Synthesis of aza-aromatic hydroxylamine-O-sulfonates and their application to tandem nucleophilic addition-electrophilic 5-endo-trig cyclization

Article abstract of DOI:10.1016/j.tet.2011.03.091

Hydroxylamine-O-sulfonic acid (HOSA) was used as an efficient nucleophilic amination reagent for 2-chloropyrimidines, 2-chloroquinolines, and 1-chloroisoquinoline. The newly obtained heteroaromatic hydroxylamine-O- sulfonates subjected to the reaction wit

Full text of DOI:10.1016/j.tet.2011.03.091

Tetrahedron 67 (2011) 3612e3618
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Synthesis of aza-aromatic hydroxylamine-O-sulfonates and their application to
tandem nucleophilic additioneelectrophilic 5-endo-trig cyclization
,
b
c
a
Jaroslaw Saczewski a , Maria Gdaniec , Patrick J. Bednarski , Anna Makowska
*
a
ꢀ
ꢀ
Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. J. Hallera 107, Gdansk 80-416, Poland
b
ꢀ
Faculty of Chemistry, Adam Mickiewicz University, Ul. Grunwaldzka 6, Poznan 60-780, Poland
c Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Greifswald, D-17487 Greifswald, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Hydroxylamine-O-sulfonic acid (HOSA) was used as an efficient nucleophilic amination reagent for 2-
chloropyrimidines, 2-chloroquinolines, and 1-chloroisoquinoline. The newly obtained heteroaromatic
hydroxylamine-O-sulfonates subjected to the reaction with acyl isothiocyanates underwent tandem
nucleophilic additioneelectrophilic 5-endo-trig cyclization. The mechanism of the cyclization was in-
Received 19 January 2011
Received in revised form 9 March 2011
Accepted 28 March 2011
Available online 2 April 2011
vestigated with use of the long-range corrected hybrid density functional
u
B97X-D/6-31þG
*
and SM8
(DMF) solvation model. The structures of the heteroaromatic hydroxylamine-O-sulfonates and N-(5-
methoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-ylidene)benzamide were confirmed by single crystal
X-ray analysis. N-(2H-[1,2,4]thiadiazolo[3,2-a]isoquinolin-2-ylidene)benzamide exhibited a pronounced
in vitro cytostatic activity against human tumor cell lines SISO, LCLC, A-427, DAN-G, and RT-4 (IC50 in the
Keywords:
Hydroxylamine-O-sulfonic acid
HOSA
5-endo-trig Cyclization
Nucleophilic addition
Aza-aromatic hydroxylamine-O-sulfonic
acids
range 1.47e2.97 mM).
Ó 2011 Elsevier Ltd. All rights reserved.
Cytostatic activity
1. Introduction
Therefore, we turned our attention to hydroxylamine-O-sulfonic
acid (HOSA), a versatile commercially available inorganic aminating
reagent with amino group behaving either as an electrophile or
nucleophile.8e10 The electrophilic properties of this reagent are
observed under basic conditions, while the nucleophilic character
is evident under neutral or acidic conditions.
The development of novel transformations that allow the rapid
construction of carbocyclic and heterocyclic scaffolds via 5-endo-
trig cyclization from simple readily available starting materials is an
active area of investigation.1e3 Of special interest are electrophile-
induced processes that do not violate the Baldwin’s rules.4 One of
the most effective ways to achieve this goal can be to implement
a reaction cascade involving mechanistically different processes in
one pot. As a part of our ongoing program on hydroxylamine-O-
sulfonates,5,6 we have now designed a facile synthesis of 1,2,4-
thiadiazole-fused ring systems via a tandem process consisting of
nucleophilic addition and electrophilic 5-endo-trig cyclization us-
ing the previously unknown aza-aromatic hydroxylamine-O-sul-
fonates. We started our research by finding a suitable method for
preparation of heteroaromatic amines with a good leaving group at
the external nitrogen atom. It is astonishing that despite enormous
progress made in the synthesis of heteroaryl amines,7 no attention
has been paid to aza-aromatic compounds bearing hydroxylamine-
O-sulfonate functionality amenable to further transformations
based on their dual electrophilic and nucleophilic properties.
2. Results and discussion
We reported on in an earlier paper that the nucleophilic ami-
nation of non-aromatic 2-chloro-4,5-dihydroimidazole with HOSA
provides a suitable entry into otherwise inaccessible 2-(4,5-dihy-
droimidazolium)-hydroxylamine-O-sulfonate.11 The present paper
expands upon this investigation by showing that by a comparably
mild synthesis starting from aza-aromatic chlorides 1e5, a new
class of 2-azinium-hydroxylamine-O-sulfonates 6e10 can be
obtained in 59e77% yield by the treatment with two-fold excess of
HOSA in aqueous or DMF solution at room temperature. The iso-
lation of the products is very simple because they proved to be
stable crystalline compounds that precipitate from the reaction
mixture and can be easily purified by crystallization (Scheme 1).
We found that this nucleophilic substitution reaction is very
sensitive to the acidity of the medium, since it was abolished upon
addition of equimolar amount of triethylamine. Apparently, under
the conditions of acid-catalyzed reaction, the electrostatic effect or
* Corresponding author. Tel.: þ48 583493252; fax: þ48 583493257;
e-mail address: js@gumed.edu.pl (J. Saczewski).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.091

J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
3613
Betaine 6 upon treatment with triethylamine was further con-
verted into the corresponding aminium salt, which can exist as
either amino (6A) or imino (6B) tautomer. Optimization of the
N
X
H2N-OSO3H
O
S
O
N
H
N
H
N
Cl
H2O or DMF
rt, 6-12 h
O
O
molecular structures of these species using DFT (B3LYP/6-31þG
*
)
1 - 5
6
computations revealed that amino tautomer 6A should prevail both
in the gas phase and in DMF solution (Scheme 1).
