Organic Syntheses, Coll. Vol. 6, p.56 (1988); Vol. 55, p.114 (1976).
C. Styrene glycol dimesylate (Note 15)
. A 300-ml., three-necked, round-bottomed flask equipped with a thermometer, an efficient stirrer (Note 16)
, and a dropping funnel
is charged with a solution of 34.5 g. (0.250 mole) of styrene glycol (Note 17)
in 90 ml. of pyridine (Note 18)
. The solution is cooled to −5° with an ice–salt bath
, and 64.7 g. (43.7 ml., 0.560 mole) of methanesulfonyl chloride (Note 19)
is added dropwise over a 1-hour period, while maintaining the temperature at or below 0° (Note 20)
. Stirring is continued for 4 hours at 2–4°, with the flask cooled with an ice-water bath
. The reaction mixture is mixed thoroughly with 600 g. of ice, and the dimesylate precipitates. After careful acidification of the mixture with 6 N hydrochloric acid
to approximately pH 3 (Note 21)
, the dimesylate is suction filtered, washed twice with 100-ml. portions of ice water, and pressed as dry as possible. This product, which is still moist, is transferred to a separatory funnel
and is shaken well with 200 ml. of dichloromethane
. The dichloromethane
is separated, and the aqueous layer is extracted further with two 20-ml. portions of dichloromethane
. The combined dichloromethane
layers are dried over anhydrous magnesium sulfate
, and 250–300 ml. of pentane
is added to the solution, until crystallization just begins. After 2 hours in a deep freeze at −25°, the crystals are collected, washed with two 30-ml. portions of pentane
precooled to 0°, and dried to constant weight in a vacuum desiccator
(10 mm.) at room temperature, yielding 62–64 g.
) of white, crystalline dimesylate, m.p. 93–94° (Note 15)
F. 1-Amino-2-phenylaziridinium acetate (Note 23)
. The pentane
solution from Step D
is stirred with a magnetic stirrer and cooled to 0°, and 3.9 ml. (0.068 mole) of acetic acid
is measured. Three drops of acetic acid
are added at first, and stirring is continued at 0° until the precipitation of white 1-amino-2-phenylaziridinium acetate
begins. If necessary, crystallization is initiated by scratching with a glass rod
or by addition of a seed crystal from a previous run. The remainder of the acetic acid
is added over a 10-minute period, and stirring is continued for an additional 20 minutes, while maintaining the temperature at 0°. The salt is filtered, washed with 30 ml. of pentane
precooled to 0°, and dried in a vacuum desiccator (10 mm.) at room temperature, yielding 10.0–10.5 g.
) (Note 26)
of product, m.p. 69–70° (Note 27)
which is suitable for preparative purposes. Recrystallization is possible; however, it must be carefully carried out to avoid the formation of a yellow product, whose melting point is lower than that of the crude product. A solution of 10 g. of 1-amino-2-phenylaziridinium acetate
in 40 ml. of dichloromethane
is prepared at a maximum temperature of 20–22°. The turbid solution is immediately filtered through Celite®, which is washed with two 10-ml. portions of dichloromethane
. The resulting clear solution is treated with 200–250 ml. of pentane
until crystallization just begins, and placed in a deep freeze at −25° for 2 hours. Filtration, washing with 30 ml. of pentane
precooled to 0°, and drying as before, afford 9.2–9.3 g.
of 1-amino-2-phenylaziridinium acetate
, m.p. 70–72° (Note 23)
and (Note 28)
N-Aminophthalimide is available from Fluka AG
or may be prepared from phthalimide
The quality is important; the m.p. should be 199–202° with subsequent resolidification of the melt due to thermal reaction. Recrystallization, if necessary, can be carried out in ethanol
. The checkers observed that with one batch of recrystallized material, the solid never really did melt, but seemed to sinter at
Technical grade (E)-stilbene obtained from Fluka AG
gives satisfactory results, although a better grade is preferable. The checkers used reagent grade material obtained from Aldrich Chemical Company, Inc.
"Purum" grade lead tetraäcetate, 85–90%
, moistened with acetic acid, obtained from Fluka AG
was used. The checkers used reagent grade material, moistened with acetic acid
, purchased from Matheson, Coleman and Bell.
The yield of the reaction, while always at least 39%
, is subject to fluctuation. The product may be contaminated with small amounts of (E)-stilbene
and/or lead salts. The presence of (E)-stilbene
can easily be monitored by TLC, using ready-prepared Silica Gel
plates available from E. Merck & Company, Darmstadt, Germany. The plates are developed with dichloromethane
, and the spots detected under UV light. In runs of smaller scale, or if product of higher purity is desired, column chromatography on silica gel may replace the work-up described; the reaction mixture is filtered through Celite®, and the resulting solution is concentrated on a rotary evaporator. The residue is then chromatographed on 570 g. of silica gel
. Eluting with dichloromethane
gives the stilbene
first, then small amounts of unidentified impurities, and finally the desired adduct in 70–73%
decomposes thermally, largely to (E)-stilbene
. In the crystalline state it is stable for several hours at room temperature, and for several weeks (probably for several months) at −20°. It decomposes within 3 days at room temperature in aprotic solvents and much more rapidly in protic solvents.3
Decomposition is still faster in the presence of traces of acids. The work-up described should be completed as quickly and as precisely
as possible, and the product should be stored in a deep freeze if it is not to be used immediately. For the use of this reagent in the α,β-epoxyketone fragmentation, see references 3
Use of lesser amounts of hydrazine hydrate
causes precipitation of the product as a pasty mass that dissolves only slowly in ether, thereby making the work-up difficult.
