A practical method for O-acylation of N -hydroxythiazole-2(3 H)-thiones

Article abstract of DOI:10.1055/s-0029-1217102

O-Acylation of 4- and 4,5-substituted N-hydroxythiazole-2(3H)-thiones occurred in solutions of acetone upon treatment with solid K²CO³ and a variety of neat acyl chlorides (primary, secondary, and tertiary alkyl, aryl; 60-87% yield; ～10 g scale).

Full text of DOI:10.1055/s-0029-1217102

538
PRACTICAL SYNTHETIC PROCEDURES
A Practical Method for O-Acylation of N-Hydroxythiazole-2(3H)-thiones
O-Acylation of
N
h
-Hydroxythi
r
azole-2(
i
3
H
)-thi
s
ones tine Schur, Andreas Groß, Jens Hartung*
Fachbereich Chemie, Organische Chemie, Technische Universität Kaiserslautern,
Erwin-Schrödinger-Straße, 67663 Kaiserslautern, Germany
Fax +49(631)2053921; E-mail: hartung@chemie.uni-kl.de
Received 24 July 2009; revised 9 September 2009
PSP
No177
Abstract: O-Acylation of 4- and 4,5-substituted N-hydroxythiazole-2(3H)-thiones occurred in solutions of acetone upon treatment with
solid K2CO3 and a variety of neat acyl chlorides (primary, secondary, and tertiary alkyl, aryl; 60–87% yield; ~10 g scale).
Key words: anhydride, acyl chloride, carbon radical, thiazolethione, thiohydroxamic acid
S
An
R2
S
CP
S
N
O
S
S
K2CO3, RCOCl
O
N
O
R1
S
or
N
O
acetone, 20 °C
60–87%
OH
H
3 examples
H
NO2
9 further examples
An = p-MeOC6H4
CP = p-ClC6H4
Scheme 1
Mixed anhydrides composed of carboxylic acids and cer- stituents in positions 4 and 5 for controlling photochemi-
tain thiohydroxamic acids constitute an important and cal and ground state properties of the thiazole-2(3H)-
quite general product class for carbon radical generation thione entity.15,16
in the absence of metal ions under pH neutral conditions.1
The compounds undergo selective N–O homolysis upon
Faced with the synthetic task to prepare batches of ~10 g
of N-acyloxythiazole-2(3H)-thiones for reasons outlined
photochemical or thermal activation thus liberating acyl-
above, we realized that none of the available low cost
oxyl radicals and after decarboxylation, respective car-
methods was adequate in our hands to solve this simple
bon radicals.2,3 The most prominent derivatives of this
task in a satisfactory and reproducible manner. A scatter
kind, that is, O-acyl derivatives of N-hydroxypyridine-
of yields ranging from poor (~5%) to satisfactory (~75%)
2(1H)-thione (PTOH, Figure 1), the ‘Barton esters’,4 have
was obtained using established sequences,11,13 for exam-
notably contributed within the past two decades to the
ple, treatment of independently prepared alkali (Li+, Na+,
progress in synthetic,3 mechanistic,5,6 photobiological,7
K+) thiohydroxamates with an acyl chloride in solutions
and even therapeutic8 application of free carbon radicals.
of, for example, dichloromethane or acetonitrile.17 Since
Thermal and photochemical instability,9,10 however, pre-
others might have encountered similar difficulties, we
wish to report here on a modified procedure for the syn-
thesis of N-acyloxythiazole-2(3H)-thiones. The method is
cludes the use of O-acylpyridine-2(1H)-thiones in in-
stances that for technical reasons require synthesis and
radical liberation to occur in separate steps. Substantial
based on a one-pot transformation of thiazole-derived cy-
evidence, however, existed from more recent develop-
clic thiohydroxamic acids, acyl chlorides, and solid potas-
ments that O-acyl derivatives of N-hydroxythiazole-
2(3H)-thiones, for example, 1–3, have the potential to fill
R
5
5
this gap.11,12 Synthesis of cyclic thiohydroxamic acids 1–
3 is feasible according to well established protocols start-
ing from substituted a-chloro or a-bromo ketones.11,13,14
This strategy allows to introduce a notable variety of sub-
S
S
S
CP
S
4
4
N
S
N
N
OH
OH
OH
CPTTOH (3)
PTOH
MTTOH (1)
MAnTTOH (2)
SYNTHESIS 2010, No. 3, pp 0538–0542
Advanced online publication: 06.11.2009
DOI: 10.1055/s-0029-1217102; Art ID: T14609SS
x
x
.
