Synthesis of thiazolidine-thiones, imino-thiazolidines and oxazolidines: Via the base promoted cyclisation of epoxy-sulfonamides and heterocumulenes

Article abstract of DOI:10.1039/c7ob02915b

Epoxy-sulfonamides react with heterocumulenes (carbon disulfide/isothiocyanates/isocyanates) in the presence of a base to afford ring expansion products in good to high yields with excellent regioselectivity. N-(2-Bromoethyl)-sulfonamides can also be employed as substrates. This reaction proceeds through a 5-exo-tet pathway without forming aziridine intermediates.

Full text of DOI:10.1039/c7ob02915b

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: K. C. K. Swamy
and M. Anitha, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB02915B.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
Synthesis of thiazolidine‐thiones, iminothiazolidines and
oxazolidines via base promoted cyclisation of epoxy‐sulfonamides
and heterocumulenes
Received 00th January 20xx,
Accepted 00th January 20xx
Mandala Anitha and K. C. Kumara Swamy*
DOI: 10.1039/x0xx00000x
Epoxy‐sulfonamides react with heterocumulenes (carbon disulfide/ isothiocyanates/isocyanates) in the presence of base to
afford ring expansion products in good to high yields with excellent regioselectivity. N‐(2‐bromoehtyl)‐sulfonamides can also
be employed as substrates. This reaction goes through a 5‐exo‐tet pathway without forming aziridine intermediates.
www.rsc.org/
Introduction
Organic isothiocyanates as well as carbon dioxide or disulfide can
participate in diverse [3+2] dipolar cycloaddition reactions.1 One
such interesting reaction is that of the ring expansion reaction
involving aziridines to afford thiazolidine‐2‐thiones, imino‐
thiazolidines or imino‐selenazolidines (Scheme 1).2 Thiazolidine‐2‐
thiones and imino‐thiazolidines/oxazolidines possess significant
pharmaceutical activity including that for diabetes mellitus and
malaria (cf. Figure 1).3 Thiazolidines can also act as chiral auxiliaries
to generate stereogenic centres in asymmetric synthesis.4 Several
other synthetic routes are also available for their synthesis,5, 6 but
new methods to obtain substituted derivatives are always desirable
for this important class of compounds.
Scheme 1. Selected examples of [3+2] ring expansion reaction of aziridines
Figure 1. Representative pharmaceutically useful thiazolidines
It is possible that even epoxides (oxiranes) behave in a manner
analogous to aziridines in their reactivity towards isothiocyanates or
carbon dioxide/disulfide. An elegant recent report by Kleij and co‐
workers delves on the divergent behaviour of oxirane appended
sulfonamides with CO2 under Al(III) catalysed ring expansion that
affords either oxazolidines or cyclic carbonates (Scheme 2a)
depending on subtle modifications in the reaction conditions.7
Sulfonamides bearing epoxides (oxiranes) can facilitate diverse
organic transformations including nucleophilic substitution/ opening
of epoxide ring to construct an array of C‐C and C‐X bonds.7, 8 Many
reports on the reaction of oxiranes with heterocumulenes such as
isothiocyanates/9f‐g isocyanates
to form
7, 9a‐b
9c‐e
9h
CO2
/CS2
heterocyclic compounds are available, but only a handful of articles
on cyclisation involving sulfonamides and heterocumulenes exist.7 It
should be noted that the normally expected reaction of an epoxide
(oxirane) with, say, carbon dioxide (cf. Scheme 2b‐c) or other
heterocumulenes, is the ring expansion reaction (1,3‐cycloaddition)
of the epoxide,9c but an interesting addition reaction is also reported
recently (Scheme 2d).9f Our interest was in a reaction of the type
a. School of Chemistry, University of Hyderabad, Hyderabad 500 046, Telangana,
India. Tel: (+91)‐40‐231348560; E‐mail: kckssc@uohyd.ac.in, kckssc@yahoo.com.
