphonium]bromide
(INT-02) in excellent yield.
Optimization for reaction condition the pyrimidine phosphorous ylide (INT-
02) was treated with benzaldehyde using various bases such as NaH 2 PO 4 , Na 2 HPO 4 ,
and sodium tripolyphosphate in three different solvents, DMSO, THF, and water
(Table-1). Sodium tripolyphosphate as base in aqueous media was found to be an
effective method to afford highly (E)-selective product of AW-01 in moderate to good
yield (Table-1).
Department of Chemistry, Saurashtra university, Rajkot-360005 57