Imidazoline-4-thiones from cyanothioformamides and aldehyde imines: Formation, aromatization, and acetylation

Article abstract of DOI:10.1002/jhet.333

(Chemical Equation Presented) The reaction of N-methyl- (3a) or N-phenylcyanothioformamide (3b) with acetaldimine (5a, as 1-amino-1-ethanol) gives 5-(amino)imidazolidine-4-thiones 6B. Product 6a reacts with a second equivalent of 3a to give 8 which in turn is oxidized to disulfide 9. Using araldimines 5b,c, only 1:2 intermediates 10 derived from 3a, b and two moles of the imine 5 are formed, but proved to be easily oxidized to disulfides 11. Acetylation of 6 occurs chemoselectively on the exocyclic nitrogen and finally also on the thione sulfur to give 14 via 13.

Full text of DOI:10.1002/jhet.333

March 2010
Imidazoline-4-thiones from Cyanothioformamides and Aldehyde
Imines: Formation, Aromatization, and Acetylation
425
Ahmed M. Sh. El-Sharief,a Roger Ketcham,b Monika Ries,c
Ernst Schaumann,c* and Gunadi Adiwidjajad
aFaculty of Science, Chemistry Department, Taibah University Al-madinah, Al-munawwarah,
Kingdom of Saudi Arabia
bSchool of Pharmacy, University of California, San Francisco, California 94143-0446
cClausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6,
38678 Clausthal-Zellerfeld, Germany
d
¨
Mineralogisch-Petrographisches Institut der Universitat Hamburg, Grindelallee 46,
20146 Hamburg, Germany
*E-mail: ernst.schaumann@tu-clausthal.de
Received July 2, 2009
DOI 10.1002/jhet.333
Published online 4 March 2010 in Wiley InterScience (www.interscience.wiley.com).
The reaction of N-methyl- (3a) or N-phenylcyanothioformamide (3b) with acetaldimine (5a, as 1-
amino-1-ethanol) gives 5-(amino)imidazolidine-4-thiones 6B. Product 6a reacts with a second equivalent
of 3a to give 8 which in turn is oxidized to disulfide 9. Using araldimines 5b,c, only 1:2 intermediates
10 derived from 3a, b and two moles of the imine 5 are formed, but proved to be easily oxidized to
disulfides 11. Acetylation of 6 occurs chemoselectively on the exocyclic nitrogen and finally also on the
thione sulfur to give 14 via 13.
J. Heterocyclic Chem., 47, 425 (2010).
INTRODUCTION
6 are also of special interest as precursors of the elusive
bicyclic heteroaromatic products of type 12 (Scheme 5).
There is continuing interest in the design and evolu-
tion of novel antioxidants as a means to alleviate oxida-
tive stress in biochemical processes [1–3]. For the
heterocyclic chemist, an attractive lead structure appears
to be the unusual amino acid family of ovothiols 1a–c
[4–7]. So, imidazole-4-thiols 2 have become attractive
targets for synthesis (Scheme 1).
RESULTS AND DISCUSSION
We selected N-methyl- (3a) and N-phenylcyanothio-
formamide (3b) as nucleophiles, and acetaldimine 5a (as
1-amino-1-ethanol [17]) or benzaldimines 5b,c as elec-
trophiles. Triethylamine was used as a catalyst.
N-Acylaminoacid thioamides are possible precursors of
ovothiols 1 [4], but their cyclization is not always repro-
ducible [5]. Similarly, the Asinger group has reported the
formation of imidazolethiols 2 from a-oxothioamides and
aldimines [8]. Recently, we have reported the synthesis of
oxazolidines 4 from cyanothioformamides 3 and alde-
hydes or ketones [9] as part of our study on heterocyclic
ring-closure reactions [10–16] and now envisaged that
cyanothioformamides 3 and N-unsubstituted aldimines
should give products of type 2, though with a 5-amino
group as additional feature which may assist in free-radi-
cal trapping. However, the position of the tautomeric equi-
librium in the probable cyclization products 6 between
iminothiones 6A, aminothiones 6B, and aminothiols 6C is
a priori open (Scheme 2). On the other hand, heterocycles
Thioamide 3a and acetaldimine 5a give a smooth
reaction to furnish 1:1 product 6a as the only defined
Scheme 1. Imidazole-4-thiols.