†Electronic Supplementary Informaꢀon (ESI) available: [Crystal data and copies of
1H/13C NMR spectra]. CCDC numbers are 1575670‐1575673 and 1587468. See DOI:
10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
shown on the left of Scheme 2a. The question was whether a simpler (i) Reaction of epoxy‐sulfonamides with carbon disulfide,
catalytic/non‐catalytic system is feasible for such a reaction or not. isothiocyanates and isocyanates
Also, the authors in this paper have used a Lewis acid catalyst. We We started with the reaction of epoxy‐sulfonamide 1a with CS2 in the
surmised that it may be possible to effect similar reactions using a presence of DMAP with K3PO4 or K2CO3 as the base in EtOH (Table 1,
normal base since it is possible to remove the NH proton, which then entries 1‐3). However, in these cases we observed only the ring
would attack the electrophilic carbon of the isothiocyanate or carbon rearrangement from epoxide 1a to aziridine product 2 (cf. Scheme 3).
disulfide (Scheme 2e). Such a reaction would be different from those Such a reaction, although interesting, has been reported before.10
shown in Scheme 2c‐d; it could also be different from that shown in When we performed the reaction in DMF with K2CO3 as the base
Scheme 2b since an intervening carbon will be there between the (entry 7), we obtained the ring modified/expanded product 3 in 10%
nitrogen and the oxirane carbon. Unlike the reaction shown in yield apart from 2. The presence of C=S (δ 196.9) and ‐OH (band at
Scheme 2a, this approach does not require a Lewis acid catalyst. 3401 cm‐1) groups in the product 3 were readily inferred by 13C NMR
Thus the pathway for our reaction is different from that reported by and IR spectra, respectively while the absence of NH moiety was
Kleij and co‐workers. One can also envisage a complementary indicated by 1H NMR. HRMS data suggested the incorporation of CS2
approach of using TsNHCH2CH2Br and isothiocyanate/isocyanate or (vide infra for X‐ray structure). In solvents like DMSO or H2O (entries
CS2 to obtain a similar cyclised product (cf. Scheme 2e), but with no 5‐6), we obtained only the aziridine 2 (IR, NMR, HRMS). In the
pendant substituent on the ring. This methodology will also be solvents THF, dioxane, toluene, acetonitrile and PEG‐400 (entries 7‐
discussed in a later section.
11) again, traces of 2 (but not 3) were observed. Pleasingly, with NMP
as the solvent and by using the inexpensive K2CO3 as the base (entry
Scheme 2. Selected reactions of epoxy systems with heterocumulenes in 12), we obtained the desired product 3 in 92% yield. Bases like K3PO4,
relation to present work
Cs2CO3, NaOH, KOH (entries 13‐16) did not enhance the yield. Thus
the optimized conditions are: 1a (0.4 mmol), CS2 (2.0 mmol), K2CO3
(0.4 mmol) in NMP (1 mL) at 80 oC for 12 h. These conditions were
utilized to obtain the desired thiazolidine‐2‐thiones 3‐10 in good to
excellent yields by starting with epoxy‐sulfonamides 1a‐h (Scheme
4). The structure of compound 3 was further proven by single crystal
X‐ray analysis (figure 2). In view of the reactions of aziridines with
isothiocyanates (cf. Scheme 1 above), we treated the (isolated)
aziridine 2 with CS2/NMP/K2CO3 (Scheme 3) and observed that this
compound 2 remained unreacted. Thus our reaction leading to
product 3 from 1a follows a pathway different from that shown in
Scheme 1.
Table 1. Optimization of the conditions for the regioselective 5‐exo‐tet
a
cyclisation of 1a with CS2
Temp (oC)/
time (h)
80/12
Entry
Base
Solvent
Yield of 3
(%)b
c
1
2
DMAP
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
EtOH
EtOH
‐
c
80/12
80/12
‐
c
3
EtOH
‐
4
DMF
110/ 10
110/ 10
100/ 12
65/ 10
10
d
5
DMSO
H2O
‐
d
6
‐
c
7
THF
‐
c
8
Dioxane
Toluene
Acetonitrile
PEG‐400
110/ 12
110/ 12
80/ 15
‐
c
9
‐
c
10
11
‐
c
110/ 12
‐
Results and Discussion
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
12
13
14
15
16
K2CO3
NMP
NMP
NMP
NMP
NMP
80/ 12
80/ 12
80/ 12
80/ 12
80/ 12
92
85
60
84
85
Scheme 4. Regioselective 5‐Exo‐tet cyclisation of epoxy‐sulfonamides 1a‐h
with CS2 leading to thiazolidine‐thiones 3‐10
K3PO4
Cs2CO3
NaOH
KOH
a Reaction conditions: 1a (0.4 mmol), CS2 (2.0 mmol), Base (0.4 mmol) in
b
c
solvent (1 mL) at the specified temperature for 10‐12 h. Isolated yields. A
d
small amount of aziridine 2 was noticed. In these cases, the main product
obtained was the aziridine 2 (see Scheme 3; yield: 40‐50% after isolation).