HET-Cl, X = N, CH
N
Next, we have obtained experimental evidence of the ability of
the newly prepared aza-aromatic hydroxylamine-O-sulfonates to
serve as the precursors of heteroarylnitrenium ions by NeO bond
heterolysis. As shown in Scheme 2, betaine 6 treated with aqueous
K2CO3 solution at room temperature afforded compound 11 as
a result of both heteroarylation of exocyclic divalent 2-pyr-
imidinylnitrenium ion and the coupling of nitrene species gener-
1, HET-Cl = 2-chloropyrimidine
O
S
O
2
, HET-Cl = 2-chloro-4-methoxypyrimidine
O
H3CO
N
H
N
H
3
, HET-Cl = 2-chloroquinoline
O
4
, HET-Cl = 2-chloro-4-methylquinoline
5
7
, HET-Cl = 1-chloroisoquinoline
CH3
H
N
O
O
O
ated by a-elimination of hydrogen sulfate (Scheme 2). The structure
O
O
O
N
H
N
H
S
O
N
H
N
H
S
O
N
H
S
O
of 11 was confirmed by IR and NMR spectroscopic data as well as by
single crystal X-ray analysis of the complex 11a obtained by co-
crystallization with imidazole (Fig. 1).
O
O
O
10
8
9
6, H2O, 6 h, yield = 67%
7, H2O, 12 h, yield = 74%
8
, DMF, 12 h, yield = 77%
R
9, DMF, 12 h, yield = 64%
R
N
K2CO3 / H2O
rt, 3 days
10
, DMF, 12 h, yield = 59%
N
N
O
O
N
N
N
H
S
Et3N
N
N
α-elimination
O
O
N
O
O
O
O
O
O
N
H
N
H
S
N
N
H
S
N
N
S
6, R = H
O
2-pyrimidyl nitrene
O
O
O
H
7
, R = OCH3
O
O
6
6A
6B
heterolysis
2-
dimerization
Scheme 1. Preparation of aza-aromatic hydroxylamine-O-sulfonates 6e10 via acid-
catalyzed nucleophilic substitution.
- SO4
of N-O bond
R
N
R
N
N
N
hydrogen bonding of HOSA to the basic azine nitrogen facilitates
chlorine substitution at the 2 position.
The structures of compounds 6e10 were fully characterized by
IR, 1H, and 13C NMR spectroscopy as well as by single crystal X-ray
diffraction analysis of 6 and 7. As seen in Fig. 1, in the solid state
these compounds exist in zwitterionic form.
N
N
N
N
N
H
R
2-pyrimidylnitreniumion
N-N'-diazopyrimidine
electrophilic substitution
R
N
HN
N
N
N
N
11, R = H
N
N
N
12
, R = OCH3
R
R
Scheme 2. Formation of (4-pyrimidylamino)-diazopyrimidines 11 and 12.
In this context it is pertinent to note, that previously Takeuchi
and Watanabe achieved N-arylation of 2-pyrimidylnitrenium ion
generated from tetrazolo[1,5-a]pyrimidine in the presence of tri-
fluoroacetic acid12 and computational studies of hetero-
arylnitrenium ions were performed by Cramer, Favley, and Di
Stefano.13e16
With aza-aromatic nitrenium ion precursors in hands, we have
subjected compounds 6e10 to the reaction with a series of acyl
isothiocyanates. As shown in Scheme 3, upon treatment of the
triethylaminium sulfonates with corresponding heterocumulene in
DMF solution at room temperature, a tandem nucleophilic addi-
tioneelectrophilic 5-endo-trig cyclization took place resulting in
the formation of 1,2,4-thiadiazolium cations E, which were further
converted into fused [1,2,4]thiadiazole derivatives 13e26 by the
treatment with triethylamine. Structure of these compounds was
confirmed by IR, NMR spectroscopic data, and X-ray analysis of
pyrimidine derivative 16 (Fig. 1).
Interestingly, the
u
B97X-D/6-31þG
*
computational studies of
the mesomeric species BeE revealed that all of them possess the
positive charge of þ0.697 e (natural) or þ0.921 e (Mulliken) located
on the sulfur atom, which indicates that contribution of resonance
structure represented by the sulfenium ion D is significant. The
Fig. 1. Molecular structure of 6 (top left), 7 (top right), 11a (middle), and 16 (bottom)
with atom labeling scheme and displacement ellipsoids shown at the 50% probability
ꢁ
ꢁ
calculated SeN distance of 1.78 A is close to a single covalent bond
level. The intramolecular O12/S9 contact is 2.1242(11) A.

3614
J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
As shown in Scheme 3, the central tent of the above reaction
RCO-N=C=S
Et3N, DMF, rt
X
X
S
sequence is the initial nucleophilic addition of the exocyclic NH
group to the C¼N bond of heterocumulene with formation of the
intermediate A, which, in turn, may suffer spontaneous heterolysis
of the rather weak NeO bond. Since the reaction takes place in DMF
solution (with its high dielectric constant), the formation of the
O
O
O
O
N
H
N
H
S
S
N
N
O
O
O
Et3NH
nucleophilic
addition
O
O
NH
6 10
-
A
R
X
= CH, N
R = Ph, CH3. EtO
2ꢀ
SO4 ion would not be highly endoenergetic.21 Then, the electro-
sulfenium-driven
2-
philic 5-endo-trig cyclization gives rise to the formation of highly
acidic but stabilized 1,2,4-thiadiazolium cation of type E, which is
expected to persist in polar solvent. Upon treatment of the reaction
mixture with a second molar equivalent of triethylamine, the
deprotonated free bases 13e26 are formed. According to calcula-
- SO4
5-endo-trig cyclization
X
X
N
X
N
N
O
N
O
N
N
O
tions performed with long-range and dispersion-corrected
u
B97X-
D functional22 with 6-31þG
*
basis set using SM8 (DMF) solvation
S
NH
S
NH
S
NH
model,23 both the heterolysis of NeO bond and the proton ab-
straction are exothermic and the heats of these processes in DMF
were estimated as 15.2 and 35.9 kcal/mol, respectively (Fig. 2).
R
R
R
D
C
B
azaaromatic
nitrenium ion
azaaromatic
nitrenium ion
sulfenium ion
OCH3
N
X
N
Et3N
N
S
N
N
N
N
S
N
S
- Et3NH
NH
N
N
O
O
O
R
E
R
R
13
16
, R = Ph
, R = Ph
1,2,4-thiadiazolium
cation
14, R = CH3
15, R = EtOCO
17, R = CH3
18, R = EtO
CH3
Fig. 2. The relative electronic energy
(DE) and Gibbs free energy (DG) profiles
(298.15 K, kcal/mol) for sulfenium-driven 5-endo-trig cyclization calculated with long-
N
S
N
S
N
S
B97X-D functional22 with 6-31þG
*
basis set using
N
N
R
N
N
R
N
N
R
range and dispersion-corrected
u
SM823 (DMF) solvation model.
