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7, 1974
t-BuO'
ArMgBr
ArCHCHF,
OH
TsCI
0%
t-BuO-
- Scheme I1
I. N a H
C,H,CH(CO,C,H&
2. D,O, A
1. LiAIH,
2. TsCl
C6H,CD2CO2C2HS
3
---+
,4rCHCHF2
t-BuOH
In order to determine kinetic isotope effects and to investigate the possibility of deuterium-hydrogen exchange,
l-fluor0-2-phenylethane-2,2-&and l,l-difluoro-2-phenylethane-2,2-& were prepared by the methods outlined in
Scheme 11. The rate constants for these compounds did not
increase with time, as they would be expected to do if extensive hydrogen-deuterium exchange were occurring before elimination. As a more sensitive check, one reaction
of each deuterium compound was quenched after approximately 1 half-life, and the mass spectrum of the recovered
starting material was compared with that of authentic
deuterated material. This indicated that no detectable
hydrogen deuterium exchange had occurred.
NaBH,
ArCOCHF,
ArCH=CF(O-t-Bu) (1)
Scheme I
CHF,COOH
ArCH=CF,
H,/Pd/C
C,H,OH
1 NaBD,
C,H,COCHF,
ArCH,CHF,
C,H,CDCHF,
2 TsCl
C,H,CD,CH,F
KF
D,
Pd/C
C6HjCDZCHF2
OTs
The rate constants that we have determined for the compounds prepared in this study are given in Table I.
In determining Hammett p values for these elimination
pared analogously using trifluoroacetic acid. The eliminareactions, we found that the a value for fluorine derived
tion reactions were carried out at 50" in tert-butyl alcohol
from the acidity of p-fluorobenzoic acid would not corresolution containing 0.1 N potassium tert-butoxide, and
late with that of other substitutents, but that the athe rate of disappearance of base was followed by titration
with standard hydrochloric acid solution. The l-fluorovalue derived from the acidity of p-fluorophenol would do
so, although less well in the case of the 2-arylethyl fluoand 1,l-difluoroethanes each consumed 1 equiv of base
and produced styrenes and a mixture of cis- and trans-@- rides than with the di- and trifluorides. It has previously
been observed that the F-nitro group also requires the use
fluorostyrenes, respectively. In the case of the l,l,l-triof a u - value for correlation in the elimination reaction of
fluoro-2-arylethanes the elimination reaction was found to
other 2-arylethyl derivatives.g
occur with the consumption of 2 mol of potassium tertThe p values found were +3.24 f 0.05 for the fluoride,
butoxide. If the reaction was carried out in an nmr tube
+3.56
0.07 for the difluoride, and +4.04 f 0.30 for the
with less than 1 equiv of base, we were able to detect
trifluoride.
some P,/3-difluorostyrene3 among the products. This iniThe results of these measurements indicate that, as
tially formed olefin apparently undergoes an additionelimination reaction analogous to that of triflu~rostyrene~ might be expected, the eliminations are highly carbanionforming ultimately a cis,trans mixture of 1-(tert-butoxy)- ic. Koch6 has postulated recently that eliminations of HF
from C6H&HClCF3 occurs with reversible formation of
1-fluoro-2-arylethylenes (eq 1).The second reaction in this
the hydrogen-bonded carbanion, a carbanion which has an
sequence appears to be faster than the first, because iniactivation energy for exchange with solvent because of
tial rate constants were identical with those calculated on
Table I
Rates of the Elimination Reaction of 2 - A r y l e t h y l
Fluorides by Potassium tert-Butoxide in
tert-Butyl A l c o h o l at 50"
Y
m-CFa
H
m-CHa
P-F
p-CHa
H
H
P-F
m-CHs
p-CHa
H
H
P-F
m-CHs
P-C&
Registry no.
kea X lod,
1. mol-* see-1
YC~H~CHZCHZF
50512-33-9
4 6 . 6 f0 . 3 6
458-87-7
1.88 f 0.01
50561-90-5
1.21 f 0.01
2343-30-8
1 . 1 0 j=0 . 0 1
50561-92-7
0.513 f 0.007
YCeH4CDzCHzF
50561-93-8
0.418 i 0,009
Y CeHaCHzCHFz
10541-59-0
11.8 i0.09
50561-95-0
9.62 f 0.05
50561-96-1
6.47 i 0 . 0 3
50561-97-2
2 . 8 8 i 0.00
YC~HICDZCHFZ
50561-98-3
4.26 f 0.03
YCGH~CH~CF~
21249-93-4
22.8 i0.45
50561-99-4
16.8 & 0.30
50562-00-0
12.7 0.50
50562-01-1
4 . 4 5 It 0 . 0 9
kn/b
4.50
2.77
Experimental Section
Melting points are uncorrected and were taken on a FisherJohns melting point apparats. Ir absorption spectra were determined on a Beckman IR-10 spectrometer. All proton nmr spectra
were determined on a Varian A-60A spectrometer using TMS as
an internal standard. All fluorine nmr spectra were recorded on a
Varian HA-100 spectrometer using FCC13 as an internal standard. Chemical shifts are reported in ppm relative to this standard. Mass spectra were recorded on either a Varian MAT CH-5
or CH-7 spectrometer at 70 eV. Microanalyses were performed by
Dr. Alfred Bernhardt Mickroanalytisches Laboratorium, Mulheim, West Germany.
Preparation of 2-Arylethyl Fluorides. All of the 2-arylethanols, with the exception of 2-phenylethanol which is commercially
available, were prepared by the reduction of the corresponding
arylacetic acid with diborane using the general procedure of
Brown and Rae.? The arylacetic acids, with the exception of the
m-trifluoromethylphenylacetic acid, were commercially available.
The latter was prepared from rn-trifluoromethylbenzyl chloride
by reaction with magnesium and C O Z . The
~
alcohols were converted into their tosylates by the method of Tips01-1,~and these in
turn converted into fluorides by the procedure of Bergman and
Shahak.lJ! 2-p-Tolylethanol: bp 69-74' (0.8-0.6 mm) [lit.lo bp
117-118" (14 mm)], 85% yield. 2-m-Tolylethanol: bp 69-74"
(0.8-0.6 mm) [lit.ll bp 112" (10 mm)], 86% yield. I-(p-Fluoro-
879
References a n d Notes
C. H . DePuy and C. A. Bishop, J. Amer. Chem. SOC..82, 2535
(1960).
G. B. Bachman
(1947).
R'
1,
R = H
4, R' = CHB
R = OCHj
b, R = COCHB
C, R = N(C,H,)S
a,
R'
2, R' = H
5, R' = CHB
R'
3, R'= H
6, R' = CH,
d, R = CH3
e, R = OCOCHS
uct. Our interest in the use of certain substituted chromenes as intermediates in the synthesis of tumor-inhibitory trichothecan mycotoxins4 prompted us to further examine those factors which influence regioselectivity in this