Sulfur promoted decarboxylative thioamidation of carboxylic acids using formamides as amine proxy

Article abstract of DOI:10.1016/j.tet.2016.02.070

An efficient decarboxylative thioamidation of arylacetic and cinnamic acids has been developed employing formamides as amine surrogate and sulfur as promoter. Thioamides with variant structural features are obtained under mild reaction conditions without the use of transition metal catalysts and oxidants.

Full text of DOI:10.1016/j.tet.2016.02.070

Tetrahedron 72 (2016) 2012e2017
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Sulfur promoted decarboxylative thioamidation of carboxylic acids
using formamides as amine proxy
*
Saurabh Kumar, Rajeshwer Vanjari, Tirumaleswararao Guntreddi, Krishna Nand Singh
Department of Chemistry (Centre of Advanced Study), Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient decarboxylative thioamidation of arylacetic and cinnamic acids has been developed em-
ploying formamides as amine surrogate and sulfur as promoter. Thioamides with variant structural
features are obtained under mild reaction conditions without the use of transition metal catalysts and
oxidants.
Received 7 December 2015
Received in revised form 6 February 2016
Accepted 29 February 2016
Available online 3 March 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Thioamides
Decarboxylation
Sulfur
Formamides
Carboxylic acids
1. Introduction
However, most of the decarboxylation reactions developed so
far necessitate the use of transition metals as catalysts.10 Recently,
The advancement of new and efficient reactions without com-
promising the product selectivity and environmental safety is the
recent trend in synthetic research. Cross-coupling and CeH acti-
vation reactions have turned out to serve the purpose primarily.1
Thioamide moiety is ubiquitous in biologically active molecules,
and is widely used as synthetic building block for many heterocy-
cles, besides its industrial applications.2 Different methods for the
preparation of thioamides are described in literature, the most
common being the WillgerodteKindler reaction,3 thionation re-
action,4 and the reaction of CS2 with Grignard reagents.5 Since
these methods often require harsh conditions, some useful thio-
amide forming reactions have been recently reported employing
aldehyde,6 benzylamine,7 and alkyne/alkene8 as starting material.
Yet, the development of greener and practical methods to prepare
thioamides from new and readily available starting materials is
desirable and demanding.
our group has developed the synthesis of thioamides using aryl-
acetic/cinnamic acids and amines as coupling partners in the
presence of simple sulfur.11b However, a practical problem arises in
case of dimethylamine, which exists either in gaseous form or is
commercially available as aqueous solution. Therefore, a viable
substitute is looked for. Since the development of efficient re-
actions utilizing readily available starting materials is always im-
perative, the use of DMF as amine source has recently been
described.12 In view of the above, and as a part of our ongoing
endeavor to develop novel strategies,13 particularly the synthesis
of thioamides,11b,14 we disclose herein a practical synthesis of
thioamides using formamides as amine source adopting a de-
carboxylation protocol in the presence of elemental sulfur and
K2CO3 (Scheme 1).
Decarboxylative coupling reactions have attracted a great deal
of attention and offer potential advantages since (i) carboxylic acids
are inexpensive and readily available with great structural diversity
both from natural and synthetic sources, (ii) they are easy to handle
and store (iii) CO2 is the only by product, which is non‒flammable
and is easily removed from the reaction mixture.9
2. Results and discussion
To begin with, a model reaction employing phenylacetic acid
(1a) and dimethylformamide (2a) was carried out in the presence
of elemental sulfur (S8, Mol. wt 32) and K2CO3 under solvent-free
conditions at 120 ꢀC. To our delight, the desired product 3a was
obtained in 76% yield (Table 1, entry 1). The reaction conditions
were then thoroughly optimized by varying different parameters
such as promoter, solvent, and base; and the overall findings are
summarized in Table 1.
