GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-thiadiazoles

Article abstract of DOI:10.1080/10426500701407755

1H, 13C and 15N NMR spectra of 2-acetylamino-1,3,4-thiadiazole and its 5-substituted derivatives have been measured and assigned based on reference data, as well as homo- and heteronuclear 2 D NMR experiments. In addition, the GIAO/DFT approach at the B3LYP level of theory using the 6-311G basis set was used to calculate the 13C NMR chemical shifts. Although this method gives reliable results for 2-arylhydrazones of 1,3-diphenylpropanetrione, 2-phenacylpyridines, (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines, 4-fluoroanilines, (1Z,3Z)-1,4-di(pyridin-2-yl)buta-1,3-dienediols and their tautomeric forms, the calculated chemical shifts for the 1,3,4-thiadiazoles studied are less satisfactory. Presence of the sulfur atom(s) seems to be responsible for such behavior.

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GIAO/DFT 13C NMR Chemical
Shifts of 1,3,4-Thiadiazoles
Hossein Loghmani-Khouzani a , Teresa Rauckyte b ,
Borys Ośmiałowski b , Ryszard Gawinecki b & Erkki
Kolehmainen c
a Department of Chemistry, Faculty of Sciences,
University of Isfahan, Isfahan
b Department of Chemistry, University of Technology
and Life Sciences, Bydgoszcz, Poland
c Department of Chemistry, University of Jyväskylä,
Finland
Version of record first published: 16 Jul 2007
To cite this article: Hossein Loghmani-Khouzani, Teresa Rauckyte, Borys Ośmiałowski,
Ryszard Gawinecki & Erkki Kolehmainen (2007): GIAO/DFT 13C NMR Chemical Shifts of
1,3,4-Thiadiazoles, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:9,
2217-2225
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Phosphorus, Sulfur, and Silicon, 182:2217–2225, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701407755
GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-Thiadiazoles
Hossein Loghmani-Khouzani
Department of Chemistry, Faculty of Sciences, University of Isfahan,
Isfahan
Teresa Rauckyte
´
Borys Osmialꢀowski
Ryszard Gawinecki
Department of Chemistry, University of Technology and Life Sciences,
Bydgoszcz, Poland
Erkki Kolehmainen
Department of Chemistry, University of Jyva¨skyla¨, Finland
1 H, 13 C and 15 N NMR spectra of 2-acetylamino-1,3,4-thiadiazole and its 5-
substituted derivatives have been measured and assigned based on reference data,
as well as homo- and heteronuclear 2 D NMR experiments. In addition, the
GIAO/DFT approach at the B3LYP level of theory using the 6-311G basis set was
used to calculate the 13 C NMR chemical shifts. Although this method gives reliable
results for 2-arylhydrazones of 1,3-diphenylpropanetrione, 2-phenacylpyridines,
(Z)-2-(2-hydroxy-2-phenylvinyl)pyridines, 4-fluoroanilines, (1Z,3Z)-1,4-di(pyridin-
2-yl)buta-1,3-dienediols and their tautomeric forms, the calculated chemical shifts
for the 1,3,4-thiadiazoles studied are less satisfactory. Presence of the sulfur atom(s)
seems to be responsible for such behavior.
Keywords 1,3,4-Thiadiazoles; ab initio calculations; NMR chemical shifts
Received February 4, 2007; accepted April 3, 2007.
We are very much indebted to the CYFRONET Regional Computing Centre of S.
Staszic University of Mining and Metallurgy in Cracow for supply of computer time and
providing programs (Grant KBN/SGI-ORIGIN-2000/ATRBydg/072/2000). Special Labo-
ratory Technician Reijo Kauppinen is acknowledged for his help in NMR measurements.
Also we are grateful to the University of Isfahan Research Council for the partial support
of this work.
