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19F NMR analyses of some cyclopropane derivatives
Journal
of Fluorine
Received:
"F
October
Chemistry,
29 (1985)
15, 1984; accepted:
NMR ANALYSES
261
1
April 7, 1985
OF SOME CYCLOPROPANE
F. CAMPS,
J. COLL, G. FABRIAS,
Instituto
de Quimica
08034-Barcelona
26 l-21
DERIVATIVES*
A. GUERRERO
Bio-Organica,
Jorge Girona
Salgado,
18-26
(Spain)
and M. FELIZ
Oepartamento Barcelona,
de Quimica Oiagonal
Organica,
Facultad
647. 08028-Barcelona
de Quimica,
Universidad
de
(Spain)
SUMMARY Structural
assignments
of all possible
ro-2-ethoxy-1-fluoro-alkylcyclopropanes "F
NMR spectra.
the fluorine shielding
The previously
signal has been
effect
in the vicinal
have been achieved
unreported
studied
diastereoisomers
effect
and found
cis-fluorine
of
through
of an ethoxyl
to promote
l-chlotheir group
in most
and a deshielding
on
cases
effect
a
when
trans to this halogen.
INTRODUCTION Empirical application value
structure-spectroscopic
of high resolution
in structural
studies
[1,2], their
of the
some possible signals
[3,4] and chemical
*Presented
at the XX Reunion
mica held in Castelldn
proved
have
during
been prepared
and
the
in the synthesis,
parameters
correlations.
H-F coupling
in the literature
Bienal de la Real Sociedad
(Spain), September
to be of great context,
unequivocally
obtained
on vicinal
shifts reported
from the
of insect sex pheromones
to 1) assign
structure-spectral
derived
In this
derivatives
in order
has been based
magnitudes
139/85/$3.30
mimics
to each of the diastereoisomers
and 2) establish Assignment
recorded
have
molecules.
pheromone
several chlorofluorocyclopropane 19F NMR spectra
right structure
0022-l
NMR spectroscopy
of organic
our recent work on fluorinated
data correlations
EspaAola
constant
[5]. de Qui-
1984.
0 Elsevier Sequoia/Printed
in The Netherlands
262 RESULTS AND DISCUSSION
The chlorofluorocyclopropanes by stereospecific
addition
dichlorofluoromethane ethers
out
the
confirm Most
and potassium
under PTC conditions
generally,
as mixtures
reaction the
vinyl
corresponding
[7]
hydroxide,
with
structural
assignment
ethers
have
prepared
and
to
the
161 (Table 1). Starting
initial
acetals
generated
in good yields in situ --
corresponding
from vinyl
vinyl ethers were used,
of _Z/E isomers; only entry 7 was repeated carrying the stereoisomerically pure -E isomer in order to been
in the presence
171. Z-Ethoxyprop-l-ene acid
(l-7) have been prepared
of chlorofluorocarbene,
the
diastereoisomers
dehydroethoxylation
7a-d. of
the
of -p-toluenesulfonic acid/quinoline by decarboxylation of 3-ethoxycrotonic
was obtained
immediately
of by
distilled
into
the
cyclopropanation
reaction
mixture.
R1
R3
R1
R3
R2 c'
R4
CHC12F e KOH/18-crown-6
R4
'w'
F
l-7 -TABLE
I
Cyclopropane
____
derivatives
- ..__--.---
Entry
(l-7) prepared --
-....--- ---. - ---
Vinyl ether
by cyclopropanation
.._.._ _.
-- ----
Reaction time (h)
of vinyl ethers
.__....-_ -. -. Reaction products
.----~- ~-Yield (%)
1
ethyl
vinyl ether
24
2
E-ethoxyprop-1-ene
2
la-b -2a-b --
64 78
76
3
1-ethoxy-2-methylprop-1-ene
3.5
3a-b --
4
1-ethoxyprop-1-ene
5.5
4a-d _-
80
5
1-ethoxybut-1-ene
6
5a-d
80
6
1-ethoxydec-1-ene
7
6a-d --
61
7
3-ethoxypent-2-ene
4
7a-d --
82
263 TABLE 2
Assignment
Comp.
of the "F
R1
NMR parameters
R2
R3
R4
to compounds
la-7d --
Chem.
Multi
Coupling
shift
constants
(Hz)
la
H
H
OEt
H
62.0
ddd
18.4, 12.7, 7.6
lb
H
H
H
OEt
83.0
ddd
19.7,
2a
H
H
OEt
Me
65.2
ddt
17.1,
7.9, 3.4
2b
H
H
Me
OEt
74.1
ddo
20.5,
9.0, 2.6
3a
Me
Me
OEt
H
68.8
dhept
14.0,
2.3
9.3, 1.5
3b
Me
Me
H
OEt
85.1
b
4a
Me
H
OEt
H
58.6
ddo
31.9, 18.4, 2.6
4b
H
Me
H
OEt
75.9
dm
13.3
4c
Me
H
H
OEt
76.4
dm
23.9
4d
H
Me
OEt
H
57.3
ddo
22.5,
13.1, 2.5
5a
Et
H
OEt
H
57.7
ddo
32.1,
17.7, 1.7
5b
H
Et
H
OEt
75.5
dm
13.3
5c
Et
H
H
OEt
75.0
dm
22.0
5d
H
Et
OEt
H
56.25
ddo
25.2, 12.6, 1.5
6a
Ott
H
OEt
H
58.2
ddt
31.9, 16.9, 1.5
6b
H
Ott
H
OEt
74.75
dm
13.6
6c
Ott
H
H
OEt
75.0
dm
23.1
6d
H
Ott
OEt
H
56.2
ddt
22.5,
7a
Me
H
OEt
Et
62.25
do
22.2,
7b
H
Me
Et
OEt
85.2
b
7c
Me
H
Et
OEt
69.1
d
7d
H
Me
OEt
Et
79.8
b
showing
secondary
*dm stands termined
for a doublet
on a first order analysis.
