A new stereoselective synthesis of 2-amino-4,5-dihydrothiophene-3- carbonitrile derivatives

Article abstract of DOI:10.1007/s11172-007-0217-7

A new stereoselective method for the synthesis of trans-isomers of 2-amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles was proposed. The method involves base-catalyzed reactions of phenacyl thiocyanate with 3-(het)aryl-2-cyanoprop-2-enethioamides. (4R,5S/4S,5R)-2-Amino-5-benzoyl-4-(2- chlorophenyl)-4,5-ihydrothiophene-3-carbonitrile was structurally characterized by X-ray diffraction analysis.

Full text of DOI:10.1007/s11172-007-0217-7

Russian Chemical Bulletin, International Edition, Vol. 56, No. 7, pp. 1431—1436, July, 2007
1431
A new stereoselective synthesis
of 2ꢀaminoꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitrile derivatives
V. V. Dotsenko,aꢀ S. G. Krivokolysko, A. N. Chernega, and V. P. Litvinov
a
b
c†
aChemEx Laboratory, V. Dal´ EastꢀUkrainian National University,
2
0a Molodyozhny kv., 91034 Lugansk, Ukraine.
Fax: + 380 (0642) 41 9151. Eꢀmail: ksg@lep.lg.ua
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya, 02094 Kiev, Ukraine.
Fax: + 380 (044) 573 2643. Eꢀmail: iochkiev@ukrpack.net
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
b
5
c
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 8837
A new stereoselective method for the synthesis of transꢀisomers of 2ꢀaminoꢀ4ꢀarylꢀ5ꢀ
benzoylꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitriles was proposed. The method involves baseꢀcataꢀ
lyzed reactions of phenacyl thiocyanate with 3ꢀ(het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides.
(
4R,5S/4S,5R)ꢀ2ꢀAminoꢀ5ꢀbenzoylꢀ4ꢀ(2ꢀchlorophenyl)ꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitrile
was structurally characterized by Xꢀray diffraction analysis.
Key words: phenacyl thiocyanate, 3ꢀ(het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides, cyanothioꢀ
acetamide, the Michael reaction, cyclocondensation, Xꢀray diffraction analysis, transꢀ2ꢀaminoꢀ
4
ꢀ(het)arylꢀ5ꢀbenzoylꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitriles.
2
ꢀAminothiophene derivatives most commonly synꢀ
methyl sulfide,14—16 which presents some preparative difꢀ
ficulties. 2ꢀAminoꢀ4,5ꢀdihydrothiophene derivatives can
also be obtained in moderate yields by baseꢀcatalyzed
cyclocondensation of chalcone and ethyl cyanoacetate
1
—3
thesized by the Gewald reaction
trum of useful properties and are convenient synthons
exhibit a broad specꢀ
4
—6
for the synthesis of various heterocyclic compounds.
Partially hydrogenated 2ꢀaminothiophene derivatives
e.g., dihydrothiophenes) are much less studied. Neverꢀ
theless, 2ꢀaminoꢀ4,5ꢀdihydrothiophenes are of interest as
starting materials for the synthesis of not easily accessible
partially hydrogenated thieno[2,3ꢀb]pyridines and ꢀpyriꢀ
midines. Earlier, it has been shown that transꢀ4,5ꢀdisubꢀ
stituted 2ꢀaminoꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitriles
can be obtained by stereoselective tandem Michael
1
8
(or their adduct) with elemental sulfur. All this creates
prerequisites for further investigations of selective and
preparatively convenient methods for the synthesis of
dihydrothiophene derivatives. The stereochemistry of
the aforementioned transꢀ4,5ꢀdisubstituted dihydrothioꢀ
phenes is quite interesting. Mutual transꢀarrangement of
the substituents in positions 4 and 5 is undoubted and
(
7
8
1
4,15
confirmed by both Xꢀray diffraction
and spectroꢀ
addition—1,5ꢀcycloelimination (Ad —E1,5) between
scopic data (the corresponding coupling constant is
N
3
11—16
3
ꢀ(het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides 1 and stabiꢀ
JC(4)H,C(5)H = 0.8—5.2 Hz).
Proceeding further in our investigations of the chemꢀ
9
—14
14—16
lized pyridinium
or sulfonium ylides.