Figure 2. ORTEP diagram of compound 3 (probability ellipsoid at 30%). The
disordered S3B atom is not shown. Selected bond lengths [Å] with esds in
parentheses: S1‐N1 1.679(3), S2‐C11 1.634(5), S3A‐C11 1.751(5), C9‐S3A
1.817(7), N1‐C11 1.378(5), C8‐C9 1.520(7).
By extending the above conditions to the reactions with aryl‐
isothiocyanates/ isocyanates (heterocumulene), the expected
thiazolidines/oxazolidines are obtained, but in addition, small
quantities of products in which the terminal –OH group undergoes
addition with isocyanate/isothiocyanate are also formed. This
problem could be readily alleviated by conducting the reaction at 80
oC for 24 h wherein the desired products 11‐17 are almost exclusively
formed (Scheme 5; the yields shown are after isolation). Only in the
reaction with Me3SiNCS, the yield of the final product 18 was slightly
lower probably because of the removal of TMS group. The structure
of compound 13 was proven by single crystal X‐ray analysis (figure
3). A ready extension to the use of isocyanates was possible as
demonstrated by the isolation of oxazolidines 19‐20.
Scheme 3. Isolation and attempted [3+2] ring expansion of aziridine 2 with
CS2 under basic conditions
Figure 3. ORTEP of compound 13 (probability ellipsoid at 30%). Selected bond
lengths [Å] with esds in parentheses: N1‐ C11 1.413(7), N2‐ C11 1.271(7), N2‐
C12 1.402(7), S2‐ C11 1.787(6), S2 C9 1.7948(18), O3‐C10 1.419(9), S1 N1
1.679(5).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
Scheme 5. Regioselective 5‐Exo‐tet cyclisation of epoxy‐sulfonamides with thiazolidine‐thione 3, but do not contain the primary alcohol group.
aryl‐isothiocyanates/ tolylisocyanate leading to thiazolidines/oxazolidines In this reaction, steric or electronic effects did not seem to affect the
11‐20
overall yield significantly. Interestingly, the 4‐nitrophenyl group was
cleaved to form the unsubstituted thiazolidine‐thione 36. The
method could be conveniently extended to the synthesis of imino
thiazolidines and imino oxazolidine 37‐44 (Scheme 8). The structures
of compounds 27 (ESI) and 40 (figure 4) were confirmed by X‐ray
crystallography.
Figure 4. ORTEP of compound 40 (probability ellipsoid at 30%). Selected bond
lengths [Å] with esds in parentheses: N2‐C9 1.269(4), N2‐ C10 1.407(4), S2‐C9
1.742(3), N1‐C7 1.470(4), S2‐C8 1.795(4), N1‐C9 1.412(4), S1‐N1 1.661(3).
Scheme 7. Synthesis of thiazolidine‐thiones 26‐36 by HBr elimination/
heterocumulene insertion
When the above reaction was conducted at rt (25 oC) for only 10 h by
increasing the stoichiometry of isocyanate or isothiocyanate, imino‐
thiazolidine carbamates 21‐24, in which the terminal ‐OH group
underwent addition, were obtained in moderate yields. It can be
noted that in compounds 21‐23, hydrolysis of the C=S to C=O also
had taken place.11 Since this was not the main theme of the present
work, we did not proceed further.