x
x
.2
0
0
9
Figure 1 Structural formula of cyclic thiohydroxamic acids 1–3
[R = H for 1, R = p-MeOC6H4 (An) for 2, CP = p-ClC6H4 for 3]15,16
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
O-Acylation of N-Hydroxythiazole-2(3H)-thiones
539
sium carbonate in acetone at ~20 °C, in combination with dissolved in a minimum volume of water. The target prod-
a straightforward workup procedure (Scheme 1).
uct was transferred into an organic absorber phase (see ex-
perimental section). Analytically pure anhydrides 5a–7a
were obtained as tan (5a and 7a) to yellowish (6a) solids,
which were preferentially kept in amber-colored vials.
Anhydride 6a was expected to be a colorless compound,
as judged on the basis of its UV/Vis spectrum. A material
showing this appearance was obtained via chromato-
graphic purification [Et2O–pentane (1:1), Rf = 0.18, yel-
lowish spot on silica gel TLC plate], although
considerable loss of thione 6a occurred upon contact with
silica gel.
Highest yields of O-acylthiazole-2(3H)-thiones from the
chosen set of substrates (see below) were obtained as fol-
lows (Table 1). To a homogeneous solution of a cyclic
thiohydroxamic acid (e.g., 1, 2, or 3) in acetone was added
an excess of solid potassium carbonate (3 equiv) at ~20 °C
in a single batch. This manipulation resulted in a slurry.
The temperature of the reaction mixture remained un-
changed, even in transformations starting from ~20 mmol
of thiohydroxamic acid. The solids changed their appear-
ance from grainy at the beginning to feathery after ap-
proximately 30 minutes. At this point, an aliquot of For reasons of favorable stability toward storage in com-
acylating reagent, which was benzoyl chloride (4a) in the bination with noteworthy reactivity upon photochemical
course of process development, was added. The feathery or thermal activation (vide infra), N-hydroxy-4-methyl-5-
precipitate almost instantaneously disappeared. Stirring at (4-methoxyphenyl)thiazole-2(3H)-thione (2)16 was cho-
ambient temperature was continued until complete con- sen for probing the more general applicability of the O-
version of acids 1–3 had occurred (~30–90 min). This acylation process. Thus, acyl chlorides 4b–g differing in
point was evident from spotting of the reaction mixture at steric congestion and polar effect of substituents attached
intervals of ~15 minutes on iron(II)-stained TLC sheets to the carboxyl C-atom were subjected to standard condi-
(Figure 2). The absence of a diagnostic greenish blue col- tions to furnish the mixed anhydrides 6b–g in yields be-
or due to complex formation between the transition metal tween 69–87% (Table 2, entries 1–6). NMR data recorded
ion and the thiohydroxamate ligand18 pointed to quantita- for mixed anhydride 6g in CDCl3 or preferentially in C6D6
tive consumption of substrates 1–3 and thus the moment showed a two-fold signal set in a 50:50 intensity ratio.
for terminating the reaction.
This observation was attributed to slow rotation of the
chiral acyl subunit about the stereogenic N–O bond and
thus the existence of diastereomers under such condi-
tions.11 Storage of N-acyloxythiazolethiones without sig-
nificant decomposition was feasible in amber colored
vials, preferentially in a refrigerator. Treatment of acid 2
with 4-nitrobenzoyl chloride under established conditions
provided the expected product, however, for unknown
reasons with a considerable scatter of yields (not shown).