Known
1
7,19
modifications of this synthesis are based on threeꢀcompoꢀ
istry of cyanothioacetamide,
we studied reactions
nent cyclocondensation of cyanothioacetamide, an aldeꢀ
of 3ꢀ(het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides 1 with
phenacyl thiocyanate (2). Earlier, this promising reꢀ
hyde, and an appropriate ylide9
—13
and recyclization of
20
5
ꢀpyridinioꢀ1,4,5,6ꢀtetrahydropyridineꢀ2ꢀthiolate derivaꢀ
agent has been successfully used for the synthesis of
1
1
21—26
27
tives. In the case of pyridinium ylides, the regiodirectivity
of the reaction is temperatureꢀdependent;
of sulfonium ylides, the yields of the target dihydroꢀ
thiophenes are usually low and the reactions are accomꢀ
panied by the formation of byꢀproducts, including diꢀ
functionalized thiazole
and pyridine derivatives. It
1
1,17
in the case
has been found that thioamides 1 easily react with thioꢀ
cyanate 2 in the presence of tertiary amines (triethylamine
or Nꢀmethylmorpholine) to give 2ꢀaminoꢀ4,5ꢀdihydroꢀ
thiopheneꢀ3ꢀcarbonitriles 3 (Scheme 1, method A). The
catalyst nature has no appreciable effect on the yields of
the target dihydrothiophenes (52—54%); however, the
†
Deceased.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1379—1383, July, 2007.
066ꢀ5285/07/5607ꢀ1431 © 2007 Springer Science+Business Media, Inc.
1

1432
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
Dotsenko et al.
Et Nꢀcatalyzed reactions proceed much more rapidly.
Compounds 3a—c are obtained in comparable yields
ment of (het)aryl and benzoyl fragments are most stable.
Two pairs of diastereomeric adducts (6A, 6B and 6C, 6D)
meet this requirement (Scheme 2). Apparently, when the
formation of the diastereomeric pair 6A and 6B is preꢀ
ferred, the reaction occurs as intramolecular nucleophilic
substitution with retention of the adduct configuration.
Elimination of the thiocyanate ion gives enantiomers 3A
and 3B (see Scheme 2, pathway A). The possibility of
nucleophilic displacement of the thiocyanate seems to be
rather unusual, although a number of reactions of this
type have been described earlier (e.g., see Refs 28—30).
The presence of the thiocyanate ion in the reaction mixꢀ
ture was unambiguously confirmed by an analytical test:
several seconds after the addition of a base to a mixture of
compounds 1 and 2, a sample was withdrawn from the
mixture and showed a positive reaction toward a solution
3
(
37—50%) via multicomponent cyclocondensation of apꢀ
propriate aldehydes 4a—c, cyanothioacetamide (5), and
thiocyanate 2; in this case, unsaturated thioamides 1 are
formed in situ (see Scheme 1, method B). The reaction is
stereoselective but not stereospecific, giving only two conꢀ
figurational isomers 3A and 3B with the 4,5ꢀtransꢀarrangeꢀ
ment of the substituents out of four possible diastereomeric
products.
Scheme 1
of FeCl . Neither the starting reagents, nor products, nor
3
catalysts form bloodꢀred complexes with iron(III). Howꢀ
ever, an alternative pathway cannot be completely exꢀ
cluded: intramolecular cyclization of structure 7 (carbꢀ
anionic tautomer of the Michael adduct 6) is followed by
dethiocarbamoylation of intermediate tetrahydrothioꢀ
phene 8 (see Scheme 2, pathway B). In this case, isomeric
dihydrothiophenes 3A and 3B are formed from adducts
6
C and 6D, respectively, with the synꢀclinal arrangeꢀ
ment of the thiocyanato and αꢀcyanoꢀαꢀthiocarbamoylꢀ
methylide groups. Evidence for the possible cyclization
7
→ 8 is provided by numerous examples of reactions of
active methylene compounds with organic thiocyanꢀ
2
3—27
ates,
occurring through an attack of the carbanionic
intermediate on the electrophilic C atom of the N≡C—S
group. Thus, the question of the mechanism of the deꢀ
scribed transformation remains open.