Scheme 6. Formation of imino‐thiazolidine/oxazolidine carbamates 21‐24
(ii) Cyclisation reaction of N‐(2‐bromoethyl)‐sulfonamides with
heterocumulenes (carbon disulfide, isothiocyanate or isocyanate)
We envisaged another viable route to the above class of compounds
(but without substitution at the five‐membered ring) by insertion of
the heterocumulenes into bromoethyl‐sulfonamides. Thus,
treatment of N‐(2‐bromoethyl)‐sulfonamides 25a‐j with carbon
disulfide in NMP at 80 oC for 5 h afforded thiazolidine‐2‐thiones 26‐
36 in good yields (Scheme 7). These compounds are similar to
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
Scheme 8. Cyclisation of N‐(2‐bromoethyl)‐sulfonamides with R’NCS/ compound remained unreacted. So the plausible pathway for the
PhNCO leading to iminothiazolidines/iminooxazolidines 37‐44
formation
of
thiazolidine‐thiones
and
imino‐
thiazolidines/oxazolidines does not involve aziridine, but instead
follows a different pathway (Scheme 10b). Initially, as we explained
before, the base abstracts proton from sulfonamide 2 and generates
aza‐anionic intermediate III. The species III attacks the central carbon
atom of the CS2/RNCS/RNCO affording thio/oxo anionic
intermediate2a, 12b IV that subsequently leads to 5‐exo‐tet cyclised
thiazolidine‐thiones and imino‐thiazolidines/oxazolidine (26‐44).
Scheme 10. Attempted [3+2] ring expansion reaction of 45 and plausible
pathway for the formation of thiazolidine‐thiones and imino‐
thiazolidines/oxazolidines from bromoethyl‐sulfonamides
(iv) Mitsunobu reaction of 5‐(hydroxymethyl)‐3‐tosylthiazolidine‐
2‐thione (3) with Ph3P/DEAD/nortriptyline
(iii) Possible pathway for the ring modification/expansion of epoxy‐
sulfonamides
and
thiazolidine‐thiones/
imino‐
Product 3 contains a pendent primary alcohol group that can
undergo C‐N coupling or dehydration via the Mitsunobu reaction13
Thus we treated 3 with Ph3P/DEAD/nortriptyline in toluene/DCM
(9:1). Surprisingly the chloro‐substituted product 46 was obtained in
good yield. Here DCM acted as the chlorine source, which is not
normal. When we performed the reaction in THF as the solvent, the
dehydration product 47 was formed in decent yields. Both the
products 46‐47 are amenable to further functionalization.
thiazolidines/oxazolidines from bromoethyl‐sulfonamides
To conclusively establish that our reaction does not take place via the
aziridine 2, we treated it with Ph‐NCS/NMP/K2CO3 and observed that
it remained unreacted. Even with Ph‐NCS/Fe(NO3)3.9H2O/H2O,2e no
significant reaction occurred. Thus our reaction leading to product 3‐
10 from 1a follows a pathway different from that of aziridines (cf.
Scheme 1). Based on the literature,2a, 7, 12a‐b a plausible pathway for
the formation of thiazolidine‐2‐thiones 3‐10 and imino‐
thiazolidines/oxazolidines 11‐20 is shown in Scheme 9. Initially, the
Scheme 11. Attempted Mitsunobu reaction of 3 using Ph3P/DEAD
base abstracts proton from epoxy‐sulfonamide
1 generating
intermediate I which attacks the central carbon atom of the
12b
CS2/RNCS/RNCO affording thio/oxo anionic intermediate IIa2a,
which will attack at the 2o carbon atom of epoxide regioselectively,
affording 5‐exo‐tet cyclised7 alkoxide intermediate IIb, which upon
protonation affords
hydroxymethyl‐thiazolidines‐thiones/
iminothiazolidines/ iminooxazolidines (3‐10, 11‐20).
Scheme 9. Plausible pathway for the formation of thiazolidine‐2‐thiones
/imino‐thiazolidines /imino‐oxazolidines from epoxy‐sulfonamides
(v) Reaction of 5‐(hydroxymethyl)‐3‐tosylthiazolidine‐2‐thione (3)
with allenylphosphonate 48
The central carbon of allenes is sp‐hybridized and hence can readily
undergo nucleophilic attack. We wanted to see if the double bonded
sulfur or OH can act as a nucleophile in such a reaction. Thus when
we treated allenylphosphonate 4812a (0.3 mmol) with compound 3 in
the presence of K2CO3 in DMSO solvent at 80 oC for 12 h, the NHTs
addition product 49 was formed most likely by cleavage of the five‐
membered ring (Scheme12). Single crystal X‐ray structure of
compound 49 (ESI) confirms its identity.
Scheme 12. Reaction of 3 with allenylphosphonate 48
We treated aziridine 4512c (prepared from 25a) with CS2/NMP/K2CO3
as well as Ph‐NCS/NMP/K2CO3 (Scheme 10a) and observed that this
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
O
O
O
O
solvent removed under reduced pressure. Purification by column
chromatography (hexane/ethyl acetate 9:1) afforded compound 3.