The use of acids MTTOH (1) and CPTTOH (3), on the
other hand gave O-(4-nitrobenzoyl)thiazole-2(3H)-
Figure 2 Probing for thiohydroxamic acids via spotting on FeCl2-
coated SiO2 TLC sheets prior to addition of 4a (A) and after complete
consumption of 1–3 (B); control refers to a solution of benzoyl chlo-
ride and K2CO3 in acetone
Table 1 O-Benzoylation of N-Hydroxythiazole-2(3H)-thiones 1–3
Table 2 Formation of Mixed Anhydrides from MAnTTOH (2) and
Acyl Chlorides 4b–g
R2
R2
An
An
S
S
O
K2CO3
S
O
S
+
R1
S
R1
S
K2CO3
acetone
20 °C
N
O
N
Cl
Ph
+
S
S
acetone
20 °C
N
Cl
R
N
O
O
OH
O
OH
1–3
4a
5a–7a
Ph
2
4b–g
6b–g
R
Entry
R1
R2
H
1–3
1
Yield (%)
5a: 84
Entry
R
4/6
b
Yield (%) of 6
1
2
3
Me
Me
1
2
3
Me
87
69
85
p-MeOC6H4
2
6a: 81
n-C9H19
c-C6H11
c
p-ClC6H4
H
3
7a: 75
d
Product isolation was accomplished in two ways. In case
of notable salt separation after quantitative thiohydroxam-
ic acid turnover, solids were removed by filtration to af-
ford a clear solution. Volatile components were removed
under reduced pressure to furnish a yellowish to dark res-
idue that was (re)crystallized from a mixture of CH2Cl2/
Et2O/pentane. In an alternative procedure, the solids were
H
4
e
73
H
5
6
f
79
74
p-MeOC6H4
g
Synthesis 2010, No. 3, 538–542 © Thieme Stuttgart · New York

540
C. Schur et al.
PRACTICAL SYNTHETIC PROCEDURES
sidual protons and those of carbons in deuterated solvents CDCl3
(dH = 7.26 ppm, dC = 77.0 ppm), C6D6 (dH = 7.16 ppm, dC = 128.06
ppm), DMSO-d6 (dH = 2.50 ppm, dC = 39.52 ppm) were used as in-
ternal standards. UV/Vis spectra were recorded in 1-cm quartz cu-
vettes with a Perkin Elmer UV/Vis 330 spectrometer and a Cary 100
Conc, spectrometer (VARIAN). Combustion analysis was per-
formed with a vario Micro cube (analytical laboratory, Technische
Universität Kaiserslautern). All solvents were purified according to
standard procedures.21 Unless otherwise indicated, solvent mixtures
are given in v/v ratios.
thiones in 63% (from 1) and 60% yield (from 3) as analyt-
ically pure compounds (Scheme 1, experimental section).
The ability of O-acyl derivatives of MAnTTOH (2) to lib-
erate free radicals was clarified with the aid of two diag-
nostic experiments. Photolysis (350 nm, Rayonet®
chamber photoreactor, 25 °C) of N-(decanoyloxy)thiaz-
ole-2(3H)-thione (6c) in a solution of BrCCl3 and benzene
provided 75% of bromononane (7) and 72% of trichlo-
romethylsulfanylthiazole 8 (Scheme 2). The underlying
chemistry agrees with reactivity described for the Barton
version of the Hunsdiecker reaction.19 Adapting condi-
tions for the conversion of 6c to the transformation of N-
[trans-(2,2-dimethyl-3-dimethylvinyl)cyclopropancarbo-
nyloxy] derivative 6e using cyclohexa-1,4-diene (CHD)
as trapping reagent gave trans-chrysanthemic acid as a
single detectable product from the acyl residue in 63%
yield (Scheme 2). The observed reactivity of thione 6e re-
flected the propensity of the underlying cyclopropanecar-
bonyloxyl radical to preferentially abstract a H-atom from
a suitable donor, such as CHD. Its decarboxylation is ex-
pected to be disfavored due to the s-character of the cy-
clopropyl radical20 that would result.
O-Acylation of N-Hydroxythiazole-2(3H)-thiones 1–3; General
Procedure
Solid K2CO3 (0.41 g, 3.00 mmol) was added to a solution of thiohy-
droxamic acid 1, 2, or 3 (1.00 mmol) in acetone (9 mL). The slurry
was stirred for 10 min at 20 °C leading to a change in the appearance
of the precipitate from grainy to feathery. To this suspension was
added in one batch the appropriate neat acid chloride (1.10 mmol)
and the stirring was continued at 20 °C (30–90 min). Consumption
of acids 1–3 was followed by spotting the reaction mixture at inter-
vals of ~15 min on FeCl2-coated TLC sheets. The end of the reac-
tion was evident from an absence of greenish blue Fe(II)-
thiohydroxamate color (Figure 2).
