New cyclic aminals derived from rac-trans-1,2-diaminocyclohexane: Synthesis and crystal structure of racemic 1,8,10,12-tetraazatetracyclo[8.3.1.1. 8,1202,7] pentadecane and a route to its enantiomerically pure (R,R) and (S,S) isomers

Article abstract of DOI:10.1016/j.tetlet.2011.11.046

New enantiomerically pure macrocyclic aminals (2R,7R)- and (2S,7S)-1,8,10,12-tetraazatetracyclo[8.3.1.1.^8,120 ^2,7]pentadecane (4a and 4b) were obtained by a three component reaction between their respective pure enantiomer of trans-1,2- diaminocyclohexane, ammonia, and formaldehyde. Additionally, the X-ray structure of the racemic compound 4 and the specific rotations of the racemic and optically pure compounds were determined. To further understand the synthetic utilities of enantiomers 4a and 4b, Mannich-type reactions with 1H-benzotriazole were performed, affording (3aR,7aR)- and (3aS,7aS)-1,1′-{[2,3,3a,4,5,6,7, 7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene)}bis-1H-benzotriazole (9 and 10) and allowing for new possibilities related to the preparation of chiral ligands for asymmetric catalysis.

Full text of DOI:10.1016/j.tetlet.2011.11.046

Tetrahedron Letters 53 (2012) 345–348
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
New cyclic aminals derived from rac-trans-1,2-diaminocyclohexane: synthesis
and crystal structure of racemic 1,8,10,12-tetraazatetracyclo[8.3.1.1.8 0 ]
pentadecane and a route to its enantiomerically pure (R,R) and (S,S) isomers
,12 2,7
a,
⇑
a
a
b
b
Augusto Rivera , Diego Quiroga , Leonardo Jiménez-Cruz , Karla Fejfarová , Michal Dušek
a
Departamento de Química, Universidad Nacional de Colombia, Ciudad Universitaria, Carrera 30 No. 45-03, Bogotá, D.C., Colombia
Institute of Physics ASCR, v.v.i., Na Slovance 2, 182 21 Praha 8, Czech Republic
b
a r t i c l e i n f o
a b s t r a c t
Article history:
New enantiomerically pure macrocyclic aminals (2R,7R)- and (2S,7S)-1,8,10,12-tetraazatetracy-
Received 26 September 2011
Revised 7 November 2011
Accepted 10 November 2011
Available online 18 November 2011
8,12 2,7
clo[8.3.1.1.
0
]pentadecane (4a and 4b) were obtained by a three component reaction between their
respective pure enantiomer of trans-1,2-diaminocyclohexane, ammonia, and formaldehyde. Additionally,
the X-ray structure of the racemic compound 4 and the specific rotations of the racemic and optically pure
compounds were determined. To further understand the synthetic utilities of enantiomers 4a and 4b, Man-
nich-type reactions with 1H-benzotriazole were performed, affording (3aR,7aR)- and (3aS,7aS)-1,
Keywords:
0
1
-{[2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene)}bis-1H-benzotriazole (9
1
,2-Diaminocyclohexane
and 10) and allowing for new possibilities related to the preparation of chiral ligands for asymmetric
catalysis.
Cyclic aminal
Chiral cyclic aminal
X-ray diffraction
Ó 2011 Elsevier Ltd. All rights reserved.
Benzotriazole derivative
Cyclic aminals for instance 1,3,6,8-tetraazatricyclo[4.4.1.13,8
]
We have previously reported that aminal 1,3,6,8-tetraazatricy-
3
,8
dodecane 1 are compounds with interesting electrophilic and
clo[4.3.1.1 ]undecane (TATU) 3 can be readily obtained by the
simple reaction of 1 with ammonium fluoride at room tempera-
1
nucleophilic behavior. As part of our ongoing interest in the chem-
4
istry of cyclic aminals, we started a detailed study with the
ture. Therefore, compound 2 was reacted with ammonium fluo-
8
,12 2,7
macrocyclic aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo
ride to afford racemic 1,8,10,12-tetraazatetracyclo[8.3.1.1.
0
]
8
,17 2,7 11,16
5a
[
8.8.1.1 .0 .0
condensation reaction procedure
diaminocyclohexane and formaldehyde.