C
V
2010 HeteroCorporation

426
A. M. S. El-Sharief, R. Ketcham, M. Ries, E. Schaumann, and G. Adiwidjaja
Vol 47
Scheme 2. Reactions of cyanothioformamides with aldehydes or acetaldimine.
product. An analogous product 6b is formed from thio-
amide 3b und 5a (Scheme 2). As to the position of the
tautomeric equilibrium, appearance of the 2-methyl sig-
Reactions of thioamides 3 with aromatic aldimines
5b,c take a different course (Scheme 4). Here, invariably
dehydrogenated 2:1 products 11a–c are formed obvi-
ously via intermediate 6, followed by Schiff base forma-
tion with a second equivalent of the imine 5 to give
azomethines 10 with loss of ammonia, and finally oxi-
dative aromatization. Even when the reactions were run
under nitrogen, conventional work-up led to oxidation
to give the aromatic disulfides 11. So, there is a strik-
ing difference in the sensitivity to oxidation between
the 2-methyl (R2 ¼ Me) products 6a,b and their 2-aryl
congeners 10.
1
nal of 6a as a doublet in the H NMR spectrum and a
low-field 13C NMR signal (ca. 182 ppm) pointing to-
ward the presence of a thiocarbonyl carbon as in 6A
and 6B allow to rule out tautomer 6C. Another low-field
13C NMR peak at d about 159 ppm occurs at definitely
lower field than for the exocyclic imino group in model
compound 7 (d 154.2 ppm) [10,11,18], and in the 1H
NMR spectrum, the two NH protons are magnetically
equivalent as expected for 6B. Moreover, the IR spectra
lack a strong vibration in the 1650–1670 cmꢀ1 range
which is observed for 7 (1659 cmꢀ1) and in other
authentic 5-imino-imidazolidine-4-thiones [13,18]. So
obviously, tautomer 6B is preferred indicating that the
greatest degree of stabilization is achieved by conjuga-
tion within the transoid S¼¼CAC¼¼N unit of tautomer
6B when compared with the corresponding cisoid sys-
tem in 6A or the aromaticity of 6C.
Attempts to cyclize 6a,b using acetic anhydride gave
no indication for the formation of the bicyclic hetarene
12, but simple monoacetylation is observed (Scheme 5).
The spectroscopic data allow no unambiguous
Scheme 3. Oxidation of imidazolinethione 6a.
Prolonged reaction times in the addition of 3a to 5a
showed that the thioamide 3a adds faster to cyclization
product 6a than to 5a giving rise to a 2:1 adduct 8 as
well as aromatic disulfide 9 as oxidation product
(Scheme 3).
An X-ray crystallographic study revealed the structure
of 9 and so implicitly also of precursor 8. As the spec-
troscopic data for 8 are similar to those of 6, we assume
that the imidazole unit in 8 has structure B as in the pre-
ferred tautomer B of 6. In the formation of 8, the second
mole of 3a has been incorporated via its nitrile function
by addition to the exocyclic imino group of 6a and this
is obviously followed by aromatization and oxidation to
the disulfide 9 (Fig. 1).
Journal of Heterocyclic Chemistry
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March 2010
Imidazoline-4-thiones from Cyanothioformamides and Aldehyde Imines:
Formation, Aromatization, and Acetylation
427
˚
Figure 1. ORTEP drawing of disulfide 9 with salient bond lengths [A]: S51-C5 1.840(9), S51-S151 2.176(4), N1-C2 1.367(11), N3-C2 1.323(10),
N3-C4 1.402(10), C4-C5 1.395(10), N41-C42 1.298(9), N43-C42 1.385(10), S45-C-44 1.676(8), N46-C44 1.295(9), S151-C105 1.712(7), N101-
C105 1.405(9), N101-C102 1.356(9), N103-C102 1.320(9), N103-C104 1.365(8), C104-C105 1.401(10), N141-C142 1.270(8), N143-C142 1.331(9),
S145-C144 1.751(8), N146-C144 1.303(10).