Address correspondence to Hossein Loghmani-Kouzani, Department of Chemistry,
Faculty of Sciences, Isfahan University, Isfahan 81746-73441, Iran. E-mail: h.log119@
sci.ui.ac.ir
2217

2218
H. Loghmani-Khouzani et al.
INTRODUCTION
Theoretically calculated NMR parameters are shown to be very help-
ful in distinguishing between two (or more) related forms of the same
compound, e.g. isomers or tautomers. In our recent papers,1−9 the NMR
signals were correctly assigned for acylmethyl derivatives of pyridine
and their prototropomers by comparing the experimental and calcu-
lated chemical shifts. Since the thiadiazole ring contains two carbon,
two nitrogen and one heavier sulfur atoms, calculation of their NMR
chemical shifts is an interesting way to test the validity of the proce-
dure used for prediction of the NMR data. Therefore, 2-acetylamino-
1,3,4-thiadiazole and its 5-substituted derivatives showing interesting
biological activities were chosen to be studied for the present arti-
cle. 2-Acetylamino-5-sulfonylamino-1,3,4-thiadiazole (acetazolamide),
5 (Scheme 1), is a potent inhibitor of carbonic anhydrase.10,11 It is used
clinically for treating glaucoma.12 2-Acetylamino-1,3,4-thiadiazole, 1,
was reported to show antitumor activity.13 There are some interest-
ing inter-and intramolecular interactions in these compounds. The
molecules of 2-acetylamino-5-sulfonylamino-1,3,4-thiadiazole, 5, are
held together in the crystal by strong N−H. . . O and N−H. . . N hy-
drogen bonds.14 The 1,3,4-thiadiazole ring in this compound is pla-
nar but both side chains are bent out of the ring planes.14 The C−S
bonds in the ring have some double character resulting from delo-
calization of the π electrons in the thiadiazole ring.14 The molecules
of bis(5-acetylamino-1,3,4-thiadiazole-2-sulfonyl)amine, 6, consist of
two nearly planar acetylaminothiadiazolesulfonyl units which are
parallel.15 Coplanarity of the acetylamino groups and the thiadiazole
rings is a consequence of π-electron delocalization over these groups and
15
. . .
by non-bonding S O interactions. In this paper multinuclear mag-
netic resonance of 2,5-disubstitued 1,3,4-thiadiazoles were described
and experimental and GIAO/DFT 13C NMR data were compared.
SCHEME 1

GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-Thiadiazoles
2219
RESULTS AND DISCUSSION
Experimental 1H, 13C and 15N NMR chemical shifts of 1–6 are collected
in Table I. It contains also the 13C NMR chemical shifts calculated at
B3LYP/6-311G//RHF/3-21G level.
Since 15N NMR chemical shifts of non-quaternary nitrogen atoms
containing the lone electron pair are known to be sensitive to solvent,
concentration and temperature17 nitrogens are not included in theoret-
ical considerations. Similarly, protons locating on the periphery of the
molecule are also subjected to more efficient intermolecular (solvent-
solute) effects than the carbon atoms18 and are left away from the the-
oretical treatment.
Geometry optimizations with the HF3-21G, 6-31G, and 6-31G**
basis sets are known to have comparable effects on the calculated
(GIAO) chemical shifts.19–21 Thus, the minimum basis set, 3-21G,
was used to provide satisfactory molecular geometries for reproduc-
tion of the 13C NMR chemical shifts. These were calculated for all
TABLE I Experimental 1H, 13C, and 15N and Calculated 13C NMR (in
Italics)a Chemical Shifts (δ/ppm) for 0.1–0.2 M DMSO-d6 Solutions
at 303 K of 1–6
Nucleus
1
2
3
4
5
6
NH
∼ 12.5s
(broad)
2.18s
∼ 12.6s
(broad)
2.20s
12.26s
12.47s
∼ 12.6s
(broad)
2.20s
12.93s
CH3
H in R
C2
2.08s
13.91s
169.45
156.99
152.31
157.49
22.33
2.17s
D
2.22s
8.26s
9.11s
—
8.24s
168.69
155.12
148.46
144.18
22.43
169.34
158.49
147.90
153.68
22.17
169.12
163.48
159.54
163.06
22.53
22.08
167.72
169.61
161.82
161.39
169.57
22.51
161.24
161.82
169.49
169.57
22.42
C5
CH3
C = O
21.95
21.89
159.61
21.83
183.72
22.03
164.51
22.03
164.39
158.55
161.84
−58.4b
−22.8b
−245.3
161.18
160.89
161.84
161.78
161.78
c
c
c
c
c
N3
N4
CONH
c
c
c
c
c
−241.5
−242.9
−244.1
−242.7
−242.6
aB3LYP/6-311G//RHF/3-21G.