Product Isolation via Filtration: Excess of solids was filtered off to
afford a clear solution, which was evaporated to dryness. Upon ad-
dition of Et2O (5 mL/mmol), the residue immediately solidified.
The resulting suspension was stirred for 15 min at 20 °C. The crys-
talline solids were collected by filtration and dried (40 °C/5 mbar).
If no solids appeared, the mixture was allowed to rest at –30 °C.
An
S
An
S
N
Product Isolation via Extraction: H2O (10 mL) was added for dis-
solving the solids to afford a mixture, which was extracted with
Et2O (2 × 10 mL) and EtOAc (2 × 10 mL). The combined organic
extracts were washed with aq 2 M NaOH (10 mL) and brine (10
mL). The combined organic phases were dried (MgSO4) and con-
centrated under reduced pressure (40 °C/800 → 8 mbar). The resi-
due was taken up in a minimum amount of CH2Cl2–Et2O (1:2).
Pentane was added at 20 °C until a slight turbidity remained upon
swirling. The mixture was allowed to rest at –30 °C. The solids that
separated were collected by suction and dried in aluminum foil
wrapped flasks (20 °C/1.5 × 10–2 mbar).
S
BrCCl3, hν
+
BrC9H19
O
O
C6H6, 25 °C
SCCl3
N
C9H19
7 (75%)
8 (72%)
6c
An
S
S
N
O
HO2C
H
O
CHD, hν
C6H6, 25 °C
H
H
H
N-Benzoyloxy-4-methylthiazole-2(3H)-thione (5a)
Yield: 210 mg (84%, 0.84 mmol); yellowish solid; 89–93 °C (dec.).
9 (63%)
6e
1H NMR (200 MHz, CDCl3): d = 2.21 (s, 3 H, 4-CH3), 6.30 (s, 1 H,
Scheme 2 Photochemical conversion of N-acyloxythiazolethiones
6c and 6e in the presence of suitable trapping reagents (see text)
H-5), 7.59–7.51 (m, 2 H), 7.75–7.68 (m, 2 H), 8.25–8.20 (m, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.5 (4-CH3), 102.5 (C-5), 125.3,
129.1, 130.7, 135.2, 137.4 (C-4), 162.4 (C=O), 181.0 (C=S).
Although the selection of N-hydroxythiazole-2(3H)-
thiones 1–3 and acyl chlorides 4a–g reflects preferences
from this laboratory and not all permutations were put into
practice, we believe that the number of examples suffices
to document the utility of a surprisingly simple as much as
useful N-acyloxythiazole-2(3H)-thione synthesis. It saves
at least one synthetic step, uses predominantly environ-
mentally benign reagents, and allows a rapid scale-up of
the protocol for larger-scale syntheses. The procedure is
therefore expected to contribute in a quite general manner
to new developments in O-acylthiohydroxamate chemis-
try.
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 320 nm [3.26].
Anal. Calcd for C11H9NO2S2 (363.50): C, 52.57; H, 3.61; N, 5.57.
Found: C, 52.51; H, 3.47; N, 5.46.
N-Benzoyloxy-4-methyl-5-(4-methoxyphenyl)thiazole-2(3H)-
thione (6a)17
Yield: 290 mg (81%, 0.81 mmol); yellowish solid; mp 86–89 °C
(dec.).
N-Benzoyloxy-4-(4-chlorophenyl)thiazole-2(3H)-thione (7a)13
Yield: 260 mg (75%, 0.75 mmol); yellowish solid; mp 102–105 °C
(dec.).
N-Acetyloxy-4-methyl-5-(4-methoxyphenyl)thiazole-2(3H)-
thione (6b)
Melting points (°C) were determined on a Koffler hot-plate melting
point microscope (Reichert). 1H and 13C NMR spectra were record-
ed with FT-NMR DPX 200, DPX 400 and DMX 600 instruments
(Bruker). Chemical shifts refer to the d-scale. The resonances of re-
Yield: 258 mg (87%, 0.87 mmol), yellowish solid; mp 79–83 °C
(dec.).
