Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

Scheme 5.10 Synthesis of (165)
123
Chapter Five
2,2-difluoro-1-phenylbut-3-en-1-ol (158) was also employed in the synthesis of the
corresponding ether. Initially the method outlined by Elshani [38] was used, however,
analysis of the crude reaction mixture by 1 H and 19 F NMR spectroscopy showed no desired
product had formed therefore the protocol by Wu [39] was adopted. A suspension of NaH in
anhydrous DMF was stirred at 0 ºC, and a solution of 2,2-difluoro-1-phenylbut-3-en-1-ol in
DMF was added to the reaction mixture dropwise. The mixture was stirred at room
temperature for 1 hour, after which benzyl bromide was added and the reaction mixture
stirred for a further 20 hours. After workup, drying over magnesium sulphate and removal
of the solvent in vacuo the crude product was purified by column chromatography [hexane:
chloroform (50:50)], affording the desired product (165) in a low 15 % yield. However,
once again the use of DMF as a solvent meant that its subsequent removal at the end of the
reaction was difficult and, therefore, may have attributed to the low yield of product
obtained.
5.2.3 Synthesis of Derivatised Difluoro phenyl alcohols
Kirihara’s protocol was also extended to the synthesis of difluorophenyl alcohols which
were derivatised on the ring. This was accomplished by reacting substituted benzaldehydes
with 3-bromo-3,3-difluoropropene and indium in water. All compounds were successfully
synthesised and purified by column chromatography both (166) and (167) were purified
using the solvent system [hexane: ethyl acetate (80:20)] affording the desired product in
moderate yields (Table 5.5). Whilst (168) was purified using [hexane: ethyl acetate
(90:10)], and (169) needed no further purification as the starting material 2,3,4,5,6-penta
fluorobenzaldehyde was fully converted to the corresponding product (167), which was
obtained as a white solid in excellent yield.
Scheme 5.11 Reaction scheme for the synthesis of derivatised difluorophenyl alcohols
(For a definition of R see Table 122)