OH
Ts
O
O
HN
O
P
P
K2CO3
(+ other
ring cleaved
products)
N
O
S
S
DMSO
S
80 o C, 12h
48
Me
49, (80% based on
allene; X-ray)
3
5‐(Hydroxymethyl)‐3‐tosylthiazolidine‐2‐thione (3). Light yellow
solid, yield 0.122 g (92%,). Mp 98‐100 oC; Rf = 0.38 (9:1 hexane/ethyl
acetate); IR (KBr) ν 3401, 2920, 1650, 1593, 1464, 1366, 1242, 1175,
1097, 1056, 808 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.95 (d, J =
8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 4.87‐4.83 (m, 1H), 4.64‐4.59 (m,
1H), 3.83‐3.78 (m, 3H), 2.47 (s, 3H), 2.27 (br, 1H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 196.9, 146.1, 133.5, 129.5, 129.2, 63.2, 58.5, 45.5,
21.8; HRMS (ESI) Calcd. for C11H14NO3S3 (M++H): m/z 304.0136.
Found: 304.0138. This compound was crystallized from DCM/ethyl
acetate/hexane (2:1:1) mixture at room temperature. X‐ray structure
was determined for this sample.
Me
Me
Conclusions
We have developed a simple and new transition metal‐free, base
mediated synthesis of thiazolidine‐thiones and
iminothiazolidines/oxazolidines via regioselective 5‐exo‐tet
cyclisation by treating epoxy‐sulfonamides with carbon disulfide/
isothiocyanates/ isocyanates. We have shown that this ring
expansion/cyclisation occurs through
a
thio/oxo anionic
intermediate but not though aziridine intermediate. A second but
equally simple route to thiazolidine‐2‐thiones and imino‐
thiazolidines /oxazolidines by insertion of the heterocumulenes into
2‐bromoethyl‐sulfonamides after dehydrohalogenation is also
reported. Compound 3 could be derivatised further as shown by the
isolation of compounds 46‐47. Representative compounds have
been characterised by single crystal X‐ray structural analysis.
5‐(Hydroxymethyl)‐3‐(phenylsulfonyl)thiazolidine‐2‐thione
(4).
Epoxy‐sulfonamide 1b (0.46 mmol) and CS2 (2.3 mmol) were used.
Gummy liquid, yield 0.109 g (81%); Rf = 0.35 (9:1 hexane/ethyl
acetate); IR (neat) ν 3387, 2928, 2875, 1463, 1447, 1361, 1235, 1169,
1063, 1022, 809, 752 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.08‐
8.06 (m, 2H), 7.72‐7.68 (m, 1H), 7.60‐7.55 (m, 2H), 4.87‐4.84 (m, 1H),
4.65‐4.60 (m, 1H), 3.84‐3.78 (m, 3H), 2.34 (br, 1H); 13C NMR (100
MHz, CDCl3) δ (ppm) 196.7, 136.5, 134.7, 129.2, 128.9, 63.3, 58.5,
45.6; HRMS (ESI): Calcd for C10H11NO3S3Na (M++Na): m/z 311.9799.
Found: 311.9797.
Experimental Section
Solvents were dried according to standard procedures.14 Epoxy‐
5‐(Hydroxymethyl)‐3‐((4‐methoxyphenyl)sulfonyl)thiazolidine‐2‐
thione (5). Epoxy‐sulfonamide 1c (0.41 mmol) and CS2 (2.0 mmol)
were used. Gummy liquid, yield 0.120 g (92%,); Rf = 0.30 (9:1
hexane/ethyl acetate); IR (neat) ν 3530, 2936, 2838, 1722, 1587,
sulfonamides and N‐(2‐bromoethyl)‐sulfonamides were synthesized
15
based on the literature procedures.7,
All isothiocyanates and
isocyanates were purchased from Aldrich and used without further
purification. 1H, 13C, 19F and 31P NMR spectra were recorded in CDCl3
or DMSO‐d6 (unless stated otherwise) solution with shifts referenced
to SiMe4, CFCl3 or ext. 85% H3PO4. Infrared spectra were recorded
neat or by using KBr pellets. Melting points were determined by using
a local hot‐stage melting point apparatus and are uncorrected (not
calibrated). For TLC, glass micro slides were coated with silica‐gel‐
GF254 (mesh size 75 μ) and spots were identified using iodine or UV
chamber as appropriate. For column chromatography, silica gel of
100−200 mesh size was used. Mass spectra were recorded using
HRMS (ESI‐TOF analyser) equipment. Crystallographic data were
collected on a Bruker APX‐II‐SMART using Mo‐K radiation ( =
0.71073 Å). Structures were solved and refined using standard
methods.16 Crystal data are given in the ESI.