]icosane 2, which was obtained via a known
pentadecane 4 as a white solid in good yield. Interestingly, by
using ammonium chloride, we were also able to obtain similar re-
sults. Based on these results, we presume the reaction must elapse
in a similar manner as that observed for aminal 1, which we have
2,3
between racemic trans-1,2-
4
b
previously described in the literature.
N
N
N
To assign the structure of product 4, detailed NMR studies,
including COSY, NOESY, and HSQC experiments were performed.
Efforts were made to crystallize this compound and X-ray crystal-
lography of a single crystal of 4 not only confirmed the expected
structure but also revealed that the crystal consists of a racemic
N
N
N
N
N
N
N
N
N
1
2
3
pair of enantiomers namely (2R,7R) and (2S,7S)-1,8,10,12-tetraaza-
N
N
N
8,12 2,7
tetracyclo[8.3.1.1.
0
]pentadecane (4a, 4b).
The structures of 4a and 4b in the racemic mixture were deter-
mined by X-ray crystallography (Figs. 1 and 2). The packing of 4 in
N
N
N
N
N
N
6
N
N
N
the crystal lattice shows that each enantiomer links by intermolec-
ular hydrogen bond interactions between the nitrogen atoms and
H O molecules, and the molecules are connected into trimers by
2
R,R
S,S
4b
4
a
5
interacting with the diamine moiety. The water and aminal mole-
cules of 4 are alternately linked. Overall, these results show a new
example of the formation of hydrates in amine cages. New hy-
drates are of particular interest because they allow for further mor-
phological studies of water clusters, and they can be utilized as
⇑
Corresponding author. Tel.: +57 1 3165000; fax: +57 1 3165220.
E-mail address: ariverau@unal.edu.co (A. Rivera).
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.046

3
46
A. Rivera et al. / Tetrahedron Letters 53 (2012) 345–348
+
+
N
-
HO
HO
COO H N
3
(
CH O)
2
n
N
N
+ 2NH
3
N
-
r.t., 8h
COO H N
3
R,R
R,R
4a
N
HCl H N
2
(
CH O)
2
n
N
N
N
+ 2NH
3
r.t., 8h
HCl H N
2
S,S
S,S
4b
Scheme 1. Three component condensations for the synthesis of 4a and 4b.
1
,2-diaminocyclohexane using the method described by Larrow
Figure 1. Molecular structure for 4. Displacement ellipsoids are drawn at 50%
probability label.
and Jacobsen (
acid).
According to the method above, pure trans-(R,R)-1,2-diamino-
cyclohexane [ -(+) tartrate] salt precipitated which was isolated
in a 43% yield by filtration. Additionally, after the addition of a
large excess of -(+)-tartaric acid, the removal of water under re-
duced pressure and the addition of concentrated HCl and acetone
to the filtrate, the trans-(S,S)-diamino cyclohexane enantiomer
was obtained as a hydrochloride salt in a 28% yield after filtration.
We next focused on the use of these enantiomerically pure dia-
mines in syntheses of the desired enantiomerically pure 4a and
4b. To our satisfaction, we found that the application of the afore-
mentioned method gave the expected condensation products 4a
and 4b in moderate yields (Scheme 1). The major impurity found
was urotropine in low yields (10% yield) and as desired, aminal
2 was not afforded. Unfortunately, to date, it has not been possible
to grow suitable, single crystals of 4a or 4b for X-ray structural
analysis.
Although the mechanism of this reaction remains speculative,
our studies on the reaction between the diamines and formalde-
L-(+)-tartaric acid in a mixture of water and acetic
versatile, cage-like building blocks for the construction of coordi-
L
7
nation polymers due to their behaviors as N-donor ligands.
With this racemic mixture in hand, we attempted to separate
the two isomers, but all of our attempts were unsuccessful. In
L
8
the meantime, Kuznetsov et al. reported that condensation of a
mixture of formaldehyde, ammonia, and aromatic 1, 2-diamines
yielded not only hexamethylenetetramine and condensation prod-
ucts from formaldehyde and diamines but also products similar to
1
,5:3,7-dimethano-1,3,5,7-benzotetrazonine 5. Because the previ-
8
ous reports have shown that reacting optically active trans-1,2-
diaminocyclohexane with four molecules of formaldehyde does
not form the respective diastereomers for 2,2 simple analogy sug-
gests that a similar three-component reaction between formalde-
hyde, ammonia, and (R,R) or (S,S)-trans-1,2-diaminocyclohexane
should obtain enantiomerically pure 4a and 4b, respectively, in a
one pot reaction.
