Synthesis and crystal structure of 2-amino-4,6,6-trimethyl-cyclohex-2-en-1, 1,3,4(S)-tetracarbonitrile

Article abstract of DOI:10.1007/s10870-010-9966-5

Crystal structure analysis of the novel 2-amino-4,6,6-trimethyl-cyclohex-2- en-1,1,3,4(S)-tetracarbonitrile, obtained in 70% yield, by the Bi(OTf) ₃ catalyzed reaction of acetone and malononitrile, at room temperature, is described. For the fir

Full text of DOI:10.1007/s10870-010-9966-5

J Chem Crystallogr (2011) 41:742–746
DOI 10.1007/s10870-010-9966-5
ORIGINAL PAPER
Synthesis and Crystal Structure of 2-Amino-4,6,6-trimethyl-
cyclohex-2-en-1,1,3,4(S)-tetracarbonitrile
•
•
•
Nitu Mahajan Pinki Kotwal Vivek K. Gupta
T. K. Razdan
Received: 13 August 2009 / Accepted: 31 December 2010 / Published online: 11 January 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Crystal structure analysis of the novel 2-amino-
4,6,6-trimethyl-cyclohex-2-en-1,1,3,4(S)-tetracarbonitrile,
obtained in 70% yield, by the Bi(OTf)3 catalyzed reaction
of acetone and malononitrile, at room temperature, is
described. For the first time Bi(OTf)3–Et3N has been used
in this inverse electron demand Diels–Alder cycloaddition
reaction involving the participation of carbonitrile p-bond.
The structure of the molecule was established by spectral
analysis and X-ray diffraction studies. The compound
crystallizes in the monoclinic space group P21/n with unit
cell parameters: a = 8.0580 (17), b = 13.038 (3), c =
Introduction
Cyclohexenes are ubiquitous in nature. A large number of
polysubstituted cyclohexanes are associated with bioac-
tivity [1–3]. Polyfunctionalized cyclohexanes, especially
bearing nitrogen functionalities serve as important syn-
thons for the preparation of bioactive nitrogen heterocyclic
compounds. The most popular method for the preparation
of cyclohexenes is the transition metal catalyzed Diels–
Alder cycloaddition reaction [4, 5]. Although, this reaction
has been carried out with a variety of substrates, including
electron rich dienes and dienophiles [6–9], the direct par-
ticipation of conjugated carbonitrile p-bonds in the cyclo-
addition reaction has not been reported so far.
˚
12.641 (3) A, b = 101.883 (4)°, Z = 4. The crystal struc-
ture was solved by direct methods and refined to
R = 0.0506 for 2,456 observed reflections. The cyclohex-
ene ring of the molecule adopts a distorted sofa confor-
mation. The molecules in the unit cell are arranged in
layers. The crystal structure in stabilized by C–H_N and
N–H_N interactions.
Earlier, the versatility of Bi(III) salts in bringing about
single-pot tandem reactions leading to polysubstituted
nitrogen heterocycles has been demonstrated in our labo-
ratory [10–13]. Herein, we report the Bi(III) triflate-
triethylamine catalyzed one-pot tandem reaction of acetone
and malononitrile, at room temperature, to afford novel
2-amino-4,6,6-trimethyl-cyclohex-2-en-1,1,3,4(S)-tetracar-
bonitrile. The reaction may involve the intermolecular
inverse electron demand Diels–Alder reaction [6], with the
participation of carbonitrile p-bonds, of conjugated dicar-
bonitriles, formed in situ.
Keywords Bismuth triflate-triethylamine Á Inverse
electron demand Diels–Alder reaction Á Crystal structure Á
Sofa Á Direct methods Á Hydrogen bonding
Experimental
N. Mahajan Á T. K. Razdan
Synthesis
P.G. Department of Chemistry, University of Jammu,
Jammu Tawi 180 006, India
A mixture of acetone and malononitrile (1 9 10-2 mol
each) in acetonitrile (10 mL) and Bi(OTf)3 (20 mol.%) and
Et3N (1 9 10-2 mol, 1 mL) was stirred at room tempera-
ture (25–28 °C). On completion of the reaction (TLC)
P. Kotwal Á V. K. Gupta (&)
P.G. Department of Physics, University of Jammu,
Jammu Tawi 180 006, India
e-mail: vivek_gupta2k5@yahoo.co.in
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J Chem Crystallogr (2011) 41:742–746
743
(24 h), the solvent was evaporated under reduced pres-
sure. The residue was taken in ethyl acetate and filtered.
