A convenient synthesis of 2-substituted thiazole-5-carboxylates

Article abstract of DOI:10.1071/CH03252

The photolysis of ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate in acetonitrile containing 0.5% trifluoroacetic acid in the presence of thioamides gives moderate (40-60%) yields of thiazole-5-carboxylate esters. In the absence of trifluoroacetic

Full text of DOI:10.1071/CH03252

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2004, 57, 599–604
A Convenient Synthesis of 2-Substituted Thiazole-5-carboxylates
Mei Fong,A Wit K. Janowski,A,∗ Rolf H. Prager,A,B and Max R. TaylorA
A
School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide SA 5001, Australia.
B Author to whom correspondence should be addressed (e-mail: rolf.prager@flinders.edu.au).
The photolysis of ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate in acetonitrile containing 0.5% tri-
fluoroacetic acid in the presence of thioamides gives moderate (40–60%) yields of thiazole-5-carboxylate esters. In
the absence of trifluoroacetic acid, the intermediate vinyl thioesters can be isolated.That addition of the thioamide to
the first formed carbene was, through sulfur, confirmed by X-ray crystal structures of 2-methylthiazole-5-carboxylic
acid and a byproduct.
Manuscript received: 23 September 2003.
Final version: 24 November 2003.
Introduction
lead to 2,5-disubstituted thiazoles, provided that the sulfur
underwent addition to the carbenoid centre.
In connection with a project directed toward the synthesis of
a series of cyclic peptide mimetics based on aminoalkyloxa-
zole and -thiazole carboxylic acids,[1,2] we have reported an
approach to the synthesis of the former, using our method-
ology based on the formation of imidoylcarbenes from
isoxazolones.[3–5] We have also reported that photolysis of
N-thioacylisoxazolones leads to thiazoles.[6] Both these reac-
tions involve the intramolecular rearrangement of the carbene
(Scheme 1).
The synthesis of 2,4-disubstituted thiazoles is generally
readily achieved by the Hanzsch synthesis[7] (Scheme 2),
the reaction of thioamides with α-bromoketones,[8,9]
or variations with α-diazoketones,[10] α-bromoamides or
lactones,[11] 2-nitrooxiranes,[12] or alkynyl(aryl)iodonium
mesylates[13] or equivalents,[14] although the reaction some-
times fails.[15] 2-Substituted thiazole-5-carboxylates, the
subject of this paper, have been obtained similarly from chlo-
rinated β-ketoesters[16] or from vinylphosphonium salts,[17]
and are of interest for their antilipolytic and hypotriglyceri-
demic activity.[16] The route shown in Scheme 3, the reac-
tion of thioamides with α-oxo or α-iminocarbenes, appears
to proceed only with certain substrates[18] but would readily
The analogous reaction of carboxamides with carbenoids
during rhodium(ii)-catalyzed decomposition of diazoma-
lonates and diazo β-ketoesters,[19] and diazophosphono
esters,[20] which generates 2,4-disubstituted oxazoles,[21]
R1
R1
H2N
O
S
ϪHY
N
S
Y
R3
R2
R2
R3
Scheme 2.
R1
R1
NH2
X
S
ϪHX
S
N
R2
R3
R2
R3
Scheme 3.
R1
X
R1
R1
X
H
N
R1C(X)Cl
N
hn or ⌬
ϪCO2
N
N
Xϭ O,S
X
O
O
R2
R2
R2
R2
O
O
Scheme 1.
∗ Deceased.
© CSIRO 2004
10.1071/CH03252
0004-9425/04/060599

600
M. Fong et al.
involves addition of the nitrogen atom to the unsaturated cen-
tre. The NH moiety of amides also reacts with 1,3-dithiolium
carbenes.[22] However, the conversion of carboxamides to
nitriles by dichlorocarbene[23] would appear to require
reaction of the amide oxygen atom with the carbene. The
realization of the pathway shown in Scheme 3 is the subject
of this paper.
N4
C3
C2
O8
C7
C5
C6
H8
O9
S1
Discussion
Fig. 1. The molecular structure of 2-methylthiazole-5-carboxylic acid,
showing crystallographic labelling and with displacement ellipsoids
drawn at the 50% probability level.
Ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate 1
is readily available from the reaction of phenylhydroxylamine
with diethyl methoxymethylenemalonate,[24] and the phenyl
group is known[25,26] to activate the molecule to form the car-
bene 2 on photolysis or flash vacuum pyrolysis. Photolysis
of 1 in the presence of three equivalents of thioacetamide
in acetone or ether at 300 nm (pyrex filter) gave a com-
plicated mixture of products, but the addition of acid gave
a cleaner product. While the use of acetic acid led to the
capture of the carbene by acetic acid,[27] the presence of
0.5% trifluoroacetic acid (TFA) led to the isolation of ethyl
2-methylthiazole-5-carboxylate 3 in 58% yield after chro-
matography. Since the 1H NMR spectrum of 3 and the
isomeric 4-ester are rather similar,[28] the ester 3 was con-
verted to the crystalline 2-methythiazole-5-carboxylic acid
(mp 138–140◦C). Schoberl and Stock[29] have reported the
synthesis of both the 4- and the 5-carboxylic acids (mp
143–145◦C and 209◦C), but we believe their assignments
are incorrect in the light of the X-ray structures for 2-
methylthiazole-5-carboxylic acid, derived from 3 (Fig. 1) and
4, below.A similar yield (62%) of 3 was obtained in ether con-
taining 0.5%TFA, but the byproducts were now more difficult
to remove.
In addition to 3, a second compound (10%) was iso-
lated, whose structure was inferred to be 4 from its spectral
data and confirmed by X-ray crystallography. The structure
of 4 was deduced from its NMR spectra, which showed
the presence of two alkenyl protons by signals at 7.85 and
6.81 ppm, the latter of which slowly exchanged with D2O,
and a thioketone group with a 13C resonanance at 204.6 ppm.
The ORTEP structure, deduced from single crystal X-ray
data, is shown in Fig. 2. The structure of this product is
important, as it presumably arises as shown in Scheme 4,
and suggests that, unlike amides,[19–22,30] thioamides react
with carbenes through the sulfur atom. Subsequent work (see
below) supports the intermediacy of compounds of the type 5.
Photolysis of 1 as above in the presence of thiobenza-
mide until reaction was complete required 12 h at a one-gram
scale. Chromatography gave only a single pure compound
(44%), identified as ethyl 2-phenylthiazole-5-carboxylate
6. Brief photolysis gave 6 (23%) and a second product
(20%) which could not be separated from it. This prod-
uct is believed to be a 3 : 1 mixture of trans- (7a) and
cis- (7b) isomers, as deduced from the coupling constants
of the vicinal protons [7a: 6.58 (H-5, d, J 5), 4.47 (H-4,
d, J 5); 7b: 6.35 (H-5, d, J 9.2), 4.78 (H-4, d, J 9.2)],
Scheme 5. Treatment of the total mixture with TFA gave 6
in 44% yield and 7 was no longer present. The identity of 6
C19
C18
C20
C17
C15
C16
O10
C3
N4
C6
C5
C2
C8
C11
C12
O7
C9
S1
C14
S13
Fig. 2. The molecular structure of 4, showing crystallographic
labelling and with displacement ellipsoids drawn at the 50% probability
level.
was confirmed by comparison of the melting point (65◦C)
with that reported in the literature[31] (60◦C; that of the 4-
ester is 47◦C[31]). In addition, the 4-ester was synthesized[32]
and had clearly distinct 1H and 13C NMR spectra.
Photolysis of 1 in the presence of acetone semithiocar-
bazone gave a crude product containing what is believed
to be the uncyclized adduct 8, probably as a mixture of
diastereoisomers. NMR evidence showed compound 8 con-
tained no sp3-hybridized carbons other than those associated
with the ester and 2-propylidene groups. Cyclization was
best achieved by refluxing with p-toluenesulfonic acid in
dry benzene, and chromatography then allowed isolation of
the thiazole ester 9 in 48% yield. The product was clearly
not the same as the isomeric ester 10, which was obtained by
Hanzsch synthesis using ethyl bromopyruvate and acetone
semithiocarbazone as described by Johne and coworkers.[33]
Since our ultimate aim was to develop strategies for the
synthesis of novel 2-aminoalkylthiazole-4- and -5-carboxylic
acids 11 and their analogues, selective α-alkylation of the
hydrazino group was investigated. The ester 9 could not be
alkylated in the absence of base, but conversion to the sodium
salt by sodium hydride in tetrahydrofuran allowed alkylation
with methyl iodide or benzyl bromide. The latter gave a mix-
ture of the two N-benzyl isomers, 12 and 13, which could
be readily separated by chromatography. The assignment of
structures to the two isomers (Scheme 6) was achieved by

A Convenient Synthesis of 2-Substituted Thiazole-5-carboxylates
601
Ph
N
Ph
N
NHPh
NHPh
CO2Et
NH2
N
NH
hn
H
O
ϩ
CH3
S
H3C
S
S
H3C
CO2Et
O
H
CO2Et
CO2Et
1
2
5
3
Hϩ
ϪPhNH2
Ph
N
N
H3C
H2N
CH3
S
S
CO2Et
CO2Et
ϪNH3
Ph
Ph
N
N
CH3CSNH2
ϪNH3
S
CO2Et
S
CO2Et
S
4
Scheme 4.