splitting
13.1, 2.0 2.6
24.2
which
could not be de-
264 Signals an internal
"F
of the
NMR spectra
sealed capillary
been assigned
(referred
tube, positive
(Table 2) on the basis of the following
i) In 1-chloro-1-fluorocyclopropanes, relative
to the fluorine
ppm; estimated deshielding
average
effect
the corresponding
11 ppm), whereas
(4~120')
of substituents
On the other
hand,
promoted
relationship
chemical
shifts
cyclopropane,
the
of
Since
the
in Scheme
groups
previously
influence
derived
unreported
an ethoxyl
1-chloro-1-fluoro-alkylcyclopropanes have deduced
the shielding
angle
a
[51. larger
than
of the known $
[3] and the
1, from the average from and
literature
absorption
group
effects
[5]
and
for
the
parent
as 63.5 ppm.
on the
has not been
shielding
data
chloro-fluoro-dimethyl-
(CFCP) can be estimated
of
-6 ppm)
is generally
as a consequence
chloro-fluoro-ethyl-
1-chloro-1-fluorocyclopropane
promote
141.
as shown
by alkyl
in cis position
groups*
average
(@=O") 181,
factors:
(ranging from 8.5 to 12.5
in a trans
3JH_F s
acid in
shifts) have
determining
of 3J,_, on the bond angle 6, the dihedral
increments
of
effect
(-3.6 to -10.5 ppm; estimated
3J H_F trans
electronegativity
the
methyl
exert a shielding
ii) In fluorocyclopropanes
dependence
to trifluoroacetic
values for upfield
"F
previously
absorption
on
described,
we
for this group from our data of the pair
isomers
3 due to the possible unambiguous assignment in this case _' 2). The low field absorption at 6 68.8 ppm was attributed to the
(Scheme
cis isomer constants shift
(F and Et0 in trans
relationship)
on the basis
of the coupling
of -3a (14.0 Hz) and -3b (broad signal). Comparison of the chemical of -3a and -3b with that of l-chloro-1-fluoro-2,2-dimethyl-
values
cyclopropane resulted effect
(65.5 ppm) indicates
in a shielding
is only 3.3 ppm.
other cases
effect Further
that substitution of
19.6
proof
ppm,
of ethoxyl
whereas
for
of the same effects
a
for a cis H trans
H
the
can be found
in
of
of
(see below).
Furthermore,
from
the
chemical
shifts
comparison
the
pair
isomers
assignment to diastereoisomers -1 with those of -3, configurational la and lb was made. From the absorptions of la and lb and the CFCP calcula-
*From
our
deshielding group.
results effect
in Table is derived
2
(cf. 4a-d and 5a-d) an average of 1 ppm -from substitution of a methyl for an ethyl
265
69.5
33,s Scheme
1
ted value
(63.5 ppm),
a shielding
increment
of an Et0 group cis to the F and an almost
of 19.5 ppm for introduction negligible
deshielding
(-1.5 ppm), when both groups were in trans relationship,
effect
were inferred.
In the pair of isomers _2 (Table 2) the high field signal at 6 74.1 ppm was attributed by comparison
65.2 ppm signal, was assigned ppm
shielding
relative in
the
geminal
to the trans
of the observed showing
coupling
constants
that
suit better
those
to -2a. As shown in Scheme 3, the results point effect for introduction of an Et0 group in
to fluorine, following
in an alkyl
discussion),
substitution,
cis/trans --
isomer -2b (F and Et0 in cis relationship) constants with those of -lb, and the
coupling
an
11
ppm
and a 9 ppm chemical
interchange
For structural
substituted
of substituents assignment
carbon
deshielding
orientation
(62b-62a).
low field doublet Hz) was attributed
at 6
69.lpprn
with
for
was undertaken
a cis coupling
constant
to 7c and the high field broad absorption
trans
(CSO) for the
7a-d an independent
of the pair 7c-d from pure (E)-3-ethoxypent-Z-ene
position
substitution
effect
difference
of compounds
out a -ca. 20 cis
(geminal
shift
of la,
synthesis 191. The
(x5,_,
24.2
to -7d. By the
266 +‘9.3
4 - yyEto+m Et0
F
Scheme
F
2
same token,
the 62.25
(3JH_F 22.2 Hz) and 85.2
signals
were
assigned
to -7a
and 7b respectively. As in the previous case, chemical shift values for the as those pair of isomers -7c-7d point to effects of the same magnitude described group
above for 2a and 2b, taking
(19.5
inversion
ppm)
obtained
shown
into account
in--Scheme 1, The
for __ 2a-2b and -_7c-7d
the pair -7a-7b of 28.5 ppm group), whereas the observed
(9.0 plus
CSD
for
the CSD for the methyl ethoxyl/alkyl
(ca 9 ppm) would 19.5
experimental
ppm
effect
geminal
lead to a CSD for due
to the
value is 23.0 ppm. We have
methyl
267
Scheme
3
rationalized presence
this upfield
of the ethoxyl,
cyclopropane with the
ring.
same
in Scheme
of an Et0 group in trans
of the
culated constants
trans values
to the
(two cis to
was
found
side of the
in other
compounds
pattern (3a-6a). On the other hand, from the -3, the average shielding effect for introduction
to the F, in an alkyl
the
induced
3, for compounds
constants,
structure
low field
absorption
substituted
carbon,
may
be
field
absorption hand,
by electronegative
[5],led
4a-d we
attributed,
on the
cal-a (the most deshielded with largest vicinal coupling
3J,_,) and, conversely,
high
3JH_F 1. On the other
hydrogens
the simultaneous
and alkyl groups on the same
the same effect
in Table
coupling
signal)
signal)
by
as-10 ppm.