The filtrate on distillation of the solvent afforded colorless
crystalline product 1. It was purified by flash chroma-
tography on silica gel using CH2Cl2–EtOAc (9:1 v/v) as
solvent system. The compound was re-crystallized from
hot methanol (yield 70%). Single crystals for X-ray
analysis were obtained by slow evaporation of the acetone
solution.
Table 1 Crystal data and other experimental details
CCDC number
733563
Crystal description
Crystal size
Colorless rectangular
0.3 9 0.2 9 0.1 mm
Empirical formula
Formula weight
C
13H13N5
239.28
Mo Ka, 0.71073 A
˚
Radiation, wavelength
Unit cell dimensions
a = 8.0580 (17), b = 13.038 (3),
˚
c = 12.641 (3) A
Compound 1 was analyzed for C13H13N5 (calculated C
65.27, H 5.47, N 29.28%; found C 65.14, H 5.35, N
29.16%). It exhibited the following spectral data. IR (KBr):
b = 101.883 (4)°
Monoclinic
P21/n
Crystal system
Space group
1
tmax cm-1 3354 (NH2), 2214 (C:N), 1588 (–C=C–). H
3
˚
Unit cell volume
1299.6 (5) A
NMR (JEOL FT-NMR AL-300 MHZ, CDCl3): dH 1.35 (d,
J = 1.7 Hz, 6H, gem. CH3 9 2), 1.39 (s, 3H, CH3), 1.95
(s, 2H, CH2), 5.31 (s br, 2H, exch. D2O, NH2); 13C-NMR
(125 MHZ, CDCl3): dC 20.4, 25.1, 26.8, 27.0, 27.9, 40.1,
46.9, 95.7, 112.3, 112.9, 113.4, 114.5, 166.8. HRMS (JEOL
inst.) rel. int.): m/z (%) 239.1123 (100) (M?), 213 (42), 183
(33), 113 (58), 93 (45), 56 (34). For the scale up of the
reaction, 1.25 mol each of acetone and malononitrile was
reacted under identical reaction conditions when 12.0 g
(approx. 70%) of the product 1 was obtained.
Number of molecules
per unit cell, Z
4
Temperature
100 (2) K
0.079 mm-1
504
Absorption coefficient
F(000)
h range for entire data collection 2.27° \ h \ 28.33°
Reflections collected/unique 8206/3130
Reflections observed (I [ 2r(I)) 2456
Refinement
Full-matrix least-squares on F2
Number of parameters refined
Final R factor
wR(F2)
215
0.0506
0.1204
1/[r2(F2o) ? (0.0715P)2 ?
0.2790P] where
Crystal Structure Determination and Refinement
Weight
P = [F2o ? 2F2c]/3
X-ray intensity data of 8,206 reflections (of which 3,130
unique) were collected at room temperature on Bruker
CCD area-detector diffractometer equipped with graphite
Goodness-of-fit
1.001
(D/r)max
0.001 (for y H521)
-3
˚
˚
monochromated Mo Ka radiation (k = 0.71073 A). The
Final residual electron density
-0.225 \ Dq \ 0.350 e A
crystal used for data collection was of dimensions
0.3 9 0.2 9 0.1 mm. The cell dimensions were deter-
mined by least-square fit of angular settings of 2,484
reflections in the h range 2.76°–28.14°. The intensities
were measured by / and x scan mode for h ranges
2.27°–28.33°. 2,456 reflections were treated as observed
(I [ 2r(I)). Data were corrected for Lorentz and polarisa-
tion factors. The structure was solved by direct methods
using SHELXS97 [14]. All non-hydrogen atoms of the
molecule were located in the best E-map. Full-matrix least-
squares refinement was carried out using SHELXL97 [14].