distinction between acetylation of the endocyclic or the
exocyclic nitrogen, but further acetylation of the product
derived from 6b yields a triacetylated product for which
structure 14 is suggested based on the magnetic equiva-
lence of two acetyl residues. Mutatis mutandis this leads
to structure 13 for the N-monoacetylated products. Simi-
larly, monoacetylation in the exocyclic position is
observed when the hydrolysis product 15 of imine 6a is
acetylated to give apparently an ester derivative 16. This
is evident particularly from the high-wavenumber car-
bonyl absorptions (1762, 1731 cmꢀ1) of the product.
CONCLUSIONS
The reaction of cyanothioformamides 3 with aldi-
mines 5 takes the expected initial course when the
Scheme 5. Acylation of imidazolinethiones 6.
Scheme 4. Cyanothioformamides and araldimines.
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A. M. S. El-Sharief, R. Ketcham, M. Ries, E. Schaumann, and G. Adiwidjaja
Vol 47
2-(1,2-Dimethyl-5-mercaptoimidazol-4-yl)amino-2-imino-N-
methyl-thioacetamide (8B) and bis[4-(imino-(N-methylthiocarba-
moyl)methyl)amino-1,2-dimethylimidazol-5-yl] disulfide (9). An
ethereal (20 mL) solution of 3a (3.24 g, 20 mmol), 6a (3.66 g,
20 mmol), and triethylamine (three drops) was stirred at 20ꢁC
for 30 min and then allowed to stand for 16 h. The solid prod-
uct was extracted several times with cold ethanol. The remain-
ing solid was recrystallized from boiling ethanol to give 8 as
yellow crystals (9.73 g, 20%); m.p. 173–175ꢁC. IR (KBr): v~ ¼
nitrogen in the thioamide moiety in 3 attacks the elec-
trophilic imine carbon of 5, whereas the nitrile function
provides the opportunity for subsequent cyclization to
give imidazolidines 6. However, among the possible tau-
tomers 6B is apparently preferred and can be isolated
for R2 ¼ methyl whereas compounds with R2 ¼ aryl
tend to add a second equivalent of imine 5 and easily
undergo oxidative dimerization. The ready oxidation of
imidazole-4-thiols had been seen before in similar exam-
ples [5,8]. Unfortunately, the disulfide form of L-ovo-
thiol A (1a) is biologically inactive [6] and this may
also be anticipated for the disulfides of this work.
1
3150–3300, 2930–2970, 1450, 1130 cmꢀ1. H NMR: d ¼ 2.50
(s, 3 H, CCH3), 2.90 (d, J ¼ 6 Hz, 3 H, NHCH3, collapses to
s with D2O), 3.56 (s, 3 H, CH3N), 7.63, 9.33, 10.40 (each s,
3H, broad NH, exchanges with D2O). Concentration of the
ethanolic extract from earlier gave 9 as reddish crystals (145
mg, 30%); m.p. 195–197ꢁC. IR (KBr): v~ ¼ 3350–3230 (broad,
1
NH), 2910–2980, 1470, 1150 cmꢀ1. H NMR: d ¼ 2.29 (s, 6
EXPERIMENTAL
H, CH3C), 3.21 (s, 6 H, CH3NH), 3.3 (s, 6 H, CH3N), 7.47,
8.99, 9.88 (each broad, NH; exchanges with D2O).
C16H24N10S4. (484.7): calcd. C 39.65, H 4.99, N 28.90, S
26.46; found C 39.60, H 5.00, N 29.00, S 26.50.
General. NMR: Bruker WP 80–FT, AMX 400, or Varian
FT–80A; CDCl3 as solvent unless stated otherwise, with TMS
as internal standard; coupling constants J are given in Hz. IR:
Perkin–Elmer FTIR 1720 X or Pye-Unicam SP3-200 spectrom-
eters. Elemental analyses: Institut fu¨r Pharmazeutische Chemie,
TU Braunschweig.