NHPh
N
N
N
R
CO2H
H
R1
Ph
S
S
CO2Et
Ph
H2N
S
R2
6
7a R1ϭ H, R2ϭ CO2Et
7b R1ϭ CO2Et, R2ϭ H
11
Scheme 5.
NHPh
NH
NH2
N
Hϩ
1
NH
N
S
N
hn
N
CO2Et
N
H
N
S
S
H
CO2Et
8
9
1. NaH
2. BzBr
Bz
N
S
N
S
N
N
ϩ
N
N
CO2Et
Bz
CO2Et
13
12
1. OHϪ
2. HCl
N
ϩ
H3N
N
COϪ2
S
Bz
14
Scheme 6.
1
comparison of the H NMR chemical shifts of H-4, which
have been studied in the two series by Forlani.[34] The more
polar ester 12 was then converted to the desired amino acid
using a base followed by protonation. Drying the resulting
hydrochloride led to formation of the zwitterionic hydrazino
acid 14. In the same way, the isomeric thiazole ester 10 was
alkylated, but in this case only a single alkylated product
15 was formed and again its structure was confirmed by

602
M. Fong et al.
COϪ2
CO2Et
CO2Et
N
N
N
ϩ
N
H3N
N
NH
N
N
S
S
S
Bz
Bz
10
15
16
Scheme 7.
1H NMR spectroscopy. Hydrolysis then gave the zwitterionic
hydrazino acid 16 (Scheme 7).
Repetition of the above on a ten-fold greater scale required 8 h for
completion, chromatography allowing the isolation of 3 and 4 in 43%
and 12% yields respectively.
(b) When acetic acid (1 mL) replaced trifluoroacetic acid in the
photolysis, NMR analysis indicated the product (26%) was the acetoxy
enamine, ethyl 2-acetoxy-3-phenylaminoacrylate.
Conclusions
Thephotolysisofethyl5-oxo-2-phenyl-2,5-dihydroisoxazole-
4-carboxlate in the presence of thioamides, followed by
acidic treatment, leads to moderate yields of thiazole-5-
carboxylates. The reaction is possibly complicated by photo-
chemically induced reactions of thioamides,[31] including the
[2+2] photocycloaddition of thioamides with the intermedi-
ate aminoalkene.[32,35] Oda and coworkers[36] have recently
reported the synthesis of 2-arylthiophenes from the photo-
chemically induced reaction of arene thiocarboxamides
with methyl furans, emphasizing the synthetic utility of
thioamides.
2-Methylthiazole-5-carboxylic Acid
Ester3(276 mg, 1.61 mmol)wasrefluxedinmethanol(3 mL)containing
sodium hydroxide (69 mg, 1.73 mmol) for 2 h.The solvent was removed,
the residue acidified with HCl, and the product was extracted with
dichloromethane and recrystallized from water as white needles, mp
138–140◦C after vacuum drying. The X-ray structure is shown in Fig. 1.
•
(Found: M+ 143.0045. C5H5NO2S requires 143.0041). vmax/cm−1
2472, 1697, 1374, 1316, 1280, 1090. δH ([D6]DMSO) 8.16 (1H, s),
2.28 (3H, s). δC ([D6]DMSO) 172.3, 162.4, 147.8, 130.3, 19.6.