As presented basis
(ca 6 ppm) as promoted
chlorine
In fact,
substitution
values depicted
estimated
shift
-b (the most shielded calculated with lower coupling constants (two
the decrease substituents,
us to assign the remaining
of the
coupling
like ethoxyl,
constants
over
high field absorption
geminal to
268
TABLE
3
Calculated
Isomer
and experimental
absorptions
for compounds
4 -
Chemical shifts (calcd.)(found)
Parent value
Substituent shielding effects*
a
63.5
- 6- 1 (- 7)
56.5
58.2
b
63.5
+11+20
(+31)
94.5
75.9
C
63.5
+20- 6 (+14)
77.5
76.4
d
63.5
+ll- 1 (+lO)
73.5
57.3
*cis-Me, -
+ll; trans-Me,
-6; _cis-EtO,
+20; trans-EtO,
-1 (see text)
structure _c and the low field signal to structure -d. Structural assignments for the isomers of -5 and -6 were based on the direct correspondence of their practically identical chemical shifts and coupling constants with those of -4. Examination 20
ppm
carbon the
for
for
of
of the cyclopropane
parent
compound
methyl-CFCP), case
of the CSD depicted
introduction
of geminal the
CFCP,
an identical
the
6 ppm
(cf. -la with Nevertheless, deviation
5a with
although
relationship
is -ca -2 ppm, by taking into mentioned steric arrangement
for
the
Z-ethyl-CFCP
and
the
-1-fluorocyclopropane
3a with
2,2-dimethyl-CFCP).
the
CSD
found
for
of -5b and -5d give rise to a notorious when compared with the literature value for between the
-5b and -5d (19.3 ppm) is in good other pairs of isomers (21.0 ppm for
-1, 16.3 for -3 and 17.3 for 5a-5c). conclusion,
effect
shifts
with
by
the estimated
above
agreement
promoted
discussed
Similarly,
compounds
In
those
out a value of -ca an unsubstituted
(see above).
of the above pattern,
2-ethyl-CFCP,
in
2-ethyl-CFCP -5c with value to that found in the previously
trans
the chemical
substituent
to F (cf. -lb with and -3b with 2,2-di-
correction
CFCP,
in Scheme 2 pointed
ethoxyl
ring and in cis relationship
substitution
corresponding
account
an
we have found
introduction derivatives
that
of
an
in
a cis
the
shielding
ethoxyl
effect
group
relationship
in to
the
generally l-chlorofluorine
269 amounts
to -ca 20 ppm. Conversely, the moiety trans to the fluorine
ethoxyl
substituents
in the cyclopropane
10 ppm
observed
were
geminal
positions
presence
of ethoxyl,
the cyclopropane ppm,
to
to
that
incorporation
the
alkyl
for
the
groups,
and alkyl
ring may require
account
of the
depends
on
presence
effects
took
substituents
observed
of around
2 and
in
vicinal
the
and
simultaneous
the
same
side
of a correction
from
an
alkyl
The
on
of
of
place
respectively:
the introduction
deviation
incorporation
the
ring. Deshielding
when
chlorine
effect
of
of ca 6
estimated
chemical
shift values.
EXPERIMENTAL
Infrared NMR
spectra
internal a
spectra were obtained
were
recorded
standard.
Varian
XL200
on
a
on a Perkin Elmer 257 spectrometer.
Bruker
WP8OSY
at
lgF NMR spectra were determined
operating
at
75.39
and
188.15
trifluoroacetic
acid as internal standard.
Chemical
6
and
are
scale
signal.
(ppm)
Elemental
General
positive
analyses
procedure
for
alkyl cyclopropanes
absorptions
were measured
the
80
MHz
using
TMS
on a Bruker WP8OSY MHz
respectively,
or on using
shifts are reported
upfield
from
the
'H as
in
reference
on a Carlo Erba 1106.
of
preparation
1-chloro-2-ethoxy-1-fluoro-3-
l-7 --
Cyclopropanes
l-7 have been prepared by the cyclopropanation reaction -[6] using longer reaction times depending by Y. Bessiere w
described
on the substrate carried
1). Control
(see Table
of the extent
1-Chloro-2-ethoxy-1-fluorocyclopropanes
From ethyl B.p. 53-55"/120 6
1.24
3.3-3.9
of the reaction
was
out by NMR analyses.
vinyl
Torr.
(t, J-7.02
(complex,
ether,
la-b --
la-b were prepared in 76% yield. -IR (Ccl,) v 1385 (C-F), 1210 (C-O) crn:l lH NMR (CDC13) Hz,
3H,
compounds
OCH,CE,),
3H, CHOCH.$H3).
1.1-1.9
Elemental
C, 43.47; H, 5.79. Found: c, 43.88; H, 5.99.
(complex,
analysis:
Calcd.