bAssignment is based on the 15N NMR shift of unsubstituted 1,3,4-thiadiazole -7.9
ppm in DMSO-d.16 In PFG 1H,15N HMBC H-5 of 1 shows cross-peaks with both ring
nitrogens, the cross-peak with the signal at -22.8 ppm being more intensive supporting
the above assignment.
cNot observed because H-5 is missing in these compounds and side chain NH is too
far and its signal is too broad to give any cross-peaks with the ring nitrogens.

2220
H. Loghmani-Khouzani et al.
TABLE II 13C NMR Chemical Shifts (δ/ppm) for Compound 1
Calculateda with Different Basis Sets
C2
C5
CH3
C = O
B3LYP/6-31G(d,p)b
B3LYP/6-31G(2d,p)b
B3LYP/6-31G(2d,2p)b
132.20
131.69
133.54
133.08
134.54
134.09
150.02
149.24
151.54
150.83
152.94
152.23
148.46
147.32
150.86
149.80
152.38
151.32
22.81
22.88
23.11
23.18
23.83
23.89
a
Chemical shifts obtained with HF/6-31G(d,p) and HF/6-31G(2d,p) methods of
geometry optimization are given in regular font and italic, respectively.
b
Basis set used in calculation of chemical shifts.
carbon atoms, i.e. C2, C5, Cmethyl and Ccarbonyl. The correlation for
the side chain Cmethyl is satisfying. However, it is easily seen that
especially for Ccarbonyl of 3 and 4 (which contain sulfur atom in the
substituent at C5) the calculated parameters differ significantly
from the experimental ones although all 13C shifts correlated by a
satisfying way for 2-aryl-hydrazones of 1,3-diphenylpropanetrione,3
2-phenacylpyridines and (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines,5
4-fluoroanilines,4 (1Z,3Z)-1,4-di(pyridin-2-yl)buta-1,3-dienediols, and
their tautomeric forms.8,9 For the ring carbons C2 and C5 adjacent
to sulfur atom the correlations were also poor. So, it is obvious that
the used theoretical model does not take into account heavy sulfur
atom(s) in a proper way. As it can be seen in Table II, more sophis-
ticated 6-31G basis sets give more satisfying results for C5 and CH3
only.
In conclusion we can point out that a GIAO/DFT approach at
the B3LYP level of theory using the 6-311G basis set does not
reliably reproduce the experimental 13C NMR chemical shifts for
2-acetylamino-1,3,4-thiadiazoles and its 5-substituted derivatives.
Presence of the sulfur atom(s) in these molecules seems to be re-
sponsible for such a behavior. In the near future, we are going to use
more sophisticated calculation methods to obtain a better agreement
between the experimental and calculated chemical shifts for these
compounds.
EXPERIMENTAL
Satisfactory analytical data ( 0.3 % for C, H, and N) were obtained for
all new compounds.

GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-Thiadiazoles
2221
2-Acetylamino-1,3,4-thiadiazole (1)
This compound was obtained by modification of the known method.22
A mixture of 9.0 g (0.10 mol) of thiosemicarbazide and 16.6 ml (14.82 g,
0.10 mol) of ethyl orthoformate was heated for 2 h at the boiling water
bath. The reaction mixture was then diluted with 250 mL of acetonitrile
and allowed to boil for a short time. The hot mixture was filtered off
to remove the solid impurities, and the filtrate obtained was cooled
down. The precipitate formed (1-ethoxymethylenethiosemicarbazide)
was collected by suction (24%). The mixture of 3.0 g (0.02 mol) of this
compound and 14.2 mL (15.31 g, 0.15 mol) of acetic anhydride was
heated at 90◦C for 1h. The black solid obtained was recrystallized from
water. 2-Acetylamino-1,3,4-thiadiazole obtained (90%) melts at 265–
267◦C (lit. 268–269◦C).23–27
2-Acetylamino-5-chloro-1,3,4-thiadiazole (2)
10.0 mL (0.33 mol) of 30% hydrogen peroxide was added portionwise to
80.0 mL (2.59 mol) of 36% hydrochloric acid (during addition the tem-
perature of the reaction mixture should be kept below 10◦C). 8.04 g (0.05
mol) of 2-acetylamino-5-mercapto-1,3,4-thiadiazole (3, POLPHARMA
S.A., Poland) and 75.0 mL (1.32 mol) of 96% acetic acid were then added
to this mixture and whole was stirred for 8 h at 10–15◦C. The solid
product was collected, washed with plenty of water and recrystallized
from ethanol. It melts at 245–246◦C (lit. 245–246◦C).28 Yield: 4.32 g
(53%).
2-Acetylamino-5-mercapto-1,3,4-thiadiazole (3)
5.30 g of anhydrous sodium carbonate and 9.20 g (0.12 mol) of car-
bon disulphide were added to 9.10 g (0.1 mol) of thiosemicarbazide
suspended in 35 mL of anhydrous ethanol. The obtained mixture was
refluxed with stirring for 1 h at temperature ca 50◦C and then heated
for 4 h on a steam bath. Solvent was removed by distillation, and the
obtained residue dissolved in 40 mL of water (40 mL) and acidified
with ca 8 mL of conc. hydrochloric acid to give 10.9 g (80%) of 2-
amino-5-mercapto-1,3,4-thiadiazole. It melts at 232–233◦C [lit. 232◦C
(decomp.)].28 Subsequently, 10.90 g (9.4 mL, 0.1 mol) of acetic anhydride
was added portionwise to the mixture of 6 mL of glacial acetic acid and
10.9 g (0.08 mol) of 2-amino-5-mercapto-1,3,4-thiadiazole. The mixture
was refluxed with stirring for 5 h. Precipitate (9.8 g, 70 %) obtained after
addition of water and cooling of the obtained solution was recrystallized
from water. It melts at 288–290◦C (lit. 290–293◦C),29 293–294◦C.30

2222
H. Loghmani-Khouzani et al.
2-Acetylamino-5-sulfo-1,3,4-thiadiazole (4)
The mixture of 24.9 mL (26.12 g, 0.435 mol) of glacial acetic acid,
28.7 mL (0.93 mol) of 36% hydrochloric acid, 8.06 g (0.046 mol) of 2-
acetylamino-5-mercapto-1,3,4-thiadiazole and 24.1 mL (0.786 mol) of
30% hydrogen peroxide was stirred for 2 h at 5-10◦C. The obtained
solid was filtrated, washed with plenty of water and recrystallized from
water. The product melts at 282–283◦C. Yield: 5.4 g (53%).