All the hydrogen atoms were located on a difference
electron density map and their positional and isotropic
thermal parameters were included in the refinement. The
final refinement cycles converged to an R = 0.0506 and
wR (F2) = 0.1204 for the observed data. Residual electron
Results and Discussion
The reaction of equimolar mixture of acetone and malon-
onitrile, at room temperature, in the presence of Bi(OTf)3
and triethylamine afforded novel 2-amino-4,6,6-trimethyl-
cyclohex-2-en-1,1,3,4(S)-tetracarbonitrile 1 (Scheme 1).
The reaction has been scaled up to multi-gram prepa-
ration of compound 1 (see ‘‘Experimental’’ section) with
almost 70% yield.
CN
O
Bi(OTf)3 ( 20 mole %) and Et3N
CH3CN, room temp.,24 hr.
CN
CN
densities ranged from -0.225 to 0.350 e A-3. Atomic
˚
+
NC
NC
CN
scattering factors were taken from International Tables
for X-ray Crystallography (1992, Vol. C, Tables 4.2.6.8
and 6.1.1.4). The crystallographic data are summarized
in Table 1. CCDC-733563 contains the supplementary
crystallographic data for this paper.
NH2
1
Scheme 1 Preparation of 2-amino-4,6,6-trimethyl-cyclohex-2-en-1,1,3,
4(S)-tetracarbonitrile
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J Chem Crystallogr (2011) 41:742–746
Scheme 2 Rationalization of
formation of compound 1
Mechanistically the reaction may be rationalized as to
involve initial condensation of acetone and malononitrile to
form an electron-rich alkene, 2-methyl-prop-1-en-1,1-dicar-
bonitrile. This intermediate compound may undergo tau-
tomeric change followed by intermolecular inverse electron
demand Diels–Alder reaction involving C:N bond
(Scheme 2) to afford compound 1.
This is the first report on the direct preparation of
aminocyclohexene carbonitriles by tandem reaction of
acetone and malononitrile involving the inverse electron
demand Diels–Alder reaction with the participation of
C:N bond in the cycloaddition. Further study on the scope
and limitation of the reaction is in progress.
Selected bond distances, bond angles and torsion angles
are listed in Table 2. An ORTEP view of the title com-
pound with atomic labeling is shown in Fig. 1 [15]. The
geometry of the molecule was calculated using the WinGX
[16] and PARST [17] softwares. Bond lengths and bond
angles of the title compound are comparable to the theo-
retical values as reported by Allen et al. [18]. The cyano
Fig. 1 ORTEP view of the molecule, showing the atom-labelling
scheme. Displacement ellipsoids are drawn at the 50% probability
level and H atoms are shown as small spheres of arbitrary radii
˚
groups mean bond length is 1.143 (2) A, which is similar to
those in cyano-substituted organic ligands [1].
˚
In cyclohexene ring, the C2–C3 distance of 1.366 (2) A
The presence of double bond at C2–C3 imposes a distorted
6b-sofa conformation, with asymmetry parameter DCs
(C3–C6) = 8.26, DC2 (C2–C3) = 15.07 [19]. Atom C6
confirms the localization of a double bond at this position.
˚
deviates by 0.673 (1) A from the mean plane through the
˚
atoms C1–C5. The absolute stereochemistry at chiral centre
C4 is decided on the basis of the slightly enhanced bond
length of the C4–C9 indicating that the methyl group
occupies the equatorial position at C4.