O
O
O
To ensure that no alternative nucleophilic 5-endo-trig cycliza-
tion was taking place, we have carried out DFT calculations on the
reaction pathway depicted in Fig. 3. A species of type A could suffer
a base-promoted abstraction of the proton from the thiourea
moiety to give the dianion F, which bears a nucleophilic sulfur at
the homoallylic position suitable for 5-endo-trig cyclization via
19, R = Ph
22, R = Ph
24, R = Ph
23
, R = EtO
20
25
, R = CH3
, R = CH3
21, R = EtO
26, R = EtO
Scheme. 3. Formation of 1,2,4-thiadiazoles 13e26 via tandem nucleophilic addi-
tioneelectrophilic 5-endo-trig cyclization.
2ꢀ
intramolecular concerted SN20 reaction with loss of a SO4 ion.
Although we succeeded in finding the transition state G for this
ꢁ
ꢁ
(1.74 A) and the distance of 2.358 A between central sulfur atom
and the oxygen atom of the neighboring C¼O group is considerably
shorter than the sum of van der Waals radii of a sulfur and an ox-
ꢁ
ygen atom (3.25 A). From the above results one could infer that self-
destruction of the nitrenium ion B initially formed upon NeO bond
heterolysis may lead to a highly electrophilic sulfenium ion D,
which is stabilized by the neighboring sp2-hybridized nitrogen and
oxygen atoms of azine and carbonyl group, respectively. It is
therefore pertinent to note that the electronic and molecular
structure of the mesomer D bears resemblance to the previously
described sulfenium,17 tellurium,18 and siliconium19 ions stabilized
by two neighboring dimethylaminoethyl groups. A characteristic
feature of such structures is the strong dependence of stabilizing
sulfurenitrogen and sulfureoxygen bond strengths and lengths on
the valence state and electronegativity of the attached substituents.
In the case of BeE, the SeN bond approaches values characteristic
of covalent bond, while SeO interaction is typical of SeO hyper-
valent bond governed by the
s interaction between the non-
Fig. 3. The relative electronic energy
(DE) and Gibbs free energy (DG) profiles
bonding orbital of the oxygen atom and the p and d orbitals of
sulfur atom.20 Thus, the electronic and molecular structure of these
species is best represented by the 1,2,4-thiadiazolium cation E.
(298.15 K, kcal/mol) for SN20-type 5-endo-trig cyclization calculated with long-range
and dispersion-corrected
(DMF) solvation model.
u
B97X-D functional22 with 6-31þG
*
basis set using SM823

J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
3615
unusual process, it is prohibited by high energy barrier of 58.3 kcal/
mol, and therefore, should not contribute to the observed mild
cyclization (Fig. 3).
temperature increase from 0 to 298.15 K and entropies. Relative
energies were obtained by subtracting the energy of the lowest-
energy structures (anion or dianion) from the energies of all the
other geometries and converting these differences into kcal/mol.
3. Conclusion
4.2. Cytotoxic activity
In conclusion, we have discovered a new reaction of hydroxyl-
amine-O-sulfonic acid (HOSA) with aza-aromatic chlorides leading
to the previously not described aza-aromatic hydroxylamine-O-
sulfonates 6e10, which may serve as useful precursors of aza-ar-
omatic nitrenium and/or sulfenium ions. The tandem nucleophilic
additioneelectrophilic 5-endo-trig cyclizations of 6e10 have been
explored and the mechanism has been proposed on the basis of DFT
calculations. Given the fact that the field of aza-aromatic nitrenium
ions is still in its infancy, we believe that the results described in
this paper will stimulate further research on the development of
new reactions. Additional studies are ongoing.
All cell lines were obtained from the German Collection of Mi-
croorganisms and Cell Cultures (DSMZ) (Braunschweig, Germany).
Cytotoxicity studies were performed with a well established
microtiter assay based on the staining of adherent cells with crystal
violet; the method has been described in detail in previous publi-
cations.27 DMF stock solutions of the compounds were diluted
1000-fold in cell culture medium (RPMI 1640 medium supple-
mented with 10% FCS) to give the final test concentration. Cells
were continuously exposed to compounds for 96 h at 37 ꢁC in
a humid atmosphere of 5% CO2/air. The IC50 values were estimated
by least squares analysis of the dose response curves to give the
concentration of substance that inhibits cell growth by 50% com-
pared to untreated controls. Reported IC50 values are the averages
of 3e6 independent determinations.
It is pertinent to note that 2-acylimino-[1,2,4]thiadiazolo[2,3-a]
pyrimidine derivatives are of considerable interest in medicinal
chemistry, for instance as antimalarial agents and in the treatment
of flu infections. Compounds 13 and 15 were prepared earlier by
oxidation
of
N1-(2-pyrimidyl)-N2-benzoyl-thioureas
with
bromine.24e26
4.3. General procedure for the heteroaromatic
hydroxylamine-O-sulfonates 6e10
The compounds 21, 24, and 26 were evaluated for their cytotoxic
activity against five human cancer cell lines: uterine cervical ade-
nocarcinoma SISO, lung cancer LCLC and A-427, pancreas adeno-
carcinoma DAN-G, and neural cell line RT-4. They were examined
for their potency of action at five successive concentrations in the
range 1e20 mM. The average IC50 values obtained in these experi-
ments are reported in Table 1. According to these results com-
pounds 21 and 26 exhibit moderate activity (IC50 values in the
range 2.93e23.14 mM), with the RT-4 cell line being the most af-
fected. Compound 24 was the most potent but on the other hand
the least selective one as it shows an antiproliferative activity
against SISO cell line, which is weakly influenced by the remaining
compounds. It appears that benzamide group in position 2 (com-
pound 24) is preferred over ethyl carbamate moiety (compounds 21
and 24), which may suggest that lipophlicity of tested compounds
plays important role.
The corresponding chloroheteroaryl substrate (10 mmol) was
stirred for 12 h at room temperature with hydroxylamine-O-sul-
fonic acid (2.26 g, 20 mmol) in water (2-chloropyrimidines, 5 mL) or
DMF (2-chloroquinolines and 1-chloroisoquinoline, 5 mL). The
precipitated product 6e10 was filtered and washed with a small
portion of pure solvent. In the case of pyrimidin-1-ium-2-ylamino
sulfate (6) the reaction mixture was filtered after 6 h. The products
were dried in desiccator over P2O5 under vacuum and used without
any further purification.
