Facile One-Pot Preparation of 3-Chloro-2-(chloromethyl)propene and an ab Initio Study of the Deamination Reaction of Nitrosoaziridine

Full text of DOI:10.1021/jo000734u

6784
J . Org. Chem. 2000, 65, 6784-6786
Sch em e 1
F a cile On e-P ot P r ep a r a tion of
3-Ch lor o-2-(ch lor om eth yl)p r op en e a n d a n
a b In itio Stu d y of th e Dea m in a tion
Rea ction of Nitr osoa zir id in e
Tomas Martinu and William P. Dailey*
Department of Chemistry University of Pennsylvania
Philadelphia, Pennsylvania 19104-6323
dailey@sas.upenn.edu
Received May 15, 2000
The facile stereospecific thermal conversion of N-
nitrosoaziridines into alkenes is a well-known reaction1
that has been studied mechanistically.2,3 The labile
N-nitrosoaziridines formed by nitrosation of N-unsubsti-
tuted aziridines (eq 1) have been observed spectroscopi-
cally4 and have been isolated under low temperature
conditions. While the deamination reaction has potential
synthetic utility for the stereospecific synthesis of al-
kenes, especially the cis-trans interconversion of al-
kenes,5 there are only a few reports of its application in
organic synthesis.6 Herein the utility of the deamination
reaction is demonstrated by the convenient large scale
one-pot preparation of 3-chloro-2-(chloromethyl)propene
(5), a compound that is a useful starting material for
many molecules including [1.1.1]propellane.7 Addition-
ally, high level ab initio molecular orbital calculations
are presented for the deamination-fragmentation reac-
tion, and these allow some insight into the mechanism
of this cheletropic reaction.
equiv of thionyl chloride are required since 1 equiv
converts the primary amino group to the N-sulfinylamino
group.10 The relative amounts of 1 and 2 are of no
consequence since both compounds are converted to the
same product in the next step. It was found that the
sulfite anion generated on base-promoted hydrolysis of
1 causes much decreased yields in the last step of the
reaction sequence. Therefore, acid-promoted hydrolysis
was performed, and the liberated sulfur dioxide was
removed by heating. Addition of base and gentle warming
allow ring closure of crude 3 to 2,2-bis(chloromethyl)-
aziridine (4). Further treatment of crude 4 with sodium
nitrite and aqueous acid results in a vigorous evolution
of gases. Steam distillation of the final product from the
reaction mixture, separation from water, drying, and
redistillation gives 5 in 55 to 60% overall yield. We
believe that this one-pot procedure is now the method of
choice for the preparation of this alkene on a laboratory
scale.
Th eor etica l a n d Com p u ta tion a l Stu d ies of th e
Den itr ogen a tion Rea ction . A theoretical examination
of the cheletropic extrusion of nitrous oxide from N-
nitrosoaziridine was presented by Woodward and Hoff-
mann.11 They suggested two different symmetry allowed
nonlinear pathways for the fragmentation reaction. The
one which they favored involved a planar aziridine
nitrogen conjugated with the NdO π system. This
nonlinear mode of fragmentation is similar to that
observed in the corresponding three-membered ring
diazene derivatives.11 The alternative suggestion involved
a nonplanar aziridine nitrogen with a nonconjugating
nitroso group. However, this possibility was considered
to be unlikely due to the rotational energy required for
typical nitrosamines. Based on the thermal stability of
N-nitroso-9-azabicylo[4.2.1]nona-2,4,7-triene toward frag-
mentation, Mock and Isaac3 proposed that the alternative
mechanism was in fact the actual pathway.
Resu lts a n d Discu ssion
The one-pot preparation of 3-chloro-2-(chlorometh-
yl)propene (5) is shown in Scheme 1. By modification of
a previously reported procedure,8 commercially available
tris(hydroxymethyl)aminomethane (TRIS) is converted to
a mixture of the N-sulfinyl 1 and a smaller amount of
the corresponding 2.9 A careful examination of this
reaction revealed that a substoichiometric amount of
pyridine is sufficient for full conversion, and about 4
* To whom correspondence should be addressed. Phone: 215-898-
2704. Fax: 215-573-2112.
(1) Bumgardner, C. L.; McCallum, K. S.; Freeman, J . P. J . Am.