,3
5b
It is known that the enantiomers of trans-(rac)-1,2-diaminocy-
clohexane can be separated by resolution via diastereomeric tar-
hyde allowed us to propose that the pathway of the reaction in-
volves the formation of methylolamines and not imines.
9
10
trates. Based on the protocol in the literature, the desired
A
resolution of relatively inexpensive trans-(rac)-1,2-diaminocyclo-
plausible pathway involving methylolamines intermediates is de-
picted in Scheme 2. In this scheme, we proposed that (R,R)-1,2-
diaminocyclohexane is liberated in the basic media employed
hexane was accomplished with
L-(+)-tartaric acid. Furthermore,
we successfully separated the (R,R)- and (S,S)-isomers of trans-
Figure 2. Invisible hydrogen bond interactions between water molecules and enantiomers 4a,b.

A. Rivera et al. / Tetrahedron Letters 53 (2012) 345–348
347
OH
NH
OH
N
+
-
-
HO
H N
HO
COO
3
-
NH
NH
H N
2
OH H N
NH2
2 CH O
2
2
2 CH O
N
N
2
N
N
N
+
+
-2 H O
-2 H O
2
2
N
H
HO
COO H N
H N
2
3
4a
7
OH
6
8
Scheme 2. Proposed mechanism for forming compounds 4a or 4b.
N
N
N
N
N
N
N
N
N
N
1
,4-dioxane, water
N
N
N
+ 2
N
Δ
N
H
R,R
3
aR,7aR
4
a
9
N
N
N
N
N
N
N
N
N
N
N
N
N 1,4-dioxane, water
+ 2
N
N
H
Δ
S,S
3
aS,7aS
10
4
b
Scheme 3. Synthesis of (3aR,7aR)-and (3aS,7aS)-enantiomers (9 and 10).
0
and then reacts with 2 equiv of formaldehyde to afford N,N -dime-
thylol-(R,R)-1,2-diamino cyclohexane 7.
4b have not only opened avenues related to the preparation of
chiral ligands for asymmetric catalysis i.e. salans but they have also
allowed for the obtention of other chiral complexes through the
developed benzotriazole methodology.
As is known, methanediamine 6 is an intermediate commonly
observed during the reaction between ammonia and formaldehyde
in the formation of cyclotrimethylenetriamine because during the
condensation reaction with formaldehyde and ammonia, urotropine
Acknowledgments
1
1
is formed. Fortunately; this urotropine formation is likely inhib-
ited by the condensation reaction between 6 and 7. Specifically, con-
densation occurs with 2 equiv of formaldehyde affording the
intermediate 8. The latter then undergoes an intramolecular con-
densation to eliminate 2 equiv of water, leading to the aminal 4a.
Notably, the aminals that are derived from a chiral vicinal dia-
mine have the potential to serve as privileged structural elements
We acknowledge the Dirección de Investigaciones, Sede Bogotá
(DIB) de la Universidad Nacional de Colombia for the financial sup-
port of this work, as well as the Institutional Research Plan No.
AVOZ10100521 of the Institute of Physics and the Praemium Aca-
demiae Project of the Academy of Sciences of the Czech Republic.
D.Q. and L.J-C. also acknowledge the Vicerrectoría Académica de
la Universidad Nacional de Colombia for the fellowships provided.
1
2
in the search for chiral catalysts and other relevant compounds.
Therefore, to further explore the reactivity of aminals 4a and 4b,
they were used in a Mannich reaction with 1H-benzotriazole
References and notes
(
Scheme 3). A simple addition of the aminal ((R,R)-4a or (S,S)-4b)
1
.
