8,11-Dichloro-N-tosyl-3-aza[5]metacyclophane: A highly strained aromatic system

Full text of DOI:10.1021/ja9634987

J. Am. Chem. Soc. 1997, 119, 615-616
615
Scheme 1a
8,11-Dichloro-N-tosyl-3-aza[5]metacyclophane: A
Highly Strained Aromatic System
Danie¨l S. van Es, Arne Egberts, Stephen Nkrumah,
Hans de Nijs, Willem H. de Wolf, and
Friedrich Bickelhaupt*
Scheikundig Laboratorium, Vrije UniVersiteit
De Boelelaan 1083, NL-1081 HV
Amsterdam, The Netherlands
Nora Veldman and Anthony L. Spek
Vakgroep Kristal en Structuurchemie
UniVersiteit Utrecht, Padualaan 8
NL-3584 CH Utrecht, The Netherlands
a (a) LiAlH4, ether (anhydrous), 6 h, reflux; (b) TsCl, pyridine, 18
h, 0 °C; (c) H2NTos, DMSO, K2CO3, 20 h, 100 °C; (d) CHCl3, t-BuOK,
benzene, 5.5 h, rt; (e) 2.10-5 mbar, 480 °C; (f) CHCl3, C19H33N(CH3)3Br,
ethanol, 50% NaOH, CH2Cl2, 18 h, 90 °C; (g) t-BuOK, DMSO, 2.5 h,
rt.
ReceiVed October 7, 1996
Small cyclophanes are challenging for their interesting
properties as well as for their difficult synthetic accessibility.
In 1984 we reported the X-ray crystal structure of the smallest
isolable [n]metacyclophane at that time: 8,11-dichloro[5]-
metacyclophane (1).1 Its benzene ring displayed a severe
boatlike distortion induced by the short pentamethylene chain,
which is reflected in a high reactivity. Despite this distortion,
the bond distances have normal aromatic values (1.389(3)-
1.400(3) Å) without cyclohexatriene-like bond alternation. The
introduction of a heteroatom such as nitrogen in the bridge was
expected to increase the distortion of the benzene ring by
shortening the bridge, due to the shorter nitrogen-carbon bond
distance; in addition, a strained heteraphane with potentially
interesting interactions between the heteroatom and the aromatic
ring might be expected. Relatively few small hetera[n]meta-
cyclophanes are known. The first reference goes back to 1919
with the (now questionable) synthesis of an aza[7]meta-
cyclophane.2a In 1985, Shea and co-workers reported the syn-
theses of various oxa[7]- and oxa[6]metacyclophanes.2b We
here report the synthesis of a substituted 3-aza[5]metacyclophane,
so far the smallest heterametacyclophane known.
Figure 1. Side view of the crystal structure of 8; the tosyl group at
nitrogen has been omitted for clarity. Selected bond lengths (Å) and
bond angles (deg) of 8: C(1)-C(2) 1.560(4), C(2)-N(1) 1.486(4),
C(8)-C(9) 1.371(5), C(9)-C(10) 1.385(4), C(10)-C(11) 1.399(4),
C(1)-C(10) 1.504(4), C(10)-C(1)-C(2) 103.7(2), C(1)-C(2)-N(3)
114.9(2), C(2)-N(1)-C(4) 121.9(2); R ) 27.4(3)° , â ) 48.7(2)°, γ
) 12.3(4)°.