Synthesis 2010, No. 3, 538–542 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
O-Acylation of N-Hydroxythiazole-2(3H)-thiones
UV (MeOH): lmax [lg (e/m2 mol–1)] = 329 nm [3.09].
541
1H NMR (200 MHz, CDCl3): d = 2.16 (d, J = 7.8 Hz, 3 H, 4-CH3),
2.43 (s, 3 H), 3.81 (s, 3 H, OCH3), 6.92 (mc, 2 H), 7.22 (m, 2 H).
13C NMR (150 MHz, CDCl3): d = 12.0 (4-CH3), 18.1, 55.5 (OCH3),
114.7, 119.2 (C-5), 122.2, 130.1, 131.4 (C-4), 160.1, 166.1 (C=O),
179.3 (C=S).
Anal. Calcd for C21H25NO3S2 (403.55): C, 62.50; H, 6.24; N, 3.47.
Found: C, 62.30; H, 6.29; N, 3.47.
N-Adamantylcarbonyloxy-4-methyl-5-(4-methoxyphenyl)thia-
zole-2(3H)-thione (6f)
Yield: 328 mg (79%, 0.79 mmol); yellowish solid; mp 106–107 °C
(dec.).
1H NMR (400 MHz, CDCl3): d = 1.81 (m, 6 H), 2.11–2.15 (m, 3 H),
2.17 (s, 3 H, 4-CH3), 2.20 (m, 6 H), 3.85 (s, 3 H, OCH3), 6.97 (mc,
2 H), 7.28 (mc, 2 H).
13C NMR (150 MHz, CDCl3): d = 12.0 (4-CH3), 27.8, 36.3, 38.7,
40.9, 55.5 (OCH3), 114.7, 119.2 (C-5), 122.4, 130.1, 131.6 (C-4),
160.1, 172.6 (C=O), 179.3 (C=S).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 332 nm [3.17].
Anal. Calcd for C13H13NO3S2 (295.38): C, 52.86; H, 4.44; N, 4.74.
Found: C, 52.21; H, 4.38; N, 4.59.
N-Decanoyloxy-4-methyl-5-(4-methoxyphenyl)thiazole-2(3H)-
thione (6c)
Yield: 281 mg (69%, 0.69 mmol); reddish oil.
1H NMR (600 MHz, CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.27–
1.34 (m, 10 H), 1.49–1.46 (m, 2 H), 1.78–1.87 (m, 2 H), 2.19 (s, 3
H, 4-CH3), 2.71 (mc, 2 H), 3.83 (s, 3 H, OCH3), 6.95 (mc, 2 H), 7.26
(mc, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.2 (4-CH3), 22.2, 24.9, 29.4,
29.5, 32.0, 34.1, 55.5 (OCH3), 68.1, 114.4, 114.5 (C-5), 114.6,
130.5, 130.6, 130.8 (C-4), 160.6, 165.9 (C=O), 178.8 (C=S).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 335 nm [3.36].
Anal. Calcd for C22H25NO3S2 (415.57): C, 63.58; H, 6.06; N, 3.37.
Found: C, 62.98; H, 5.88; N, 3.37.
N-(4-Methoxybenzoyl)-4-methyl-5-(4-methoxyphenyl)thiazole-
2(3H)-thione (6g)
Yield: 287 mg (74%, 0.74 mmol); yellow solid; mp 112–116 °C
(dec.).
1H NMR (400 MHz, CDCl3): d = 2.25 (s, 3 H, 4-CH3), 3.84 (s, 3 H,
OCH3), 3.91 (s, 3 H, OCH3), 6.96 (mc, 2 H), 7.03 (mc, 2 H), 7.30
(mc, 2 H), 8.21 (mc, 2 H).
13C NMR (100 MHz, CDCl3): d = 12.2 (4-CH3), 55.6 (OCH3), 55.8
(OCH3), 114.6, 114.9, 119.0 (C-5), 122.7, 126.8, 130.2, 132.4,
133.20 (C-4), 160.3, 162.2, 165.4 (C=O), 179.8 (C=S).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 300 nm [2.95].