* Corresponding author. Tel.: þ91 542 670 2485; fax: þ91 542 2368127; e-mail
addresses: knsinghbhu@yahoo.co.in, knsingh@bhu.ac.in (K.N. Singh).
http://dx.doi.org/10.1016/j.tet.2016.02.070
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

S. Kumar et al. / Tetrahedron 72 (2016) 2012e2017
2013
However, the reaction of 1e under standard conditions did not
succeed and required a change in base from K2CO3 to DABCO to
afford the desired product 3e. The substituent such as 4-OH (1g), 4-
F (1h) and 4-Ph (1j) were well tolerated during the course of re-
action, but the NO2 group (1d & 1k) was eventually reduced to NH2
(3d & 3k). A heteroaromatic acid viz., thiophene-3-acetic acid (1i)
also participated nicely in the reaction. However, indole-3-acetic
acid, a-naphthyl acetic acid and valeric acid did not give rise to
the desired product. Formamides such as N-formyl morpholine (2c)
and N-formyl piperidine (2b) also reacted well to provide the cor-
responding tertiary thioamides (3m & 3n) in reasonably high
yields.
To extend the scope of the reaction, the optimized conditions
were then applied to the reaction of cinnamic acid derivatives
(4ae4g) with formamides 2a. Gratifyingly, cinnamic acids bearing
different electronic and steric properties (4ae4g) underwent the
reaction smoothly to afford the corresponding thioamides (5ae5f)
in reasonably good yields (Table 3). The NO2 group in the substrate
4e was again reduced to NH2 (5e). Surprisingly, the compound 4g
Table 2
Scope of the reaction with arylacetic acidsa
Scheme 1. Thioamidation using formamides.
Absence of base or altering K2CO3 to Na2CO3 or DABCO did not
bring about any positive change (entries 2, 3 & 4). Making use of
different solvents was also worthless, as it rather reduced the yields
considerably (entries 5 to 10), although the use of 1,4-dioxane and
pyridine had little diminution effect as compared to DMSO, toluene,
acetic acid, and t-BuOH. Addition of some copper metal salts to
sulfur also reduced the product yields significantly (entries 11, 12 &
13). After having established the optimized conditions (Table 1,
entry 1), the generality of the reaction was examined using di-
versely substituted arylacetic acids (1) and formamides (2) to
provide the corresponding thioamides 3 in 52e81% yield (Table 2).
Arylacetic acids containing both the electron-rich and electron-
deficient substituents on aromatic ring (1aek) underwent the re-
action smoothly to afford the thioamidated products 3aen.
Table 1
Optimization of the reaction conditionsa
Entry
Promoter
Solvent
Base
Yield (%)b
1
2
3
4
5
6
7
8
S8
S8
S8
S8
S8
S8
S8
S8
d
K2CO3
d
76
31
53
68
16
20
62
72
0
d
d
Na2CO3
DABCO
K2CO3
K2CO3
K2CO3
K2CO3
d
d
DMSO
Toluene
1,4-Dioxane
Pyridine
Acetic acid
t-BuOH
d
9
S8
S8
10
11
12
13
K2CO3
25c
23
30
26
CuIþS8
CuBrþS8
d
aReaction conditions: 1 (1 mmol), 2 (1 mL), K2CO3 (2 equiv), S8 (4 equiv),
Cu(OAc)2$2H2OþS8
d
a
120 °C, 24 h.
Reaction conditions: 1 (1 mmol), 2 (1 mL), base (2 equiv), S8 (4 equiv), Solvent
(1 mL), Cu (10 mol %), 120 ꢀC, 24 h.
bIsolated yield after column chromatography.
cDABCO was used.
b
Isolated yield after column chromatography.
c
100 ꢀC.

2014
S. Kumar et al. / Tetrahedron 72 (2016) 2012e2017
Table 3
Scope of the reaction with cinnamic acidsa
Fig. 1. X-ray Crystal Structure of 3 h (drawn at 30% probability).15
Finally to probe the mechanism, some control experiments were
conducted (Scheme 2). Addition of radical scavengers such as
TEMPO and BHT to the reaction completely inhibited the formation
of product, showing radical involvement in the reaction (eq. 1).
When N-formylaniline alone was subjected to the standard re-
action conditions, the formation of the amine was not observed (eq.