2H,
CHCli2C),
for C5HsC1FO:
1-Chloro-2-ethoxy-1-fluoro-2-methylcyclopropanes
3-Ethoxycrotonic flask and heated yield
pure
acid
of Freon
(55 mg], previously dissolve
the precipitate,
distilled
from potassium
the acid)
of cyclopropanes from isolated
at 0°C. After the
separated
to yield
1.0-1.5
was
added to
and the organic
phase
0.279 g (54% overall yield from
1.2 (t, J=6.6 Hz, 3H, OCH,Cti,), 1.6
(m, Ct12C).
Yield 78%. B. p. 67-70"/100 (CDCl,] 6 1.25 (complex,
Torr.
9H, 3xCH3],
3a-b
[7]
IR (Ccl,) u 1395, 1120 cm:1
2.95
(s, lH, CH of compound
lH
NMR
3a), 3.1
Hz, lH, CE of compound -3b), 3.6 (q, J=6.8 Hz, 2H, 0Cti2CH~.
1-Chloro-2-ethoxy-1-fluoro-3-methylcyclopropanes
Yield 80%. B. p. 60-62"/60 (CDCl,)
collected
and 18-crown-6
water
l-Chloro-2-ethoxy-l-fluoro-3,3-dimethylcyclopropanes
(d, J=12.0
to
2a-b was 2a-2b. In another run a 64% yield of --vinyl ether. B. p. 65-67"/80 Torr. IR (Ccl,) w 1385
(C-F), 1215 (C-O] cm.-' lH NMR (CDCl,) 6 (m, 3H, CH2CCl&],
(9 ml)
2 h reaction,
layers were
carbonate
in a distilling
was directly
55% KOH solution
21 (5 ml),
cooled
was placed
the acid was decarboxylated
[7]. The enol ether
Z-ethoxy-prop-1-ene
over a mixture
obtained
(0.78 g, 6 mmole)
at 160". After sublimation,
2a-b
6
1.1
(complex,
(complex,
Torr.
IR (Ccl,) I) 1390,
3H, Ct13CH), 1.2
lH, CH), 3.2-3.9 -
(complex,
It, J=6.8
Hz,
1130 cmT1 3H,
lH
CH2CE3),
NMR 1.6
3H, CH$l and CHO). -
1-Chloro-2-ethoxy-1-fluoro-3-ethylcyclopropanes Yield 80%. B. p. 43-45"/65
4a-d --
Torr.
IR (CC14)
5a-d --
v 1390, 1130 cmT1
lH NMR
(CDCl,) 6 1.05 (t, J=7.2 Hz, 3H, CCH,Cli,), 1.23 (t, J=7.2 Hz, 3H, 0C%Cli3), 1.5 (complex, Elemental
3H, CH 3.25-3.9 (complex, 3H, Cli,O and CHO). _ and CHCsCH3), analysis: Calcd. for C,H,, ClFO: C, 50.45; H, 7.20. Found: C,
50.19; H, 7.12. 1-Chloro-Z-ethoxy-1-fluoro-3-octylcyclopropanes Yield 61%. B. p. 90-95"/0.55
Torr.
IR (Ccl,] v 2960, 2930, 2860, 1290
cm-! 'H NMR (CDC13)
6 0.89 (t, 3H, CH$i,],
and CHCH,],
(complex,
3.3-3.9
for CT3H24C1FO:
C, 62.40;
3H, CYO
6a-d --
1.02-1.7
(b, 21H, CCYC,
and CHO). Elemental _
analysis:
H, 9.60. Found: C, 62.72; H, 9.91.
0CH2CljX Calcd.
271 l-Chloro-2-ethoxy-2-ethyl-l-fluoro-3-methylcyclopropanes
Yield 82%. 8. p. 70-75"/80 cm:' lH NMR (CDCl,)
6 0.85-1.30
3H, CCli2CH3 and Cl$H3),
Torr.
3.35-3.80
lysis: Calcd. for CeH1,CIFO:
IR (Ccl,) v
2980,
9H, 3xC&),
(complex,
(complex,
7a-d -1150,
2880,
1.30-2.10
1070
(complex,
ZH, OCtl,CH,). Elemental
ana-
C, 53.31; H, 7.83. Found: C, 53.28; H, 7.81.
ACKNOWLEDGEMENTS
We
gratefully
Cientifica Superior
acknowledge
y Tecnica
Comision
for financial
de Investigaciones
Asesora
support
Cientificas
de
Investigation
(Grant N"1664/82)
for a predoctoral
and Consejo
fellowship
to one
of us (G. F.).
REFERENCES
1 F. Camps,
J. Coll, G. Fabrias,
A. Guerrero
and M. Riba, Tetrahedron
Lett.
(1983) 3387. 2 F. Camps,
J. Coll, G. Fabrias
and A. Guerrero,
Tetrahedron,
-40 (1984)
2871. 3 K. L. Williamson,
Y. L. Hsu, F. H. Hall, S. Swagen
and M. S. Coulter,
J.
Am. Chem. Sot., -90 (1968) 6717. 4 A. M. Ihrig and S. L. Smith, J. Am. Chem. Sot., -92 (1970) 759. J. W. Emsley and L. Phillips in 'Progress in Nuclear Magnetic Resonance 5 Spectroscopy' 6 Perganon,
Eds. J. W. Emsley,
Oxford
Y. Bessiere,
J. Feeney
and L. H. Sutcliffe,
Vol. 7,
1971, pp. 262-265.
0. Ngoc-Hue
Savary and M. Schlosser,
Helv. Chim. Acta, -60
(1977) 1739. 7 A. Guerrero,
Ph. D. Thesis,
Universidad
de Barcelona
1974, and referen-
ces cited therein. 8 A. Gaudemer
in 'Stereochemistry,
gan, Vol. 1, G. Thieme 9 M. P. Strobel,
C. G. Andrieu,
J. Chim., 4 (1980) 101.
Fundamentals
Pub., Stuttgart
and Methods'
Ed. H. B. Ka-
1977, pp. 44, 116.