The structures of dihydrothiophenes 3 were confirmed
by elemental analysis and spectroscopic data. For instance,
the IR spectra of the reaction products contain absorption
–
1
bands due to amino, cyano (ν = 2200—2195 cm ), and
–
1
carbonyl groups (ν = 1675—1670 cm ) and show no
–
1
1
bands at 2170—2130 cm (S—C≡N). The H NMR specꢀ
tra of dihydrothiophenes 3 exhibit signals at δ 4.80—4.87
and 5.18—5.20 (C(4) and C(5)H, respectively) as multipꢀ
3
lets or broadened doublets ( J
= 2.9—3.2 Hz)
C(4)H,C(5)H
1
, 3, 4: Ar = 2ꢀClC H (a), 2ꢀfuryl (b), Ph (c);
6 4
B = Nꢀmethylmorpholine, Et N
resulting from overlap of the signals for the protons in
isomeric structures 3A and 3B. Another distinctive feaꢀ
ture of the spectra of compounds 3 is the presence of a
3
Presumably, the first step of the reaction is the formaꢀ
tion of the Michael adduct 6. It should be noted that
broadened singlet for the NH protons (δ 7.01—6.93).
2
(
E)ꢀ2ꢀcyanoꢀ3ꢀ[4ꢀ(dimethylamino)phenyl]propꢀ2ꢀeneꢀ
To elucidate the stereochemical aspects of the reacꢀ
tion and the spatial structures of dihydrothiophenes 3, we
examined compound 3a by Xꢀray diffraction analysis.
We found that the crystal of compound 3a consists of
two crystallographically independent molecules A and B
with very close geometrical parameters. The general
view of structure 3aA with selected geometrical paramꢀ
eters is shown in Fig. 1. The central fiveꢀmembered
S(1)C(1)—C(4) ring is nonplanar (deviations of the atoms
thioamide (1, Ar = 4ꢀMe NC H ), which is inert to
nucleophiles in the Michael reaction because of the strong
donating effect of the Me N group, does not enter into
this reaction. Undoubtedly, the key step that determines
the stereochemistry of products is the formation of adꢀ
duct 6. It is obvious that bulky benzoyl and (het)aryl
substituents will be trans to each other, which is sterically
favorable. Thus, adducts with the antiꢀperiplanar arrangeꢀ
2
6
4
2

2
ꢀAminoꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitriles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
1433
Scheme 2
from the rootꢀmeanꢀsquare plane are 0.138 Å) and exists
in the halfꢀchair conformation: in both molecules, the
S(1)C(1)—C(3) atoms are coplanar to within 0.011 Å,
and the fragment S(1)—C(3)—C(4) makes with this plane
a dihedral angle of 21.0°. For steric hindrances, the benꢀ
zene rings C(6)—C(11) and C(13)—C(18) are rotated relaꢀ
tive to the fiveꢀmembered ring through 74.5° and 72.5° in
molecule A and through 66.5° and 74.5° in molecule B,
respectively. In the crystal, the fiveꢀmembered rings of
molecules A and B make a dihedral angle of 66.5°. The
N(1) atom has a trigonal planar bond configuration (the
sum of the bond angles at this atom is 360° to within the
1.339(4) Å in molecule B) is substantially shorter than the
single N(sp )—C(sp ) bond with characteristic values
2
2
3
1,32
of 1.43—1.45 Å.
In the crystal, molecules 3a are
3
3
united into infinite chains through the hydrogen bonds:
N(1B)—H O(1A) (N—H 0.89(4) Å, N O 2.858(4) Å,
H O 2.04(4) Å; angle N—H—O 152(3)°) and
N(1A)—H O(1B) (N—H 0.86(4) Å, N O 2.856(4) Å,
H O 2.08(4) Å; angle N—H—O 149(3)°) (Fig. 2).
To sum up, baseꢀcatalyzed reactions of phenacyl thioꢀ
cyanate with 3ꢀ(het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides
are a novel and accessible stereoselective route to 4ꢀ
(het)arylꢀ5ꢀbenzoylꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitrile
derivatives obtained as a pair of transꢀdiastereomers.
.
..
...
.
..
.
..
...
.