2). But the presence of amine has been detected during the course
of the reaction between N-formylaniline and phenylacetic acid,
which necessitates the use of the acid in reaction.11a When the
reaction was conducted by replacing phenylacetic acid by benzal-
dehyde with DMF, the formation of the product was noticed albeit
in low yield (eq. 3), which shows the possibility of reaction via an
aldehyde intermediate. When styrene was admitted to the stan-
dard reaction conditions, no product formation was observed;
which rules out the possibility of reaction via styrene in case of
cinnamic acids (eq. 4).
aReaction conditions: 4 (1 mmol), 2 (1 mL), K2CO3 (2 equiv), S8 (4 equiv),
100 °C, 24 h.
bIsolated yield after column chromatography.
led to formation of the product 3f with an unusual removal of two
carbon atoms.
Another interesting result was realized by using N-formylani-
lines 6 as coupling partner for its reaction with arylacetic acids 1 to
afford the secondary thioamides 7 (Table 4). The CHO group of N-
formylanilines is always lost during the course of reaction to afford
N-mono substituted thioamides in high yields (7a-e). However, the
reaction of cinnamic acid with N-formylaniline could not succeed.
The structure of a representative product 3h has been conclu-
sively proved by single crystal X-ray (Fig. 1).15
Table 4
Scope of the reaction with N-formylanilinesa
Scheme 2. Control experiments.
Based on the above control experiments and existing litera-
ture,11 a plausible mechanism is outlined in Scheme 3. Arylacetic
aReaction conditions: 1 (1 mmol), 6 ( 5 equiv), K2CO3 (2 equiv), S8 (4 equiv),
DMSO (1 mL), 120 °C, 24 h.
bIsolated yield after column chromatography.
Scheme 3. Plausible mechanism for the formation of 3.

S. Kumar et al. / Tetrahedron 72 (2016) 2012e2017
2015
acid 1 is initially assumed to form an
a
-oligo sulfide I under the
4.1.1. N,N-Dimethylbenzothioamide (3a).12f Yellow solid; yield (76%,
WillgerodteKindler conditions, which might be a radical process.
Decarboxylation along with SeS bond cleavage then leads to the
thioaldehyde II; CO2 generation being a thermodynamic driving
force for the conversion. The reaction of II with amine and ele-
mental sulfur affords the intermediate III, which eventually leads to
the formation of product 3 by the elimination of H2S (Scheme 3).
Accordingly in case of cinnamic acids, the involvement of the
intermediate(s) IV and/or V is postulated. The cinnamic acid 4 in
presence of elemental sulfur and base forms the intermediate IV via
125 mg); mp: 68e70 ꢀC; 1H NMR (CDCl3, 300 MHz):
d 7.30e7.32 (m,
5H), 3.14 (s, 3H), 3.58 (s, 3H); 13C NMR (75 MHz, CDCl3):
143.3, 128.4, 128.2, 125.6, 43.9, 43.0.
d 201.2,
4.1.2. N,N,2-Trimethylbenzothioamide (3b).12f Yellow amorphous
solid; yield (55%, 98 mg); 1H NMR (CDCl3, 300 MHz):
7.13e7.27
(m, 4H), 3.60 (s, 3H), 3.04 (s, 3H), 2.24 (s, 3H); 13C NMR (75 MHz,
CDCl3): 201.1, 143.3, 131.5, 130.4, 128.1, 126.2, 125.1, 42.7, 42.1, 18.7.
d
d
the attack of amine at
b
-position followed by sulfur insertion at
a
-
4.1.3. 3-Methoxy-N,N-dimethylbenzothioamide (3c). Yellow amor-
phous solid; yield (72%, 140 mg); 1H NMR (CDCl3, 300 MHz):
7.23
(t, J¼7.8 Hz, 1H), 6.84 (d, J¼8.1 Hz, 3H), 3.80 (s, 3H), 3.58 (s, 3H), 3.16
position. The intermediate IV upon decarboxylation and removal of
H2S, forms the intermeiate V, which may undergo Wilgerodt-
Kindler type rearrangement to give the product 5 (Scheme 4).
d
(s, 3H); 13C NMR (75 MHz, CDCl3):
d 200.9, 159.4, 144.5, 129.4, 117.7,
114.3, 111.2, 55.2, 43.9, 42.9; HRMS (ESIþ): (MþH)þcalcd. For
C10H13NOS: 196.0791; Found: 196.0789.
4.1.4. 3-Amino-N,N-dimethylbenzothioamide (3d). Yellow amor-
phous solid; yield (64%, 115 mg); 1H NMR (CDCl3, 300 MHz):
7.06
(t, J¼7.2 Hz, 1H), 6.56 (d, J¼7.8 Hz, 3H), 3.65 (s, 2H), 3.55 (s, 3H), 3.14
d
(s, 3H); 13C NMR (75 MHz, CDCl3):
d 201.3, 146.5, 144.2, 129.1, 115.2,
115.0, 112.1, 43.8, 42.8; HRMS (ESIþ): (MþH)þ calcd. For C9H12N2S:
181.0794; Found: 181.0783.
4.1.5. 3-Chloro-N,N-dimethylbenzothioamide (3e). Yellow amor-
phous solid; yield (56%, 111 mg); 1H NMR (CDCl3, 300 MHz):
d
7.16e7.29 (m, 4H), 3.58 (s, 3H), 3.17 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d 199.3, 144.8, 134.3, 129.8, 128.7, 125.9, 123.8, 44.0, 43.1;
HRMS (ESIþ): (MþH)þ calcd. For C9H10ClNS: 200.0295; Found:
200.0299.
4.1.6. 4-Chloro-N,N-dimethylbenzothioamide (3f).12g Yellow solid;
yield (73%, 145 mg); mp: 79e81 ꢀC; 1H NMR (CDCl3, 300 MHz):
7.24e7.34 (m, 4H), 3.58 (s, 3H), 3.17 (s, 3H); 13C NMR (75 MHz,
Scheme 4. Plausible mechanism for the formation of 5.
d
CDCl3):
d 199.9, 141.6, 134.5, 129.5, 128.9, 128.5, 127.3, 44.0, 43.2.
4.1.7. 4-Hydroxy-N,N-dimethylbenzothioamide (3g). Yellow solid;
yield (52%, 94 mg); 1H NMR (DMSO, 500 MHz):
d 9.74 (s, 1H), 7.13
3. Conclusions
(d, J¼5.1 Hz, 2H), 6.68 (d, J¼5.1 Hz, 2H), 3.42 (s, 3H), 3.13 (s, 3H); 13
C
In conclusion, a practical decarboxylative approach has been
developed for the synthesis of thioamides by the reaction of phe-
nylacetic/cinnamic acids with formamides as amine coupling
partner. The present methodology offers a useful alternative par-
ticularly in the light of the practical difficulties faced in using
dimethylamine which exists in gaseous form and is commercially
available in aqueous form. The protocol has also been successfully
applied to N-formylanilines as aniline coupling partner to prepare
N-phenyl thioamides.
NMR (125 MHz, DMSO):
d 200.0, 158.4, 134.5, 128.7, 114.9, 44.6,
43.7; HRMS (ESIþ): (MþH)þ calcd. For C9H11NOS: 182.0634; Found:
182.0607.
4.1.8. 4-Fluoro-N,N-dimethylbenzothioamide (3h). Yellow solid;
yield (63%, 115 mg); mp: 69e71 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
7.00e7.07 (m, 2H), 7.29e7.34 (m, 2H), 3.59 (s, 3H), 3.18 (s, 3H); 13
C
NMR (75 MHz, CDCl3):
d 200.3, 164.3, 161.0, 139.5, 128.0, 127.9,
115.4, 115.2, 44.1, 43.2; HRMS (ESIþ): (MþH)þ calcd. For C9H10FNS:
184.0591; Found: 184.0596.
4. Experimental section
4.1.9. N,N-Dimethylthiophene-3-carbothioamide (3i).11a Yellow oil;
yield (66%, 112 mg); 1H NMR (CDCl3, 300 MHz):
d 7.35 (s, 1H),
4.1. General procedure for the synthesis of thioamides
7.25e7.28 (m, 1H), 7.13 (d, J¼5.1 Hz, 1H), 3.55 (s, 3H), 3.26 (s, 3H);
13C NMR (75 MHz, CDCl3):
43.1.
d 195.0, 142.9, 126.9, 125.3, 123.6, 43.9,
Elemental sulfur powder (S8, Mol. wt 32, 4 mmol) and K2CO3
(2 equiv) were added to a vial (10 mL) containing phenylacetic acid
1 or cinnamic acid 4 (1 mmol) and DMF (1 mL). The reaction
mixture was heated at 120/100 ꢀC in an oil bath for 24 h. After
completion of the reaction as determined by TLC, reaction mixture
was allowed to cool to room temperature, diluted with water and
then extracted with ethyl acetate (3ꢁ10 mL). The combined organic
phase was evaporated under reduced pressure, and the resulting
crude was separated through column chromatography using hex-
aneeethyl acetate as an eluent to afford the pure product 3/5. The
formation of the products 7, however, required the use of DMSO for
smooth reaction.
4.1.10. N,N-Dimethyl-[1,1ʹ-biphenyl]-4-carbothioamide (3j). Yellow
solid; yield (59%, 142 mg); mp: 98e100 ꢀC; 1H NMR (CDCl3,
300 MHz): d 7.55e7.57 (m, 4H), 7.37e7.46 (m, 5H), 3.61 (s, 3H), 3.21
(s, 3H); 13C NMR (75 MHz, CDCl3): d 201.1, 142.2, 141.5, 140.3, 128.8,
127.6, 127.0, 126.3, 44.1, 43.1; HRMS (ESIþ): (MþH)þ calcd. For
C15H15NS: 242.0998; Found: 242.1001.
4.1.11. 4-Amino-N,N-dimethylbenzothioamide (3k).12f Yellow solid;
yield (61%, 109 mg); mp:139e141 ꢀC; 1H NMR (CDCl3, 300 MHz):
d
7.16 (d, J¼8.1 Hz, 2H), 6.57 (d, J¼8.1 Hz, 2H), 3.87 (s, 2H), 3.56 (s,

2016
S. Kumar et al. / Tetrahedron 72 (2016) 2012e2017
3H), 3.23 (s, 3H); 13C NMR (75 MHz, CDCl3):
128.2, 126.8, 126.6, 113.9, 44.3,43.5.
d
201.9, 147.5, 133.1,
d
9.02 (br s, 1H), 7.80 (d, J¼7.2 Hz, 2H), 7.56 (d, J¼8.1 Hz, 2H),
7.38e7.48 (m, 3H), 7.20 (d, J¼8.1 Hz, 2H), 2.36 (s, 3H); 13C NMR
(75 MHz, CDCl3):
126.7, 123.9, 21.0.
d 198.5, 143.0, 137.0, 136.5, 131.2, 129.6, 128.6,
4.1.12. Phenyl(piperidin-1-yl)methanethione (3l).11a Yellow amor-
phous solid; yield (74%, 151 mg); 1H NMR (CDCl3, 300 MHz):
d
7.25e7.31 (m, 5H), 4.34 (s, 2H), 3.49 (t, J¼4.2 Hz, 2H),1.74e1.80 (m,
4.1.23. N-(4-Methoxyphenyl)benzothioamide (7c).17 Yellow solid;
yield (70%, 170 mg); mp: 127e129 ꢀC; 1H NMR (CDCl3, 300 MHz):
4H), 1.54e1.55 (m, 2H); 13C NMR (75 MHz, CDCl3):
d 199.4, 143.3,
128.3, 128.2, 125.3, 52.9, 50.4, 26.6, 25.2, 23.8.
d
9.09 (br s, 1H), 7.75 (d, J¼7.5 Hz, 2H), 7.33e7.54 (m, 5H), 6.86 (d,
J¼8.7 Hz, 2H), 3.78 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 198.3, 158.2,
4.1.13. Morpholino(phenyl)methanethione (3m).11a Yellow amor-
142.6, 132.0, 131.1, 128.5, 126.7, 125.7, 114.0, 55.3.
phous solid; yield (81%, 167 mg); 1H NMR (CDCl3, 300 MHz):
d
7.27e7.34 (m, 5H), 4.42 (t, J¼4.8 Hz, 2H), 3.86 (t, J¼4.5 Hz, 2H),
4.1.24. N-(Pyridin-2-yl)benzothioamide (7d).11a Yellow solid; yield
(73%, 156 mg); mp: 129e131 ꢀC; 1H NMR (CDCl3, 300 MHz):
9.17
3.60e3.62 (m, 4H); 13C NMR (75 MHz, CDCl3):
d
201.0, 142.4, 128.8,
d
128.5, 125.8, 66.6, 66.3, 52.3, 49.4.
(br s, 1H), 8.28e8.29 (m, 1H), 7.78e7.88 (m, 3H), 7.42e7.51 (m, 4H),
7.14e7.26 (m, 1H); 13C NMR (75 MHz, CDCl3):
d 197.9, 152.4, 148.4,
4.1.14. (4-Bromophenyl)(piperidin-1-yl)methanethione
143.6, 138.2, 131.5, 128.7, 126.8, 121.5, 115.0.
(3n).11a Yellow solid; yield (68%, 193 mg); mp: 90e92 ꢀC; 1H NMR
(CDCl3, 300 MHz):
d
7.46 (d, J¼8.1 Hz, 2H), 7.14 (d, J¼8.1 Hz, 2H),
4.1.25. 3-Methoxy-N-phenylbenzothioamide (7e).18 Yellow solid;
yield (75%, 182 mg); mp: 90e92 ꢀC; 1H NMR (CDCl3, 300 MHz):
4.30 (t, J¼5.4 Hz, 2H), 3.49 (t, J¼5.4 Hz, 2H), 1.74e1.77 (m, 4H),
1.56e1.57 (m, 2H); 13C NMR (75 MHz, CDCl3):
d
197.9, 142.0, 131.4,
d
9.15 (br s, 1H), 7.66 (d, J¼7.2 Hz, 2H), 7.23e7.40 (m, 6H), 6.99 (s,
127.1, 122.3, 53.0, 50.4, 26.6, 25.2, 23.8.
1H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
198.1, 159.5, 144.3,
138.9, 129.5, 128.9, 126.9, 123.8, 118.3, 117.2, 112.6, 55.4.
4.1.15. N,N-Dimethyl-2-phenylethanethioamide
(5a).12f Yellow
solid; yield (72%, 128 mg); mp: 74e76 ꢀC; 1H NMR (CDCl3,
Acknowledgements
300 MHz): d 7.24e7.31 (m, 5H), 4.28 (s, 2H), 3.45 (s, 3H), 3.16 (s, 3H);
13C NMR (75 MHz, CDCl3):
50.4, 41.9.
d 200.2, 135.4, 128.4, 127.7, 126.6, 50.4,
We are thankful to the Department of Science and Technology
(Grant No. SR/S1/OC-78/2012) for providing financial assistance.
S.K., R.V. and T.G. are thankful to the CSIR, New Delhi for providing
research fellowships.
4.1.16. N,N-Dimethyl-2-(p-tolyl)ethanethioamide
solid; yield (72%, 138 mg); mp: 58e60 ꢀC; 1H NMR (CDCl3,
300 MHz):
7.19 (d, J¼7.8 Hz, 2H), 7.09 (d, J¼7.5 Hz, 2H), 4.24 (s,
2H), 3.45 (s, 3H), 3.17 (s, 3H), 2.31 (s, 3H); 13C NMR (75 MHz, CDCl3):
200.5, 136.1, 132.3, 129.1, 128.6, 127.7, 125.6, 50.0, 44.3, 41.9, 20.6.
(5b).12f Yellow
d
Supplementary data
d
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.02.070.
4.1.17. 2-(4-Methoxyphenyl)-N,N-dimethylethanethioamide
(5c).12f Yellow solid; yield (68%, 142 mg); mp: 118e120 ꢀC; 1H NMR
References and notes
(CDCl3, 300 MHz):
d
7.24e7.31 (m, 2H), 6.84 (d, J¼8.4 Hz, 2H), 4.23
(s, 2H), 3.79 (s, 3H), 3.48 (s, 3H), 3.21 (s, 3H); 13C NMR (75 MHz,
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4. (a) Coats, S.; Link, J. S.; Hlasta, D. Org. Lett. 2003, 5, 721; (b) Shibahara, F.; Su-
CDCl3):
42.0.
d 201.2, 158.6, 129.2, 127.9, 127.6, 114.1, 113.5, 55.1, 49.9, 44.7,
ꢀ
ꢀ
4.1.18. 2-(2-Chlorophenyl)-N,N-dimethylethanethioamide
(5d).12f Yellow amorphous solid; yield (63%, 134 mg); 1H NMR
(CDCl3, 300 MHz):
d 7.36e7.38 (m, 2H), 7.18e7.24 (m, 2H), 4.32 (s,
2H), 3.53 (s, 3H), 3.19 (s, 3H); 13C NMR (75 MHz, CDCl3):
133.9, 133.5, 129.4, 129.3, 128.3, 127.2, 47.4, 44.5, 42.0.
d 199.9,
ꢀ
giura, R.; Murai, T. Org. Lett. 2009, 11, 3064; (c) Szostak, M.; Aube, J. Chem.
4.1.19. 2-(4-Aminophenyl)-N,N-dimethylethanethioamide
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2890; (f) Curphey, T. J. J. Org. Chem. 2002, 67, 6461.
5. Katritzky, A. R.; Moutou, J. L.; Yang, Z. Synthesis 1995, 12, 1497.
6. (a) Zubruyev, O. I.; Stiasni, N.; Kappe, C. O. J. Comb. Chem. 2003, 5, 145; (b)
Aghapoor, K.; Mohsenzadeh, F.; Khanalizadeh, G.; Darabi, H. R. Monatsh. Chem.
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31, 53.
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8. (a) Nguyen, T. B.; Tran, M. Q.; Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2014, 16,
310; (b) Sun, Y.; Jiang, H.; Wu, W.; Zenga, W.; Li, J. Org. Biomol. Chem. 2014, 12,
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(5e).11a Yellow solid; yield (59%, 114 mg); mp: 116e118 ꢀC; 1H NMR
(CDCl3, 300 MHz):
2H), 3.57 (s, 2H), 3.48 (s, 3H), 3.20 (s, 3H); 13C NMR (75 MHz,
CDCl3): 201.6,145.3,129.1,128.3,125.4,115.4,114.0, 50.1, 44.9, 42.1.
d 7.10e7.27 (m, 2H), 6.59e6.66 (m, 2H), 4.19 (s,
d
4.1.20. N,N-Dimethyl-2-(thiophen-2-yl)ethanethioamide
(5f).16 Yellow amorphous solid; yield (62%, 114 mg); 1H NMR
(CDCl3, 300 MHz):
d
7.18 (t, J¼2.7 Hz, 1H), 6.95 (s, 2H), 4.44 (s, 2H),
3.48 (s, 3H), 3.30 (s, 3H); 13C NMR (75 MHz, CDCl3):
126.8, 125.6, 124.7, 45.3, 44.7, 42.1.
d 199.6, 137.6,
10. (a) Shang, R.; Huang, Z.; Chu, L.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 4240; (b) Shang,
R.; Huang, Z.; Xiao, X.; Lu, X.; Fu, Y.; Liu, L. Adv. Synth. Catal. 2012, 354, 2465; (c)
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C. H.; Carmack, M. J. Org. Chem. 1947, 12, 76.
4.1.21. N-Phenylbenzothioamide (7a).17 Yellow solid; yield (69%,
146 mg); mp: 91e93 ꢀC; 1H NMR (CDCl3, 300 MHz):
9.08 (br s,1H),
7.71e7.82 (m, 4H), 7.24e7.48 (m, 6H); 13C NMR (75 MHz, CDCl3):
198.6, 143.1, 139.0, 131.3, 129.0, 128.6, 127.0, 126.7, 123.8.
d
d
4.1.22. 4-Methyl-N-phenylbenzothioamide (7b).11a Yellow solid;
yield (71%, 161 mg); mp: 119e121 ꢀC; 1H NMR (CDCl3, 300 MHz):

S. Kumar et al. / Tetrahedron 72 (2016) 2012e2017
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