D. Paquer, M. Vazeux and C. C. Pham, Nouv.
of Fluorine
Received:
"F
October
Chemistry,
29 (1985)
15, 1984; accepted:
NMR ANALYSES
261
1
April 7, 1985
OF SOME CYCLOPROPANE
F. CAMPS,
J. COLL, G. FABRIAS,
Instituto
de Quimica
08034-Barcelona
26 l-21
DERIVATIVES*
A. GUERRERO
Bio-Organica,
Jorge Girona
Salgado,
18-26
(Spain)
and M. FELIZ
Oepartamento Barcelona,
de Quimica Oiagonal
Organica,
Facultad
647. 08028-Barcelona
de Quimica,
Universidad
de
(Spain)
SUMMARY Structural
assignments
of all possible
ro-2-ethoxy-1-fluoro-alkylcyclopropanes "F
NMR spectra.
the fluorine shielding
The previously
signal has been
effect
in the vicinal
have been achieved
unreported
studied
diastereoisomers
effect
and found
cis-fluorine
of
through
of an ethoxyl
to promote
l-chlotheir group
in most
and a deshielding
on
cases
effect
a
when
trans to this halogen.
INTRODUCTION Empirical application value
structure-spectroscopic
of high resolution
in structural
studies
[1,2], their
of the
some possible signals
[3,4] and chemical
*Presented
at the XX Reunion
mica held in Castelldn
proved
have
during
been prepared
and
the
in the synthesis,
parameters
correlations.
H-F coupling
in the literature
Bienal de la Real Sociedad
(Spain), September
to be of great context,
unequivocally
obtained
on vicinal
shifts reported
from the
of insect sex pheromones
to 1) assign
structure-spectral
derived
In this
derivatives
in order
has been based
magnitudes
139/85/$3.30
mimics
to each of the diastereoisomers
and 2) establish Assignment
recorded
have
molecules.
pheromone
several chlorofluorocyclopropane 19F NMR spectra
right structure
0022-l
NMR spectroscopy
of organic
our recent work on fluorinated
data correlations
EspaAola
constant
[5]. de Qui-
1984.
0 Elsevier Sequoia/Printed
in The Netherlands
262 RESULTS AND DISCUSSION
The chlorofluorocyclopropanes by stereospecific
addition
dichlorofluoromethane ethers
out
the
confirm Most
and potassium
under PTC conditions
generally,
as mixtures
reaction the
vinyl
corresponding
[7]
hydroxide,
with
structural
assignment
ethers
have
prepared
and
to
the
161 (Table 1). Starting
initial
acetals
generated
in good yields in situ --
corresponding
from vinyl
vinyl ethers were used,
of _Z/E isomers; only entry 7 was repeated carrying the stereoisomerically pure -E isomer in order to been
in the presence
171. Z-Ethoxyprop-l-ene acid
(l-7) have been prepared
of chlorofluorocarbene,
the
diastereoisomers
dehydroethoxylation
7a-d. of
the
of -p-toluenesulfonic acid/quinoline by decarboxylation of 3-ethoxycrotonic
was obtained
immediately
of by
distilled
into
the
cyclopropanation
reaction
mixture.
R1
R3
R1
R3
R2 c'
R4
CHC12F e KOH/18-crown-6
R4
'w'
F
l-7 -TABLE
I
Cyclopropane
____
derivatives
- ..__--.---
Entry
(l-7) prepared --
-....--- ---. - ---
Vinyl ether
by cyclopropanation
.._.._ _.
-- ----
Reaction time (h)
of vinyl ethers
.__....-_ -. -. Reaction products
.----~- ~-Yield (%)
1
ethyl
vinyl ether
24
2
E-ethoxyprop-1-ene
2
la-b -2a-b --
64 78
76
3
1-ethoxy-2-methylprop-1-ene
3.5
3a-b --
4
1-ethoxyprop-1-ene
5.5
4a-d _-
80
5
1-ethoxybut-1-ene
6
5a-d
80
6
1-ethoxydec-1-ene
7
6a-d --
61
7
3-ethoxypent-2-ene
4
7a-d --
82
263 TABLE 2
Assignment
Comp.
of the "F
R1
NMR parameters
R2
R3
R4
to compounds
la-7d --
Chem.
Multi
Coupling
shift
constants
(Hz)
la
H
H
OEt
H
62.0
ddd
18.4, 12.7, 7.6
lb
H
H
H
OEt
83.0
ddd
19.7,
2a
H
H
OEt
Me
65.2
ddt
17.1,
7.9, 3.4
2b
H
H
Me
OEt
74.1
ddo
20.5,
9.0, 2.6
3a
Me
Me
OEt
H
68.8
dhept
14.0,
2.3
9.3, 1.5
3b
Me
Me
H
OEt
85.1
b
4a
Me
H
OEt
H
58.6
ddo
31.9, 18.4, 2.6
4b
H
Me
H
OEt
75.9
dm
13.3
4c
Me
H
H
OEt
76.4
dm
23.9
4d
H
Me
OEt
H
57.3
ddo
22.5,
13.1, 2.5
5a
Et
H
OEt
H
57.7
ddo
32.1,
17.7, 1.7
5b
H
Et
H
OEt
75.5
dm
13.3
5c
Et
H
H
OEt
75.0
dm
22.0
5d
H
Et
OEt
H
56.25
ddo
25.2, 12.6, 1.5
6a
Ott
H
OEt
H
58.2
ddt
31.9, 16.9, 1.5
6b
H
Ott
H
OEt
74.75
dm
13.6
6c
Ott
H
H
OEt
75.0
dm
23.1
6d
H
Ott
OEt
H
56.2
ddt
22.5,
7a
Me
H
OEt
Et
62.25
do
22.2,
7b
H
Me
Et
OEt
85.2
b
7c
Me
H
Et
OEt
69.1
d
7d
H
Me
OEt
Et
79.8
b
showing
secondary
*dm stands termined
for a doublet
on a first order analysis.
