Highly efficient synthesis of methylenecyclopropane

Article abstract of DOI:10.1055/s-2002-33122

An efficient procedure for the preparation of methylenecyclopropane (3), a valuable starting material in organic synthesis, has been developed from methallyl chloride (1) and alkali metal [bis(trimethylsilyl)]amide [M(BTMSA) (M = Na, K), 2b,c]. The advantages of this new method are the higher yield of methylenecyclopropane up to 79% and a homogenous reaction mixture, i.e. both substrates are soluble in organic solvents such as toluene and dibutyl ether.

Full text of DOI:10.1055/s-2002-33122

1344
SHORT PAPER
Highly Efficient Synthesis of Methylenecyclopropane
Synthesis of
M
a
e
thylenecy
u
clopropane l Binger,*1 Axel Brinkmann, Petra Wedemann
Max-Planck-Institut für Kohleforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
Fax +49(631)2053921
Received 19 February 2002; revised 18 April 2002
and are soluble in organic solvents like aromatic hydro-
carbons or dialkyl ethers.
Abstract: An efficient procedure for the preparation of methyle-
necyclopropane (3), a valuable starting material in organic synthe-
sis, has been developed from methallyl chloride (1) and alkali metal
[bis(trimethylsilyl)]amide [M(BTMSA) (M = Na, K), 2b,c]. The
advantages of this new method are the higher yield of methylenecy-
clopropane up to 79% and a homogenous reaction mixture, i.e. both
substrates are soluble in organic solvents such as toluene and dibu-
tyl ether.
Slow addition of methallyl chloride (1) to a vigorously re-
fluxing solution of 2b or 2c in toluene, o-xylene or dibutyl
ether immediately causes a gas stream of C4H6-hydrocar-
bons 3 and 4 whose compositions and yields depend
mainly on the base used, and to a minor extent on the boil-
ing point of the solvent (Scheme).9
Key words: methylenecyclopropane, methallyl chloride, elimina-
The best results are obtained with 2c (M = K) in refluxing
toluene or Bu2O that directly affords methylenecyclopro-
pane (3) in good purity and yield (see Scheme). Amide 2b
(M = Na) produces the C4H6-hydrocarbons in comparable
yields, but 3 is now contaminated with larger amounts of
1-methylcyclopropene (4). To obtain pure 3 it is therefore
necessary to isomerize 4 into 3 in a second step that is con-
veniently performed by bubbling the 3/4-mixture through
a 50 °C warm solution of t-BuOK in DMSO.3,4 Interest-
ingly no C4H6-hydrocarbons are obtained when
LiN(SiMe3)2 (2a) is used as the base under otherwise
identical conditions. This is remarkable because it is well
known that strong lithium bases, e.g. LDA (lithium diiso-
propylamide) metalate allyl chlorides in the -position at
low temperatures. Therefore it is reasonable to assume
that -metalation takes place, but subsequent reactions
other than -elimination of LiCl, e.g. C C-coupling, are
faster.10,11 On the other hand it has been reported that 1 re-
acts with two equivalents of pure, lithium bisamide-free
phenyl lithium to give 1-lithium-2-methylcyclopropene in
a yield as high as 60–80%.12 These difficulties can be cir-
cumvented by adding a second base, e.g. t-BuOK, to the
reaction mixture, e.g. a 1:1 mixture of 2a and t-BuOK in
toluene at 110 °C, readily liberates a 3/4-mixture in the ra-
tio 88:12 and a yield of 73%. Addition of t-BuOK to 2b
has also a beneficial effect on the yield and 3/4-ratio; e.g.
from 1 and the base mixture 2b/t-BuOK in boiling Bu2O
a 3/4-mixture is obtained in the ratio 91:9 and a yield of
81%. The latter observation indicates that a metal–metal
exchange occurs and the so formed 2c acts as the active
base.
tion
Based on a publication of Fisher and Applequist who re-
ported the preparation of 1-methylcyclopropene (4) from
3-chloro-2-methylpropene (methallyl chloride, 1) and so-
dium amide in refluxing THF,2 we developed some years
ago a synthesis of methylenecyclopropane (3) using the
same starting materials but modified the solvent and the
reaction conditions.3 With sodium amide, a mixture of 3
and 4 (80:20) was obtained in boiling Bu2O in a maximum
yield of 75% whereas potassium amide in the same boil-
ing solvent produced 3 in 61% yield with 94% purity. The
C4H6-hydrocarbon mixture of 3 and 4 can be isomerized
into pure 3 by bubbling through a solution of t-BuOK in
DMSO with only little loss.3,4 Pure 3 has also been synthe-
sized from 1 (43%) by application of the base mixture
NaNH2/t-BuONa.5,6,7a These syntheses suffers from some
disadvantages which hinder the preparation of 3 in larger
amounts. This, however, is necessary if 3 should be used
as starting material in organic synthesis.7b–d The most im-
portant disadvantages are the following: 1) sodium and
potassium amides are insoluble in organic solvents and
must be applied as powder, which is too dangerous in
technical procedures; and 2) two of the three reaction
products, the C4H6-hydrocarbons and ammonia are gases
at room temperature and must be separated in an addition-
al step, conveniently by bubbling through an aqueous
H2SO4 solution.3,6
To circumvent these disadvantages we looked for soluble
bases with similar or even better properties than MNH2
and found these in the alkali metal [bis(tirmethylsi-
lyl)]amides [M(BTMSA)] 2b (M = Na) and 2c (M = K).8
Amides 2b and 2c are strong bases with special properties.
They are conveniently available also in larger amounts
In summary, we have developed an efficient and simple
procedure to synthesize pure 3 in large amounts.
2-Methyl-3-chloropropene (methallyl chloride, 1) was
purchased from Merck KGaA and used without further
purification. Amide 2a was prepared from BuLi and hex-
amethyldisilazane, (Merck KGaA), and 2b,c were pre-
pared from MNH2 and hexamethyldisilazane according to
a literature procedure.8 The solvents THF, toluene, o-xy-
lene and Bu2O were dried before use. All reactions were
Synthesis 2002, No. 10, 30 07 2002. Article Identifier:
1437-210X,E;2002,0,10,1344,1346,ftx,en;Z03602SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