Starting from diester 2,3,4 the bistosylate 3 was prepared in
two steps.5 Ring closure of 3 with N-tosylamide yielded 4 in
a yield of 48% (Scheme 1). Dichlorocarbene addition to 4 gave
the spiro compound 5. This was converted to 6 by flash vacuum
thermolysis. Dichlorocarbene addition to 6 yielded the propel-
lane 7. Treatment of 7 with potassium tert-butoxide gave the
desired cyclophane 8 by double elimination of hydrogen chloride
with concomitant opening of the three-membered ring, in
analogy to the synthesis of 1.1
In view of the expected higher strain in 8, it was of special
interest to compare its X-ray crystal structure6 (Figure 1) with
that of its carbon analogue 1. Surprisingly both the bow (R)
and the stern (γ) of the benzene ring of 8 are only slightly more
distorted than those of 1 (R, 27.4(3)° versus 26.8°; γ, 12.3(4)°
versus 12.0°, respectively). Also, the projected angle â of the
benzylic methylene groups with the plain of the four central
carbons of the benzene ring is not significantly increased
(48.7(2)° versus 48.0°). The total bending of the boat of the
benzene ring of 8 (R + γ ) 39.7°) as well as that of 1 (R + γ
) 38.8°)1 is practically identical to those of [6]paracyclophanes
(38.9-41°).7a-c Like in 1, the bond distances in the cyclophane
benzene ring of 8 have normal aromatic values (1.371(5)-
1.399(4) Å): bond alternation is not observed. Note in
particular that the molecule has Cs symmetry, therefore a
distortion toward a cyclohexatriene structure can be excluded.
Thus, contrary to our initial expectation, an increase in strain
is not indicated by the distortion of the benzene ring.
The differences in the bridges of both cyclophanes are more
1
striking. First of all, the H NMR spectra taken both at room
temperature and at -60 °C showed a frozen conformation of
the bridge,8 with the nitrogen atom pointing away from the
cyclophane benzene ring (see Figure 1; the eight-membered-
ring containing the nitrogen possesses a chair-chair conforma-
tion). This is in contrast to the all-carbon analogue 1, in which
an 85:15 equilibrium between the chair-chair and the boat-
(1) Jenneskens, L. W.; Klamer, J. C.; de Boer, H. J. R.; de Wolf, W. H.;
Bickelhaupt, F.; Stam, C. H. Angew. Chem. 1984, 96, 236-237.
(2) (a) von Braun, J.; Neumann, L. Chem. Ber. 1919, 52, 2015-2019.
(b) Shea, K. J.; Burke, L. D.; Doedens, R. J. J. J. Am. Chem. Soc. 1985,
107, 5305-5306.
(3) Ishino, Y.; Nishiguchi, I.; Kim, M.; Hirashima, T. Synthesis 1982,
740-742.
(4) The spectroscopic and analytical data ((0.4% for, C, H, Cl, and N)
for all new compounds are in accord with the assigned structures (see
Supporting Information).
(5) Baldew, A. U. Ph.D. Thesis, Vrije Universiteit, Amsterdam, The
Netherlands, 1993; pp 102-103.
(6) Crystal data of 8: C17H17NSO2Cl2, Mr ) 370.30, orthorhombic,
spacegroup P212121, a ) 6.7855(5) Å, b ) 10.5456(4) Å, c ) 23.4215(13)
Å, V ) 1675.98(17) Å3, Dx 1.4676(1) g cm-3, Z ) 4, T ) 150 K, R )
0.0478 for 3836 reflections with I > 2σ(I).
(7) (a) Krieger, C.; Liebe J.; Tochtermann, W. Tetrahedron Lett. 1983,
707-710. (b) Tobe, Y.; Kakiuchi, Y.; Odaira, Y.; Hosaki, T.; Kai, Y.; Kasai,
N. J. Am. Chem. Soc. 1983, 105, 1376-1377. (c) Tobe, Y.; Ueda, K.;
Kakiuchi, Y.; Odaira, Y.; Kai, Y.; Kasai, N. Tetrahedron 1986, 42, 1851-
1858.