Chem. Soc. 1961, 83, 4417.
(2) Clark, R. D.; Helmkamp, G. K. J . Org. Chem. 1964, 29, 1316.
(3) Mock, W. L.; Isaac, P. A. H. J . Am. Chem. Soc. 1972, 94, 2749.
(4) Rundel, W.; Mu¨ller, E. Chem. Ber. 1963, 96, 2528.
(5) Carlson, R. M.; Lee, S. Y. Tetrahedron Lett. 1969, 10, 4001.
(6) Lee, K.; Kim, Y. H. Synth. Commun. 1999, 29, 1241 and
references therein.
(7) (a) Semmler, K.; Szeimies, G.; Belzner, J . J . Am. Chem. Soc.
1985, 107, 6410. (b) Lynch, K. M.; Dailey, W. P. J . Org. Chem. 1995,
60, 4666. (c) Lynch, K. M.; Dailey, W. P. Org. Synth. 1998, 75, 89 and
references therein.
To further probe the mechanism of the denitrogention
reaction, ab initio calculations were carried out on the
ground and transition states for the fragmentation reac-
tion of N-nitrosoaziridine (NA) to ethene and nitrous
oxide. The calculations were carried out using the Gauss-
ian 94 package12 and used the G2MP2 level of theory.13
(8) Boikov, Y. A.; Bakhmenko, V. B.; V’yunov, K. A.; Ginak, A. I. J .
Org. Chem. USSR 1986, 22, 261.
(9) If desired, compounds 1, 3, and 4 can be isolated and purified
at the appropriate points of the preparation. See Experimental
Section.
(10) For a review of the preparation and reactions of sulfinylamines
and related compounds, see: Kresze, G.; Wucherpfennig, W. Angew.
Chem., Int. Ed. Engl. 1967, 6, 149 and references therein.
(11) Hoffmann, R.; Woodward, R. B. Angew. Chem., Int. Ed. Engl.
1969, 8, 781.
10.1021/jo000734u CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/14/2000

Notes
J . Org. Chem., Vol. 65, No. 20, 2000 6785
F igu r e 1. Selected (MP2/6-31G*) structural data for the two
transition structures (TS-syn and TS-a n ti) leading to loss of
nitrous oxide from N-nitrosoaziridine.
Previous computational work on these systems is limited
to a study of their CD spectra and the rotational energy
barrier of the N-nitroso group.14 No electronic structure
calculations on transition structures for fragmentation
were found. An intensive search at the MP2/6-31G* level
led to the discovery of two different transition structures
for the fragmentation of nitrous oxide from NA. While
no symmetry constraints were imposed during the search,
both transition structures are very close to Cs symmetry
with a strongly bent NNO bond angle. The two transition
structures differ mainly by the orientation of the oxygen
atom as either syn (TS-syn ) or anti (TS-a n ti) to the
cyclopropane ring.15 Selected geometric parameters of
the two different transition structures derived from
MP2/6-31G* optimized geometries are shown in Figure
1. The total and relative energies of the structures of
interest are given in Table 1.
Energetically, there is a huge difference between the
two transition structures. TS-syn is much lower in
energy than TS-a n ti. Based on G2MP2 energies, the
transition structures are calculated to lie 21.4 and 47.6
kcal/mol above the ground state, while the overall reac-
tion is predicted to be downhill by 27.9 kcal/mol.The
magnitude of the difference in energy between the two
transition structures (26.2 kcal/mol) is remarkable given
F igu r e 2. Simple frontier molecular orbital interaction
between the LUMO of N2O and HOMO of ethene showing the
secondary orbital interactions proposed in the TS-syn and TS-
a n ti transition structures.