N-Methylcyanothioformamide (3a) [9] and cyanothioforma-
nilide (3b) [19] were prepared as previously described, though
in the preparation of 3b we found use of THF as solvent ad-
vantageous. For the synthesis of imine 5a see ref. [17], for
benzaldimine (5b) see ref. [20]; imine 5c [21] was prepared
analogously.
Bis(4-benzylidenamino-1-methyl-2-phenyl-imidazole)-5,50-diyl
disulfide (11a). An ethereal solution (20 mL) of 3a (1.0 g, 10
mmol), 5b (1.05 g, 10 mmol), and triethylamine was stirred at
20ꢁC for 0.5–2 h to provide yellow crystals (750 mg, 51%),
m.p. 187–190ꢁC. IR (KBr): v~ ¼ 1605, 1573. 1H NMR: d ¼
3.85 (s, 3 H, CH3), 7.2–7.78 (m, 10 H, Ph, CH), 8.99 (s, 1 H,
PhCH¼¼N). 13C NMR: d ¼ 158.6 (N¼¼CH), 155.7 (C-2), 149.8
(C-4), 136.3, 130.9, 128.9, 128.7, 128.6, 128.4, 128.2 (Ar),
116.4 (C-5), 32.5 (NCH3). MS: m/z (%) ¼ 585 (48) [M þ H],
481 (58), 437 (59), 393 (92), 349 (100). C34H28N6S2 (584.8):
calcd. for C 69.83, H 4.83, N 14.37, S 10.97; found C 69.13,
H 4.96, N 14.51, S. 10.65.
5-Amino-2,3-dimethyl-5-imidazoline-4-thione (6a). An ethe-
real (20 mL) solution of 3a (2.38 g, 20 mmol), 5a (3.66 g, 20
mmol), and triethylamine (three drops) was stirred for 30 min at
20ꢁC to give 6a as reddish–brown crystals (745 mg, 26%); m.p.
137ꢁC (dec.). IR (KBr): v~ ¼ 3370, 3180, 2950, 1470, 1140
Bis(4-benzylidenamino-1,2-diphenyl-imidazole)-5,50-diyl di-
sulfide (11b). An ethereal solution (20 mL) of 3a (1.62 g, 10
mmol), benzaldimine 5b (2.10 g, 20 mmol), and triethylamine
(three drops) was stirred for 30 min and allowed to stand over-
night. The yellow crystals were collected and recrystallized
from dichloromethane/methanol; yield 1.60 g (45%). m.p.
195ꢁC (dec.). Repeated crystallization afforded a product with
m.p. 207ꢁC (dec.). IR (KBr): v~ ¼ 1605, 1573, 1503, 1316
1
cmꢀ1. H NMR: d ¼ 1.44 (d, J ¼ 6.4, 3 H, CCH3), 3.36 (s, 3
H, CH3N), 5.13 (q, J ¼ 6.4, 1 H, CH), 5.58 (broad, 2 H, NH).
13C NMR: d ¼ 181.96 (C¼¼S), 159.37 (N¼¼C), 84.64 (CAMe),
32.28 (NAMe), 18.80 (Me). MS: m/z (%) ¼ 143 (100) [M], 128
(23) [MACH3], 74 (28), 69 (31). HRMS for (C5H9N3S þ H):
calcd 144.0595, found 144.0601.
cmꢀ1
.
1H NMR: d ¼ 6.96–7.48 (m, 13H), 9.11 (s, 1 H,
PhCH¼¼N). 13C NMR: d ¼ 159.3 (N¼¼CH), 155.7 (C-4), 148.6
(C-2), 136.62, 136.41, 129.52 (Ar), 130.94, 129.07, 128.90,
128.58, 128.48, 128.43, 127.88 (ArH), 119.0 (C-5). MS: m/z
(%) ¼ 709 (100) [M þ H], 337 (18), 289 (9), 161 (19), 105
(8). C44H32N6S2 (708.9): calcd C 74.55, H 4.55, N 11.86; S
9.05 found C 74.19; H 4.69; N 11.82; S 8.82.