(a) Alexakis, A.; Lensen, N.; Mangeney, P. Tetrahedron Lett. 1991, 25, 1171–
174; (b) Alexakis, A.; Sedrani, R.; Normant, J. F.; Mangeney, P. Tetrahedron:
to a stirred solution of 1H-benzotriazole in dioxane/water (3:2) fol-
lowed by refluxing for 8 h and cooling to ambient temperature,
gave (3aR,7aR)- and (3aS,7aS)-1,1 -{[2,3,3a,4,5,6,7,7a-octahydro-
1
1
Asymmetry 1990, 1, 283–286; (c) Gosiewska, S.; Soni, R.; Clarkson, G. J.; Wills,
M. Tetrahedron Lett. 2010, 51, 4214–4217; (d) Rivera, A.; Maldonado, M.;
Núñez, M. E.; Joseph-Nathan, P. Heterocycl. Commun. 2004, 10, 77–80; (e)
Rivera, A.; Gallo, G. I.; Joseph-Nathan, P. Synth. Commun. 1997, 27, 163–168; (f)
Rivera, A.; Quevedo, R. Tetrahedron Lett. 2004, 45, 8335–8338; (g) Rivera, A.;
Gallo, G. I.; Gayón, M. E.; Joseph-Nathan, P. Synth. Commun. 1993, 23, 2921–
0
H-1,3-benzimidazole-1,3-diyl]bis (methylene)}bis-1H-benzotria-
13
zole (9 and 10) in a 65% and a 60% yields, respectively.
In summary, we have synthesized a new aminal cage 4 by two
different methodologies. Both afforded 4 as a racemic mixture with
a difficult resolution. X-ray crystallography of a single crystal of 4
confirmed the structure as a racemic pair of enantiomers ((R,R)-
2929; (h) Rivera, A.; Ríos-Motta, J.; Quevedo, R.; Joseph-Nathan, P. Rev. Colomb.
Quím. 2005, 34, 105–115.
Murray-Rust, P.; Riddell, F. G. Can. J. Chem. 1975, 53, 1933–1935.
2
.
3. Glister, J.; Vaughan, K.; Biradha, K.; Zaworotko, M. J. J. Mol. Struct. 2005, 749,
4
a and (S,S)-4b). We also have identified a new one-pot three com-
ponent synthesis for preparing enantiomerically pure aminals
R,R)-4a and (S,S)-4b. The synthesis of aminals (R,R)-4a and (S,S)-
78–83.
4
.
(a) Rivera, A.; Núñez, M. E.; Morales-Ríos, M. S.; Joseph-Nathan, P. Tetrahedron
Lett. 2004, 45, 7563–7565; (b) Rivera, A.; Núñez, M. E.; Avella, E.; Ríos-Motta, J.
Tetrahedron Lett. 2008, 49, 2154–2158.
(

3
48
A. Rivera et al. / Tetrahedron Letters 53 (2012) 345–348
8
,17 2,7 11,16
5
.
(a) Reaction of (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo [8.8.1.1 .0 .0
]
6. (a) Crystal data for compound 4, 3(C11
Xcalibur Atlas Gemini ultra diffractometer using the following parameters:
Oxford Diffraction at 120 K, M = 661, monoclinic, C2/c, a = 25.985(3) Å, b =
11.9676(13) Å, c = 12.2514(15) Å, V = 3441.9(8) Å , Z = 4, Dx = 1.275 Mg m
CuK X-ray source (radiation), k = 1,5418 Å, and F(000) = 1448 colorless prism
H
20
N
4
)ꢂ2(H
2
O), were collected using an
icosane 2 with ammonium fluoride: A solution of ammonium fluoride (74 mg,
2
1
mmol) in water (5.0 mL) was added to
a
solution of (2R,7R,11S,16S)-
]icosane 2 (276 mg, 1 mmol)
in ethanol (10.0 mL). The reaction mixture was stirred at room temperature for
h, after which the solvent was slowly evaporated at room temperature over a
period of about 1 week, and the solid residue was extracted with chloroform
r
,8,10,17-tetrazapentacyclo[8.8.1.1. 0.2,70
8
,17
11,16
3
ꢃ3
,
a
8
0.39 ꢀ 0.03 ꢀ 0.01 mm. All non-hydrogen atoms were refined with anisotropic
2
thermal parameters using full-matrix least squares procedures on F to give
(
3 ꢀ 5.0 mL). The organic layer was dried over anhydrous sodium sulfate,
R = 0.074, wR = 0.187 for 2282 independently observed reflections and 220
parameters. Crystallographic data (excluding structural factors) for the given
structure in this LETTER have been deposited at the Cambridge
Crystallographic Data Centre (CCDC) as supplementary publication number
CCDC 844994. Copies of these data can be obtained, free of charge, upon
request to the CCDC at 12 Union Road, Cambridge. CB2 IEZ, UK. Fax: +44
(0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk. Program used to refine
structure: (b) Pet rˇ í cˇ ek, V.; Dus eˇ k, M.; Palatinus, L. JANA2006. Institute of
Physics, Praha, Czech Republic. 2006.
