Organic Syntheses, Coll. Vol. 6, p.327 (1988); Vol. 59, p.113 (1979).
, which is used in Part B of this procedure, is highly pyrophoric. Accordingly, this reagent must be kept under a nitrogen
atmosphere; exposure to air must be avoided during transfers.
. A 500-ml., three-necked, round-bottomed flask
fitted with a mechanical stirrer
, a reflux condenser
protected with a calcium chloride tube
, and a rubber septum
is charged with 100 ml. of N,N-dimethylformamide (Note 1)
and 60.6 g. (0.600 mole) of triethylamine (Note 2)
. The solution is stirred while 32.6 g. (0.300 mole) of chlorotrimethylsilane (Note 3)
and 24.5 g. (0.250 mole) of cyclohexanone
are injected in succession through the septum into the flask. The resulting mixture is stirred and heated under reflux for 6 hours, cooled to room temperature, and diluted with 300 ml. of pentane
. The triethylamine hydrochloride
that precipitates is removed by filtering through a coarse, sintered-glass Büchner funnel
, and the filter cake is washed with three 100-ml. portions of pentane
. The filtrates are combined and washed with three 300-ml. portions of ice-cold sodium hydrogen carbonate
solution. The organic layer is washed rapidly with 100 ml. of ice-cold 3% hydrochloric acid
and 100 ml. of ice-cold sodium hydrogen carbonate
in succession. The pentane
solution is washed with 50 ml. of sodium chloride
solution, dried over anhydrous sodium sulfate
, and evaporated. The residual liquid is distilled at reduced pressure through a 10-cm. Vigreux column
, affording, after separation of a small forerun, 33–35.5 g.
) of 1-trimethylsilyloxycyclohexene
, b.p. 74–75° (20 mm.)
. A 250 ml., three-necked, round-bottomed flask
is equipped with a magnetic stirring bar
, a pressure-equalizing dropping funnel
, a reflux condenser bearing a nitrogen inlet
at its top, and a rubber septum. The apparatus is purged with nitrogen
, flamed dry, and allowed to cool (Note 5)
. The flask is charged with 130 ml. of diethyl ether (Note 6)
, 17.0 g. (0.100 mole) of 1-trimethylsilyloxycyclohexene
, and 18.5 g. (0.146 mole) of diethylzinc (Note 7)
, each being added through the septum with a syringe. The solution is stirred and maintained at room temperature with a water bath
while 40.2 g. (0.150 mole) of diiodomethane (Note 8)
is added slowly from the dropping funnel over a 1-hour period (Note 9)
. The reaction mixture is stirred and heated under reflux for 8 hours (Note 10)
. After the reaction is complete (Note 11)
, the contents of the flask are stirred and cooled in an ice-water bath
as 5.4 ml. of concentrated aqueous ammonium chloride
is added over ca.
30 minutes. A large amount of gas is evolved, and a white solid is formed during the hydrolysis. The salts are separated by filtering through a sintered-glass Büchner funnel and washed with 100 ml. of a 1:1 (v/v) ether–pentane
solution. The combined filtrates are washed with four 50-ml. portions of ice-cold saturated aqueous ammonium chloride
and two 100-ml. portions of ice-cold aqueous sodium chloride
. The solution is filtered through a pad of anhydrous sodium sulfate
and evaporated. The residual liquid is distilled through a 17.5-cm. Vigreux column
under reduced pressure, affording a forerun of 2.1–3.5 g.
, b.p. 65–80° (12 mm.)
, and 14.2–15.2 g.
) of 1-trimethylsilyloxybicyclo[4.1.0]heptane
, b.p. 80–82° (12 mm.) (Note 12)
. A 250-ml., three-necked, round-bottomed flask
equipped with a mechanical stirrer, a pressure-equalizing dropping funnel bearing a nitrogen inlet at its top, and a thermometer
is charged with 17.9 g. (0.110 mole) of anhydrous iron(III) chloride (Note 13)
. The flask is immersed in an ice-water bath, stirring is begun, and 70 ml. of N,N-dimethylformamide (Note 1)
is added slowly (Note 14)
. When all the iron(III) chloride
has dissolved, a solution of 9.2 g. (0.050 mole) of 1-trimethylsilyloxybicyclo[4.1.0]heptane
in 20 ml. of N,N-dimethylformamide
is added dropwise through the dropping funnel over 1 hour while the internal temperature is maintained at 0–5°. After the addition is complete, the brown solution is stirred at room temperature for 2 more hours, then poured into ca. 200 ml. of ice-cold 1 N hydrochloric acid
. The aqueous solution is extracted with three 50-ml. portions of chloroform
. The combined chloroform
extracts are washed successively with 50-ml. portions 1 N hydrochloric acid
, saturated sodium hydrogen carbonate
, and sodium chloride
solution. The solution is dried by filtration through a pad of anhydrous sodium sulfate
and evaporated. The remaining liquid (Note 15)
is dissolved in 50 ml. of methanol
saturated with sodium acetate
and heated at reflux for 3 hours. The volume is reduced to ca.
25 ml. by evaporation under reduced pressure, 50 ml. of water is added, and the mixture is extracted with three 30-ml. portions of ether
. The combined extracts are dried over anhydrous sodium sulfate
, the ether
is evaporated, and the residual liquid is distilled under reduced pressure through a 17.5-cm. Vigreux column, yielding after separation of a 0.4–1.0 g. forerun, 4.3–4.5 g.
) of 2-cyclohepten-1-one
as a colorless liquid, b.p. 73–76° (18 mm.) (Note 16)
Chlorotrimethylsilane is available from Aldrich Chemical Company, Inc.
The reagent was distilled before use.