Anal. Calcd for C21H29NO3S2 (407.59): C, 61.88; H, 7.17; N, 3.44.
Found: C, 61.75; H, 7.32; N, 3.71.
N-Cyclohexylcarbonyloxy-4-methyl-5-(4-methoxyphenyl)thia-
zole-2(3H)-thione (6d)
Yield: 309 mg (85%, 0.85 mmol); yellowish solid; mp 89–91 °C
(dec.).
1H NMR (400 MHz, CDCl3): d = 1.25–1.41 (m, 4 H), 1.64–1.72 (m,
3 H), 1.86 (mc, 2 H), 2.08–2.10 (mc, 1 H), 2.17 (s, 3 H, 4-CH3), 3.83
(s, 3 H, OCH3), 6.94 (mc, 2 H), 7.24 (mc, 2 H).
13C NMR (150 MHz, CDCl3): d = 12.0 (4-CH3), 25.1, 25.3, 29.4,
41.0, 55.5 (OCH3), 114.7, 119.2 (C-5), 122.4, 130.2, 131.5 (C-4),
160.2, 171.3 (C=O), 179.4 (C=S).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 334 nm [3.27].
Anal. Calcd for C19H17NO4S2 (387.47): C, 58.90; H, 4.42; N, 3.61.
Found: C, 58.74; H, 4.57; N, 3.58.
N-(4-Nitrobenzoyl)-4-methylthiazole-2(3H)-thione
Yield: 187 mg (63%, 0.63 mmol); tan solid; mp 127–131 °C (dec.).
1H NMR (200 MHz, DMSO-d6): d = 2.26 (s, 3 H, 4-CH3), 6.93 (s,
1 H, H-5), 8.50–8.40 (m, 4 H).
13C NMR (50 MHz, DMSO-d6): d = 12.6 (4-CH3), 103.9 (C-5),
124.3, 130.1, 131.8, 137.2 (C-4), 151.3, 160.7 (C=O), 179.9 (C=S).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 334 nm [3.33].
Anal. Calcd for C18H21NO3S2 (363.50): C, 59.48; H, 5.82; N, 3.85.
Found: C, 59.14; H, 5.74; N, 3.75.
N-[trans-2,2-Dimethyl-3-(2-methylpropenyl)cyclopropanecar-
bonyloxy]-5-(4-methoxyphenyl)-4-methylthiazole-2(3H)-thione
(6e)
Yield: 295 mg (73%, 0.73 mmol); yellowish solid; mp 86–87 °C
(dec.).
UV (CH2Cl2): lmax [lg (e/m2 mol–1)] = 318 nm [3.02].
Anal. Calcd for C18H14N2O5S2 (296.32): C, 44.59; H, 2.72; N, 9.45.
Found: C, 44.65; H, 2.73; N, 9.42.
1H NMR (400 MHz, CDCl3): d = 1.25 (s, 3 H), 1.27 (s, 3 H), 1.34
(s, 3 H), 1.40 (s, 3 H), 1.71 (d, J = 7.0 Hz, 2 H), 1.72 (s, 6 H), 1.74
(s, 6 H), 2.17 (s, 3 H, 4-CH3), 2.20 (s, 3 H, 4-CH3), 2.23–2.29 (m, 2
H), 3.82 (s, 6 H, OCH3), 4.98 (d, J = 6.2 Hz, 2 H), 6.63 (d, J = 8.8
Hz, 4 H), 7.25 (d, J = 8.6 Hz, 4 H).
1H NMR (600 MHz, C6D6): d = 0.94 (s, 3 H), 1.03 (s, 3 H), 1.28 (s,
3 H), 1.52 (s, 3 H), 1.57 (s, 3 H), 1.59 (s, 3 H), 1.66 (s, 3 H), 1.74 (s,
4 H), 1.77 (s, 4 H), 2.39 (d, J = 5.2 Hz, 2 H), 3.24 (s, 6 H, OCH3),
4.85 (d, J = 8.0 Hz, 2 H), 6.59 (d, J = 7.4 Hz, 4 H), 6.81 (d, J = 7.4
Hz, 4 H).