..
experimental error). The amino N(1)H group is virtually
2
coplanar with the fiveꢀmembered ring (the corresponding
dihedral angle in molecules A and B does not exceed
Experimental
2
.3°). This conformation is very favorable for conjugaꢀ
tion of the lone electron pair of the N(1) atom with
the πꢀsystem of the double C(1)=C(2) bond. Indeed,
the N(1)—C(1) bond (1.342(4) Å in molecule A and
1H NMR spectra were recorded on a Varian Gemini 200
instrument (200 MHz) in DMSOꢀd with Me Si as the internal
6
4
standard. IR spectra were recorded on an IKSꢀ29 spectrophoꢀ

1434
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
Dotsenko et al.
O(1B)
C(16)
C(17)
C(15)
C(18)
b
C(14)
S(1)
N(1B)
C(13)
O(1A)
C(12)
N(1)
O(1)
C(1)
C(2)
C(4)
C(3)
N(1A)
O(1´B)
Cl(1)
C(5)
C(6)
C(7)
C(11)
C(10)
N(2)
c
0
C(8)
C(9)
a
N(1´B)
O(1´A)
Fig. 1. General view of structure 3aA. Selected bond lengths:
S(1)—C(1) 1.759(3) Å, S(1)—C(4) 1.759(3) Å, C(1)—C(2)
1
.348(4) Å, C(2)—C(3) 1.509(4) Å, and C(3)—C(4) 1.557(4) Å;
and bond angles: C(1)—S(1)—C(4) 91.9(2)°, S(1)—C(1)—C(2)
1
1
13.6(2)°, C(1)—C(2)—C(3) 116.7(3)°, C(2)—C(3)—C(4)
05.9(2)°, and S(1)—C(4)—C(3) 107.6(2)°.
N(1´A)
Fig. 2. Crystal packing of compound 3a. Intermolecular
tometer (in Nujol). Elemental analysis was carried out on a
Perkin—Elmer C,H,NꢀAnalyser instrument. The course of the
reaction was monitored and the purity of the compounds obꢀ
tained was checked by TLC on Silufol UV 254 plates in acꢀ
etone—heptane (1 : 1). Spots were visualized in the iodine vapor
or under UV light. Melting points were determined on a Kofler
hot stage and are given uncorrected.
.
..
N—H O hydrogen bonds are indicated with dashed lines; primed
atoms are obtained from the initial atoms via the symmetry
operation code (x, y – 1, z).
amide (5) (0.5 g, 5 mmol) in EtOH (10 mL). After 0.5ꢀh stirring,
thiocyanate 2 (0.89 g) and Et N (1.04 mL, 7.5 mmol) or
3
3
ꢀ(Het)arylꢀ2ꢀcyanopropꢀ2ꢀenethioamides 1 and cyanothioꢀ
Nꢀmethylmorpholine (0.83 mL, 7.5 mmol) were added. The
reaction mixture was stirred to complete homogenization and
kept at ~20 °C for 24 h (in the case of 3b, for 1.5 h). The
precipitate of dihydrothiophene 3a—c was filtered off and reꢀ
crystallized from an appropriate solvent.
3
4
acetamide (5) were prepared according to known procedures.
Phenacyl thiocyanate (2) was prepared according to a modiꢀ
fied procedure.22 Acetone (70 mL) was added to a mixture of
phenacyl bromide (23.5 g, 0.118 mol) and potassium thiocyanate
(
12.6 g, 0.13 mol). The mixture was refluxed with vigorous stirꢀ
(4R,5S/4S,5R)ꢀ2ꢀAminoꢀ5ꢀbenzoylꢀ4ꢀ(2ꢀchlorophenyl)ꢀ4,5ꢀ
dihydrothiopheneꢀ3ꢀcarbonitrile (3a). Yield 52% (method A) and
49% (B), bright yellow crystals, m.p. 243—245 °C (decomp.)
ring for 1 h, concentrated to half the initial volume, and cooled
to ~20 °C. Water (50 mL) was added. The precipitate that formed
was filtered off, washed with water and twice with cooled
(Me CO—EtOH (1 : 1)). Found (%): C, 63.01; H, 3.88; N, 8.18.
2
5
0% EtOH. The yield of compound 2 was 20.6 g (98.5%), colorꢀ
less crystals, m.p. 74—75 °C (cf. Ref. 22: m.p. 75—77 °C).