1
1494, 1463, 1412, 1360, 1314, 1267, 839, 740 cm‐1; H NMR (400
MHz, CDCl3) δ (ppm) 8.02‐7.98 (m, 2H), 7.03‐7.00 (m, 2H), 4.84‐4.80
(m, 1H), 4.61‐4.56 (m, 1H), 3.90 (s, 3H), 3.81‐3.76 (m, 3H), 2.73 (br,
1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 195.5, 163.2, 130.3, 126.2,
112.7, 61.9, 57.2, 54.5, 44.1; HRMS (ESI): Calcd. for C11H14NO4S3
(M++H): m/z 320.0085. Found: 320.0086.
3‐((4‐Chlorophenyl)sulfonyl)‐5‐(hydroxymethyl)thiazolidine‐2‐
thione (6). Epoxy‐sulfonamide 1d (0.40 mmol) and CS2 (2.0 mmol)
were used. Light yellow solid, yield 0.117 g (90%). Mp 76‐78 oC; Rf =
0.4 (9:1 hexane/ethyl acetate); IR (KBr) ν 3365, 3096, 2931, 2874,
1582, 1474, 1360, 1231, 1164, 1092, 1066, 1009, 813, 756, 699, 617
cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.01(d, J = 8.4 Hz, 2H), 7.54
(d, J = 8.8 Hz, 2H), 4.86‐4.83 (m, 1H), 4.64‐4.60 (m, 1H), 3.83 (br, 3H),
2.46 (br, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.4, 141.5, 134.7,
130.6, 129.3, 63.2, 58.6, 45.7; HRMS (ESI): Calcd for C10H11ClNO3S3
(M++H) and (M++H+2): m/z 323.9589, 325.9560. Found: 323.9590
and 325.9563.
1‐Tosylaziridin‐2‐yl)methanol (2) [HRMS (ESI) calcd for C10H14NO3S
(M++H) m/z 228.0694, found 228.0694] was prepared by using a
literature method.10
General
procedure
for
the
synthesis
of
5‐
hydroxymethylthiazolidine‐2‐thiones 3‐10
3‐((4‐Bromophenyl)sulfonyl)‐5‐(hydroxymethyl)thiazolidine‐2‐
thione (7). Epoxy‐sulfonamide 1e (0.34 mmol) and CS2 (1.7 mmol)
were used. Light yellow solid, yield 0.114 g (91%). Mp 98‐100 oC; Rf =
0.41 (9:1 hexane/ethyl acetate); IR (KBr) ν 3530, 3354, 3091, 2931,
1567, 1469, 1391, 1366, 1231, 1169, 1071, 1009, 823, 735, 699 cm‐1;
1H NMR (400 MHz, CDCl3) δ (ppm) 7.91 (d, J = 8.8 Hz, 2H), 7.69 (d, J =
8.8 Hz, 2H), 4.81 (d, J = 10.8 Hz, 1H), 4.62‐4.59 (m, 1H), 3.80 (br, 3H),
3.08 (br, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.3, 135.3, 132.3,
To a solution of epoxy‐sulfonamide 1a (100 mg, 0.46 mmol) and CS2
(0.167 g, 2.1 mmol) in NMP (1 mL) was added anh. K2CO3 (60 mg, 0.8
mmol) and the reaction mixture heated with stirring at 80 oC for 12
h. After the completion of the reaction as monitored by TLC, ethyl
acetate (25 mL) was added and the solution was washed with water
(3 x 30 mL); the aqueous layer was extracted with ethyl acetate (3x
20 mL). The combined organic portion was dried over Na2SO4 and the
6 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 7 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
130.6, 130.2, 63.2, 58.6, 45.7; HRMS (ESI): Calcd for C10H11BrNO3S3 CDCl3) δ (ppm) 8.00 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.08
(M++H) & (M++H +2): m/z 367.9084, 369.9064. Found: 367.9082 and (d, J = 7.6 Hz, 2H), 6.66 (d, J = 8.4 Hz, 2H), 4.36‐4.32 (m, 1H), 4.13‐
369.9062.