5-Amino-2-methyl-3-phenyl-5-imidazoline-4-thione (6b). An
ethereal (25 mL) solution of 3b (1.62 g, 10 mmol), 5a (1.83 g,
10 mmol), and triethylamine (three drops) was stirred for 15
min and then diluted with hexane. The gummy residue was
extracted several times with hexane. These extracts were com-
bined with the ether-hexane solution. Removal of the solvents
under reduced pressure gave 6b as reddish brown crystals (308
mg, 15%); m.p. 125–127ꢁC. IR (KBr): v~ ¼ 3350, 3270, 2950,
Bis[4-(4-methoxybenzylidenamino)-1-methyl-2-(4-methoxy-
phenyl)-imidazole]-5,50-diyl disulfide (11c). Prepared by the
procedure described for 11 using 5c in place of 5b. Yield
55%, m.p. 155ꢁC. IR (KBr): v~ ¼ 1600, 1470, 1210 cmꢀ1. MS:
m/z (%) ¼ 352 (25) [M/2], 351 (100), 176 (14), 151 (48).
C38H36N6O4S2 (704.86) calcd. C 64.75 H 5.15 N 11.92, S
9.10; found C 64.70, H 5.50, N 12.00, S 9.10.
1470, 1130 cmꢀ1
.
1H NMR: d ¼ 1.33 (d, J ¼ 6.4 Hz, 3 H,
CH3), 5.78–5.60 (q, J ¼ 6.4, 1 H, CH and broad, 2 H, NH2,
exchangeable with D2O), 7.48 (m, 5 H, ArH). 13C NMR: d ¼
181.80 (C¼¼S), 159.03 (N¼¼C), 129.49, 128.44, 125.01 (Ph),
85.47 (CAMe), 19.63 (Me). MS: m/z (%) ¼ 205 (68) [M], 204
(8), 190 (7), 135 (12), 70 (100). C10H11N3S (205.3); calcd C
58.51, H 5.40, N 20.47, S. 15.62; found C 58.31, H 5.52, N
20.10, S 15.23.
N-(1,2-Dimethyl-5-thioxo-3-imidazolin-4-yl)acetamide (13a). A
solution of 6a (100 mg, 0.7 mmol) in acetic anhydride (1.4
mL, 14.8 mmol) was allowed to stand for 16 h. Removal of
acetic anhydride under reduced pressure gave a gummy prod-
uct which was triturated with water to afford dark pink crys-
tals of 13a (36 mg, 28%); m.p. 107–109ꢁC. IR: v~ ¼ 3191,
5-Imino-1-methyl-3-phenyl-4-thioxoimidazolidin-2-one (7). The
compound had been prepared before [10,16]. IR (KBr): 1766
(C¼¼O), 1659 (C¼¼N) cmꢀ1
.
13C NMR (CH3): d ¼181.9
1
1686, 1666, 1537 cmꢀ1. H NMR: d ¼ 1.63 (d, J ¼ 5.6, 3 H,
(C¼¼S), 154.8 (C¼¼O), 154.2. (C¼¼NH), 132.5 (Ar), 129.4,
CH3CN2), 2.67 (s, 3 H, CH3CO), 3.39 (s, 3 H, CH3N), 5.51
129.3, 126.9 (ArH), 26.8 (NCH3).
Journal of Heterocyclic Chemistry
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March 2010
Imidazoline-4-thiones from Cyanothioformamides and Aldehyde Imines:
Formation, Aromatization, and Acetylation
429
(q, J ¼ 5.6, 1 H, CH). 13C NMR: d ¼ 181.02 (C¼¼S), 170.07
(C¼¼O), 155.77 (C¼¼N), 74.28 (C-2), 84.64 (CAMe), 31.2
(NAMe), 25.72 (Ac-CH3), 18.68 (2-Me). MS: m/z (%) ¼ 185
(89) [M], 143 (100), 128 (14). HRMS for (C7H11N3OS þ H):
calcd 186.0701, found 186.0696.