4.3.1. Pyrimidin-1-ium-2-ylamino sulfate (6). A white solid (1.28 g,
67%), mp 225 ꢁC dec; [Found: C, 25.02; H, 2.72; N, 21.79. C4H5N3O4S
requires C, 25.13; H, 2.64; N, 21.98]; nmax (KBr) 3200, 3110, 3033,
2895, 2827, 1625, 1543, 1453, 1337, 1291, 1250, 1207, 1047, 797,
709 cmꢀ1
; dH (500 MHz, DMSO-d6) 7.07 (1H, t, J 5.2 Hz, CH), 8.64
Table 1
(2H, d, J 5.2 Hz, CH), 12.40 (2H, br s, NH); dC (50 MHz, DMSO-d6)
111.5, 155.4, 156.9.
IC50 values (
m
M) ꢂ S.D. in five human cancer cell lines being an average of 3e6 in-
dependent experiments
Compound Cell lines
SISO
4.3.2. 4-Methoxypyrimidin-1-ium-2-ylamino sulfate (7). A white
solid (1.64 g, 74%), mp 212e216 ꢁC; [Found C, 26.99; H, 3.31; N,
18.72. C5H7N3O5S requires C, 27.15; H, 3.19; N, 19.00]; nmax (KBr)
3114, 3028, 2958, 1637, 1490, 1398, 1287, 1264, 1201, 1186, 1060,
LCLC
6.72ꢂ0.91
1.86ꢂ0.09
A-427
DAN-G
RT-4
21
24
26
13.00ꢂ1.12
1.90ꢂ0.08
3.68ꢂ1.17
2.97ꢂ0.55
6.13ꢂ2.53 2.93ꢂ1.79
1.99ꢂ0.08 1.41ꢂ0.51
1004, 851, 825, 733, 629 cmꢀ1
; dH (200 MHz, DMSO-d6) 3.97 (3H, s,
23.15ꢂ2.79 12.94ꢂ0.42 16.12ꢂ5.75 18.01ꢂ1.01 9.13ꢂ2.14
OCH3), 6.51 (1H, d, J 7.0 Hz, CH), 8.08 (1H, d, J 7.0 Hz, CH), 12.85 (2H,
br s, NH); dC (125 MHz, DMSO-d6) 56.3, 101.3, 146.7, 156.0, 172.1.
4. Experimental section
4.1. General
4.3.3. Quinolinium-2-ylamino sulfate (8). A white solid (1.85 g,
77%), mp 210 ꢁC dec; [Found C, 45.12; H, 3.41; N, 11.62. C9H8N2O4S
requires C, 45.00; H, 3.36; N, 11.66]; nmax (KBr) 3530, 3456, 3171,
3051, 2858, 2760, 1665, 1616, 1401, 1295, 1269, 1220, 1072, 1043,
All the calculations presented in this paper were carried out
with the Spartan 08 program package provided by Wavefunction,
Inc. The geometries were fully optimized in vacuum with DFT
825, 778, 741, 690 cmꢀ1
; dH (500 MHz, DMSO-d6) 7.04 (1H, d, J
9.5 Hz, CH), 7.47 (1H, t, J 7.8 Hz, CH), 7.74 (1H, t, J 7.8 Hz, CH), 7.88
(1H, d, J 7.8 Hz, CH), 8.07 (1H, d, J 7.8 Hz, CH), 8.33 (1H, d, J 9.5 Hz,
CH), 13.30 (2H, br s, NH); dC (50 MHz, DMSO-d6) 110.2, 118.2, 121.6,
125.4, 128.8, 132.5, 135.6, 142.5, 150.8.
u
B97X-D22 or B3LYP method using diffuse functions 6-31þG
*
basis
set. Frequency calculations were performed for all structures to
prove the energy minima. The geometry of the transition state
found showed single imaginary frequency pertaining the NeS bond
formation and NeO bond breakage. The reaction energy profiles
4.3.4. 4-Methylquinolinium-2-ylamino sulfate (9). A white solid
(1.63 g, 64%), mp 228 ꢁC dec; [Found C, 47.17; H, 4.22; N, 10.81.
C10H10N2O4S requires C, 47.24; H, 3.96; N, 11.02]; nmax (KBr) 3160,
3074, 2973, 2934, 2884, 1666, 1613, 1299, 1263, 1248, 1231, 1057,
were derived from DFT
u
B97X-D/6-31þG
*
calculations with ap-
plication of DMF SM823 solvation models. The Gibbs free energies
were obtained from the electronic energies corrected with the
zero-point vibrational energies (ZPE), thermal energies involving
845, 766, 736, 618 cmꢀ1
; dH (200 MHz, DMSO-d6) 2.63 (3H, s, CH3),

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J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
6.89 (1H, s, CH), 7.48e7.55 (1H, m, CH), 7.73e7.80 (1H, m, CH), 7.97
(1H, d, J 8.0 Hz, CH), 8.10 (1H, d, J 8.0 Hz, CH), 13.20 (2H, br s, NH); dC
(50 MHz, DMSO-d6) 19.3, 108.9, 118.8, 122.1, 125.6 (two signals),
132.5, 135.6, 150.6, 152.3.
until the slightly exothermic reaction had subsided (ca. 10 min)
Upon treatment of the reaction mixture with a second equivalent of
triethylamine (0.35 mL, 2.5 mmol), the desired product pre-
cipitated. Compounds 13e19, 21e24, or 26 thus obtained were
collected by suction, washed with DMF and purified by crystalli-
zation from DMF. Compounds 20 and 25, which are soluble in DMF
were isolated upon quenching the reaction mixture with water
(5 mL) followed by extraction with methylene chloride (2ꢃ5 mL).
The combined organic layers were dried over anhydrous sodium
sulfate and evaporated under reduced pressure. The oily residue
thus obtained was purified on silica with use of Chromatotron
(CH2Cl2).