Ta ble 1. Tota l En er gies (h a r tr ees) a n d Rela tive
En er gies (k ca l/m ol u sin g G2MP 2 en er gies) of Selected
Str u ctu r es Ba sed on G2MP 2 Ca lcu la tion s
relative
compound
NA
TS-syn
TS-a n ti
ethene
MP2/6-31G*
G2MP2
E( kcal/mol)
-262.456475
-262.408382
-262.359830
-78.2942862
-184.213683
-262.802286
-262.768222
-262.726459
-78.4143044
-184.432465
0.0
21.4
47.6
-27.9
nitrous oxide
that the main difference between them is the orienta-
tion of the oxygen as syn or anti to the three-mem-
bered ring. It is tempting to speculate that the difference
arises from secondary orbital interactions in the tran-
sition states between the bent nitrous oxide and the
ethene that is forming. According to frontier molecular
orbital theory,16 the reaction can be approximated as the
interaction between the HOMO of ethene and the
LUMO of the bent nitrous oxide. Simple representations
of these orbitals in TS-syn and TS-a n ti arrangements
are shown in Figure 2. The TS-syn arrangement allows
a stabilizing interaction between the orbitals of the
carbon atoms and the orbital of the oxygen atom while
the TS-a n ti arrangement will have a destabilizing
secondary orbital interaction between the orbitals of the
carbon atoms and the orbital of the middle nitrogen atom.
That these secondary orbital effects would be so large is
surprising and suggests further study of these systems
is in order.
(12) Gaussian 94, Revision E.2, Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Petersson, G. A.; Montgomery, J . A.; Raghavachari,
K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Cioslowski, J .; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A.; Gaussian, Inc., Pittsburgh, PA, 1995.
(13) Curtiss, L. A.; Ragavachari, K.; Pople, J . A. J . Chem. Phys.
1993, 98, 1293.
(14) Shustov, G. V.; Kachanov, A. V.; Kadorkina, G. K.; Kosty-
anovsky, R. G.; Rauk, A. J . Am. Chem. Soc. 1992, 114, 8257.
(15) Both transition structures had one imaginary frequency. TS-
(16) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: New York, 1978; pp 23-32.
syn : ν ) -703 i cm-1; TS-a n ti: ν ) -537 i cm-1
.

6786 J . Org. Chem., Vol. 65, No. 20, 2000
Notes
1,3-dichloro-2-(chloromethyl)propene20). If desired, the product
may be further purified by distillation through a 15 cm column
packed with glass helices (bp 137 °C); 1H NMR (360 MHz,
CDCl3): δ 5.30 (s, 2H), 4.18 (s, 4H); 13C NMR (91 MHz, CDCl3):
δ 141.17, 118.91, 44.66.
Exp er im en ta l Section
Ma ter ia ls. Tris(hydroxymethyl)aminomethane (TRIS), thio-
nyl chloride (97%), pyridine, and sodium nitrite (97%) were
purchased from Aldrich. All other chemicals used were products
of Fisher Scientific.
3-Ch lor o-2-(ch lor om eth yl)p r op en e (5). A 3 L four-necked
round-bottomed flask was equipped with a mechanical stirrer,
a thermometer reaching to the bottom, a pressure-equalizing
dropping funnel, and a reflux condenser connected to a bubbler.
The flask was filled with 150.0 g (1.24 mol) of TRIS and 390
mL (5.19 mol) of thionyl chloride. A large ice-water bath
surrounded the flask. With good stirring, 50 mL (0.62 mol) of
pyridine was cautiously added dropwise over the course of 10
min. After the addition was complete, the cooling bath was
replaced with a heating mantle. The contents of the flask were
allowed to stir without heating until gas evolution slowed (ca.
45 min) and then were slowly heated so that the final temper-
ature reached 120 °C at the end of 6 h.17 The brown mixture18
was cooled in an ice-water bath to 20 °C, and 50 mL of water
was added dropwise, slowly and very cautiously, over the course
of 30 min with good stirring and cooling. An additional 250 mL
of water was added. Then a solution of 70 mL (1.26 mol) of
concentrated sulfuric acid in 300 mL of water was added over
the course of 10 min. After the addition was complete, the
contents of the flask were refluxed until gas evolution ceased.