filtered, and the solvent was evaporated under reduced pressure. The crude
reaction product was purified by column chromatography on Silica gel, eluting
with a chloroform–methanol (7:3) to afford racemic compound 4 (mp 78–
8
1
1
0 °C, an 85% yield): H NMR (400.1 MHz, CDCl
3
): d 1.31 (m, 2H), 1.40 (m, 2H),
2
.80 (m, 2H), 1.85 (m, 2H), 2.60 (d, J = 8.8 Hz, 2H), 3.84 (dd,
gem
J =
4
2
4
1
3.4 Hz, J
w
= 1.2 Hz, 2H), 4.01 (dd,
J
gem = 14.0 Hz, J
w
= 1.2 Hz, 2H), 4.57 (dd,
2
4
2
4
13
J
gem = 14.0 Hz, J
w
= 1.6 Hz, 2H), 4.59 (dd,
J
gem = 13.4 Hz, J
w
= 1.6 Hz, 2H).
C
3
NMR (100.6 MHz, CDCl ): d 26.27, 34.06, 65.59, 75.12, 78.29. The sign of the
optical rotation was determined with a polarimeter model ADP440+ from
Bellingham and Stanley (Bogotá, Colombia) and the value is the average of ten
7. (a) Laus, G.; Kahlenberg, V.; Wurst, K.; Lörting, T.; Schottenberger, H. Cryst. Eng.
Comm. 2008, 10, 1638–1644; (b) Kirillov, A. M. Coordin. Chem. Rev. 2011, 255,
1603–1622.
8. (a) Kuznetsov, A. I.; Shukkur, A. H.; Kamara, K. Russ. Chem. Bull., Int. Ed. 2007, 56,
563–565; (b) Kuznetsov, A. I.; Shukkur, A. H.; Kamara, K. Russ. Chem. Bull., Int.
Ed. 2008, 57, 1575–1577.
2
0
measures,
diaminocyclohexane[
½
a
ꢁ
=-12.0 (c 0.6; CH
2
Cl
-(+)-tartrate]salt, ammonia, and formaldehyde: trans-(R,R)-
,2-diaminocyclohexane [ -(+)-tartrate] salt (264 mg, 1.0 mmol) was mixed
25% aqueous solution of ammonia (1.1 mL, 7 mmol) and
2
). (b) Reaction of trans-(R,R)-1,2-
D
L
1
L
with
a
paraformaldehyde (150 mg, 5 mmol) was added in small portions with
vigorous stirring for 1 h. The reaction mixture was stirred at room
9. Larrow, J. F.; Jacobsen, E. N. Org. Synth. 1997, 75, 1.
10. Rivera, A.; Ríos-Motta, J. Tetrahedron Lett. 2005, 46, 5001–5004.
11. (a) Richmond, H. H.; Myers, G. S.; Wright, G. F. J. Am. Chem. Soc. 1948, 70, 3659–
3664; (b) Nielsen, A. T.; Moore, D. W.; Ogan, M. D.; Atkins, R. L. J. Org. Chem.