2-Acetylamino-5-sulfonylamino-1,3,4-thiadiazole (5)
80 mL (2.64 mol) of 30% hydrogen peroxide was added portion wise
to stirred 36% hydrochloric acid (50 mL, 1.62 mol). During addition
temperature of the reaction mixture was kept at 10–15◦C. 5.0 g
(0.029mol) of 2-acetylamino-5-mercapto-1,3,4-thiadiazole was then
added to reaction mixture in the same manner. The obtained solid
of 2-acetylamino-5-sulfochloro-1,3,4-thiadiazole was collected at the
Bu¨chner funnel and washed with ice water. This crude byproduct
was added as small portions to the stirred 25% aqueous ammonia at
temperature not exceeding 20◦C. Reaction mixture was then heated for
2 h at 50◦C (to remove excess of ammonia) and refluxed for ten minutes
with charcoal. The filtrate obtained after removing the charcoal was
cooled down and acidified with conc. hydrochloric acid to pH 1. The
obtained precipitate was collected and recrystallized from water. It
melts at 256–257◦C (lit. 258–259◦C).31 Yield: 2.05 g (32%).
Bis(5-acetylamino-1,3,4-thiadiazole-2-sulfonyl)amine (6)
2-Acetylamino-5-sulfochloro-1,3,4-thiadiazole was obtained in the
following manner. 80 mL (2.64 mol) of 30% hydrogen peroxide was
added to 50 mL of 36% hydrochloric acid 5–10◦C. To this mixture were
added successively: 5.0 g (0.029 mol) of 2-acetylamino-5-mercapto-
1,3,4-thiadiazole and 50.4 mL, 52.84 g (0.88 mol) of glacial acetic acid.
The obtained reaction mixture was then stirred for 2 h at 5–10◦C.
The solid 2-acetylamino-5-sulfochloro-1,3,4-thiadiazole formed was
filtrated off and washed with ice water. This wet by-product was
added at 5–10◦C directly to the suspension of 2.2 g (0.01 mol) of
2-acetylamino-5-sulfamino-1,3,4-thiadiazole in the solution of 0.4 g
(0.01 mol) of sodium hydroxide in 100 mL of water at 5–10◦C. Stirring
at the same temperature was continued for additional 1.5 h. Non-
reacted starting materials were removed and the filtrate treated with
40% aqueous solution of sodium hydroxide (to pH 12). The solid formed
after 24 h was collected and dissolved in minimum amount of water.

GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-Thiadiazoles
2223
36% hydrochloric acid was then added to this (hot) solution to pH 1.
After cooling down the white crystals precipitate from the solution.
The product melts at 307–311◦C (lit. 318◦C).32 Yield: 0.65 g (16%).
Spectra
All NMR spectra were recorded for 0.1–0.2 M solutions in DMSO-d6 so-
lutions at 303 K with a Bruker Avance DRX 500 FT NMR spectrometer
equipped with an inverse detection 5-mm diameter broad-band probe
head and z-gradient accessory working at 500.13 MHz (1H), 125.76 MHz
1
(13C) and 50.59 MHz (15N), respectively. In H NMR experiments the
spectral width was 8500 Hz (17 ppm), the number of data points 65 K,
the flip angle 30◦, and the number of scans 32. The FIDs were multiplied
by an exponential window function of the digital resolution (0.13 Hz)
1
prior to Fourier Transform (FT). The H NMR chemical shifts are ref-
erenced to the trace signal of CHCl3 (δ = 7.26 ppm from internal TMS).
In proton composite pulse decoupled (Waltz-16) 13C NMR experi-
ments the spectral width was 30300 Hz (240 ppm), the number of data
points 65 K, the flip angle 30◦, and the number of scans typically >10000
in order to observe reliably also the weak signals of the possible minor
contributors. The FIDs were multiplied by an exponential window func-
tion of the digital resolution (0.92 Hz) prior to Fourier Transform (FT).
The 13C NMR chemical shifts are referenced to the center peak of sol-
vent CDCl3 (δ = 77.00 ppm from TMS).