4.3.5. Isoquinolinium-1-ylamino sulfate (10). A white solid (1.42 g,
59%), mp 207e210 ꢁC; [Found C, 44.88; H, 3.49; N, 11.38. C9H8N2O4S
requires C, 45.00; H, 3.36; N, 11.66]; nmax (KBr) 3164, 3076, 2922,
1655, 1622, 1606, 1551, 1490, 1376, 1307, 1256, 1234, 1212, 1067,
1007, 799, 706, 614 cmꢀ1
; dH (200 MHz, DMSO-d6) 7.29 (1H, d, J
7.0 Hz, CH), 7.63e7.98 (4H, m, CH), 8.43 (1H, d, J 7.0 Hz, CH), 12.97
(2H, br s, NH); dC (50 MHz, DMSO-d6) 112.6, 115.3, 124.8, 127.9,
128.0, 129.1, 134.9, 136.7, 150.6.
4.5.1. N-(2H-[1,2,4]Thiadiazolo[2,3-a]pyrimidin-2-ylidene)benza-
mide (13). A white solid (0.34 g, 53%), mp 260 ꢁC dec (lit. 24 mp
230 ꢁC); [Found C, 56.01; H, 3.32; N, 21.57. C12H8N4OS requires C,
56.24; H, 3.15; N, 21.86]; nmax (KBr) 3107, 3055, 1605, 1534, 1522,
4.4. Generalprocedurefortheformationof(4-pyrimidylamino)-
diazopyrimidines 11, 11a, and 12
Compound 6 or 7 (0.01 mol) was dissolved in a 10% aqueous
solution of K2CO3 (25 mL) and the reaction mixture was left at room
temperature for 6 days. The red-colored solid that precipitated was
collected by filtration and purified by crystallization from DMF
(compound 11) or by preparative TLC using Chromatotron (12).
Crystals of 11a suitable for X-ray analysis were obtained by slow
evaporation of the solution of equimolar amounts of 11 (0.28 g,
1 mmol) and imidazole (68 mg, 1 mmol) in methanol/water (2:1).
1479,1452,1438,1381,1349,1174, 939, 714, 682 cmꢀ1
; dH (200 MHz,
DMSO-d6) 7.48 (1H, dd, 3J¼6.3 Hz, 3J¼4.5 Hz, CH), 7.54e7.67 (3H, m,
CH), 8.24e8.28 (2H, m, CH), 9.12 (1H, dd, 3J¼4.5 Hz, 4J¼2.1 Hz, CH),
9.44 (1H, dd, 3J¼6.3 Hz, 4J¼2.1 Hz, CH); dC (125 MHz, CF3COOH/
C6D6) 116.8, 129.0, 129.7, 135.5,137.2, 144.2, 156.7, 164.1, 170.4, 170.8.
4.5.2. N-(2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-ylidene)acetamide
(14). A white solid (0.09 g, 19%), mp 220 ꢁC dec; [Found C, 42.97; H,
3.37; N, 28.63. C7H6N4OS requires C, 43.29; H, 3.11; N, 28.85]; nmax
(KBr) 3103, 3054, 3032, 2995, 1607, 1533, 1488, 1456, 1375, 1337,
4.4.1. N-(2-(Pyrimidin-2-yldiazenyl)pyrimidin-5-yl)pyrimidin-2-
amine (11). An orange solid (0.28 g, 30%), mp 234e236 ꢁC; [Found
C, 51.50; H, 3.51; N, 44.87. C12H9N9 requires C, 51.61; H, 3.25; N,
45.14]; nmax (KBr) 3415, 3252, 3166, 3079, 3017, 1606, 1569, 1528,
1257, 1020, 997, 808, 788, 732, 684 cmꢀ1
; dH (200 MHz, CF3COOH/
C6D6) 2.27 (3H, s, CH3), 6.98 (1H, t, J 5.0 Hz, CH), 8.28 (1H, d, J 5.0 Hz,
CH), 8.70 (1H, d, J 5.0 Hz, CH); dC (50 MHz, CF3COOH/C6D6) 20.1,
117.2, 144.9, 157.6, 164.4, 169.8, 177.0.
1499, 1450, 1419, 1392, 1211, 821 cmꢀ1
; dH (500 MHz, DMSO-d )
6
7.08 (1H, t, J 4.9 Hz, CH), 7.71 (1H, t, J 4.9 Hz, CH), 8.66 (2H, d, J
4.9 Hz, CH), 9.07 (2H, d, J 4.9 Hz, CH), 9.46 (2H, s, CH), 10.58 (1H, s,
NH); dC (125 MHz, DMSO-d6) 115.1, 122.8, 137.6, 147.7, 159.2, 159.8,
160.1, 160.6, 167.8.
4.5.3. Ethyl 2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-ylidenecarba-
mate (15). A white solid (0.21 g, 37%); mp 238e240 ꢁC (lit. 26 mp
237e240 ꢁC); [Found C, 42.56; H, 3.93; N, 24.69. C8H8N4O2S re-
quires C, 42.85; H, 3.60; N, 24.99]; nmax (KBr) 3083, 2987,1593,1531,
1481, 1455, 1406, 1382, 1367, 1329, 1302, 1227, 1210, 1126, 1074, 912,
4.4.2. N-(2-(Pyrimidin-2-yldiazenyl)pyrimidin-5-yl)pyrimidin-2-
amine x imidazole (11a). A red solid (0.26 g, 76%), mp 247e250 ꢁC;
nmax (KBr) 3449, 3177, 3117, 3078, 2932, 1629, 1568, 1525, 1495,
816, 788 cmꢀ1
; dH (500 MHz, DMSO-d6) 1.29 (3H, t, J 7.0 Hz, CH3),
4.27 (2H, q, J 7.0 Hz, CH2), 7.38e7.40 (1H, m, CH), 9.03e9.04 (1H, m,
CH), 9.35e9.37 (1H, m, CH); dC (50 MHz, CF3COOH) 12.8, 68.6, 116.8,
144.9, 156.8, 158.6, 164.5, 172.7.
1447, 1422, 1381, 1258, 1206, 1078 cmꢀ1
; dH (500 MHz, DMSO-d )
6
7.00 (2H, br s, CH), 7.08 (1H, t, J 4.9 Hz, CH), 7.62 (1H, s, CH), 7.71 (1H,
t, J 4.9 Hz, CH), 8.66 (2H, d, J 4.9 Hz, CH), 9.07 (2H, d, J 4.9 Hz, CH),
9.46 (2H, s, CH), 10.58 (1H, s, NH), 12.00 (1H, br s, NH); dC (125 MHz,
DMSO-d6) 115.1, 122.8, 135.8, 137.6, 147.7, 159.2, 159.8, 160.1, 160.6,
167.8.