C16H24N10S4, Mr ¼ 484.7, monoclinic, a ¼ 755.2(1), b ¼
22726(1), c ¼ 1992.8(1) pm, b ¼ 100.32(1)ꢁ, V ¼ 2.352 ꢂ
109 pm3, T ¼ room temp., space group Cc, Z ¼ 4, dcal. 1.38 g
cmꢀ1, lCu Ka ¼ 38.7 cmꢀ1 [22].
N-(2-Methyl-1-phenyl-5-thioxo-3-imidazolin-4-yl)acetamide
(13b). A solution of 6b (4.10 g, 20 mmol) in acetic anhydride
(10 mL) was allowed to stand at 20ꢁC for 30 min. Removal of
the reagent under reduced pressure gave 13b as yellow crystals
(990 mg, 20%); m.p. 115–117ꢁC. IR (KBr): v~ ¼ 3210, 1720,
Acknowledgments. The authors gratefully acknowledge the
support from the Fonds der Chemischen Industrie, Frankfurt/
Main. Mass spectra were provided by the Mass Spectrometry Fa-
cility, University of California. San Francisco, with support from
the NIH, Division of Research Resources Grant RR 01614.
1
1450, 1120 cmꢀ1. H NMR: d ¼ 1.5 (d, J ¼ 6.0, 3 H, 2-CH3),
2.7 (s, 3 H, CH3CO), 5.5 (q, J ¼ 6.0, 1 H, 2-H), 7.5 (m, 5 H,
ArH,), 9.4 (broad s,
1 H, NH, exchanges with D2O).
REFERENCES AND NOTES
C12H13N3OS (247.3): calcd C 58.28, H 5.30, N 16.99, S
12.97; found C 58.19, H 5.16, N 17.11, S 12.89.
[1] (a) Sies, H. Angew Chem 1986, 98, 1061; (b) Sies, H.
Angew Chem Int Ed 1986, 25, 1058.
N-(5-Acetylthio-2-methyl-1-phenyl-imidazol-4-yl)diacetamide
(14). The earlier reaction was repeated, but allowed to run for
16 h to give 14 as yellow crystals (1.66 g, 25%); m.p. 110–
[2] Schafer, F. Q.; Buettner, G. R. Free Radic Biol Med 2001,
30, 1191.
1
111ꢁC. IR (KBr): v~ ¼ 2970, 2910, 1690 cmꢀ1. H NMR: d ¼
[3] Bhabak, K. P.; Mugesh, G. Chem Eur J 2008, 14, 8640.
[4] Spaltenberg, A.; Holler, T. P.; Hopkins, P. B. J Org Chem
1987, 52, 2977.
2.1, 2.3 (each, s, 3 H, CH3), 2.4 (s, 6 H, Ac2N), 7.0–7.6 (m, 5
H, ArH). MS: m/z (%) ¼ 331 (3) [M], 289 (20), 247 (93), 205
(100). C16H17N3O3S (331.4): calcd. C 57.99, H 5.17, N 12.68,
S 9.68; found C 57.80, H 5.26, N 12.66, S 9.55.
[5] Zoete, V.; Bailly, F.; Catteau, J.-P.; Bernier, J.-L. J Chem
Soc Perkin Trans 1 1997, 2983.
¨
[6] Rohl, I.; Schneider, B.; Schmidt, B.; Zeeck, E. Z Natur-
1,2-Dimethyl-5-thioxoimidazolidin-4-one (15) and (1,2-di-
methyl-5-thioxo-3-imidazolin-4-yl) acetate (16). A suspension
of thione 6a (50 mg, 0.35 mmol) in EtOH (2.1 mL), and 2M
HCl (0.35 mL) was refluxed for 30 min. After cooling, water
(3.5 mL) was added. Sticky yellow crystals could be removed
by filtration and were used as such in the subsequent step.
forsch 1999, 54c, 1145.
[7] Bailly, F.; Zoete, V.; Vamecq, J.; Catteau, J.-P.; Bernier,
J.-L. FEBS Lett 2000, 486, 19.
[8] Asinger, F.; Saus, A.; Offermanns, H.; Krings, P.; Andree,
H. Liebigs Ann Chem 1971, 744, 51.
[9] Ketcham, R.; Schaumann, E.; Niemer, T. Synthesis 1980, 869.