The reaction temperature must be carefully controlled. At temperatures above 48° the yield is markedly reduced by decomposition of the product, and below 43° the reaction time is greatly lengthened.
Before working up the reaction mixture, it is recommended to test whether the reaction is complete by TLC (Note 6)
. If (E)-stilbene
is observed, the reaction should be interrupted immediately. The checkers found that the work-up was complicated by formation of emulsions; small quantities of brine were used to aid separation of the phases.
: 3340, 1603, 1495, 1450, 1085, 1070, 1030 (a weak band at 960 cm.−1
is due to (E
)-stilbene, as there is always some decomposition of the trans-1-amino-2,3-diphenylaziridine
during the recording of the spectrum) (Note 7)
H NMR (CDCl3
), δ (multiplicity, coupling constant J
in Hz., number of protons, assignment): 3.10 (broad m, 2H, NH2
), 3.22 and 3.36 (AB q, 2H, J
= 5), 7.1–7.6 (m, 10H). The nonequivalence of the two methine protons is due to slow inversion at nitrogen
, and confirms the trans
The melting-point tube
is placed in the bath at 85° and heated rapidly.
A second crystallization from dichloromethane–pentane
is sometimes necessary to achieve material having this melting point. Styrene glycol dimesylate
must be stored in a refrigerator, since slow decomposition takes place at room temperature.
Toward the end of the reaction, the mixture becomes quite viscous. Unless the stirring assembly is capable of mixing material at the flask walls, homogeneous temperature control cannot be guaranteed.
Styrene glycol is available from Aldrich Chemical Company, Inc., or from Eastman Organic Chemicals
. Alternatively, it may be prepared by hydrolysis of styrene oxide
If the glycol melts at lower than 63°, it should be recrystallized before use.
"Purum" grade methanesulfonyl chloride supplied by Fluka AG or 98% pure material supplied by Eastman Organic Chemicals
About 110–120 ml. of 6 N hydrochloric acid
is needed. The temperature should not be allowed to rise above 5°.
The rate of the reaction is influenced by the speed of stirring. At slow speeds, 30 hours may be required for completion without any decrease in the final yield. The role of pentane
is to continuously remove newly formed product from the hydrazine solvent.
decomposes at temperatures over 0°, and must therefore be stored in a deep freeze at −25°, at which temperature it is crystalline. 1-Amino-2-phenylaziridinium acetate
is somewhat more stable, but it too decomposes within 2 days at room temperature. It can be kept unchanged in a deep freeze for months. For the use of these two reagents in the α,β-epoxyketone fragmentation, see references 3
In order to minimize decomposition, the distillation should be carried out on small portions at the lowest possible temperature and pressure.
The distilled product has the following 1
H NMR spectrum (CDCl3
), δ (number of protons, assignment): 1.91, 1.98, and 2.06 (2H, AB part of ABX), 2.50, 2.58, 2.64, and 2.72 (1H, X part of ABX), 3.60 (2H, NH2
), 7.25 (5H). Undistilled material shows substantially the same spectrum.
By the addition of two further drops of acetic acid
to the mother liquor, and overnight cooling at −25°, an additional 0.3–0.4 g.
) of product, m.p. 60–62°
, can be isolated.
For the melting point determination the capillary is placed in the apparatus at 60°, and the temperature is raised 4°/minute.
Recrystallized 1-amino-2-phenylaziridinium acetate
has the following 1
H NMR spectrum (CDCl3
), δ (number of protons, assignment): 1.95–2.20 (5H, AB part of ABX and CH3
at δ 2.02), 2.67–2.95 (1H, X part of ABX), 6.50–6.70 (3H, NH3
) 7.0–7.4 (5H).
Chemical Abstracts Nomenclature (Collective Index Number);
potassium carbonate (584-08-7)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
diethyl ether (60-29-7)
potassium hydroxide (1310-58-3)
hydrazine hydrate (7803-57-8)
Styrene oxide (96-09-3)
magnesium sulfate (7487-88-9)
pyridine hydrochloride (628-13-7)
Methanesulfonyl chloride (124-63-0)
1-Amino-2-phenylaziridinium acetate (37079-43-9)
Styrene glycol dimesylate (32837-95-9)
1-aziridinamine, (±)-2-phenyl- (19615-20-4)
phosphorus pentoxide (1314-56-3)
1-Aziridinamine, trans-(±)-2,3-diphenyl- (28161-60-6)
lead tetraacetate (546-67-8)
1-aziridinamine, monoacetate, (±)-2-phenyl-
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