Photolysis of 1 with Thiobenzamide
Isoxazolone 1 (1.0 g, 4.3 mmol) was photolyzed as above in the presence
of thiobenzamide (1.77 g, 12.9 mmol) in acetonitrile (1000 mL) andTFA
(5 mL), requiring 12.5 h for completion (1H NMR monitoring). Chro-
matography on silica with mixtures of dichloromethane-light petroleum
Experimental
Proton and carbon NMR spectra were recorded using a Varian Gemini
Spectrometer at 300 MHz and 75.5 MHz respectively, in deuteriochloro-
form (CDCl3), unless otherwise stated. Infrared spectra were recorded
on a Perkin–Elmer 1600 FTIR spectrometer; solids were analyzed as
Nujol mulls, and liquids as films. High resolution mass spectra were
recorded at Monash University, and microanalyses at the University of
Otago. Melting points were determined on a Reichert hot-stage appara-
tus and remain uncorrected. Radial chromatography was performed with
silica gel 60 PF 254 coated glass rotors using a Chromatotron (model
7924T). GC-MS analysis was performed on a Varian Saturn 4D instru-
ment, using a 5% phenylmethyl polysiloxane column (30 m, 0.25 mm
ID, 0.25 mm thickness). Photolyses were performed under nitrogen in
freshly distilled solvents, using a Hanovia medium-pressure mercury
arc source considered to be nominally 300 nm or above.
•
gave 6 (439 mg, 44%), mp 64–65◦C (lit[31] 58–60◦C). (Found: M+
233.0514. C12H11NO2S requires 233.0511). vmax/cm−1 1711, 1415,
1297, 1246, 1092. δH 8.42 (1H, s), 7.97–7.6 (2H, m), 7.48–7.46 (3H, m),
4.39 (2H, q J 7.2), 1.40 (3H, t J 7.5). δC 173.3, 161.4, 149.1, 133.0,
131.2, 129.1, 129.0, 126.9, 61.7, 14.3. m/z 233 (M, 100%), 188 (46),
160 (32), 105 (29), 57 (38).
The isomeric ethyl 2-phenylthiazole-4-carboxylate, mp 47◦C, was
synthesized following the literature procedure.[32] vmax/cm−1 1712,
1415, 1300, 1249, 1149, 1093. δH 8.16 (1H, s), 8.05 (2H, m), 7.44
(3H, m) 4.45 (2H, q J 7.6), 1.43 (3H, t J 7.6). δC 169.0, 161.6, 148.2,
132.8, 130.7, 129.1, 127.1, 126.7, 61.4, 14.2. m/z 233 (M, 100%), 205
(50), 188 (50), 160 (45), 104 (24), 57 (48).
When the above photolysis was interrupted after 3.5 h, the presence
of an intermediate product 7 could be seen. Chromatography at this
stage allowed its isolation as a pale yellow oil (43%), containing the
isomers 7a and 7b (20%) in the ratio of 3 : 1, in addition to 6 (23%).
They were characterized by doublets at 6.58 and 4.47 ppm (J 5.0), and
at 6.35 and 4.78 ppm (J 9.2), respectively. These signals disappeared,
and were replaced by those characteristic of the thiazole, on addition of
TFA to the solution.
Photolysis of 1 with Thioacetamide
(a) A solution of 1[24] (100 mg, 0.4 mmol) and thioacetamide (70 mg,
2.3 equiv.) in acetonitrile (100 mL) and trifluoroacetic acid (0.5 mL) was
degassed and irradiated for 3 h under nitrogen at 300 nm through pyrex.
The solvent was removed, replaced with ether (20 mL), and the solution
was washed with sat Na2CO3, and 1 M HCl. Chromatography on silica
in ether/light petroleum (4 : 1) gave 3•(40 mg, 58%) as a colourless oil,
RF (silica, ether) 0.65. (Found: M+ 171.0353. C7H9NO2S requires
171.0354). vmax/cm−1 1715, 1443, 1303, 1258, 1091. δH 8.24 (1H, s),
4.35 (2H, q J 7.2), 2.75 (3H, s), 1.37 (3H, t J 7.0). δC 172.0, 161.3,
148.1, 129.3, 61.5, 19.7, 14.3. m/z 171 (M, 56%), 143 (54), 126 (100),
98 (53), 57 (74).