splitting
13.1, 2.0 2.6
24.2
which
could not be de-
264 Signals an internal
"F
of the
NMR spectra
sealed capillary
been assigned
(referred
tube, positive
(Table 2) on the basis of the following
i) In 1-chloro-1-fluorocyclopropanes, relative
to the fluorine
ppm; estimated deshielding
average
effect
the corresponding
11 ppm), whereas
(4~120')
of substituents
On the other
hand,
promoted
relationship
chemical
shifts
cyclopropane,
the
of
Since
the
in Scheme
groups
previously
influence
derived
unreported
an ethoxyl
1-chloro-1-fluoro-alkylcyclopropanes have deduced
the shielding
angle
a
[51. larger
than
of the known $
[3] and the
1, from the average from and
literature
absorption
group
effects
[5]
and
for
the
parent
as 63.5 ppm.
on the
has not been
shielding
data
chloro-fluoro-dimethyl-
(CFCP) can be estimated
of
-6 ppm)
is generally
as a consequence
chloro-fluoro-ethyl-
1-chloro-1-fluorocyclopropane
promote
141.
as shown
by alkyl
in cis position
groups*
average
(@=O") 181,
factors:
(ranging from 8.5 to 12.5
in a trans
3JH_F s
acid in
shifts) have
determining
of 3J,_, on the bond angle 6, the dihedral
increments
of
effect
(-3.6 to -10.5 ppm; estimated
3J H_F trans
electronegativity
the
methyl
exert a shielding
ii) In fluorocyclopropanes
dependence
to trifluoroacetic
values for upfield
"F
previously
absorption
on
described,
we
for this group from our data of the pair
isomers
3 due to the possible unambiguous assignment in this case _' 2). The low field absorption at 6 68.8 ppm was attributed to the
(Scheme
cis isomer constants shift
(F and Et0 in trans
relationship)
on the basis
of the coupling
of -3a (14.0 Hz) and -3b (broad signal). Comparison of the chemical of -3a and -3b with that of l-chloro-1-fluoro-2,2-dimethyl-
values
cyclopropane resulted effect
(65.5 ppm) indicates
in a shielding
is only 3.3 ppm.
other cases
effect Further
that substitution of
19.6
proof
ppm,
of ethoxyl
whereas
for
of the same effects
a
for a cis H trans
H
the
can be found
in
of
of
(see below).
Furthermore,
from
the
chemical
shifts
comparison
the
pair
isomers
assignment to diastereoisomers -1 with those of -3, configurational la and lb was made. From the absorptions of la and lb and the CFCP calcula-
*From
our
deshielding group.
results effect
in Table is derived
2
(cf. 4a-d and 5a-d) an average of 1 ppm -from substitution of a methyl for an ethyl
265
69.5
33,s Scheme
1
ted value
(63.5 ppm),
a shielding
increment
of an Et0 group cis to the F and an almost
of 19.5 ppm for introduction negligible
deshielding
(-1.5 ppm), when both groups were in trans relationship,
effect
were inferred.
In the pair of isomers _2 (Table 2) the high field signal at 6 74.1 ppm was attributed by comparison
65.2 ppm signal, was assigned ppm
shielding
relative in
the
geminal
to the trans
of the observed showing
coupling
constants
that
suit better
those
to -2a. As shown in Scheme 3, the results point effect for introduction of an Et0 group in
to fluorine, following
in an alkyl
discussion),
substitution,
cis/trans --
isomer -2b (F and Et0 in cis relationship) constants with those of -lb, and the
coupling
an
11
ppm
and a 9 ppm chemical
interchange
For structural
substituted
of substituents assignment
carbon
deshielding
orientation
(62b-62a).
low field doublet Hz) was attributed
at 6
69.lpprn
with
for
was undertaken
a cis coupling
constant
to 7c and the high field broad absorption
trans
(CSO) for the
7a-d an independent
of the pair 7c-d from pure (E)-3-ethoxypent-Z-ene
position
substitution
effect
difference
of compounds
out a -ca. 20 cis
(geminal
shift
of la,
synthesis 191. The
(x5,_,
24.2
to -7d. By the
266 +‘9.3
4 - yyEto+m Et0
F
Scheme
F
2
same token,
the 62.25
(3JH_F 22.2 Hz) and 85.2
signals
were
assigned
to -7a
and 7b respectively. As in the previous case, chemical shift values for the as those pair of isomers -7c-7d point to effects of the same magnitude described group
above for 2a and 2b, taking
(19.5
inversion
ppm)
obtained
shown
into account
in--Scheme 1, The
for __ 2a-2b and -_7c-7d
the pair -7a-7b of 28.5 ppm group), whereas the observed
(9.0 plus
CSD
for
the CSD for the methyl ethoxyl/alkyl
(ca 9 ppm) would 19.5
experimental
ppm
effect
geminal
lead to a CSD for due
to the
value is 23.0 ppm. We have
methyl
267
Scheme
3
rationalized presence
this upfield
of the ethoxyl,
cyclopropane with the
ring.
same
in Scheme
of an Et0 group in trans
of the
culated constants
trans values
to the
(two cis to
was
found
side of the
in other
compounds
pattern (3a-6a). On the other hand, from the -3, the average shielding effect for introduction
to the F, in an alkyl
the
induced
3, for compounds
constants,
structure
low field
absorption
substituted
carbon,
may
be
field
absorption hand,
by electronegative
[5],led
4a-d we
attributed,
on the
cal-a (the most deshielded with largest vicinal coupling
3J,_,) and, conversely,
high
3JH_F 1. On the other
hydrogens
the simultaneous
and alkyl groups on the same
the same effect
in Table
coupling
signal)
signal)
by
as-10 ppm.
As presented basis
(ca 6 ppm) as promoted
chlorine
In fact,
substitution
values depicted
estimated
shift
-b (the most shielded calculated with lower coupling constants (two
the decrease substituents,
us to assign the remaining
of the
coupling
like ethoxyl,
constants
over
high field absorption
geminal to
268
TABLE
3
Calculated
Isomer
and experimental
absorptions
for compounds
4 -
Chemical shifts (calcd.)(found)
Parent value
Substituent shielding effects*
a
63.5
- 6- 1 (- 7)
56.5
58.2
b
63.5
+11+20
(+31)
94.5
75.9
C
63.5
+20- 6 (+14)
77.5
76.4
d
63.5
+ll- 1 (+lO)
73.5
57.3
*cis-Me, -
+ll; trans-Me,
-6; _cis-EtO,
+20; trans-EtO,
-1 (see text)
structure _c and the low field signal to structure -d. Structural assignments for the isomers of -5 and -6 were based on the direct correspondence of their practically identical chemical shifts and coupling constants with those of -4. Examination 20
ppm
carbon the
for
for
of
of the cyclopropane
parent
compound
methyl-CFCP), case
of the CSD depicted
introduction
of geminal the
CFCP,
an identical
the
6 ppm
(cf. -la with Nevertheless, deviation
5a with
although
relationship
is -ca -2 ppm, by taking into mentioned steric arrangement
for
the
Z-ethyl-CFCP
and
the
-1-fluorocyclopropane
3a with
2,2-dimethyl-CFCP).
the
CSD
found
for
of -5b and -5d give rise to a notorious when compared with the literature value for between the
-5b and -5d (19.3 ppm) is in good other pairs of isomers (21.0 ppm for
-1, 16.3 for -3 and 17.3 for 5a-5c). conclusion,
effect
shifts
with
by
the estimated
above
agreement
promoted
discussed
Similarly,
compounds
In
those
out a value of -ca an unsubstituted
(see above).
of the above pattern,
2-ethyl-CFCP,
in
2-ethyl-CFCP -5c with value to that found in the previously
trans
the chemical
substituent
to F (cf. -lb with and -3b with 2,2-di-
correction
CFCP,
in Scheme 2 pointed
ethoxyl
ring and in cis relationship
substitution
corresponding
account
an
we have found
introduction derivatives
that
of
an
in
a cis
the
shielding
ethoxyl
effect
group
relationship
in to
the
generally l-chlorofluorine
269 amounts
to -ca 20 ppm. Conversely, the moiety trans to the fluorine
ethoxyl
substituents
in the cyclopropane
10 ppm
observed
were
geminal
positions
presence
of ethoxyl,
the cyclopropane ppm,
to
to
that
incorporation
the
alkyl
for
the
groups,
and alkyl
ring may require
account
of the
depends
on
presence
effects
took
substituents
observed
of around
2 and
in
vicinal
the
and
simultaneous
the
same
side
of a correction
from
an
alkyl
The
on
of
of
place
respectively:
the introduction
deviation
incorporation
the
ring. Deshielding
when
chlorine
effect
of
of ca 6
estimated
chemical
shift values.
EXPERIMENTAL
Infrared NMR
spectra
internal a
spectra were obtained
were
recorded
standard.
Varian
XL200
on
a
on a Perkin Elmer 257 spectrometer.
Bruker
WP8OSY
at
lgF NMR spectra were determined
operating
at
75.39
and
188.15
trifluoroacetic
acid as internal standard.
Chemical
6
and
are
scale
signal.
(ppm)
Elemental
General
positive
analyses
procedure
for
alkyl cyclopropanes
absorptions
were measured
the
80
MHz
using
TMS
on a Bruker WP8OSY MHz
respectively,
or on using
shifts are reported
upfield
from
the
'H as
in
reference
on a Carlo Erba 1106.
of
preparation
1-chloro-2-ethoxy-1-fluoro-3-
l-7 --
Cyclopropanes
l-7 have been prepared by the cyclopropanation reaction -[6] using longer reaction times depending by Y. Bessiere w
described
on the substrate carried
1). Control
(see Table
of the extent
1-Chloro-2-ethoxy-1-fluorocyclopropanes
From ethyl B.p. 53-55"/120 6
1.24
3.3-3.9
of the reaction
was
out by NMR analyses.
vinyl
Torr.
(t, J-7.02
(complex,
ether,
la-b --
la-b were prepared in 76% yield. -IR (Ccl,) v 1385 (C-F), 1210 (C-O) crn:l lH NMR (CDC13) Hz,
3H,
compounds
OCH,CE,),
3H, CHOCH.$H3).
1.1-1.9
Elemental
C, 43.47; H, 5.79. Found: c, 43.88; H, 5.99.
