Organic Syntheses, Vol. 78, 142-151
Checked by Florence Geneste and Andrew B. Holmes.
1. Procedure
2. Notes
2.
Ether is obtained from E. Merck
or Aldrich Chemical Company, Inc., and dried using
a common procedure.
titanium tetraisopropoxide
is obtained from ABCR or Aldrich Chemical Company,
Inc. (97% purity).
3.
Ethylmagnesium bromide
(EtMgBr) in ether (3 M) was purchased from Aldrich Chemical Company, Inc.
The submitters also prepared it from
bromoethane and
magnesium.
The concentration of EtMgBr was determined as follows:
1
mL of the Grignard solution was poured into 30 mL of ice-cold
water;
4.00 mL of 1 N HCl solution
was added, and the mixture was stirred until a clear solution was formed. Excess HCl
was measured by titration with
0.1 N NaOH solution.
4. In the course of addition, the extensive evolution of
ethane
is observed, and therefore it is not necessary to maintain a stream of
nitrogen.
5. While the precipitate is dissolving, an
ice bath
should be used to keep the mixture cool. The dissolution proceeds more rapidly when
the precipitate is scraped off the walls of the flask from time to time with a spatula
(the stirrer should be stopped for this operation).
6. Only one extraction with
ether
is necessary.
8.
1-Cyclopropylcyclopropanol
is a rather unstable compound that rapidly rearranges into
cyclopropyl ethyl
ketone (IR 1707 cm
−1) in the presence of acids and bases
or upon heating. Therefore, it should be used immediately. The checkers stored the
sample overnight at -78°C. If necessary, it should be stored no longer than 2-3
days at -78°C. Quantities of 20-30 g can be distilled, bp 65-68°C (32 mm);
distillation of larger quantities is accompanied by the formation of a significant
amount of
cyclopropyl ethyl ketone. The physical properties are
as follows:IR (film) cm
−1:
3332, 3084, 3007, 1217, 1009 and 935;
1H NMR (250 MHz, CDCl
3) δ: 0-0.9
(m, 2 H), 0.21 (dd, 2 H, J = 6.5, 5.1), 0.25-0.33 (m, 2
H), 0.50 (dd, 2 H, J = 6.5, 5.1), 1.1-1.2 (m, 1 H),
3.83 (s, 1 H), [impurities at 0.6-0.9 (m), 1.1 (d,
J = 6.2), 3.83 (m)];
13C NMR (62.5 MHz, CDCl
3) δ: 2.51,
11.20, 16.20, 56.37, [impurities at 8.07,
21.59, 24.89, 63.84]; MS (ES
+) m/z (rel intensity) 121
[100, (M + Na)
+]. Anal. Calcd for C
6H
10O:
C, 73.4; H, 10.3. Found: C, 71.7; H, 10.4.
9. Technical grade
triphenylphosphine
as obtained from BASF or Aldrich Chemical Company,
Inc., is satisfactory.
Dichloromethane
is obtained from E. Merck or Fluka Chemical Corp.
and dried according to commonly used procedures.
Pyridine
is obtained from Aldrich Chemical Company, Inc., or J.
T. Baker ("Baker" grade) and dried by distillation over calcium
hydride.
Bromine was obtained from
Aldrich Chemical Company, Inc., and used as supplied.
CAUTION: Bromine
is a severe irritant, causes burns, and is very poisonous.
10. The checkers added pellets of dry ice continuously to the acetone,
cooling the bath to maintain the required temperature.
11. The checkers bent Pyrex glass tubing (o.d. 2 cm) to a 90°
angle. The arm lengths were 17 and 16 cm and terminated in a male 24/29 ground glass
joint. The longer arm was inserted in the distillation flask to accommodate bumping
during the distillation.
12. The conditions of this bulb-to-bulb distillation are of prime
importance: the oil bath must not be overheated, and the distillation performed with
strict temperature control inside the first flask, otherwise lower yields are obtained.
This operation takes 2-3 hr.
13. The submitters obtained 99.4-120.9 g (66-79%) from 1 mol of
cyclopropylcyclopropanol;
they found it essential to carry out the last 5 min of the bulb-to-bulb distillation
under full pumping power with the valve between the pump and the receiving flask completely
open; bp 69-73°C (88 mm). The physical properties are as follows: IR (film) cm
−1: 3084, 3039,
1724, 1446, 1415, 1381, 1188,
1112, 1099, 1020 and 955;
1H NMR (250
MHz, CDCl
3) δ: 0.25-0.30 (m, 2 H), 0.56-0.60 (m,
2 H), 0.70 (dd, 2 H, J = 6.5, 6.5), 1.03 (dd, 2 H, J = 6.5,
6.5), 1.51-1.66 (m, 1 H);
13C NMR (62.5 MHz, CDCl
3)
δ: 6.07, 14.24, 20.58, 36.80.
High resolution mass spectrum is as follows: (EI)
m/z 160.9965 [(M+H)
+; calcd for C
6H
1079Br:
160.9966]. Anal. Calcd for C
6H
9Br: C, 44.75 ; H, 5.6. Found:
C, 45.3, H. 5.7. The mixture has a tendency to foam upon distillation; if desired,
a vacuum distillation capillary can be used to facilitate the distillation.
14.
Potassium tert-butoxide
is obtained from ABCR GmbH & Co., Karlsruhe, Germany
or Aldrich Chemical Company, Inc. (95% purity).
15. The checkers purchased
dimethyl sulfoxide
from Aldrich Chemical Company, Inc., and dried it
by distillation (water aspirator) from calcium hydride. The submitters obtained
dimethyl
sulfoxide from J. T. Baker ("Baker" grade) and used it without purification.
16. During this stirring, the
nitrogen inlet
and outlet are at the top of the
reflux condenser to avoid
losses of the volatile product by evaporation. The
nitrogen flow
rate was kept to a minimum.
17. In several cases, the bulb-to-bulb distillation of bicyclopropylidene
from the reaction mixture was incomplete when the system was evacuated only once.
Therefore, it is recommended that distillation be interrupted as soon as no more condensation
of product in the receiving flask is observed, that the apparatus be flushed with
nitrogen, and then evacuation of the apparatus be repeated to continue bulb-to-bulb
distillation. This procedure may have to be repeated one or two more times. Because
the melting point of bicyclopropylidene is only -10°C, care must be taken to prevent
the connecting tube from clogging with solid bicyclopropylidene. The checkers used
a cold trap similar in design to the Aldrich cold trap, catalog No Z10, 310-1.
18. The submitters obtained a yield of
39.1-42.2 g (
75-81%)
from
1 mol of 1-bromo-1-cyclopropylcyclopropane.
Bicyclopropylidene can be
distilled (
bp 100-102°C); however,
polymerization may occur in the distillation flask reducing the yield. The physical
properties are as follows: IR (film) cm
−1:
3051, 2983, 1410, 1247, 1071
1046, 1016 and 994;
1H NMR (250 MHz, CDCl
3) δ:
1.17 (s, 8 H);
13C NMR (62.5 MHz, CDCl
3) δ: 2.8, 110.2.
The
1H and
13C NMR spectra indicated a sample purity =
95% (the submitters reported 95-97%).
Anal. Calcd for C
6H
8: C, 89.94 ; H, 10.06. Found: C, 89.03,
H. 10.04. The sample was analyzed by gas chromatography (retention time 2.8 min) on
an SGE capillary column BP5 (
5% methylphenylsiloxane),
internal diameter 0.32 mm, film thickness 0.25 μm, length 25 m, flow velocity 30
cm/s, injection temp 150°C, flame ionization detector 300°C. The column temperature
was raised from 50°C at 10°C/min to 250°C. The checkers found that within
a retention time of 3 min the sample purity ranged from
91-97%, but over 25 min the purity ranged from
88-91%. The checkers were unable to record
a mass spectrum.
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
This procedure is also applicable to the production of a number of spirocyclopropanated
bicyclopropylidenes
2
in good yields. Bicyclopropylidene with its high-lying HOMO
3 was demonstrated
to possess unique reactivity toward a wide range of electrophiles and cyclophiles
including nucleophilic carbenes to give complex skeletons and heterocycles in high
yields.
4
Functional derivatives can also be prepared directly from bicyclopropylidene.
5 Transition metal-catalyzed reactions of
bicyclopropylidene
6 including Heck coupling
7 allow
the preparation of carbocycles, polyenes and heterocyclic compounds
8 that are not readily available by other
synthetic methods.
Bicyclopropylidene
has also been prepared by Simmons-Smith monocyclopropanation of the terminal double
bond in
ethenylidenecyclopropane(
15% yield),
9
dimerization of
1-lithiocyclopropene
in the presence of
lithium amide
in
liquid ammonia over a
period of 1 month (
30% yield),
10 and several
multistep syntheses starting from
acetylcyclopropane
(
15-30% overall yields).
11 12 13 14
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