Photolysis of 1 in the Presence of Acetone Thiosemicarbazone
A solution of 1 (2.3 g, 10 mmol), acetone thiosemicarbazone[37] (1.6 g,
12 mmol), and TFA (1 mL) in acetonitrile (800 mL) was irradiated
for 8 h under nitrogen through pyrex. After removal of solvent, the
product was chromatographed on silica (CH2Cl2/EtOAc). The first
two fractions contained aniline and unreacted thiosemicarbazone. The
third fraction, containing what is believed to be intermediate 8,
was refluxed with p-toluenesulfonic acid (1 g) in benzene (100 mL)
for 1 h, and then ether (100 mL) was added. After being washed
with cold saturated Na2CO3 and water, the solution was evaporated
and chromatographed. The first fraction (CH2Cl2) contained ethyl
2-[2-(1-methylethylidene)hydrazino]thiazole-5-carboxylate 9 and was
recrystallized from acetone as pale yellow crystals (1.07 g, 48%), mp
178–179◦C. (Found: C 47.75, H 5.4, N 18.4%. C9H13N3O2S requires
C 47.6, H 5.8, N 18.5%). δH 9.1 (1H, br, exch.), 7.90 (1H, s), 4.32 (2H,
A colourless solid 4 (6 mg), mp 228◦C, remained undissolved in the
ethereal phase above and was recrystallized from ethanol. (Found: C
59.3, H 5.1, N 4.6%, M+• 305.0554. C15H15NO2S2 requires C 59.0, H
4.95, N 4.6%, M+• 305.0544.). vmax/cm−1 1716, 1484, 1274, 1221. δH
7.85 (1H, s), 7.64–7.62 (3H, m), 7.41–7.38 (2H, m), 6.81 (1H, s, (slow
D2O exch), 4.37 (2H, q J 7.2), 2.61 (3H, s), 1.38 (3H, t J 7.2). δC 204.6,
163.8, 161.6, 137.8, 136.0, 130.5, 130.5, 126.5, 110.3, 61.8, 37.5, 14.3.
m/z 305 (M, 36%), 196 (100), 168 (22), 77 (22). 4 decomposed on GC
analysis.

A Convenient Synthesis of 2-Substituted Thiazole-5-carboxylates
603
q, J 7.5), 2.08 (3H, s), 1.96 (3H, s), 1.30 (3H, t, J 7.5). δC 174.9, 162.2,
151.8, 146.6, 118.1, 60.8, 25.1, 17.8, 14.4.
T 203(2) K. Dc (Z 4) 1.366 Mg m−3. µMo 0.357 mm−1; specimen
0.43 × 0.16 × 0.14 mm3. ꢀρmax 2.10 e Å−3
.
Benzylation of Thiazole 9
Crystal Structure Determination and Refinement
To a suspension of sodium hydride (48 mg, 2 mmol) in THF (15 mL)
was added a solution of thiazole 9 (470 mg, 2 mmol) in THF
(10 mL), and the mixture was stirred under nitrogen for 15 min at RT.
Benzyl bromide (342 mg, 2 mmol) was added, and the mixture was
stirred for 2 days at RT. Ether (40 mL) was added, and the mix-
ture washed with sat NaCl. Chromatography of the residue on silica
eluted two products. The first (CH2Cl2) was isolated as yellow crystals,
mp 122–123◦C (150 mg, 24%), identified as ethyl 3-benzyl-2-[(1-
methylethylideneamino)imino]-2,3-dihydrothiazole-5-carboxylate 13.
(Found: C 60.8, H 6.1, N 13.1%, M+• 317.1199. C16H19N3O2S requires
C 60.5, H 6.0, N 13.2%, M+• 317.1198). vmax/cm−1 1698, 1630. δH 7.40
(1H, s), 7.28 (5H, m), 5.00 (2H, s), 4.21 (2H, q J 7.5), 2.05 (3H, s) 2.02
(3H, s), 1.38 (3H, t J 7.5). δC 164.1, 161.8, 161.5, 135.7, 135.4, 128.9,
128.3, 128.3, 108.5, 61.0, 50.7, 24.9, 18.5, 14.3.
Unit-cell and intensity data for both compounds were measured on a
Siemens SMART CCD diffractometer using graphite-monochromated
MoKα X-radiation at the University of Auckland, New Zealand. The
structuresweresolvedbyusing SIR97;[38] otherwisecomputerprograms
of the Xtal 3.7 system[39] were used for all calculations. Non-hydrogen
atomic coordinates and anisotropic displacement parameters for all
atoms were refined by full-matrix least-squares on F2.
For 2-methylthiazole-5-carboxylic acid a total of 3233 reflections
were measured which when averaged (Rint 0.009) gave 708 unique
reflections, of which there were 705 with F2 > 0. The structure was
refined on 705 reflections with F2 > 0 and 82 variables to convergence
[R(F2 > 2σ(F2)) 0.022, wR 0.063, S 1.139]. Hydrogen atoms were
placed from the penultimate difference map and not refined.