ꢀAminoꢀ4ꢀ(het)arylꢀ5ꢀbenzoylꢀ4,5ꢀdihydrothiopheneꢀ3ꢀ
carbonitriles 3 (general procedure). Method A. Triethylamine
0.94 mL, 6.75 mmol) or Nꢀmethylmorpholine (0.75 mL,
.75 mmol) was added to a stirred suspension of unsaturated
C H ClN OS. Calculated (%): C, 63.43; H, 3.84; N, 8.22. IR,
18
13
2
–
1
ν/cm : 3415, 3310, 3200 (NH ); 2195 (C≡N); 1675 (C=O);
2
1
3
2
1645 (δ(NH )). H NMR, δ: 4.80 (br.d, 1 H, C(4)H, J =
2
2.9 Hz); 5.18 (m, 1 H, C(5)H); 7.01 (br.s, 2 H, NH ); 7.21—7.57
2
(
6
(m, 7 H, 4ꢀClC H , C(3)HPh—C(5)HPh); 7.85 (br.d, 2 H,
6
4
3
C(2)HPh, C(6)HPh, J = 7.1 Hz).
thioamide 1a,b (4.5 mmol) and thiocyanate 2 (0.8 g, 4.5 mmol)
in EtOH (15 mL). The reaction mixture was stirred to homoꢀ
genization and left at ~20 °C for 24 h (in the case of 3b, for 1.5 h).
The precipitate of dihydrothiophene 3a,b was filtered off and
recrystallized from an appropriate solvent.
(4R,5S/4S,5R)ꢀ2ꢀAminoꢀ5ꢀbenzoylꢀ4ꢀ(2ꢀfuryl)ꢀ4,5ꢀdihydroꢀ
thiopheneꢀ3ꢀcarbonitrile (3b). Yield 54% (method A) and
50% (B), light brown crystals, m.p. 208—210 °C (EtOH—diꢀ
oxane (1 : 1)). Found (%): C, 64.64; H, 4.10; N, 9.53.
C H N O S. Calculated (%): C, 64.85; H, 4.08; N, 9.45. IR,
16
12
2
2
–
1
Method B. An appropriate aldehyde 4a—c (5 mmol) and a
ν/cm : 3405, 3290, 3170 (NH ); 2200 (C≡N); 1670 (C=O);
2
1
3
drop of a tertiary amine (Et N or Nꢀmethylmorpholine) were
1640 (δ(NH )). H NMR, δ: 4.87 (br.d, 1 H, C(4)H, J =
3
2
3
successively added to a stirred suspension of cyanothioacetꢀ
3.0 Hz); 5.20 (br.d, 1 H, C(5)H, J = 3.0 Hz); 6.29 and 6.35

2
ꢀAminoꢀ4,5ꢀdihydrothiopheneꢀ3ꢀcarbonitriles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 7, July, 2007
1435
(
both m, 1 H each, C(3)Hfur, C(4)Hfur (hereafter, fur stands for
5. V. P. Litvinov, V. V. Dotsenko, and S. G. Krivokolysko, Izv.
Akad. Nauk, Ser. Khim., 2005, 847 [Russ. Chem. Bull., Int.
Ed., 2005, 54, 864].
6. E. A.ꢀG. Bakhite, Phosphorus, Sulfur, Silicon, Relat. Elem.,
2003, 178, 929.
furyl)); 6.98 (br.s, 2 H, NH ); 7.45—7.65 (m, 4 H, C(5)Hfur,
C(3)HPh—C(5)HPh); 7.94 (br.d, 2 H, C(2)HPh, C(6)HPh
3
2
,
J = 7.1 Hz).
(
4S,5S/4R,5R)ꢀ2ꢀAminoꢀ5ꢀbenzoylꢀ4ꢀphenylꢀ4,5ꢀdihydroꢀ
thiopheneꢀ3ꢀcarbonitrile (3c). Yield 37% (method B), yellow
7. H. Maruoka, K. Yamagata, and M. Yamazaki, Liebigs Ann.
Chem., 1993, 1269; H. Maruoka, M. Yamazaki, and
Y. Tomioka, J. Heterocycl. Chem., 2004, 41, 641.
8. H. Maruoka, F. Yamagata, and M. Yamazaki, J. Heterocycl.
Chem., 2001, 38, 269.
crystals, m.p. 207—209 °C (Me CO—EtOH (1 : 1)) (cf. Ref. 15:
2
for the (4R,5R)ꢀisomer, m.p. 206—207 °C (from Me CO)).