The product has the following spectral properties: IR (neat) cm.−1
: 1675 (C=C); 1
H NMR, δ (multiplicity, number of protons, assignment): 0.16 (s, 9H, Si(CH3
), 1.3–2.1 (m, 8H, 4CH2
), 4.78 (m, 1H, vinyl H
A slight positive pressure of nitrogen
is maintained in the apparatus throughout this procedure.
Diethylzinc in a cylinder pressurized with nitrogen was purchased from Alfa Division, Ventron Corporation
, and distilled at atmospheric pressure under a nitrogen
atmosphere before use, b.p. 118°
. The distillate was collected in a two-necked receiver
fitted with a rubber septum and kept under a nitrogen
atmosphere. Aliquots of diethylzinc
were withdrawn with a gas-tight syringe. The checkers destroyed excess or waste reagent by injecting it cautiously beneath the surface of ice-cold water through which argon
was vigorously bubbled.
Diiodomethane from both Eastman Organic Chemicals and Aldrich Chemical Company, Inc.
, was used by the checkers after distillation under reduced pressure, b.p. 68–70° (12 mm.)
The solution becomes somewhat cloudy as the diiodomethane
The checkers found considerable variation in the rate of the reaction in different runs, the time required for its completion ranging from 3 to 10 hours. It is therefore advisable to monitor the progress of the reaction. For this purpose small aliquots (ca.
0.05 ml.) were withdrawn from the flask with a syringe and hydrolyzed by injection into a vial containing ether
and saturated ammonium chloride
. The relative amounts of enol silane and cyclopropoxy silane were determined by GC on an 0.6 cm. × 3.7 m. column
of 3% OV-17 coated on 100–120 mesh Chromosorb W. With a column temperature of 120° and a carrier gas flow rate of 20 ml. per minute, the retention times for the enol silane and the cyclopropoxy silane are ca.
1.9 and 2.3 minutes, respectively.
In one run that was particularly slow, an additional 9.9 g. of diiodomethane
was added. The reaction then proceeded quickly to completion.
The spectral properties of the product are as follows: IR (neat) cm.−1
: 1250, 1209, 1010, 900, 865, 840; 220-MHz. 1
H NMR (CDCl3
), δ (multiplicity, coupling constant J
in Hz., number of protons, assignment): 0.13 [s, 9H, Si(CH3
], 0.29 (t, J
= 5, 1H, endo
at C-7), 0.84 (d of d, J
= 5 and J
= 11, 1H, exo
at C-7), 0.98–1.70 (m, 6H, cyclohexyl H
), 1.82–2.18 (m, 3H, cyclohexyl H
). A GC analysis as described in (Note 10)
indicated the purity of the product to be ca.
95–98%, the remainder being 3–5% of unreacted enol silane.
Anhydrous iron(III) chloride was purchased by the submitters from Merck & Company, Inc.
The checkers obtained the reagent from Aldrich Chemical Company, Inc. The reagent was dried at 60–70° under reduced pressure for several hours before use.
A GC analysis on the liquid by the submitters using a Carbowax 20 M (polyethylene glycol) column at 170° showed a major peak assigned to 3-chlorocycloheptanone
and minor peak for 2-cycloheptenone
. The spectral properties of 3-chlorocycloheptanone
are as follows: IR (neat) cm.−1
: 1705 (C=O); 1
H NMR (CCl4
), δ (multiplicity, number of protons, assignment): 1.4–2.3 [m, 6H, (CH2
-CHCl], 2.3–2.6 (m, 4H, CH2
), 4.1–4.4 (m, 1H, CH
Cl); mass spectrum, m/e
(intensity ratio): M
+, 146 and 148 (3:1).
A GC analysis by the submitters as described in the preceding note indicated that the purity of the product was 98%. The purity of the product obtained by the checkers was estimated at 95% by a GC analysis at 140° as described in (Note 10)
has the following spectral properties: IR (neat) cm.−1
: 1700 (C=O), 1660 (C=C), 1445, 1090, 888; 1
H NMR, δ (multiplicity, coupling constant J
in Hz., number of protons, assignment): 1.75 [m, 4H, CH2
], 2.45 [m, 4H, CH2
], 5.90 (d, J
= 13, 1H, CH=CH
CO), 6.52 (d of t, J
= 5 and J
= 13, 1H, CH
This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous α,β-unsaturated ketones.2
The key step in the sequence is the iron(III) chloride
-induced cleavage of the central bond of trimethylsilyloxycyclopropanes which are obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene
described in Part A is that of House, Czuba, Gall, and Olmstead.3
PREPARATION OF 2-CYCLOALKENONES AND CYCLOALKANE-1,3-DIONES BY IRON(III) CHLORIDE-INDUCED RING OPENING OF 1-TRIMETHYLSILYLOXY-AND 1,2-BIS(TRIMETHYLSILYOXY)BICYCLO[n.1.0]ALKANES
2-Cycloalkenone or Cycloalkane-1,3-dione
aThe scale was 0.002–0.005 mole except as noted.
bThis reaction was conducted on a 0.05-mole scale.
cThis compound was a mixture of cis and trans isomers.
The regiospecificity of the iron(III) chloride
-induced ring cleavage contrasts with that observed in reactions of 1-silyloxybicyclo[n
.1.0]alkanes with bromine9
and potassium tert-butoxide
Although the mechanism of the reaction is not known with certainty, it is reasonable to suppose that an alkoxy radical is involved, that this radical undergoes homolytic scission of the more highly substituted carbon–carbon bond of the cyclopropane ring, and that the resulting carbon radical abstracts a chlorine atom from iron(III) chloride
This preparation is referenced from:
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