In order to distinguish the spin systems belonging to possible differ-
ent tautomeric forms as well as to assign the 1H NMR spectra reliably
1
also the 2 D double quantum filtered (DQF) H,1H COSY33–34 experi-
ments were run. In these experiments the data matrix size was 1024
points (f2-axis) × 128 points (f1-axis), which was zero filled to 512 points
along the f1-axis prior to FT. 32 scans were accumulated for every f1-
increment (f2-spectrum). A shifted sine-bell window function was used
along both axes prior to FT.
2 D pulsed field gradient (PFG) selected 1H,13C HMQC35,36 and
1H,13C HMBC37 experiments were run to assign reliably the 13C NMR
spectra. In HMQC the matrix size was typically 2500 Hz/512 points
(1H = f2-axis) × 10000 Hz/512 points (13C = f1-axis), which was multi-
plied by a sine-bell window function along both axes prior to FT. The
number of scans was 32 and a composite pulse decoupling (graph) was
used to remove proton couplings. In HMBC measurements, 64 scans
were accumulated for each f1-increment; the matrix size and window-
ing were the same as in HMQC. A low-pass filter (to remove correlations
transmitted via direct couplings) and a 50 msec delay [for an evolution
of nJ(C,H) couplings] were included in the HMBC pulse sequence.

2224
H. Loghmani-Khouzani et al.
1
In order to determine the 15N NMR chemical shifts, PFG H,15N
HMBC experiments were run. In these experiments, the size of data
matrix was 2500 Hz/512 points (1H) × 22500 Hz/1024 points (15N-axis).
The 15N NMR chemical shifts were referenced to an external neat ni-
tromethane (δ = 0.0 ppm) sample in a 1 mm diameter capillary tube
inserted coaxially inside the 5 mm NMR sample tube. A sine-bell mul-
tiplication was done along both axes prior to FT. 64 scans were accu-
mulated for every 15N = f1-increment. A 50 msec delay for an evolution
of nJ(N,H) couplings was included in this HMBC pulse sequence.
Calculations
Quantum chemical calculations were performed at the HF and B3LYP
levels of theory with the Gaussian 03 package.38 Geometries were op-
timized to the global minima at the ab initio HF level with the 3-21G
basis set using C1-symmetry (no symmetry constraint). The GIAO/DFT
calculations for 13C chemical shifts were performed at the B3LYP level
with 6-311G basis set as in our previous paper.5 Chemical shifts are
referenced to TMS.
REFERENCES
[1] R. Gawinecki, B. Os´mialꢀowski, E. Kolehmainen, and H. Janota, Heterocycl. Com-
mun., 9, 275 (2003).
[2] B. Os´mialꢀowski, H. Janota, and R. Gawinecki, Polish J. Chem., 77, 169 (2003).
[3] R. Gawinecki, E. Kolehmainen, H. Janota, R. Kauppinen, M. Nissinen, and
B. Os´mialꢀowski, J. Phys. Org. Chem., 14, 797 (2001).
[4] A. Zakrzewska, E. Kolehmainen, B. Os´mialꢀowski, and R. Gawinecki, J. Fluorine
Chem., 111, 1 (2001).
[5] B. Os´mialꢀowski, E. Kolehmainen, and R. Gawinecki, Magn. Reson. Chem., 39, 334
(2001).
[6] E. Kolehmainen, B. Os´mialꢀowski, T. M. Krygowski, R. Kauppinen, M. Nissinen, and
R. Gawinecki, J. Chem. Soc., Perkin Trans. 2, 1259 (2000).
[7] E. Kolehmainen, B. Os´mialꢀowski, M. Nissinen, R. Kauppinen, and R. Gawinecki,
J. Chem. Soc., Perkin Trans. 2, 2185 (2000).
[8] B. Os´mialꢀowski, E. Kolehmainen, M. Nissinen, T. M. Krygowski, and R. Gawinecki,
J. Org. Chem., 67, 3339 (2002).
[9] B. Os´mialꢀowski, E. Kolehmainen, and R. Gawinecki, Chem. Eur. J., 9, 2710 (2003).