SHORT PAPER
Synthesis of Methylenecyclopropane
1345
In Bu2O: A mixture of 3 and 4 (GC: 85.8% 3 and 14.2% 4) was ob-
tained from 1 (22.6 g, 0.25 mol) and 2b (57.2 g, 0.31 mol); yield:
9.9 g (13.8 mL, d = 0.72 g/mol, 73%).
In Toluene: A mixture of 3 and 4 (GC: 55% 3 and 45% 4) was ob-
tained from 1 (22.6 g, 0.25 mol) and 2b (57.2 g, 0.31 mol); yield:
9.8 g (13.6 mL, 72%).
In o-Xylene: A mixture of 3 and 4 (GC: 76% 3, 24% 4) was obtained
from 1 (25.5 g, 0.28 mol) and 2b (64.3 g, 0.38 mol); yield: 10.8 g
(15.0 mL, 71%).
Method 2: With KN(SiMe3)2 (2c)
Apparatus and procedure were the same as described under Method
1. A slight excess of 2c (1:2c = 1:1.2) was used. The Table summa-
rizes the results obtained in different solvents.
Method 3; With Base Mixture 2a and t-BuOK: The base 2a (58.3 g,
0.35 mol) and t-BuOK (51.0 g, 0.46 mol) were dissolved in toluene
(150 mL) whereby a heat evolution to ca. 40 °C was observed. The
mixture was heated to a rigorous reflux (110 °C) and at this temper-
ature 1 (31.6 g, 0.35 mol) was added within 45 min. Immediately
C4H6-hydrocarbons escaped which were condensed in a –80 °C
cold trap; yield: 19 mL (13.7 g, 73%); colorless liquid containing
88% 3 and 12% 4 (GC). When this procedure was carried out with
a slightly molar excess of 2a or t-BuOK no C4H6-hydrocarbon was
obtained.
Scheme
Method 4; With 2b and t-BuOK: The base 2b (62.2 g, 9.34 mol) and
t-BuOK (10.1 g, 0.09 mol) were dissolved in Bu2O (100 mL). The
mixture was heated to a vigorous reflux (ca. 130 °C) and the chlo-
ride 1 (20.8 g, 0.23 mol) was added within 30 min. The C4H6-hydro-
carbons were condensed in a –80 °C trap: 14 mL [10.1 g, 81%,
composition (GC): 90.8% 3 and 9.2% 4]. The above procedure car-
ried out with equimolar amounts of 2b (48g, 0.20 mol), t-BuOK
(22.6, 0.20 mol) and 1 (18.1 g, 0.20 mol) led to the formation of 8.8
g (82%) of 97% 3 contaminated with 3% of 4.
carried out under argon. Yield and 3/4-ratio of the C4H6-
hydrocarbons, as well as the purity of 3 were determined
by GC (50 m OV1/3046 capillary column, N2, FD, 40–
260 °C, 8/min).
Methylenecyclopropane (3) from Methallyl Chloride (1); Gen-
eral Procedures
Method 1: With NaN(SiMe3)2 (2b)
Large Scale Preparation of Methylecyclopropane (3)
The base 2b (500 g, 2.73 mol) was dissolved in toluene (700 mL) in
a 3 L four-necked flask, equipped with a 250 mL dropping funnel,
a water-cooled Dimroth condenser, a KPG-stirrer, an argon gas
bubbler and an inlet tube connected to a –80 °C cold 250 mL trap.
The mixture was heated to a vigorous reflux and at this temperature