(8) 1H NMR (400 MHz, CDCl3, rt): δ 7.56 (d, J ) 8.3 Hz, 2 H), 7.17
(d, J ) 8.3 Hz, 2 H), 6.67 (s, 2 H), 4.24 (A part of AB-system, JAB ) 13.1
Hz, J ) 11.2 Hz, 3.1 Hz, 2 H), 3.73 (A part of AB-system, JAB ) 14.5 Hz,
J ) 2.7 Hz, 2.6 Hz, 2 H), 2.51 (B part of AB-system, JAB ) 13.0 Hz, J )
2.1 Hz, 1.9 Hz, 2 H), 2.32 (s, 3 H), 2.51 (B part of AB-system, JAB ) 14.5
Hz, J ) 11.2 Hz, 2.2 Hz, 2 H).
S0002-7863(96)03498-1 CCC: $14.00 © 1997 American Chemical Society

616 J. Am. Chem. Soc., Vol. 119, No. 3, 1997
Communications to the Editor
chair conformations was observed at low temperature.9 The
increased rigidity may be attributed to the shortening of the
bridge caused by the shorter C-N bond lengths (1.486(4) Å in
8 versus 1.566(3) Å in 1).1 In 1, the C-C-C bond angles in
the bridge vary from 120° at the homobenzylic group to 122°
at the central methylene group. This implies a large amount of
angle strain for a bridge consisting of sp3-hybridized carbon
atoms. In 8, the C-C-N bond angle is 114.9(2)°, which
indicates a decrease in angle strain at the homobenzylic
methylene carbons. The C-N-C bond angle is 121.9(2)°,
identical with the corresponding angle in 1, but larger than the
C-N-C bond angle of about 114° in the unstrained N,N-
dimethyl-p-toluenesulfonamide.10a Sulfonamides are more flex-
ible than methylene groups in adjusting their bond angles; in
the former, the C-N-C angles can range from 107° to 118.5°
in both cyclic10 b-h and acyclic10a,i sulfonamides. The C-C-C
bond angles at the benzylic carbon atoms (104.0° averaged),
however, are nearly equal to those reported for 1 (104.7°).1 In
addition, the elimination of some H-H repulsion in the bridge
when replacing a methylene group by a sulfonamide group will
help in decreasing the total strain in the bridge.
Scheme 2a
a (a) TCNE, CDCl3, rt, 12 h; R ) CN.
When 8 was reacted with dienophiles such as dimethyl
acetylenedicarboxylate (DMAD) or tetracyanoethylene (TCNE),
either no reaction (DMAD) or a slow reaction (TCNE) was
observed (Scheme 2). This is only partly due to the presence
of the two chlorine substituents, since 1 also exhibits a lower
reactivity than the parent [5]metacyclophane.12 However, when
TCNE (<1 equiv) was added to an NMR solution containing
both 8 and 1, the all carbon analogue 1 reacted more than five
times faster than 8. The most probable cause of the lack of
reactivity of 8 must be the aforementioned relief of strain in
the bridge, compared to that of 1, since both the benzene rings
of 8 and 1 display similar deformations from planarity.
This unpredicted decrease in overall strain of 8 compared to
1 is reflected in the high thermal stability and low (chemical)
reactivity of 8. In 1 and similar [5]metacyclophanes, the
benzene ring undergoes Diels-Alder additions with dienophiles
at room temperature as a consequence of considerable strain
release.11
Acknowledgment. The authors thank Dr. F. J. J. de Kanter and
Dr. B. L. M van Baar for the 400 MHz NMR and HR-MS measure-
ments, respectively. This work was financially supported by SON/
NWO (N.V., A.L.S.).
(9) Turkenburg, L. A. M.; de Wolf, W. H.; Bickelhaupt, F.; Cofino, W.
P.; Lammertsma, K. Tetrahedron Lett. 1983, 24, 1821-1824.
Supporting Information Available: Experimental procedures and
spectral data ; tables of atomic coordinates, thermal parameters, bond
lengths, and bond angles (17 pages). See any current masthead page
for ordering and Internet access instructions.
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H.; Massa, W.; Lumm, M.; Baum, G. Angew. Chem. 1985, 97, 859-860.
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JA9634987
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