2
Found (%): C, 70.29; H, 4.65; N, 9.11. C H N O S. Calcuꢀ
21
18
4
1
2
–
lated (%): C, 70.56; H, 4.61; N, 9.14. IR, ν/cm : 3400, 3285,
175 (NH ); 2200 (C≡N); 1675 (C=O); 1640 (δ(NH )).
3
9. A. M. Shestopalov, D. Sc. (Chem.) Thesis, IOKh AN SSSR,
Moscow, 1991 (in Russian).
2
2
1
3
H NMR, δ: 4.84 (br.d, 1 H, C(4)H, J = 3.2 Hz); 5.18 (m,
1
H, C(5)H); 6.93 (br.s, 2 H, NH ); 7.26—7.59 (m, 8 H,
10. L. A. Rodinovskaya, D. Sc. (Chem.) Thesis, IOKh RAN,
Moscow, 1994 (in Russian).
11. A. M. Shestopalov, O. P. Bogomolova, L. A. Rodinovskaya,
V. P. Litvinov, and Yu. A. Sharanin, Dokl. Akad. Nauk
SSSR, 1991, 317, 112 [Dokl. Chem., 1991, 317 (Engl.
Transl.)].
2
Ar); 7.90 (br.d, 2 H, C(2)H , C(6)H (b stands for benzoyl),
b
b
3
J = 8.0 Hz).
Xꢀray diffraction analysis of compound 3a was carried out
at ~20 °C for a single crystal (0.35×0.42×0.49 mm) on an
Enraf—Nonius CADꢀ4 automatic fourꢀcircle diffractometer
(
MoꢀKα radiation, λ = 1.71069 Å, 2θ/ω = 1.2, θmax = 25°,
12. L. A. Rodinovskaya, A. M. Shestopalov, and V. P. Litvinov,
Dokl. Akad. Nauk, 1994, 339, 214 [Dokl. Chem., 1994, 339
(Engl. Transl.)].
13. A. M. Shestopalov, O. P. Bogomolova, and V. P. Litvinov,
Synthesis, 1991, 277.
14. K. M. Dawood, Synth. Commun., 2001, 31, 1647.
15. A. V. Samet, A. M. Shestopalov, V. N. Nesterov, and V. V.
Semenov, Synthesis, 1997, 623.
16. A. V. Samet, A. M. Shestopalov, V. N. Nesterov, and V. V.
Semenov, Izv. Akad. Nauk, Ser. Khim., 1998, 127 [Russ.
Chem. Bull., 1998, 47, 127 (Engl. Transl.)].
sphere segment –17 < h < 10, 0 < k < 16, –17 < l < 16). The
total number of reflections was 6408 (5984 symmetrically indeꢀ
pendent reflections, the averaging factor Rint = 0.013). Crystals
of compound 3a are triclinic: a = 8.880(3) Å, b = 13.585(4) Å,
c = 14.805(4) Å, α = 93.56(2)°, β = 107.44(2)°, γ = 90.01(2)°,
V = 1700.3(9) Å , M = 681.7, Z = 4 (two independent molꢀ
ecules), d
group P1 (No. 2). The structure was solved by the direct method
and refined by the leastꢀsquares method in the fullꢀmatrix anisoꢀ
3
= 1.33 g cm–3, µ = 3.52 cm , F(000) = 704, space
–1
calc
–
3
5
tropic approximation with the CRYSTALS program package.
In refinement, 3382 reflections with I > 3σ(I ) were used (431 paꢀ
rameters refined, the number of reflections per parameter
was 7.8). All hydrogen atoms were located from the electron
density difference map. All hydrogen atoms were refined with
fixed coordinates and thermal parameters (only the H atoms in
the amino group were refined isotropically). The Chebyshev
weighting scheme3 with five parameters (1.04, 0.24, 0.68, –0.14,
and 0.14) was used in refinement. Final residuals were R = 0.051
and Rw = 0.053, GOF = 0.903. The residual electron densities
were 0.35 and –0.31 e Å . Absorption correction was applied
by azimuthal scanning.37 Comprehensive Xꢀray diffraction data
for compound 3a have been deposited with the Cambridge Crysꢀ
tallographic Data Center (CCDC 609934; CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK, fax: +44ꢀ1223/336ꢀ033;
eꢀmail: deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk).
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6
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Received July 3, 2006;
in revised form April 27, 2007
1