Table 2 Selected bond lengths (A), bond angles (°) and torsion
angles (°) for non hydrogen atoms (esd’s are given in parentheses)
C2–C3
1.3662 (17)
1.1415 (19)
1.1515 (17)
124.58 (11)
178.20 (15)
178.87 (14)
-7.48 (18)
-39.86 (15)
-52.90 (13)
C2–N5
1.3391 (16)
1.1395 (19)
1.1434 (18)
115.95 (11)
176.72 (15)
176.19 (15)
11.84 (17)
60.67 (14)
28.75 (16)
C7–N1
C8–N2
Packing view of the molecules in the unit cell viewed
down the a-, b- and c axis is shown in Figs. 2, 3 and 4,
respectively. Molecules in the unit cell are packed together
to form well defined layers. Molecules within the layers are
arranged in an antiparallel manner. In the crystal the
molecules are linked by two different N–H_N intermo-
lecular hydrogen bonds between amino hydrogen atoms
and carbonitrile nitrogen atoms. In addition, the crystal
C9–N3
C10–N4
N5–C2–C3
N1–C7–C1
N3–C9–C3
C1–C2–C3–C4
C3–C4–C5–C6
C5–C6–C1–C2
N5–C2–C1
N2–C8–C1
N4–C10–C4
C2–C3–C4–C5
C4–C5–C6–C1
C6–C1–C2–C3
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J Chem Crystallogr (2011) 41:742–746
745
Fig. 2 The crystal packing projected on to the bc plane
Fig. 4 The crystal packing projected on to the ab plane
Table 3 Hydrogen-bonding geometry (esd’s in parentheses)
˚
˚
˚
D–H_A
D–H (A) H_A (A) D_A (A) D–H_A (°)
N5–H511_N4i
N5–H521_N3ii
0.92 (2) 2.12 (2)
0.88 (2) 2.18 (2)
C12–H121_N3iii 0.99 (2) 2.59 (2)
3.015 (2) 163 (1)
3.049 (2) 168 (1)
3.462 (2) 147 (1)
Symmetry code: (i) -1/2 ? x, 1/2 - y, 1/2 ? z (ii) -x, -y, 1 - z
(iii) 1/2 ? x, 1/2 - y, 1/2 ? z
of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgment The authors are thankful to Prof. P. K. Bhar-
adwaj, Department of Chemistry, IIT, Kanpur, India, for the use of the
data collection facility.
Fig. 3 The crystal packing projected on to the ac plane
packing exhibits one C–H_N interaction between the
methyl hydrogen and carbonitrile nitrogen atom. The
geometry of N–H_N and C–H_N interactions is given in
Table 3.
References
1. Zhang XM, Lu JT (2007) Acta Crystallogr E63:3861
2. Mehta G, Singh V (1999) Chem Rev 99:881
3. Fillion E, Beingessner RL (2003) J Org Chem 68:9484
4. Nakamura H, Aoyagi K, Shim JG, Yamamoto Y (2001) J Am
Chem Soc 123:372
5. Alonso F, Beletskaya IP, Yus M (2004) Chem Rev 104:3079
6. Wender PA, Rieck H, Fuji M (1998) J Am Chem Soc 120:10976
7. Wender PA, Husfeld CO, Langkopf E, Love JA, Pleuss N (1998)
Tetrahedron 54:7203
Supplementary Material
CCDC-733563 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
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J Chem Crystallogr (2011) 41:742–746
8. Hollis TK, Odenkirk W, Robinson NP, Whelan J, Bosnich B
(1993) Tetrahedron 49:5415
14. Sheldrick GM (1997) SHELX97. University of Gottingen,
Gottingen
9. Zeni G, Larock RC (2004) Chem Rev 104:2285
10. Verma AK, Koul S, Pannu APS, Razdan TK (2007) Tetrahedron
63:8715
11. Verma AK, Koul S, Razdan TK, Kapoor KK (2006) Can J Chem
84:1064
12. Verma AK, Koul S, Razdan TK, Kapoor KK (2006) Tetrahedron
Lett 47:837
13. Verma AK, Koul S, Kapoor KK, Razdan TK (2007) Aust J Chem
60:883
15. Farrugia LJ (1997) J Appl Crystallogr 30:565
16. Farrugia J (1999) J Appl Crystallogr 32:837
17. Nardelli M (1995) J Appl Crystallogr 28:659
18. Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG,
Taylor R (1987) J Chem Soc Perkin Trans II:S1–S19
19. Duax WL, Norton DA (1975) Atlas of steroid structures, vol 1.
Plenum, New York
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