4.5.4. N-(5-methoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-yli-
dene)benzamide (16). A white solid (0.30 g, 42%), mp 250e253 ꢁC;
[Found C, 54.48; H, 3.63; N, 19.39. C13H10N4O2S requires C, 54.54; H,
3.52; N, 19.57]; nmax (KBr) 3091, 3064, 2954, 1610, 1522, 1506, 1447,
4.4.3. 4-Methoxy-N-(4-methoxy-2-((4-methoxypyrimidin-2-yl)dia-
zenyl)pyrimidin-5-yl)pyrimidin-2-amine (12). An orange solid
(0.41 g, 33%), mp 175e178 ꢁC; [Found C, 48.72; H, 4.33; N, 33.85.
C15H15N9O3 requires C, 48.78; H, 4.09; N, 34.13]; Rf (AcOEt) 0.22;
nmax (KBr) 3421, 2951, 1584, 1562, 1527, 1488, 1423, 1405, 1376, 1331,
1355, 1257, 1028, 976, 777, 720 cmꢀ1
; dH (500 MHz, CF3COOD) 3.93
(3H, s, OCH3), 6.73 (1H, d, J 6.8 Hz, CH), 7.31 (2H, t, J 7.0 Hz, CH), 7.48
(1H, t, J 7.0 Hz, CH), 7.88 (2H, d, J 7.0 Hz, CH), 8.48 (d, J 6.8 Hz, 1H,
CH); dC (125 MHz, CF3COOD) 57.5, 109.3, 126.6, 130.2, 131.0, 138.2,
142.9, 160.2, 171.9, 173.1, 174.6.
1193,1021 cmꢀ1
; dH (500 MHz, CDCl3) 4.02 (3H, s, OCH3), 4.12 (3H, s,
OCH3), 4.26 (3H, s, OCH3), 6.35 (1H, d, J 5.8 Hz, CH), 6.82 (1H, d, J
5.8 Hz, CH), 7.66 (1H, br s, NH), 8.23 (1H, d, J 5.8 Hz, CH), 8.62 (1H, d,
J 5.8 Hz, CH), 9.93 (1H, s, CH); dC (50 MHz, CDCl3) 54.7, 55.0, 55.7,
101.7, 109.1, 124.7, 143.6, 158.1, 158.8, 159.0, 159.1, 159.5, 167.5, 171.0,
171.6.
4.5.5. N-(5-methoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-yli-
dene)acetamide (17). A white solid (0.09 g, 16%), mp 221 ꢁC dec;
[Found C, 42.77; H, 3.84; N, 24.80. C8H8N4O2S requires C, 42.85; H,
3.60; N, 24.99]; nmax (KBr) 3092, 3051, 3001, 2949, 1624, 1531, 1514,
1412, 1378, 1275, 1267, 1042, 1000, 823, 776 cmꢀ1
; dH (200 MHz,
CF3COOH/C6D6) 2.25 (s, 3H, CH3), 3.93 (s, 3H, OCH3), 6.47 (1H, d, J
7.0 Hz, CH), 7.78 (1H, d, J 7.0 Hz, CH); dC (50 MHz, CF3COOH/C6D6)
20.2, 56.6, 108.2, 141.5, 158.8, 170.6, 173.2, 176.2.
4.5. General procedure for the reactions of heteroaromatic
hydroxylamine-O-sulfonates with acyl isothiocyanates
A suspension of corresponding heteroarylinium-ylamino sulfate
6e10 (2.5 mmol) in DMF (3 mL) was treated with triethylamine
(0.35 mL, 2.5 mmol) at room temperature and the resulting mixture
was stirred until a clear solution was obtained (ca. 2 min). Then, the
suitable acyl isothiocyanate was added and stirring was continued
4.5.6. Ethyl 5-methoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-yli-
denecarbamate (18). A white solid (0.23 g, 36%), mp 214e215 ꢁC;
[Found C, 42.46; H, 4.06; N, 21.97. C9H10N4O3S requires C, 42.51; H,
3.96; N, 22.03]; nmax (KBr) 3093, 2984, 2914, 1626, 1593, 1544, 1519,
1497, 1441, 1374, 1333, 1270, 1256, 1223, 1072, 1010, 970, 824,

J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
3617
787 cmꢀ1
;
dH (500 MHz, CF3COOH/C6D6) 1.27 (3H, t, J 7.0 Hz, CH3),
121.1, 122.1, 124.2, 125.9, 126.1, 128.0, 129.0, 129.9, 131.4, 135.7, 136.1,
136.7, 155.2, 168.3, 169.8.
3.97 (3H, s, OCH3), 4.35 (2H, q, J 7.0 Hz, CH2), 6.56 (1H, d, J 7.3 Hz,
CH), 7.93 (1H, d, J 7.3 Hz, CH); dC (50 MHz, CF3COOH/C6D6) 12.7, 56.4,
68.1, 107.7, 141.3, 156.1, 159.6, 172.9, 173.2.
4.5.13. N-(2H-[1,2,4]thiadiazolo[3,2-a]isoquinolin-2-ylidene)acet-
amide (25). A white solid (0.09 g, 15%), mp 248 ꢁC dec; [Found C,
58.89; H, 4.02; N, 17.00. C12H9N3OS requires C, 59.24; H, 3.73; N,
17.27]; Rf (AcOEt) 0.57; nmax (KBr) 3102, 3048, 2923, 2853, 1630,
4.5.7. N-(2H-[1,2,4]thiadiazolo[2,3-a]quinolin-2-ylidene)benzamide
(19). A white solid (0.25 g, 33%), mp 283e285 ꢁC; [Found C, 67.01;
H, 3.97; N, 13.80. C17H11N3OS requires C, 66.87; H, 3.63; N, 13.76];
nmax (KBr) 3067, 2923, 1615, 1587, 1518, 1474, 1446, 1399, 1337, 1295,
1545, 1506, 1423, 1381, 1361, 1340, 982, 815, 746, 701 cmꢀ1
; dH
(200 MHz, CF3COOH/C6D6) 2.29 (3H, s, CH3), 7.25 (1H, d, J 7.0 Hz,
CH), 7.49 (1H, d, J 7.0 Hz, CH), 7.63e7.77 (3H, m, CH), 8.51 (1H, d, J
7.8 Hz, CH); dC (50 MHz, CF3COOH/C6D6) 20.3, 121.1, 122.7, 124.3,
126.6, 128.0, 131.5, 135.8, 136.0, 158.8, 166.9, 175.2.