13C NMR (100 MHz, CDCl3): d = 12.1 (4-CH3), 18.7, 18.9, 20.7,
22.0, 22.1, 25.7, 31.2, 31.3, 31.5, 32.6, 35.5, 55.5 (OCH3), 114.8,
118.8, 119.3 (C-5), 120.0 (C-5), 122.7, 130.2, 131.7, 131.8, 137.3,
138.1 (C-4), 138.2 (C-4), 160.2, 168.1 (C=O), 168.5 (C=O), 179.5
(C=S), 179.6 (C=S).
13C NMR (100 MHz, C6D6): d = 11.6 (4-CH3), 11.7 (4-CH3), 18.4,
18.8, 20.6, 20.8, 21.7, 21.9, 25.5, 25.6, 30.7, 31.7, 31.8, 32.1, 35.1,
35.5, 54.7 (OCH3), 114.6, 117.9, 119.6 (C-5), 120.6 (C-5), 122.9,
130.2, 131.4, 131.6, 136.7, 138.1 (C-4), 160.2, 168.4 (C=O), 168.8
(C=O), 179.8 (C=S), 180.0 (C=S).
N-(4-Nitrobenzoyl)-4-(4-chlorophenyl)thiazole-2(3H)-thione
Yield: 240 mg (61%, 0.61 mmol); tan solid; mp 165–171 °C (dec.).
1H NMR (200 MHz, CDCl3): d = 6.67 (s, 1 H, H-5), 7.34–7.45 (m,
4 H), 8.23–8.34 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 105.4 (C-5), 124.1, 126.1, 129.4,
130.5, 131.8, 136.7, 140.0 (C-4), 151.6, 160.6 (C=O), 181.4 (C=S).
UV(CH2Cl2): lmax [lg (e/m2 mol–1)] = 322 nm [2.99].
Anal. Calcd for C16H9ClN2O4S2 (392.84): C, 48.92; H, 2.31; N,
7.13. Found: C, 48.88; H, 2.22; N, 6.98.
Photoreaction of N-Acyloxythiazole-2(3H)-thiones; General
Procedure
To an oxygen-free solution of N-(acyloxy)thiazole-2(3H)-thione 6c
or 6e (1.0 equiv) in anhyd C6H6 (12 mL/1.0 mmol thiazolethione)
were added CHD (10.0 equiv) or BrCCl3 (10.0 equiv). The reaction
mixture was irradiated for 90 min (6c) or 7.5 h (6e) at 20 °C in a
Rayonet® photochamber (lmax = 350 nm). Product analysis was per-
formed by 1H and 13C NMR spectroscopy. Yields were determined
Synthesis 2010, No. 3, 538–542 © Thieme Stuttgart · New York

542
C. Schur et al.
PRACTICAL SYNTHETIC PROCEDURES
References
1
via integration of H NMR signals versus pentachlorbenzene (400
MHz, CDCl3: d = 7.55) as internal standard.
(1) Barton, D. H. R.; Crich, D.; Motherwell, W. B. J. Chem.
Soc., Chem. Commun. 1983, 939.
(2) Motherwell, W. B.; Imboden, C. In Radicals in Organic
Synthesis, Vol. 1; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001, 109–134.
(3) Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413.
(4) Shaw, E. J. Am. Chem. Soc. 1949, 71, 67.
(5) Schneiders, N.; Gottwald, T.; Hartung, J. Eur. J. Org. Chem.
2009, 799.
(6) Barton, D. H. R.; Blundell, P.; Jaszberenyi, J. Cs. J. Am.
Chem. Soc. 1991, 113, 6937.
Bromononane (7) and 4-Methyl-5-(4-methoxyphenyl)-2-
(trichloromethylsulfanyl)thiazole-2(3H)-thione (8)
Transformation of thiazolethione 6c (363 mg, 0.89 mmol) and
BrCCl3 (1.76 g, 0.9 mL, 8.9 mmol) in C6H6 (11 mL) was carried out
according to the general procedure.
Bromononane (7)22
Yield: 138 mg (75%, 0.67 mmol).
4-Methyl-5-(4-methoxyphenyl)-2-(trichloromethylsulfanyl)thi-
azole-2(3H)-thione (8)
Yield: 227 mg (72%, 0.64 mmol); mp 61–62 °C.