For 4 a total of 8206 reflections were measured which when aver-
aged (Rint 0.062) gave 3019 unique reflections, of which there were
2990 with F2 > 0). The structure was refined on 2497 reflections with
F2 > 2σ(F2) and 181 variables to convergence [R(F2 > 2σ(F2)) 0.123,
wR 0.303, S 2.22]. Hydrogen atoms were placed in calculated positions
and not refined. Although the plot of displacement ellipsoids (Fig. 2)
did not show any abnormalities, the final difference map showed several
large peaks that could not be interpreted. Consequently, the data for 4
was not deposited.
The second fraction, ethyl 2-[1-benzyl-2-(1-methylethylidene)-
hydrazino]thiazole-5-carboxylate 12, was isolated as a colourless oi•l
•
(280 mg, 44%). (Found: M+ 317.1197. C16H19N3O2S requires M+
–1
317.1198). vmax/cm 1700. δH 8.00 (1H, s), 7.3 (5H, m), 5.05 (2H,
s), 4.31 (2H, q J 7.5), 2.08 (3H, s), 1.75 (3H, s), 1.33 (3H, t J 7.5).
δC 177.8, 174.5, 162.2, 147.8, 135.8, 128.5, 127.7, 118.5, 60.7, 56.8,
24.6, 20.0, 14.4.
Ethyl 2-[1-Benzyl-2-(1-methylethylidene)hydrazino]thiazole-
4-carboxylate 15
Acknowledgments
The thiazole 10[33] (470 mg, 2 mmol) was reacted with benzyl bro-
mide as above. Column chromatography gave the pure tit•le compound
The authors are grateful for support of this project by the
Australian Research Council. We thank Assoc. Prof.
C. Rickard of the University of Auckland, New Zealand, who
collected the X-ray diffraction data.
(580 mg, 92%) as
a
colourless oil. (Found: M+ 317.1199.
C16H19N3O2S requires 317.1198). vmax/cm−1 1713, 1650, 1480, 1385,
1092. δH 7.55 (1H, s), 7.3 (5H, m), 4.88 (2H, s), 4.15 (2H, q, J 7), 2.02
(3H, s), 1.74 (3H, s), 1.38 (3H, t, J 7).
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1995, 32, 937.
•
(Found: M+ 249.0572. C11H11N3O2S requires 249.0572). vmax/cm−1
3618, 3019, 2361, 1665. δH 7.83 (1H, s) 7.4–7.3 (5H, m), 4.91 (2H, s),
4.5 (3H, br, exch.). δC 178.6, 164.1, 148.1, 135.0, 128.8, 128.4, 128.0,
118.7, 56.6.
2-(1-Benzylhydrazino)thiazole-4-carboxylic Acid 16
The ester 15 (1.26 g, 4 mmol) was treated with NaOH (5 mmol) as above
for 30 min at 50◦C. After acidification, the product was extracted into
dichloromethane, evaporated, and the residue stirred with water (10 mL)
containing one drop of conc HCl. After 30 min, the water was decanted,
and the solid product was recrystallized from ether as colourless crys-
tals (690 mg, 69%), mp 189–190◦C. (Found: C 53.0, H 4.2, N 16.8%.
C11H11N3O2S requires C 53.0, H 4.45, N 16.9%). vmax/cm−1 3424 br,
3019, 1679. δH ([D6]DMSO) 7.58 (1H, s), 7.4–7.3 (5H, m), 4.82 (2H, s),
4.0 (3H, br, exch.). δC ([D6]DMSO) 174.7, 162.7, 144.2, 136.4, 128.7,
128.2, 127.6, 118.7, 56.7.
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Crystal Data for 2-Methylthiazole-5-carboxylic Acid
C5H5NO2S, M 143.17. Orthorhombic, space group Pna21, a 13.675(1),
b 11.473(1), c 3.853(1) Å, V 604.51(17) Å3, T 203(2) K. Dc (Z 4)
1.573 Mg m−3. µMo 0.448 mm−1; specimen 0.37 × 0.12 × 0.12 mm3.
ꢀρmax 0.23(2) e Å−3. CCDC deposition no. 219844.
Crystal Data for 4
C
15H16NO2S2,
M 306.44. Monoclinic, space group P21/n, a
6.770(1), b 11.683(1), c 18.849(1) Å, β 92.22(1)◦, V 1489.7(3) Å3,

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