1979, 44, 1678–1684.
temperature for 8 h, and the product was extracted with CHCl
The extract was concentrated under reduced pressure and the residue was
purified by column chromatography on Silica gel and eluted with
3
(4 ꢀ 5 mL).
a
chloroform–methanol
(7:3)
mixture,
to
afford
(2R,7R)-1,8,10,12-
12. Rondot, C.; Zhu, J. Org. Lett. 2005, 7, 1641–1644.
13. Preparations of (3aR,7aR) and (3aS,7aS)-1,1 -{[2,3,3a,4,5,6,7,7a-octahydro-1H-
tetraazatetracyclo[8.3.1.1.8 02,7]penta decane 4a (mp 68–70 °C, a 60% yield):
,12
0
+
HR-ESI-MS in its positive mode m/z: [M+H] calcd for C11
H
N
21 4
: 209.1766,
1,3-benzimidazole-1,3-diyl]bis(methylene)}bis-1H-benzotriazole (9 and 10):
A
found: 209.1756; The sign of the optical rotation was determined with a
polarimeter model ADP440+ from Bellingham and Stanley (Bogotá, Colombia)
solution of the respective aminal (208 mg, 1,00 mmol) (2R,7R) or (2S,7S)-
1,8,10,12-tetraazatetracyclo [8.3.1.1.8
,12
0
2,7
]pentadecane (4a, 4b), in dioxane
2
0
and the value is the average of ten measures, ½
a
ꢁ
=-51.9 (c 0.6; CH
2
Cl
2
). (c)
(3 mL) and water (4 mL) was added dropwise into a dioxane solution (3 mL)
containing 2 equiv of 1H-benzotriazole (238 mg, 2,00 mmol) in a two-necked
round-bottomed flask. The mixture was refluxed for approximately 8 h or until
the precipitation of a colorless solid. The resulting solid was collected by
D
Reaction of trans-(S,S)-1,2-diaminocyclohexane dihydrochloride salt, ammonia,
and formaldehyde: trans-(S,S)-1,2-diaminocyclohexane dihydro chloride salt
(
7
187 mg, 1.0 mmol) was mixed with 25% aqueous solution of ammonia (1.1 mL,
mmol) and paraformaldehyde (150 mg, 5 mmol) was added in small portions
with vigorous stirring for 1 h. The reaction mixture was stirred at room
temperature for 8 h, and the product was extracted with CHCl
filtration, washed with cold methanol, and dried under vacuum to give the
1
product 9 or 10 (mp 123–124 °C, a 60–65% yield): H NMR (400.1 MHz, CDCl
3
):
3
(4 ꢀ 5 mL). The
d 1. 17 (m, 2H), 1.27 (m, 2H), 1.82 (m, 2H), 2.18 (m, 2H), 2.39 (m, 2H), 4.03 (s,
2
2
extract was concentrated under reduced pressure, and the residue was purified
by column chromatography on Silica gel and eluted with a chloroform–
2H), 5.42 (d,
J
J
J
gem = 14.0 Hz, 2H), 5.47 (d,
Jgem = 14.0 Hz, 2H), 7.36 (dd,
3
3
4
4
H,H = 8.4 Hz, JH,H = 1.6 Hz, 2H), 7.46 (m, 4H), 8.04 (dd,
J
H,H = 8.4 Hz,
13
methanol (7:3) mixture, to afford (2S,7S)-1,8,10,12-tetraazatetracyclo
H,H = 1.6 Hz, 2H). C NMR (100.6 MHz, CDCl ): d 23.86, 28.18, 61.62, 64.85,
3
[
8.3.1.1.8,120 ]penta decane 4b (mp 68–70 °C, a 55% yield): HR-ESI-MS in its
2,7
69.32, 109.37, 119.92, 123.96, 127.66, 133.74, 145.80. The sign of the optical
rotation was determined with a polarimeter model ADP440+ from Bellingham
and Stanley (Bogotá, Colombia) and the value is the average of ten measures:
+
positive mode m/z: [M+H] calcd for C11
H
N
21 4
: 209.1766, found: 209.1756; The
sign of the optical rotation was determined with a polarimeter model ADP440+
from Bellingham and Stanley (Bogotá, Colombia) and the value is the average of
2
0
for the (3aR,7aR) enantiomer 9: ½
a
ꢁ
D
2 2
=-42.6 (c 0.3; CH Cl ); for the (3aS,7aS)
2
0
20
ten measures, ½
aꢁ
= +52.0 (c 0.6; CH
2
2
Cl ).
enantiomer 10: ½
aꢁ
D
2 2
=+45.5 (c 0.5; CH Cl ).
D