(complex,
analysis:
Calcd.
2H,
CHCli2C),
for C5HsC1FO:
1-Chloro-2-ethoxy-1-fluoro-2-methylcyclopropanes
3-Ethoxycrotonic flask and heated yield
pure
acid
of Freon
(55 mg], previously dissolve
the precipitate,
distilled
from potassium
the acid)
of cyclopropanes from isolated
at 0°C. After the
separated
to yield
1.0-1.5
was
added to
and the organic
phase
0.279 g (54% overall yield from
1.2 (t, J=6.6 Hz, 3H, OCH,Cti,), 1.6
(m, Ct12C).
Yield 78%. B. p. 67-70"/100 (CDCl,] 6 1.25 (complex,
Torr.
9H, 3xCH3],
3a-b
[7]
IR (Ccl,) u 1395, 1120 cm:1
2.95
(s, lH, CH of compound
lH
NMR
3a), 3.1
Hz, lH, CE of compound -3b), 3.6 (q, J=6.8 Hz, 2H, 0Cti2CH~.
1-Chloro-2-ethoxy-1-fluoro-3-methylcyclopropanes
Yield 80%. B. p. 60-62"/60 (CDCl,)
collected
and 18-crown-6
water
l-Chloro-2-ethoxy-l-fluoro-3,3-dimethylcyclopropanes
(d, J=12.0
to
2a-b was 2a-2b. In another run a 64% yield of --vinyl ether. B. p. 65-67"/80 Torr. IR (Ccl,) w 1385
(C-F), 1215 (C-O] cm.-' lH NMR (CDCl,) 6 (m, 3H, CH2CCl&],
(9 ml)
2 h reaction,
layers were
carbonate
in a distilling
was directly
55% KOH solution
21 (5 ml),
cooled
was placed
the acid was decarboxylated
[7]. The enol ether
Z-ethoxy-prop-1-ene
over a mixture
obtained
(0.78 g, 6 mmole)
at 160". After sublimation,
2a-b
6
1.1
(complex,
(complex,
Torr.
IR (Ccl,) I) 1390,
3H, Ct13CH), 1.2
lH, CH), 3.2-3.9 -
(complex,
It, J=6.8
Hz,
1130 cmT1 3H,
lH
CH2CE3),
NMR 1.6
3H, CH$l and CHO). -
1-Chloro-2-ethoxy-1-fluoro-3-ethylcyclopropanes Yield 80%. B. p. 43-45"/65
4a-d --
Torr.
IR (CC14)
5a-d --
v 1390, 1130 cmT1
lH NMR
(CDCl,) 6 1.05 (t, J=7.2 Hz, 3H, CCH,Cli,), 1.23 (t, J=7.2 Hz, 3H, 0C%Cli3), 1.5 (complex, Elemental
3H, CH 3.25-3.9 (complex, 3H, Cli,O and CHO). _ and CHCsCH3), analysis: Calcd. for C,H,, ClFO: C, 50.45; H, 7.20. Found: C,
50.19; H, 7.12. 1-Chloro-Z-ethoxy-1-fluoro-3-octylcyclopropanes Yield 61%. B. p. 90-95"/0.55
Torr.
IR (Ccl,] v 2960, 2930, 2860, 1290
cm-! 'H NMR (CDC13)
6 0.89 (t, 3H, CH$i,],
and CHCH,],
(complex,
3.3-3.9
for CT3H24C1FO:
C, 62.40;
3H, CYO
6a-d --
1.02-1.7
(b, 21H, CCYC,
and CHO). Elemental _
analysis:
H, 9.60. Found: C, 62.72; H, 9.91.
0CH2CljX Calcd.
271 l-Chloro-2-ethoxy-2-ethyl-l-fluoro-3-methylcyclopropanes
Yield 82%. 8. p. 70-75"/80 cm:' lH NMR (CDCl,)
6 0.85-1.30
3H, CCli2CH3 and Cl$H3),
Torr.
3.35-3.80
lysis: Calcd. for CeH1,CIFO:
IR (Ccl,) v
2980,
9H, 3xC&),
(complex,
(complex,
7a-d -1150,
2880,
1.30-2.10
1070
(complex,
ZH, OCtl,CH,). Elemental
ana-
C, 53.31; H, 7.83. Found: C, 53.28; H, 7.81.
ACKNOWLEDGEMENTS
We
gratefully
Cientifica Superior
acknowledge
y Tecnica
Comision
for financial
de Investigaciones
Asesora
support
Cientificas
de
Investigation
(Grant N"1664/82)
for a predoctoral
and Consejo
fellowship
to one
of us (G. F.).
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J. Coll, G. Fabrias,
A. Guerrero
and M. Riba, Tetrahedron
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J. Coll, G. Fabrias
and A. Guerrero,
Tetrahedron,
-40 (1984)
2871. 3 K. L. Williamson,
Y. L. Hsu, F. H. Hall, S. Swagen
and M. S. Coulter,
J.
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Oxford
Y. Bessiere,
J. Feeney
and L. H. Sutcliffe,
Vol. 7,
1971, pp. 262-265.
0. Ngoc-Hue
Savary and M. Schlosser,
Helv. Chim. Acta, -60
(1977) 1739. 7 A. Guerrero,
Ph. D. Thesis,
Universidad
de Barcelona
1974, and referen-
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in 'Stereochemistry,
gan, Vol. 1, G. Thieme 9 M. P. Strobel,
C. G. Andrieu,
J. Chim., 4 (1980) 101.
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and Methods'
Ed. H. B. Ka-
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