[10] Ketcham, R.; Schaumann, E. J Org Chem 1980, 45, 3748.
[11] Khattak, I.; Ketcham, R.; Schaumann, E.; Adiwidjaja, G.
J Org Chem 1985, 50, 3431.
Yield 20 mg (40%). IR (KBr): 3455, 3368, 3211, 1731 cmꢀ1
.
1H NMR (MeOD): 1.64 (d, J ¼ 6.2 Hz, 2-CH3), 3.42 (d, J ¼
1.2 Hz, 1-CH3), 5.52 (q þ q), J ¼ 1.2; 6.2 Hz, 2-H). 13C
NMR (MeOD): d ¼177.7 (C¼¼S), 157.5 (C¼¼O), 77.9 (C-2),
32.9 (1-CH3), 18.2 (2-CH3). Lactam 15 (17 mg, 0.12 mmol)
was added to Ac2O (0.24 mL, 2.54 mmol) and the mixture
allowed to stand at room temperature for 16 h. After concen-
tration in vacuo, water was added and the precipitate isolated
by filtration. Yield 10 mg (46%), m. p. 125ꢁC. IR: v~ ¼ 1762,
[12] Ketcham, R.; Schaumann, E.; Adiwidjaja, G. Eur J Org
Chem 2001, 1695.
[13] El-Sharief, A. M. Sh.; El-Gaby, M. S. A.; Atalla, A. A.;
El-Adasy, A.-B. A. A. M. Heteroatom Chem 2005, 16, 218.
[14] El-Sharief, A. M. Sh.; Ammar, Y. A.; El-Gaby, M. S. A.
Afinidad 2004, 61, 240.
1
1731, 1533 cmꢀ1. H NMR: d ¼ 1.68 (d, J ¼ 5.8 Hz, 3 H, 2-
[15] El-Sharief, A. M. Sh.; Al-Amri, A. M.; Al-Raqa, S. Y.
J Sulfur Chem 2006, 27, 245.
CH3), 2.65 (s, 3 H, AcACH3), 3.42 (s, 3 H, CH3N), 5.44 (q, J
¼ 5.8 Hz, 1 H, 2-H). 13C NMR: d ¼ 180.6 (C¼¼S), 169.8
(C¼¼O), 156.1 (C¼¼N), 72.3 (C-2), 33.3 (1-CH3), 25.2
(AcACH3), 18.7 (1-CH3). MS: m/z (%) ¼ 186 (74) [M], 144
(75), 129 (18), 74 (100).
[16] Al-Raqa, S. Y.; El-Sharief, A. M. Sh.; Khalil, S. M. E.;
Al-Amri, A. M. Heteroatom Chem 2006, 17, 634.
[17] Nielsen, A. T.; Atkins, R. L.; Moore, D. W.; Scott, R.;
Mallory, D.; LaBerge, J. M. J Org Chem 1973, 38, 3288.
[18] Papadopoulos, E. P. J Org Chem 1979, 44, 3858.
[19] Reissert, A.; Bru¨ggemann, K. Ber Dtsch Chem Ges 1924, 57,
981.
Crystal structure determinations of disulfide 9. Intensity
data were collected with a CAD 4-SDP single-crystal diffrac-
tometer (Enraf-Nonius) using graphite-monochromated Cu Ka
radiation in the rage y < 60ꢁ. The final refinements were based
on 1657 symmetry-independent reflections with I > 3r for I.
The structure was solved by the direct-methods program MUL-
TAN. The E map revealed the position of all the heavy atoms.
Because of the thinness of the crystal, the positions of the
hydrogen atoms were geometrically calculated, but difficult to
refine. Convergence was achieved at R ¼ 0.060 (Rw ¼ 0.071).
[20] Gazzola, C.; Kenyon, G. L. J Labelled Comp Radiopharm
1978, 15, 181.
[21] Busch, M.; Wolff, J. J Prakt Chem 1899, 60, 197.
[22] Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication no.
CCDC 733961 The data can be obtained free of charge from the
CCDC, via www.ccdc.cam.ac.uk/data_request/cif.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet