Organic Syntheses, Coll. Vol. 10, p.658 (2004); Vol. 75, p.98 (1998).
. Into a 1-L, three-necked, round-bottomed flask
, equipped with an efficient mechanical stirrer
, a thermometer
, and a condenser equipped with a potassium hydroxide drying tube
, are placed
54.1 g (0.403 mol) of 3-chloro-2-(chloromethyl)propene
212 g (0.805 mol) of bromoform
1.70-2.00 g (14.4-16.9 mmol) of pinacol
1.45 g (3.94 mmol) of dibenzo-18-crown-6
. With very vigorous stirring (Note 5)
312 g of an aqueous 50%
solution that has been cooled to 15°C is added in one portion. The reaction mixture turns orange, then brown, then black within 5 min, and the temperature of the reaction mixture begins to rise. Within 20 min, the internal reaction temperature is 49-50°C at which point the reaction flask is cooled with a room-temperature water bath
, and the reaction temperature decreases to ca. 20°C. After 1 hr, the bath is removed and the reaction mixture is heated to 40°C (internal temperature) with an oil bath
. The vigorously stirred mixture is maintained at this temperature for 4 days (Note 6)
. The reaction mixture is cooled to room temperature, diluted with 500 mL of water, and filtered through a pad of Celite on a glass-fritted funnel (pore size C)
, using a water aspirator (Note 7)
. Up to an additional 1-L of water is used to rinse the thick black reaction mixture from the flask. The resulting golden-yellow filtrate is discarded (Note 8)
. The black, solid residue in the frit, and any material remaining in the reaction flask are transferred to a 1-L beaker
, and a glass rod
, and the solution is vigorously stirred with an additional
500 mL of a 1:1 (v/v) solution of acetone and pentane
for 30 min. This mixture is filtered through a glass-fritted funnel using a minimal layer of Celite. The Celite pad is washed thoroughly with 1:1 pentane
solution, and the resulting brown filtrate is dried over
. Concentration using a rotary evaporator
, followed by distillation under reduced pressure (bp 75-85°C/0.4 mm), and low temperature (ca. −20°C) recrystallization from pentane
(ca. 1 mL/g of product), provide 70-95 g
yield) of the product as small, white crystals (mp 47.5-50°C
) (Note 9)
and (Note 10)
. A 500-mL, three-necked, round-bottomed flask
that has been flame dried under reduced pressure and purged with argon
, is equipped with a vacuum adapter equipped with an argon balloon
, an efficient mechanical stirrer, and a pressure-equalizing, 150-mL addition funnel
equipped with a rubber septum
. The flask is charged with a
25-g (0.085 mol) portion of material obtained from part A
25 mL of pentane
. A diethyl ether solution of methyllithium, 132 mL of a 1.4 M (0.185 mol)
solution (Note 12)
, is transferred to the addition funnel via cannula under a flow of argon
. The reaction flask is cooled to −78°C and the methyllithium
is added over 15 min with vigorous stirring. The reaction mixture is maintained at −78°C for 10 - 15 min; then the −78°C cooling bath is replaced with an ice-water bath
(0°C), and the addition funnel is replaced with a rubber septum equipped with an argon
balloon. Stirring is continued for an additional hour; then the volatile materials are transferred under reduced pressure to a flame-dried flask that is cooled to −196°C (Note 13)
. Based on the recovery of the thiophenol
adduct, the yield of [1.1.1]propellane
is between 75 and 88%
Determination of the yield of propellane.
Wiberg and Waddell have shown that propellane
reacts spontaneously in normal room light with thiophenol
bicyclo[1.1.1]pentyl phenyl sulfide
A slight modification of their method provides a good estimate of the yield of propellane
. Thus, a
3.0-mL portion of the propellane
solution is transferred via a gas-tight syringe to a tared, flame-dried, argon-purged, 10-mL, round-bottomed flask
equipped with a stirring bar and maintained under a static atmosphere of argon
is added in slight excess via syringe and the mixture is stirred under room light for 15 min. Concentration of the solution provides a mixture of thiophenol
and bicyclo[1.1.1]pentyl phenyl sulfide
. The ratio of compounds may be determined by 1
H NMR or GLC, and the yield of propellane
calculated (Note 14)
. Alternatively, the mixture may be diluted with pentane
, washed with 1 M sodium hydroxide
, dried with magnesium sulfate
, and concentrated to provide bicyclo[1.1.1]pentyl phenyl sulfide
from which the yield of propellane
is calculated. The reaction of thiophenol
is assumed to be quantitative; thus yields for
are 75 to 88%
based on 1
Wiberg and Waddell also noted that propellane
reacts with iodine
Alber and Szeimies report a somewhat lower yield (61%
) when an ethereal solution of propellane
is treated with a solution of iodine
while being irradiated.3
Thus, titration of a portion of the resulting propellane
solution with iodine
provides an estimate of the minimum yield. A
3.0-mL portion of the propellane
solution is transferred as noted above. Small pieces of iodine
are added with stirring under room light over 10 min until just before the dark color persists. Concentration of the solution provides 1,3-diiodobicyclo[1.1.1]pentane
from which the minimal concentration of the propellane
solution and minimal yield of propellane
may be estimated if iodine
is not added in excess. Alternatively, a solution of iodine
in diethyl ether
may be added instead of neat iodine
was prepared according to the method of Lynch and Dailey.4
Percent purity was determined by GLC, and 0.400 mol of starting material was calculated accordingly. A typical experiment used ca. 54 g of alkene that was 92-93% pure by GLC
Bromoform (96%) stabilized with 1-3% ethanol, was purchased from the Aldrich Chemical Company, Inc.
, and used without further purification.
Pinacol was purchased from the Aldrich Chemical Company, Inc.
, and used without further purification.
Dibenzo-18-crown-6 (98%) was purchased from the Aldrich Chemical Company, Inc.
, and used without further purification.
A Glas Col GT-21 mechanical stirrer
was used at maximum speed.
In some runs, the internal temperature varied between 37-43°C over the 4-day period without a significant change in yield.
Aspirator filtration through a pad of Celite was beneficial to prevent small particulate matter from clogging the fritted funnel. However, it was necessary to break up the pad of Celite to allow for effective filtration.
extraction of the primarily aqueous filtrate provides only an additional 4 g (3%) of product.
If solvents have not been evaporated completely, a forerun may be recovered with bp up to 50°C/0.5-1 mm. This should be trapped with a dry ice-acetone bath
. If the sample is evaporated well prior to distillation, crystallization of the product will occur upon standing. Stirring a pentane
solution of the crude product with decolorizing
, followed by filtration, and low temperature (ca. −20°C) recrystallization gives material that is suitable for many applications (mp 44-45°C
H NMR (CDCl3
) δ: 1.80 (s, 2 H), 3.19 (s, 4 H)
C NMR (CDCl3
) δ: 32.02 (s), 33.89 (t), 35.20 (s), 47.58 (t)
Reactions that were stirred for up to 5 or 6 days had slightly higher yields (up to 80%) and needed minimum purification. Reactions that were stirred for less than 3 days or more than 6 days had slightly lower yields (60% after recrystallization). The checkers found that distilled 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane
was sufficiently pure (1
H NMR and mp) for the subsequent step and did not require recrystallization. The procedure has been carried out on a 1-mol scale with comparable results.
High purity grade
pentane was purchased from Fisher Scientific Company or Burdick and Jackson Inc.
and was used without further purification. Recently opened solvent was always used.
Methyllithium (1.4 M, low halide) in diethyl ether, was purchased from the Aldrich Chemical Company, Inc.
, and was used without further purification. Titration using the method of Watson and Eastham5
was used to determine the molarity. The best and most reproducible results (ca. 88% yield) were obtained when freshly opened methyllithium
was used. The yield was severely depressed when 0.86 M methyllithium
was used (< 33%). The checkers used a recently purchased, freshly opened bottle of methyllithium
and did not determine its molarity by titration.
The volatile materials are transferred under essentially static conditions. Bulb-to-bulb vacuum transfer may be accomplished with a standard 24/40 short path distillation apparatus. The reaction flask may be warmed slightly (40°C) with a water bath and the receiving flask is cooled in a liquid nitrogen bath
. Vacuum is applied intermittently to allow for effective transfer of the volatile material. It is helpful to continue stirring the reaction flask during the transfer.
Integration and normalization of the 1
H NMR peaks for the acidic proton of thiophenol
(d 3.4 ppm) and the bicyclo[1.1.1]pentyl
group (d 1.96 ppm) were used to calculate the yield of propellane
C NMR (125 MHz, CDCl3
) δ: 1.0 and 74.2.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
This preparation of 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane
is a modification of the method reported by Szeimies and co-workers,6
and represents a significant improvement in both the convenience of the workup and the yield of the reaction. In the present method, dilution and filtration of the reaction mixture leave behind a mostly solid residue from which the product is easily obtained. Most significantly, the problematic emulsion that forms in the Szeimies method is effectively eliminated.
The cocatalytic effects of pinacol
in the phase transfer catalysis (PTC) of dihalocarbene additions to alkenes were noted by Dehmlow and co-workers who showed that pinacol
accelerates the PTC deprotonation of substrates up to pKa 27.7
Dehmlow also studied the effects of various crown ethers as phase transfer catalysts in the addition of dibromocarbene
to allylic bromides.8
In Dehmlow's study, elevated temperature (40°C) and dibenzo-18-crown-6
did not give the highest ratio of addition/substitution to allyl bromide
. However, the submitters' use of pinacol
, and heat in the addition of dibromocarbene
lead to good yields and a procedure with a significantly more facile work-up. In the course of the submitters' work in this area, Della and Taylor also reported an improvement in the synthesis of 1
however, the submitters were unable to reproduce their results, even with several attempts.
The synthesis of [1.1.1]propellane
is essentially as reported by Michl and co-workers,10
with only a slight modification in the process of transferring the crude propellane
solution. As a result of the submitters' improvements in the preparation of 3-chloro-2-(chloromethy)propene
, many of the difficulties in the Szeimies route to [1.1.1]propellane
have been eliminated.
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
Cyclopropane, 1,1-dibromo-2,2-bis(chloromethyl)- (11);
1-Propene, 3-chloro-2-(chloromethyl)- (8,9);
Methane, tribromo- (8,9);
2,3-Butanediol, 2,3-dimethyl- (8,9);
Dibenzo[b,k][1,4,7,10,13,16]hexaoxacyclooctadecin, 6,7,9,10,17,18,20,21- (8,9);
Lithium, methyl- (8,9);
Bicyclo[1.1.1]pentyl phenyl sulfide:
Bicyclo[1.1.1]pentane, 1-(phenylthio)- (11);
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved