Chemoselectivity in coupling of azides with thioacids in solution-phase and solvent-free conditions

Article abstract of DOI:10.1080/00397911.2011.606043

Solvent-free rapid coupling of monothiocarboxylic acid with azide affords carboxamide chemoselectively. Triphenyl phosphine included as an additive influences the chemoselectivity, yielding carboxamide and thioamide. Similar variation in the chemoselectivity is observed in the absence and presence of triphenyl phosphine in solution-phase methodology. Rapidity and ecofriendliness of the solvent-free approach to yield the products in just 15min is noteworthy compared to the solution-phase protocol, which has a long reaction time (1-3 days).

Full text of DOI:10.1080/00397911.2011.606043

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Chemoselectivity in Coupling of Azides
with Thioacids in Solution-Phase and
Solvent-Free Conditions
Sangaraiah Nagarajan a , Poovan Shanmugavelan a , Murugan
Sathishkumar a , Namachivayam Priyadharshini a , Padmanaban
Sudakar a & Alagusundaram Ponnuswamy a
a Department of Organic Chemistry, School of Chemistry, Madurai
Kamaraj University, Tamilnadu, India
Accepted author version posted online: 21 Feb 2012.Version of
record first published: 13 Nov 2012.
To cite this article: Sangaraiah Nagarajan, Poovan Shanmugavelan, Murugan Sathishkumar,
Namachivayam Priyadharshini, Padmanaban Sudakar & Alagusundaram Ponnuswamy (2013):
Chemoselectivity in Coupling of Azides with Thioacids in Solution-Phase and Solvent-Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:5, 668-680
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Synthetic Communications1, 43: 668–680, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.606043
CHEMOSELECTIVITY IN COUPLING OF AZIDES WITH
THIOACIDS IN SOLUTION-PHASE AND SOLVENT-FREE
CONDITIONS
Sangaraiah Nagarajan, Poovan Shanmugavelan,
Murugan Sathishkumar, Namachivayam Priyadharshini,
Padmanaban Sudakar, and Alagusundaram Ponnuswamy
Department of Organic Chemistry, School of Chemistry,
Madurai Kamaraj University, Tamilnadu, India
GRAPHICAL ABSTRACT
Abstract Solvent-free rapid coupling of monothiocarboxylic acid with azide affords
carboxamide chemoselectively. Triphenyl phosphine included as an additive influences the
chemoselectivity, yielding carboxamide and thioamide. Similar variation in the chemo-
selectivity is observed in the absence and presence of triphenyl phosphine in solution-phase
methodology. Rapidity and ecofriendliness of the solvent-free approach to yield the products
in just 15 min is noteworthy compared to the solution-phase protocol, which has a long
reaction time (1–3 days).
Keywords Amide; chemoselectivity; glycerol bath; MW irradiation; solvent-free;
thioamide
INTRODUCTION
Amides and thioamides are prevalent in organic biomolecules,[1] natural
products,[2] and potential drugs.[3] Their synthetic potential has been realized as they
serve as intermediates in the fabrication of oxazoline, thiazoline, and thiazoles.[4]
Hence, attention is being directed toward the search for elegant, efficient and
environmentally friendly protocols for their syntheses.
Received May 15, 2011.
Address correspondence to Alagusundaram Ponnuswamy, Department of organic Chemistry,
School of Chemistry, Madurai Kamaraj University, Tamil Nadu 625 021, India. E-mail: ramradkrish@
yahoo.co.in
668

COUPLING OF AZIDES WITH THIOACIDS
669
Scheme 1. Synthesis of amide via direct coupling reactions.
In the prevailing protocols, the methodologies of choice employed for amide
synthesis are the direct coupling of carboxylic acid or its derivatives either with
amine[5] or Staudinger’s phosphazene[6,7] (generated from the organic azide and
triarylphosphine) (Scheme 1).
On the other hand, most often thioamide is obtained by thionation[8]
(Scheme 2) of the corresponding amide. Alternatively, dithioacid couples with azide
to afford thioamide.[9]
Recently, Park et al.[10] have described the first successful amide formation by
coupling monothiocarboxylic acid with triarylphosphazene (Scheme 3).
Generally, most of the prevailing methodologies, including those mentioned
previously, are solution-phase protocols wherein the limitations associated with (i)
the polarity, refluxing temperature, and toxicity of the solvent; (ii) usage of corrosive
coupling reagents; and=or (iii) catalyst would restrict their broad scope and eco-
friendliness. Limitations such as loading of catalysts for large-scale preparation
and difficulties in reactivation=reusability of deactivated catalysts may preclude
the scope of their applicability. Thus, search for newer protocols overcoming such
limitations is worth the attempt.
In this regard, we have recently reported an efficient and elegant solvent-free,
microwave=preheated glycerol bath–accelerated synthesis (MAS=GBAS)[11] of
Scheme 2. Synthesis of thioamide via thionation=coupling reaction.
Scheme 3. Amide formation from monothiocarboxylic acid and triarylphosphazene.

670

671

672

COUPLING OF AZIDES WITH THIOACIDS
673
Table 2. Chemoselectivity in benzylazide=thioacetic acid coupling in solvents in the presence of triphenyl
phosphine (TPP)
Amide:Thioamidea
Entry
Solvent
Time
OPb
Sqc
1
2
3
4
5
Acetonitrile
Benzene
Toluene
60 h
36 h
12 h
5 h
59:41
85:15
89:11
81:19
84:16
100:nil
100:nil
100:nil
100:nil
100:nil
Xylene
Mesitylene
30 min
aRatio in the crude reaction mixture determined by 1H NMR.
bOne-pot procedure.
amides, wherein the limitations associated with the solution-phase protocols have
been eradicated. Further, the exploration of the broad scope of MAS and GBAS
has been fruitful[12]. In the present study, a rapid and chemoselective one-pot,
solvent-free reaction of monothiocarboxylic acid, azide, and triphenyl phosphine
(TPP) affording amide and thioamide (Table 1) has been accomplished via MAS
and GBAS. Further, the chemoselectivity in the coupling reaction conducted in
solvent-free condition without TPP and solution-phase protocol both with and with-
out TPP is compared to representative examples. Also, thorough comparisons of the
chemoselective results between a sequential and one-pot procedure are provided in
Tables 1 and 2.
RESULTS AND DISCUSSION
Typically, in the optimized protocol, azide was added dropwise to a solvent-
free intimate mixture of triphenyl phosphine and monothiocarboxylic acid and
heated at 180 ꢀC using microwave irradiation (CEM Discover, Benchmate model,
single-mode design with built-in infrared sensor) for 15 min to afford amide
and thioamide, such that the former always predominated. The broad scope of the
protocol was accomplished by coupling benzyl azide, 2-azidoethylacetate, 2-
azidomethylacetate, tosyl azide, and 1-azido-3-phenyl-2-cyclohexene with monothio-
carboxylic acids (viz., thioacetic acid or thiobenzoic acid) in the presence of triphenyl
phosphine to afford the corresponding products (Table 1), which were isolated by
column chromatograpy.
Additionally, GBAS of amide and thioamide was accomplished via the
same one-pot reaction at 180 ꢀC in 15 min under solvent-free conditions using the

674
S. NAGARAJAN ET AL.
conventional preheated glycerol bath as an alternative to microwave irradiation. The
yields were identical to that obtained via MAS. This substantiates that the rate of
heating, rather than the source of heating, is crucial to the coupling reaction.
It is pertinent to mention here that using the same substrates (viz., monothio-
carboxylic acids, organic azides, and triphenylphosphine), Park et al.[10] have
attempted thioamide preparation via a solution-phase protocol in a slightly different
approach. The difference in their protocol is the preparation of phosphazene in acet-
onitrile first, followed by the addition of monothiocarboxylic acid, wherein they have
obtained only amide. In particular, they have mentioned that they failed to detect
thioamide in their investigation even though its formation would be expected via
the dual mechanism (Scheme 4) proposed by them.
Moreover, as per their report, the solution-phase protocol in acetonitrile for
amide synthesis took days (nearly 3 days; see Scheme 4) for completion. Thus, the
ecofriendly solvent-free protocol of the present study is very rapid and discloses
the first chemoselective formation of amide and thioamide.
In view of the varying chemoselectivity and rate of amide synthesis by our
present solvent-free approach as compared to that of the solution-phase protocol[10]
,
we were further tempted to revisit our one-pot approach via the solution-phase
methodology to understand whether the absence or presence of solvent would bring
about any change in the chemoselectivity of the reaction. Hence, we conducted the
one-pot reaction in different solvents. Surprisingly, here too, in the solution-phase
approach, we were able to detect the formation of thioamide in addition to amide
(Table 2). The products were interpreted by the NMR spectra (1H and 13C, Fig. 1)
of the crude reaction mixture.
We revisited the coupling in representative cases under solvent-free condition
without TPP and in solution-phase without TPP. Herein, in absence of TPP, only
amide was obtained. The overall result with regard to the chemoselectivity is
summarized in Table 3.
It is evident from Table 3 that thioamide is obtained in addition to amide only
when triphenyl phosphine is present as one of the components in the coupling reac-
tion (entries 2, 4, 7 and 8). Thus, though the attempt to prepare thioamide by Park et
al.[10] (Scheme 4) was found to be not successful via their protocol (preparation of
phosphazene followed by coupling with monothiocarboxylic acid), it has been real-
ized through our approach wherein triphenyl phosphine was added to the mixture of
monothiocarboxylic acid and azide (Scheme 5, route b, followed by routes c, d, e).
Scheme 4. Coupling of monothiocarboxylic acid with phosphazene via dual mechanism.

COUPLING OF AZIDES WITH THIOACIDS
675
Figure 1. Diagnostic signals of amide and thioamide in the 1H=13C NMR of crude reaction mixture.
(Figure is provided in color online.)
Table 3. Chemoselectivity in coupling reactions of thioacids with azides
Entry
1
Azide
Thioacid
Solvent
—
Additive
Amide
Thioamide
X
p
—
p
p
2
—
TPP
p
p
p
p
p
3
4
5
6
7
—
—
TPP
—
X
p
—
Mesitylene
Mesitylene
Acetonitrile
X
—
X
p
TPP
p
p
8
Acetonitrile
TPP

676
S. NAGARAJAN ET AL.
Scheme 5. Plausible mechanism for the chemoselective formation of amide and thioamide.
The plausible mechanism sketched in Scheme 5 clearly shows the various poss-
ible routes in the one-pot reaction. The reaction is initiated by the attack of either the
conjugate base of the thioacid (route a) or triphenyl phosphine (route b) on one of
the nitrogens of the azide. Following this, while route a, not involving the partici-
pation of TPP,[13] affords amide as the exclusive product through the five-membered
cyclic intermediate,[14] route b, involving TPP, first gives the phosphazide, which
branches in three different pathways (routes c, d, and e). These pathways lead to
the formation of amide and thioamide through phosphazene[11] and=or six-
membered cyclic intermediates. Of the four possible pathways, except route e
(affording thioamide), all the other pathways (routes c, d, and e) yield amide, thus
explaining the predominant formation of the amide in the chemoselective reaction.
Further, the multifold increase in the rate of amide and thioamide synthesis in
solvent-free protocol may be due to the high collision between the intimate polar
components in the fused molten phase at higher temperatures.
CONCLUSIONS
In conclusion, the present study dealing with solvent-free, one-pot coupling
reaction of monothiocarboxylic acid with azide in the presence=absence of TPP is
novel in (i) eradicating the limitations associated with solution-phase protocol and
(ii) effecting multifold increase in the rate of amide and thioamide synthesis. Further,
the findings disclose for the first time the chemoselectivity in the coupling. Further
studies in this regard are in progress.
EXPERIMENTAL
All chemicals, reagents, and solvents were of commercially high purity
purchased from Acros Organics Synthesis Pvt. Ltd. and Sigma-Aldrich Ltd., India.
Silica gel (60–120 mesh) was used for column chromatographic isolation and purifi-
cation of the amides synthesized. Organic azides used in the investigation were pre-
pared according to the literature procedures. Melting points were obtained on an
electrothermal apparatus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded in CDCl3 on a Bruker Avance 300-MHz spectrometer, and the chemical
shifts are reported as d values in parts per million (ppm) relative to tetramethylsilane

COUPLING OF AZIDES WITH THIOACIDS
677
(TMS), with J values in hertz. The splitting patterns in 1H NMR spectra are reported
as follows: s, singlet; d, doublet; t, triplet; q, quartet; br s, broad singlet; br d, broad
doublet; and m, multiplet. 13C NMR data are reported with the solvent peak
(CDCl3 ¼ 77.0) as the internal standard. Elemental analyses of new compounds were
performed in a CNRS-Vernaison and agreed with the calculated values within
ꢁ0.4%. The spectral data of all known compounds are consistent with those reported
previously.
General Procedure
To a well-ground, intimate mixture of monothiocarboxylic acid (1.0 mmol) and
triphenyl phosphine (1.1 mmol) in a microwave vial (10 mL) equipped with a mag-
netic stirring bar, azide (1.0 mmol) was added in drops while stirring. Stirring was
continued until liberation of nitrogen ceased, and the reaction vessel was sealed with
a septum. It was then placed into the cavity of a focused monomode microwave reac-
tor (CEM Discover, benchmate) and operated at 180 ꢀC (temperature monitored by
a built-in IR sensor), power 180 W, for 15 min. The reaction temperature was main-
tained by modulating the power level of the reactor. Alternatively, the microwave
vial with the mixture was conventionally heated around 180 ꢀC by immersing it in
a preheated glycerol bath for 15 min. The reaction vessel was then cooled to room
temperature, water (10 mL) was added and the solution was extracted with dichlor-
omethane. The combined organic layer was washed with saturated NaHCO3 and
brine, dried over Na2SO4, and concentrated. The residue was then subjected to col-
umn chromatography on silica gel using petroleum ether–ethyl acetate (95:5 to
80:20) as mobile phase. This resulted in the isolation of pure amide and thioamide
from the by-products (viz., triphenyl phosphine sulfide and oxide). Yields: amide
(59–88%) and thioamide (5–15%).
Selected Data
N-(3-Phenylcyclohex-2-enyl)acetamide[11] (1a). White solid. Mp 97 ꢀC. 1H
NMR (300 MHz, CDCl3): d 1.55–2.47 (m, 6 H), 2.05 (s, 3 H), 5.76 (br s, 1 H), 5.88
(br s, 1 H), 5.98 (m, 1 H), 7.25–7.70 (m, 5 H). 13C NMR (75 MHz, CDCl3): d 20.33,
23.42, 27.24, 29.11, 45.55, 122.76, 125.15, 127.13, 128.58, 140.33, 141.27, 169.30.
Anal. calc. for C14H17NO: C, 78.10; H, 7.96; N, 6.51. Found: C, 78.12; H, 7.97;
N, 6.50.
N-(3-Phenylcyclohex-2-enyl)ethanethioamide (1b). Viscous matter. 1H
NMR (300 MHz, CDCl3): d 1.63–2.50 (m, 6H), 2.54 (s, 3H), 5.31 (br s, 1H), 6.02
(m, 1H), 7.24-7.39 (m, 5H). 13C NMR (75 MHz, CDCl3): d 20.32, 27.42, 29.63,
34.54, 51.90, 122.36, 125.25, 127.64, 128.36, 140.97, 141.79, 199.70. Anal. calc. for
C14H17NS: C, 72.68; H, 7.41; N, 6.05; S, 13.86. Found: C, 72.70; H, 7.41; N, 6.06;
S, 13.88.
N-(3-Phenylcyclohex-2-enyl)benzamide[11] (2a). White solid. Mp 154 ꢀC.
1H NMR (300 MHz, CDCl3): d 1.39–1.53 (m, 1 H), 1.65–1.77 (m, 2 H), 1.95–2.07
(m, 1 H), 2.20–2.42 (m, 2 H), 4.60 (br s, 1 H), 5.60 (br d, J ¼ 8.4 Hz, 1 H), 6.00
(br s, 1 H), 7.29-7.75 (m, 10 H). 13C NMR (75 MHz, CDCl3): d 20.42, 27.27,

678
S. NAGARAJAN ET AL.
29.19, 45.06, 123.61, 125.18, 126.41, 126.91, 128.45, 131.31, 134.70, 138.61, 140.40,
148.27, 166.79. Anal. calc. for C19H19NO: C, 82.28; H, 6.90; N, 5.05. Found: C,
82.30; H, 6.89; N, 5.05.
1
N-Benzylacetamide[15] (3a). White solid. Mp 59 ꢀC. H NMR (300 MHz,
CDCl3): d 2.06 (s, 3 H), 4.46 (d, J ¼ 5.7 Hz, 2 H), 7.27–7.31 (m, 5 H). 13C NMR
(75 MHz, CDCl3): d 23.17, 43.74, 128.39, 128.55, 128.66, 133.26, 169.87. Anal. calc.
for C9H11NO: C, 72.46; H, 7.43; N, 9.39. Found: C, 72.45; H, 7.42; N, 9.40.
N-Benzyl-thioacetamide[16] (3b). White solid. Mp 65 ꢀC. 1H NMR
(300 MHz, CDCl3): d 2.58 (s, 3 H), 4.80 (d, J ¼ 5.1 Hz, 2 H), 7.25–7.39 (m, 5 H).
13C NMR (75 MHz, CDCl3): d 34.06, 50.59, 128.12, 128.31, 128.87, 135.97,
200.75. Anal. calc. for C9H11NS: C, 65.41; H, 6.71; N, 8.48; S, 19.40. Found: C,
65.43; H, 6.70; N, 8.49; S, 19.41.
Methyl 2-ethanethiomidoacetate (5b). Viscous matter. 1H NMR
(300 MHz, CDCl3): 2.62 (s, 3H), 3.82 (s, 3H), 4.41 (d, J ¼ 4.5 Hz, 2H), 7.89 (br s,
1H). 13C NMR (75 MHz, CDCl3): d 33.39, 47.40, 52.69, 169.39, 201.74. Anal. calc.
for C5H9NO2S: C, 40.80; H, 6.16; N, 9.52; S, 21.78. Found: C, 40.82; H, 6.15; N,
9.50; S, 21.76.
1
Ethyl 2-ethanethiomidoacetate (7b). Viscous matter. H NMR (300 MHz,
CDCl3): 1.33 (t, J ¼ 7.2 Hz, 3H), 2.63 (s, 3H), 4.28 (q, J ¼ 7.2 Hz, 2H), 4.39 (d,
J ¼ 4.5 Hz, 2H), 7.83 (br s, 1H). 13C NMR (75 MHz, CDCl3): d 14.02, 33.67,
47.59, 61.92, 168.90, 201.48. Anal. calc. for C6H11NO2S: C, 44.70; H, 6.88; N,
8.69; S, 19.89. Found: C, 44.69; H, 6.89; N, 8.70; S, 19.91.
Ethyl 2-benzamidoacetate[17] (8a). White solid Mp 62 ꢀC. 1H NMR
(300 MHz, CDCl3): d 1.29 (t, J ¼ 6.9 Hz, 3H), 4.22 (m, 4H), 7.01 (br s, 1H),
7.28–8.07 (m, 5H). 13C NMR (75 MHz, CDCl3): d 14.09, 41.83, 61.56, 127.06,
128.52, 131.70, 133.67, 167.55, 170.10. Anal. calcd. for C11H13NO3: C, 63.76; H,
6.32; N, 6.76. Found: C, 63.77; H, 6.31; N, 6.75.
Ethyl 2-phenythioamidoacetate[18] (8b). Viscous matter. 1H NMR
(300 MHz, d 1.34 (t, J ¼ 6.9 Hz, 3H), 4.32 (q, J ¼ 7.2 Hz, 3H), 4.56 (d, J ¼ 4.2 Hz,
2H), 7.26–7.83 (m, 5H). 13C NMR (75 MHz, CDCl3): d 14.51, 30.06, 48.47, 62.46,
127.15, 128.93, 131.77, 169.50, 199.59. Anal. calcd. for C11H13NO2S: C, 59.17; H,
5.87; N, 6.27; S, 14.36. Found: C, 59.18; H, 5.88; N, 6.28; S, 14.36.
ACKNOWLEDGMENTS
The authors thank Intensification of Research in Higher Priority Areas
(IRHPA), Department of Science and Technology, for providing the 300-MHz
NMR instrument for recording the NMR spectra. S. N., P. S., and M. S. acknowl-
edge their grateful thanks to the University Grants Commission for the sanction of
junior research fellowships.

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679
REFERENCES
1. Tinnis, F.; Adolfsson, H. Asymmetric transfer hydrogenation of ketones catalyzed by
rhodium complexes containing amino acid triazole ligand. Org. Biomol. Chem. 2010, 8,
4536–4539.
2. Zenker, N.; Hubbard, L. S.; Wright, W. Inhibition of dopamine b-hydroxylase by goitrin,
a natural antithyroid compound. J. Nat. Prod. 1988, 51, 862–865.
´
3. Jagodzinski, T. S. Thioamides as useful synthons in the synthesis of heterocycles. Chem.
Rev. 2003, 103, 197–228.
4. Wipf, P.; Miller, C. P.; Venkatraman, S.; Fritch, P. C. Thiolysis of oxazolines: A new,
selective method for the direct conversion of peptide oxazolines into thiazolines.
Tetrahedron Lett. 1995, 36, 6395–6398.
5. (a) Petersson, M. J.; Marchal, C.; Loughlin, W. A.; Jenkins, I. D.; Healy, P. C.;
´
Almesaker, A. Unexpected regiospecific reactivity of a substituted phthalic anhydride.
Tetrahedron 2007, 63, 1395–1401; (b) Maki, T.; Ishihara, K.; Yamamoto, H. New
boron(III)-catalyzed amide and ester condensation reactions. Tetrahedron 2007, 63,
8645–8657; (c) Perreux, L.; Loupy, A.; Volatron, F. Solvent-free preparation of amides
from acids and primary amines under microwave irradiation. Tetrahedron 2002, 58,
2155–2162.
¨
6. (a) Staudinger, H.; Meyer, J. Uber neue organische phosphorverbindungen III: Phosphin-
methylenderivate und phosphinimine. Helv. Chim. Acta 1919, 2, 635–646; (b) Gololobov,
Y. G.; Zhmurova, I. N.; Kasukhin, L. F. Frequency and type of confrontation over time
within the first therapy interview. Tetrahedron 1981, 37, 437–472; (c) Gololobov, Y. G.;
Kasukhin, L. F. Recent advances in the Staudinger reaction. Tetrahedron 1992, 48,
1353–1406.
´
7. (a) Garcıa, J.; Urpı, F.; Vilarrasa, J. New synthetic ‘‘tricks’’: Triphenylphosphine-mediated
amide formation from carboxylic acids and azides. Tetrahedron Lett. 1984, 25, 4841–4844;
´
(b) Kovacs, L.; Osz, E.; Domokos, V.; Holzer, W.; Gyorgydesk, Z. An easy access to
´
¨
anomeric glycosyl amides and imines (Schiff bases) via transformation of glycopyranosyl
trimethylphosphinimides. Tetrahedron 2001, 57, 4609–4621; (c) Malkinson, J. P.;
Falconer, R. A.; Toth I. Synthesis of C-terminal glycopeptides from resin-bound glycosyl
azides via a modified Staudinger reaction. J. Org. Chem. 2000, 65, 5249–5252; (d) Urpı, F.;
´
Vilarrasa, J. New synthetic ‘‘tricks’’: Advantages of using triethylphosphine in some
phosphorus-based reactions. Tetrahedron Lett. 1986, 27, 4623–4624; (e) Shalev, D. E.;
Chiacchiera, S. M.; Radkowsky, A. E.; Kosower, E. M. Sequence of reactant combination
alters the course of the Staudinger reaction of azides with acyl derivatives. Bimanes, 30. J.
´ ´
Org. Chem. 1996, 61, 1689–1701; (f) Bosch, I.; Gonzalez, A.; Urpı, F.; Vilarrasa, J. On the
reaction of acyl chlorides and carboxylic anhydrides with phosphazenes. J. Org. Chem.
1996, 61, 5638–5643.
8. (a) Coats, S. J.; Link, J. S.; Hlasta, D. J. Alternative solvents for elevated-temperature
solid-phase parallel synthesis: Application to thionation of amides. Org. Lett. 2003, 5,
721–724; (b) Charette, A. B.; Grenon, M. Mild method for the conversion of amides to
thioamides. J. Org. Chem. 2003, 68, 5792–5794; (c) Ilankumaran, P.; Ramesha, A. R.;
Chandrasekaran, S. A facile conversion of amides and lactams to thioamides and thiolac-
tams using tetrathiomolybdate. Tetrahedron Lett. 1995, 36, 8311–8314 and references
quoted therein.
9. Kolakowski, R. V.; Shangguan, N.; Williams, L. J. Thioamides via thiatriazolines.
Tetrahedron Lett. 2006, 47, 1163–1166.
10. Park, S.-D.; Oh, J.-H.; Lim, D. A new type of amide formation from thiocarboxylic acid
and alkyl azide. Tetrahedron Lett. 2002, 43, 6309–6311

680
S. NAGARAJAN ET AL.
11. Sathishkumar, M.; Shanmugavelan, P.; Nagarajan, S.; Maheswari, M.; Dinesh, M.;
Ponnuswamy, A. Solvent-free protocol for amide bond formation via trapping of nascent
phosphazenes with carboxylic acids. Tetrahedron Lett. 2011, 52, 2830–2833.
12. Sathishkumar, M.; Nagarajan, S.; Shanmugavelan, P.; Dinesh, M.; Ponnuswamy, A.
Microwave-assisted clean synthesis of amides via aza-Witting reaction under solvent-free
conditions. J. Braz. Chem. Soc. 2011, 22, 2065–2069.
13. Rosen, T.; Lico, I. M.; Chu, D. T. W. A convenient and highly chemoselective method for
the reductive acetylation of azides. J. Org. Chem. 1988, 53, 1580–1582.
14. Shangguan, N.; Katukojvala, S.; Greenberg, R.; Williams, L. J. The reaction of thio acids
with azides: A new mechanism and new synthetic applications. J. Am. Chem. Soc. 2003,
125, 7754–7755.
15. Shi, M.; Cui, S.-C. Transamidation catalyzed by a recoverable and reusable polyDMAP-
based hafnium chloride and montmorillonite KSF. Synth. Commun. 2005, 35, 2847–2858.
16. Pathak, U.; Pandey, L. K.; Mathur, S.; Suryanarayana, M. V. S. Ketoximes to
N-substituted thioamides via PSCl3-mediated Beckmann rearrangement. Chem. Commun.
2009, 5409–5411.
17. Yoo, W.-J.; Li, C.-J. Highly efficient oxidative amidation of aldehydes with amine
hydrochloride salts. J. Am. Chem. Soc. 2006, 128, 13064–13065.
18. Yde, B.; Yousif, N. M.; Pedersen, U.; Thomsen, I.; Lawesson, S.-O. Studies on organo-
phosphorus compounds, XLVII: Preparation of thiated synthons of amides, lactams,
and imides by use of some new p,s-containing reagents. Tetrahedron 1984, 40, 2047–2052.