1H NMR (CDCl3, 600 MHz): d = 2.57 (s, 3 H, 4-CH3), 3.86 (s, 3 H,
OCH3), 6.89 (d, J = 8.5 Hz, 2 H), 7.41–7.49 (d, J = 8.8 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): d = 16.4 (4-CH3), 55.5 (OCH3), 97.3
(SCCl3), 114.5, 123.1 (C-5), 130.6, 141.7, 149.9 (C-4), 150.4 (CS),
160.1.
(7) Theodorakis, E. A.; Xiang, X.; Lee, M.; Gibson, T.
Tetrahedron Lett. 1998, 39, 3383.
(8) Castagnino, E.; Cangiotti, M.; Tongiani, S.; Ottaviani, M. F.
J. Controlled Release 2005, 108, 215.
(9) Barton, D. H. R.; Parekh, S. I. In Half a Century of Free
Radical Chemistry; Cambridge University Press:
Cambridge, 1993, Chap. 5, 46–90.
(10) Garner, P.; Anderson, J. T.; Dey, S. J. Org. Chem. 1998, 63,
5732.
(11) Hartung, J.; Schur, C.; Kempter, I.; Altermann, S.; Stapf, G.;
Bergsträßer, U.; Gottwald, T.; Heubes, M. Tetrahedron
2009, 65, 7527.
(12) Barton, D. H. R.; Crich, D.; Kretschmar, G. J. Chem. Soc.,
Perkin Trans. 1 1986, 39.
MS (EI): m/z (%) = 359 (1), 357 (7), 355 (19), 353 (18), 321 (3), 319
(4), 248 (8), 238 (10), 236 (100), 203 (27), 192 (17), 179 (5), 177
(38), 160 (21), 145 (26), 134 (8), 121 (3), 119 (5), 117 (5), 108 (10).
UV (MeOH): lmax [lg (e/m2 mol–1)] = 324 (3.44), 227 (3.36), 203
nm (3.62).
(13) Hartung, J.; Schwarz, M.; Svoboda, I.; Fueß, H.; Duarte, M.-
T. Eur. J. Org. Chem. 1999, 1275.
(14) Hartung, J.; Schwarz, M. Synlett 2000, 371.
(15) Hartung, J.; Schwarz, M. Org. Synth. Coll. Vol. 10; Wiley:
New York, 2004, 437–441.
(16) Gross, A.; Schneiders, N.; Daniel, K.; Gottwald, T.;
Hartung, J. Tetrahedron 2008, 64, 10882.
(17) Hartung, J.; Altermann, S.; Svoboda, I.; Fuess, H. Acta
Anal. Calcd for C12H10Cl3NOS2 (354.69): C, 40.64; H, 2.84; N,
3.95; S, 18.06. Found: C, 40.81; H, 2.99; N, 3.90; S, 18.51.
trans-2,2-Dimethyl-3-(2-methylpropen-1-yl)cyclopropanecar-
boxylic Acid23
Transformation of thiazolethione 6e (100 mg, 0.25 mmol) and CHD
(200 mg, 2.5 mmol) in C6H6 (3 mL) was carried out according to the
general procedure.
Crystallogr., Sect. E 2005, 61, o1738.
(18) Chimiak, A.; Pryzchodzen, W.; Rachon, J. Heteroat. Chem.
2002, 13, 169.
Yield: 26.5 mg (63%, 0.16 mmol).
(19) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahedron 1987,
Acknowledgment
43, 4321.
(20) Giese, B.; Stellmach, J. Chem. Ber. 1980, 113, 3294.
(21) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification
of Laboratory Chemicals; 2nd ed., Pergamon Press: Oxford,
1980.
This work is part of Ph.D. theses of C.S. and A.G. It was supported
by the state of Rheinland-Pfalz (scholarship for A.G.). We express
our gratitude to Prof. Helmut Ritter (Universität Düsseldorf) for sti-
mulating discussions.
(22) Midgley, G.; Thomas, C. B. J. Chem. Soc., Perkin Trans. 2
1987, 1103.
(23) Wang, M.-X.; Feng, ; G, Q. J. Org. Chem. 2003, 68, 621.
Synthesis 2010, No. 3, 538–542 © Thieme Stuttgart · New York