1275,1221, 1163, 1122, 899, 750, 722, 701 cmꢀ1
; dH (500 MHz,
DMSO-d6) 7.58 (2H, t, J 7.3 Hz, CH), 7.65 (1H, t, J 7.3 Hz, CH), 7.70 (1H,
t, J 7.8 Hz, CH), 7.85 (1H, d, J 9.0 Hz, CH), 7.95 (1H, t, J 7.8 Hz, CH), 8.18
(1H, d, J 7.8 Hz, CH), 8.28 (2H, d, J 7.3 Hz, CH), 8.34 (1H, d, J 7.8 Hz,
CH), 8.53 (1H, d, J 9.0 Hz, CH); dC (50 MHz, CF3COOH/C6D6) 116.0,
118.0, 126.0, 126.4, 129.6, 130.2, 130.5, 131.3, 135.3, 135.6, 137.5,
144.4, 154.9, 169.1, 170.1.
4.5.14. Ethyl 2H-[1,2,4]thiadiazolo[3,2-a]isoquinolin-2-ylidenecarba-
mate (26). A white solid (0.43 g, 63%), mp 233e235 ꢁC; [Found C,
57.10; H, 4.29; N, 15.08. C13H11N3O2S requires C, 57.13; H, 4.06; N,
15.37]; nmax (KBr) 3052, 2988, 2919, 1630, 1579, 1562, 1513, 1393,
4.5.8. N-(2H-[1,2,4]thiadiazolo[2,3-a]quinolin-2-ylidene)acetamide
(20). A white solid (0.05 g, 8%), mp 230 ꢁC dec; [Found C, 59.08; H,
3.87; N, 16.99. C12H9N3OS requires C, 59.24; H, 3.73; N, 17.27]; Rf
(AcOEt) 0.57; nmax (KBr) 3048, 1630, 1546, 1506, 1423, 1381, 1361,
1378, 1361, 1329, 1241, 1222, 1131, 1112, 1086, 805, 747, 696 cmꢀ1
; dH
(200 MHz, CF3COOH/C6D6) 1.27 (3H, t, J 7.2 Hz, CH3), 4.32 (2H, q, J
7.2 Hz, CH2), 7.21 (1H, d, J 7.1 Hz, CH), 7.45 (1H, d, J 7.1 Hz, CH),
7.61e7.75 (3H, m, CH), 8.45 (1H, d, J 8.1 Hz, CH); dC (50 MHz,
CF3COOH/C6D6) 13.0, 67.7, 120.8, 122.6, 124.4, 126.8, 128.0, 131.5,
135.9, 136.0, 156.2, 157.5, 170.2.
1340, 982, 815, 746, 701 cmꢀ1
; dH (500 MHz, CF3COOH/C6D6) 2.19
(3H, s, CH3), 7.06 (1H, d, J 6.8 Hz, CH), 7.27 (1H, d, J 6.8 Hz, CH), 7.51
(1H, d, J 7.8 Hz, CH), 7.56e7.59 (2H, m, CH), 7.61e7.64 (2H, m, CH),
8.43 (1H, d, J 7.8 Hz, CH); dC (50 MHz, CF3COOH/C6D6) 20.5, 121.1,
122.7, 124.3, 126.6, 128.0, 131.5, 135.8, 136.0, 155.8, 166.9, 175.2.
Supplementary data
General experimental details; crystallographic data; Cartesian
coordinates, computed electronic energies, and Gibbs free energies
for structures A, E, F, G and 15 along with relative energies reported
in the paper; exemplary 1H NMR, 13C NMR, and IR spectra for
compounds 8, 16, 19, and 20. Supplementary data related to this
article can be found online at doi:10.1016/j.tet.2011.03.091.
4.5.9. Ethyl 2H-[1,2,4]thiadiazolo[2,3-a]quinolin-2-ylidenecarbamate
(21). A white solid (0.20 g, 30%), mp 208e213 ꢁC; [Found C, 56.89;
H, 4.34; N, 15.20. C13H11N3O2S requires C, 57.13; H, 4.06; N, 15.37];
nmax (KBr) 3028, 2976, 2926, 1592, 1576, 1494, 1448, 1410, 1368,
1317, 1274, 1194, 1078, 832, 789, 754 cmꢀ1
; dH (200 MHz, CF3COOH/
C6D6) 1.25 (3H, t, J 7.2 Hz, CH3), 4.29 (2H, q, J 7.2 Hz, CH2), 7.17 (1H, d,
J 9.0 Hz, CH), 7.32e7.60 (4H, m, CH), 7.86 (1H, d, J 9.0 Hz, CH); dC
(50 MHz, CF3COOH/C6D6) 13.2, 67.8, 116.2, 117.7, 125.1, 129.6, 130.9,
134.7, 135.0, 143.6, 156.0, 156.5, 170.3.
References and notes
1. Examples of nucleophilic 5-endo-trig cyclizations: (a) Ichikawa, J.; Wada, Y.;
Fujiwara, M.; Sakoda, K. Synthesis 2002, 1917e1936; (b) Sakoda, K.; Mihara, J.;
Ichikawa, J. Chem. Commun. 2005, 4684e4686; (c) Ohno, H.; Kadoh, Y.; Fujii, N.;
Tanaka, T. Org. Lett. 2006, 8, 947e950; (d) Ichikawa, J.; Iwai, Y.; Nadano, R.; Mori,
T.; Ikeda, M. Chem.dAsian J. 2008, 3, 393e406; (e) Jones, A. D.; Redfern, A. L.;
Knight, D. W.; Morgan, I. R.; Williams, A. C. Tetrahedron 2006, 62, 9247e9257.
2. Examples of electrophilic 5-endo-trig cyclizations: (a) Tanabe, H.; Ichikawa, J.
Chem. Lett. 2010, 39, 248e249; (b) Bravo, F.; Castillon, S. Eur. J. Org. Chem. 2001,
507e516; (c) Andrey, O.; Ducry, L.; Landais, Y.; Planchenault, D.; Weber, V.
Tetrahedron 1997, 53, 4339e4352; (d) Jones, A. D.; Knight, D. W.; Redfern, A. L.;
Gilmore, J. Tetrahedron Lett. 1999, 40, 3267e3270.