1 (199 g, 2.2 mol) was added under stirring within 4 h. From the be-
ginning of the addition of 1, a continuous gas stream of 3 and 4 es-
caped via the condenser and the inlet tube, which was condensed in
the trap at –80 °C. After an additional 1 h reflux, whereby a slow
stream of argon transported the rest of 3 and 4 into the trap, a mix-
ture of 3 and 4 (138 mL, d = 1.72 g/mL, 99.4 g; 84%, GC: 78% 3
and 22% 4) was collected as a colorless liquid. From the remaining
reaction mixture, a white suspension, all volatiles were removed at
r.t. and 0.01 bar; the colorless distillate (921 g) had the composition
(GC): 61.5% toluene and 38.5% hexamethyldisilazane [calcd 355 g
Compound 2b (57.2 g, 0.31 mol) was dissolved in a solvent (THF,
toluene, o-xylene or dibutyl ether, 100 mL) in a 250 mL three-
necked flask, equipped with a 25 mL dropping funnel, water-cooled
Dimroth condenser, magnetic stirrer, an argon gas bubbler and an
inlet tube connected to a –80 °C cold trap. To this vigorous boiling
solution was added 1 (22.7 g, 0.25 mol) over ca. 20 min. Product 3
or a mixture of 3 and 4 that escaped from the flask through the con-
denser was condensed via the inlet tube in a trap at –80 °C as a col-
orless liquid. After an additional 30 min reflux, the reaction was
over.
In THF: A mixture of 3 and 4 (GC: 80% 3 and 20% 4) was obtained
from 1 (22.6 g, 0.25 mol) and 2b (57.2 g, 0.31 mol); yield: 5.9 g (8.2
mL, d = 0.72 g/mol, 44%).
Table Reaction of Methallyl Chloride (1) with 2c
1
2c
Solvent
C4H6-Hydrocarbons
g
mol
0.25
0.25
0.28
0.25
g
mol
0.31
0.31
0.34
0.31
(100 mL)
mL
1.2
g
Yield (%)
3
4
0
4
4
4
22.6
22.6
25.3
22.6
61.7
61.7
67.6
61.7
THF
0.86
6.4
76
100
96
96
96
Bu2O
14.3
13.0
12.0
10.3
9.4
toluene
o-xylene
70
8.6
64
Synthesis 2002, No. 10, 1344–1346 ISSN 0039-7881 © Thieme Stuttgart · New York

1346
P. Binger et al.
SHORT PAPER
(100%)]. The remaining residue (275 g) was a white powder. The
above described procedure carried out with 1 (390 g, 4.3 mol) and
2b (791 g, 4.3 mol) in Bu2O (1.5 L) led to the formation of 199 g
(77%) of C4H6-hydrocarbons with the composition (GC): 91.6% 3
and 8.4% 4.
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Pure Methylenecyclopropane (3)
A mixture of 3 and 4 (138 mL, 99.4 g, 1.84 mol) was bubbled
through a solution of t-BuOK (9.8 g, 88 mmol) in DMSO (60 mL)
at 50 °C and recondensed in a –80 °C flask. The resulting 3 (130 g,
94%) was 99.4% pure (GC).
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Synthesis 2002, No. 10, 1344–1346 ISSN 0039-7881 © Thieme Stuttgart · New York