The clear orange solution was cooled to 10 °C using an ice-
water bath and was made alkaline (pH∼13) by dropwise addition
of a 30% (w/w) aqueous solution of sodium hydroxide (ca. 360
mL) while maintaining the reaction mixture below 30 °C. Once
alkaline, the mixture was treated with a solution of 75.0 g (1.88
mol) of sodium hydroxide in 250 mL of water and was heated at
50 °C for 3 h with good stirring. After the mixture was cooled to
room temperature,19 a solution of 88.0 g (1.24 mol) of sodium
nitrite in 200 mL of water was added. Then, a cold solution of
260 mL of concentrated hydrochloric acid in 260 mL of water
was added dropwise into the vigorously stirred mixture over the
course of 30 min. The temperature of the reaction mixture was
allowed to rise above 50 °C, and colorless gases were smoothly
generated throughout the addition. After the addition was
complete, the reflux condenser was replaced with a distillation
condenser. The green-brown mixture was heated with a heating
mantle, and the product steam distilled into an ice-cooled
receiver. After all the product had distilled, the two layers from
the condensate were separated, the light blue organic layer was
dried over magnesium sulfate and distilled with a short-path
condenser to give 85.0 g (55% overall yield) of colorless liquid
(bp 136-144 °C), >95% pure by GC (the major impurity being
Ack n ow led gm en t. Financial support provided by
the University of Pennsylvania Research Fund. T.M.
gratefully acknowledges the Alfred Bader Fund for a
Graduate Fellowship.
Su p p or tin g In for m a tion Ava ila ble: Complete G2MP2
geometries and energies for the structures in Table 1. This
material is available free of charge via the Internet at
http://www.pubs.acs.org.
J O000734U
(17) If the reaction is scaled down to 25 g of TRIS, the heating time
may be reduced to 3 h.
(18) TRIS is converted to a mixture of 1 and 2 in a ca. 4:1 ratio.
This was found by precipitation of salts with dichloromethane and
analyzing solid and mother liquor separately. Tr is(ch lor om eth yl)-
N-su lfin ylm eth yla m in e (1): bp 72-74 °C (0.02 mmHg); 1H NMR
(200 MHz, CDCl3): δ 4.01 (s, 6H); 13C NMR (50 MHz, CDCl3): δ 72.37,
44.95; MS (CI) 221.9 (M + H). Tr is(ch lor om eth yl)m eth yla m m o-
n iu m ch lor id e (2): mp 251-254 °C (dec); 1H NMR (200 MHz, DMSO-
d6): δ 9.27 (bs, 3H), 4.04 (s, 6H); 13C NMR (50 MHz, DMSO-d6):
59.11, 44.33; MS (CI) 176.0 (M - Cl).
δ
(19) 2,2-Bis(ch lor om eth yl)a zir id in e (4). To the reaction mixture
was added 400 mL of methylene chloride, and two layers were
separated. Aqueous layer was extracted with 4 × 400 mL of dichlo-
romethane. Combined organic layers were washed with 100 mL of
water and dried over sodium sulfate. The solvent was removed by
evaporation under water aspirator pressure at 35 °C, and pyridine was
thoroughly removed by high-vacuum distillation (0.01 mmHg) at room
temperature. The resulting brown liquid was distilled to give 121.1 g
(70%) of clear colorless liquid, bp 42 °C (0.01 mmHg), which was first
stirred with
1 g of sodium hydroxide pellets overnight at room
temperature and then was kept refrigerated. 1H NMR (360 MHz,
CDCl3): δ 3.85 (d, J ) 11.8 Hz, 1H), 3.65 (d, J ) 11.5 Hz, 1H), 3.59 (d,
J ) 11.8 Hz, 1H), 3.36 (d, J ) 11.5 Hz, 1H), 1.99 (d, J ) 9.9 Hz, 1H),
1.70 (d, J ) 8.0 Hz, 1H), 0.83 (bs, 1H). 13C NMR (91 MHz, CDCl3): δ
47.61, 47.26, 39.22, 32.02. HRMS (CI): 140.0039 (M + H); calcd:
140.0034 for C4H8Cl2N.
(20) 1,3-Dich lor o-2-(ch lor om eth yl)p r op en e. 1H NMR (360 MHz,
CDCl3): δ 6.39 (s, 1H), 4.35 (s, 2H), 4.21 (s, 2H); 13C NMR (91 MHz,
CDCl3): δ 135.06, 122.49, 43.77, 38.28. Formation of trichloropropene
under the employed reaction conditions is precedented by Boikov, Yu.
A.; V’yunov, K. A.; Ginak, A. I. J . Org. Chem. USSR 1982, 18, 2010.