3. Examples of radical 5-endo-trig cyclizations: (a) Bommezijn, S.; Martin, C. G.;
Kennedy, A. R.; Lizos, D.; Murphy, J. A. Org. Lett. 2001, 3, 3405e3407; (b) Ta-
niguchi, T.; Tamura, O.; Uchiyama, M.; Muraoka, O.; Tanabe, G.; Ishibashi, H.
Synlett 2005, 1179e1181; (c) Bogen, S.; Goddard, J.-P.; Fensterbank, L.; Malacria,
M. ARKIVOC 2008, 8, 126e138.
4. (a) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734e736; (b) Baldwin, J. E.;
Cutting, J.; Dupont, W.; Kruse, L.; Silberman, L.; Thomas, R. C. J. Chem. Soc.,
Chem. Commun. 1976, 736e738; (c) Baldwin, J. E.; Thomas, R. C.; Kruse, L. I.;
Silberman, L. J. Org. Chem. 1977, 42, 3846e3852.
5. Sa˛czewski, J.; Gdaniec, M. Tetrahedron Lett. 2007, 48, 7624e7627.
6. Sa˛czewski, J.; Gdaniec, M. Eur. J. Org. Chem. 2010, 2387e2394.
7. Recent examples of amination of heteroaromatic chalides: (a) Lundgren, R. J.;
Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49,
4071e4074; (b) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.dEur. J. 2006,
12, 5142e5148; (c) Meng, F.; Zhu, X.; Li, Y.; Xie, J.; Wang, B.; Yao, J.; Wan, Y. Eur. J.
Org. Chem. 2010, 6149e6152; (d) Cherng, Y.-J. Tetrahedron 2002, 58, 887e890;
Bonnet, V.; Mongin, F.; Trecourt, F.; Queguiner, G.; Knochel, P. Tetrahedron 2002,
58, 4429e4438.
4.5.10. N-(5-methyl-2H-[1,2,4]thiadiazolo[2,3-a]quinolin-2-ylidene)
benzamide (22). A white solid (0.42 g, 52%), mp 295 ꢁC dec; [Found
C, 67.71; H, 4.29; N, 13.19. C18H13N3OS requires C, 67.69; H, 4.10; N,
13.16]; nmax (KBr) 3093, 2984, 2914, 1626, 1593, 1544, 1519, 1497,
1441, 1374, 1333, 1270, 1256, 1223, 1072, 1010, 970, 824, 787 cmꢀ1
;
dH (200 MHz, CF3COOH/C6D6) 2.34 (3H, s, CH3), 7.11e7.65 (7H, m,
CH), 7.66e7.70 (1H, m, CH), 8.02e8.08 (2H, m, CH); dC (50 MHz,
CF3COOH/C6D6) 19.3, 115.9, 118.2, 125.7, 126.4, 127.3, 129.4, 129.5,
130.3, 134.3, 134.6, 137.1, 154.0, 155.0, 168.3, 169.5.
4.5.11. Ethyl 5-methyl-2H-[1,2,4]thiadiazolo[2,3-a]quinolin-2-ylide-
necarbamate (23). A white solid (0.33 g, 46%), mp 207e213 ꢁC dec;
[Found C, 58.31; H, 4.88; N, 14.63. C14H13N3O2S requires C, 58.52; H,
4.56; N, 14.62]; nmax (KBr) 3062, 2985, 2932, 1618, 1566, 1523, 1488,
1454, 1406, 1367, 1321, 1291, 1253, 1222, 1092, 1076, 790, 750 cmꢀ1
;
dH (200 MHz, CF3COOH/C6D6) 1.28 (3H, t, J 7.2 Hz, CH3), 2.46 (3H, s,
CH3), 4.32 (2H, q, J 7.2 Hz, CH2), 7.29e7.31 (2H, m, CH), 7.51e7.66
(2H, m, CH), 7.76e7.80 (1H, m, CH); dC (50 MHz, CF3COOH/C6D6)
13.1, 19.0, 67.8, 116.0, 118.2, 125.5, 127.3, 129.5, 134.2, 134.7, 155.2,
155.8, 155.9, 170.3.
4.5.12. N-(2H-[1,2,4]thiadiazolo[3,2-a]isoquinolin-2-ylidene)benza-
mide (24). A white solid (0.44 g, 58%), mp 283e285 ꢁC; [Found C,
66.74; H, 3.77; N, 13.65. C17H11N3OS requires C, 66.87; H, 3.63; N,
13.76]; nmax (KBr) 3110, 3056, 1630, 1523, 1503, 1445, 1379, 1355,
8. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; John Wiley & Sons:
New York, NY, 1967; 481.
9. Wallace, R. G. Org. Prep. Proced. Int. 1982, 14, 265e307.
10. Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, 2000.
11. Sa˛czewski, F.; Sa˛czewski, J.; Gdaniec, M. J. Org. Chem. 2003, 68, 4791e4796.
12. Takeuchi, H.; Watanabe, K. J. Phys. Org. Chem. 1998, 11, 478e484.
13. Sullivan, M. B.; Cramer, C. J. J. Am. Chem. Soc. 2000, 122, 5588e5596.
14. Cramer, C. J.; Falvey, D. E. Tetrahedron Lett. 1997, 38, 1515e1518.
15. Di Stefano, M.; Rosi, M.; Sgamellotti, A.; Negri, F. Chem. Phys. 2004, 302,
295e308.
1237, 1129, 925, 797, 719, 695, 687 cmꢀ1
; dH (500 MHz, CF3COOH/
C6D6) 7.27e7.35 (1H, m, CH), 7.39e7.46 (2H, m, CH), 7.53e7.62 (2H,
m, CH), 7.66e7.72 (2H, m, CH), 7.73e7.79 (1H, m, CH), 7.98e8.04
(2H, m, CH), 11.37 (1H, d, J 7.8 Hz, CH); dC (50 MHz, CF3COOH/C6D6)

3618
J. Saczewski et al. / Tetrahedron 67 (2011) 3612e3618
16. For review see: (a) Borodkin, G. I.; Shubin, V. G. Russ. Chem. Rev. 2008, 77,
395e419; (b) Borodkin, G. I.; Shubin, V. G. Russ. J. Org. Chem. 2005, 41, 473e504.
17. (a) Kobayashi, K.; Sato, S.; Horn, E.; Furukawa, N. Tetrahedron Lett. 1998, 39,
2593e2596; (b) Gressenbuch, M.; Kersting, B. Z. Anorg. Allg. Chem. 2010, 636,
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