[10] K. Gobis, H. Foks, Z. Zwolska, and E. Augustynowicz-Kopee, Phosphorus, Sulfur,
and Sillicon, 180, 2653 (2005).
[11] W. H. Miller, A. M. Dessert, and R. O. Roblin, J. Am. Chem. Soc., 72, 4893 (1950).
[12] T. H. Maren, Physiol. Rev., 47, 595 (1967).
[13] M. Miyahara, M. Nakadate, Sh. Sueyoshi, M. Tanno, M. Miyahara, and Sh. Kamiya,
Chem. Pharm. Bull., 30, 4402–4406 (1982).
[14] M. Mathew, and G. J. Palenik, J. Chem. Soc., Perkin Trans. 2, 532 (1974).
[15] M. Vinkovic´, and S. Mutak, Acta Cryst., Sect. C, 50, 1099–1101 (1994).

GIAO/DFT 13C NMR Chemical Shifts of 1,3,4-Thiadiazoles
2225
[16] L. Stefaniak, J. D. Roberts, M. Witanowski, and G. A. Webb, Org. Magn. Reson., 22,
215 (1985).
[17] G. C. Levy and R. L. Lichter, Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy,
(Wiley, New York, 1979) pp. 32–33.
[18] M. Barfield and P. Fagerness, J. Am. Chem. Soc., 119, 8699 (1997).
[19] B. Pullman, A. Pullman, Adv. Heterocycl. Chem., 13, 77 (1971).
[20] J. S. Kwiatkowski and B. Pullman, Adv. Heterocycl. Chem., 18, 199 (1975).
[21] M. Karelson, U. Maran, and A. R. Katritzky, Tetrahedron, 52, 11325 (1996).
[22] M. Kanaoka, J. Pharm. Soc. Japan, 75, 1149 (1955); Chem. Abstr., 50, 5647a (1956).
[23] W. Kruckenberg and L. Eue, Ger. 964, 548 (1957); Chem. Abstr., 54, 3840b (1960).
[24] G. Werber and F. Maggio, Ann. Chim., 51, 944 (1961).
[25] C. Ainsworth, J. Am. Chem. Soc., 78, 1973 (1956).
[26] K. A. Jensen and Ch. Pedersen, Acta Chem. Scand., 15, 1124 (1961).
[27] G. Werber, F. Buccheri, and M. Gentile, J. Heterocycl. Chem., 14, 1263 (1977).
[28] V. Petrow, O. Stephenson, A. J. Thomas, and A. M. Wild, J. Chem. Soc., 1508 (1958).
[29] S. Hoff, Tetr. Lett., 10, 843 (1974).
[30] L. Dashkevich and Z. Korbelajnen, Khim. Geterotsykl. Soed., 441, (1968).
[31] O. R. Roblin and J. W. Clapp, J. Am. Chem. Soc., 72, 4890 (1950).
[32] C. Saˆrbu, T. Hodian, S. Gocan and C. Liteanu, Farmacia (Bucharest), 29, 105 (1981).
[33] M. Rance, O. W. Sørensen, G. Bodenhausen, G. Wagner, R. R. Ernst, and K. Wu¨thrich,
Biochem. Biophys. Res. Commun., 117, 479 (1984).
[34] A. Derome and M. Willamson, J. Magn. Reson., 88, 177 (1990).
[35] A. Bax and S. J. Subramanian, J. Magn. Reson., 67, 565 (1986).
[36] A. Bax, R. H. Griffey, B. L. Hawkins, J. Magn Reson., 55, 301 (1983).
[37] A. Bax and M. F. Summers, J. Am. Chem. Soc. 108, 2093 (1986).
[38] Gaussian 03, Revision B.04, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G.
Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai,
M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J.
W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick,
A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S.
Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi,
R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, and
J. A. Pople, Gaussian, Inc., Pittsburgh PA, 2003.