4.09 (m, 1H), 3.76‐3.65 (m, 3H), 2.48 and 2.31 (2s, 6H); 13C NMR (100
MHz, CDCl3) δ (ppm) 151.2, 147.4, 144.9, 134.5, 133.9, 129.5, 129.2,
129.1, 120.5, 63.5, 51.3, 43.8, 21.7, 20.9; HRMS (ESI): Calcd for
3‐((4‐(Tert‐butyl)phenyl)sulfonyl)‐5‐(hydroxymethyl)thiazolidine‐
2‐thione (8). Epoxy‐sulfonamide 1f (0.37 mmol) and CS2 (1.8 mmol) C18H21N2O3S2 (M++H): m/z 377.0993. Found: 377.0992.
were used. Gummy liquid, yield 108 g (85%,); Rf = 0.42 (9:1
hexane/ethyl acetate); IR (neat) ν 3411, 2962, 2869, 1588, 1459, (Z)‐(2‐((4‐Chlorophenyl)imino)‐3‐tosylthiazolidin‐5‐yl)methanol
1366, 1242, 1169, 1082, 828, 803, 751, 622 cm‐1; 1H NMR (400 MHz, (13). Epoxy‐sulfonamide 1a (0.43 mmol) and 4‐chlorophenyl
CDCl3) δ (ppm) 8.00‐7.78 (m, 2H), 7.58‐7.55 (m, 2H), 4.87‐4.84 (m, isothiocyanate (0.52 mmol) were used. White solid, yield 0.104 g
1H), 4.64‐4.59 (m, 1H), 3.86‐3.78 (m, 3H), 1.36 (s, 9H); 13C NMR (100 (73%). Mp 126‐128 oC; Rf = 0.52 (9:1 hexane/ethyl acetate); IR (KBr)
MHz, CDCl3) δ (ppm) 196.7, 158.9, 133.3, 129.1, 125.9, 63.2, 58.5, ν 3434, 2957, 2874, 1638, 1591, 1484, 1354, 1262, 1170, 1085, 1034,
45.5, 35.4, 31.0; HRMS (ESI): Calcd for C14H20NO3S3 (M++H): m/z 865, 812, 663 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.07 (d, J = 7.6
346.0605. Found: 346.0606.
Hz, 2H), 6.46 (d, J = 8.0 Hz, 2H), 6.32 (d, J = 8.4 Hz, 2H), 5.79 (d, J = 8.0
Hz, 2H), 3.45 (d, J = 10.0 Hz, 1H), 3.23‐3.19 (m, 1H), 2.80 (d, J = 7.6
Hz, 3H), 1.58 (s, 4H); 13C NMR (100 MHz, CDCl3) δ (ppm) 151.3, 147.3,
Epoxy‐ 144.1, 133.2, 128.5, 128.2, 128.0, 127.9, 121.1, 62.3, 50.4, 42.8, 20.6;
5‐(Hydroxymethyl)‐3‐((2,4,6‐
triisopropylphenyl)sulfonyl)thiazolidine‐2‐thione
(9).
sulfonamide 1g (0.28 mmol) and CS2 (1.4 mmol) were used. White HRMS (ESI): Calcd for C17H18ClN2O3S2 (M++H), (M++H+2): m/z
solid, yield 0.108 g (90%). Mp 96‐98 oC; Rf = 0.43 (9:1 hexane/ethyl 397.0447, 399.0417. Found: 397.0449, 399.0405. This compound
acetate); IR (KBr) ν 3437, 2957, 2931, 2864, 1598, 1562, 1469, 1428, was crystallized from ethyl acetate/hexane (2:1) mixture at room
1371, 1340, 1247, 1169, 1066, 880 cm‐1; 1H NMR (400 MHz, CDCl3) δ temperature. X‐ray structure was determined for this sample.
(ppm) 7.18 (s, 2H), 4.75‐4.61 (m, 2H), 4.00‐3.86 (m, 5H), 2.95‐2.88
(m, 2H), 1.30‐1.24 (m, 18H); 13C NMR (100 MHz, CDCl3) δ (ppm) (Z)‐(2‐(Benzylimino)‐3‐tosylthiazolidin‐5‐yl)methanol (14). Epoxy‐
197.1, 154.7, 151.6, 131.2, 124.0, 63.2, 56.5, 46.0, 34.2, 29.7, 24.6, sulfonamide 1a (0.43 mmol) and benzyl isothiocyanate (0.52 mmol)
24.3, 23.5; HRMS (ESI): Calcd for C19H30NO3S3 (M++H): m/z 416.1388. were used. White solid, yield 0.135 g (82%). Mp 108‐110 oC; Rf = 0.53
Found: 416.1391.
(9:1 hexane/ethyl acetate); IR (KBr) ν 3306, 3029, 2925, 1699, 1645,
1597, 1519, 1159, 1086, 812, 751 cm‐1; 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.85 (d, J = 6.6 Hz, 2H), 7.27‐7.23 (m, 3H), 7.19 (d, J = 4.0 Hz,
5‐(Hydroxymethyl)‐3‐(naphthalen‐2‐ylsulfonyl)thiazolidine‐2‐
thione (10). Epoxy‐sulfonamide 1h (0.37 mmol) and CS2 (1.8 mmol) 2H), 7.11‐7.10 (m, 2H), 4.42‐4.29 (m, 3H), 4.04‐4.01 (m, 1H), 3.77‐
were used. Yellow solid, yield 0.090 g (70%). Mp 104‐106 oC; Rf = 0.38 3.70 (m, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 150.8,
(9:1 hexane/ethyl acetate); IR (KBr) ν 3411, 3055, 2926, 1619, 1583, 144.5, 139.3, 134.7, 129.2, 128.8, 128.1, 127.4, 126.6, 63.4, 59.4,
1
1500, 1459, 1355, 1242, 1164, 1071, 860, 658 cm‐1; H NMR (400 51.1, 44.0, 21.6; HRMS (ESI): Calcd for C18H21N2O3S2 (M++H): m/z
MHz, CDCl3) δ (ppm) 8.71 (d, J = 1.2 Hz, 1H), 8.04‐7.93 (m, 4H), 7.73‐ 377.0993. Found: 377.0996.
7.64 (m, 2H), 4.96‐4.92 (m, 1H), 4.72‐ 4.67 (m, 1H), 3.85‐3.79 (m, 3H),
2.22‐2.06 (br, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 196.7, 135.7, (Z)‐(2‐(Phenethylimino)‐3‐tosylthiazolidin‐5‐yl)methanol
(15).
133.1, 132.1, 131.6, 129.9, 129.8, 129.2, 128.0, 122.9, 63.3, 58.7, Epoxy‐sulfonamide 1a (0.43 mmol) and phenethyl isothiocyanate
45.6; HRMS (ESI): Calcd for C14H14NO3S3 (M++H): m/z 340.0136. (0.52 mmol) were used. Gummy liquid, yield 0.142 g (83%); Rf = 0.54
Found: 340.0133. Rf Value of this compound is 0.42.
(9:1 hexane/ethyl acetate); IR (neat) ν 3369, 3025, 2926, 2872, 1704,
1
1651, 1598, 1454, 1350, 1160, 1088, 813, 748 cm‐1; H NMR (400
(Z)‐(2‐(Phenylimino)‐3‐tosylthiazolidin‐5‐yl)methanol (11). Epoxy MHz, CDCl3) δ (ppm) 7.86 (d, J = 8.4 Hz, 2H), 7.27‐7.20 (m, 5H), 7.07
sulfonamide 1a (0.43 mmol) and phenyl isothiocyanate (0.52 mmol) (d, J = 6.4 Hz, 2H), 4.25‐4.22 (m, 1H), 3.94‐3.91 (m, 1H), 3.69‐3.59 (m,
were used. Gummy liquid, yield 0.091 (70%); Rf = 0.48 (9:1 3H), 3.40‐3.35 (m, 2H), 2.82 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H); 13C NMR
hexane/ethyl acetate); IR (neat) ν 3411, 3049, 2915, 2874, 1634, (100 MHz, CDCl3) δ (ppm) 149.8, 144.5, 140.0, 134.8, 129.1, 129.0,
1
1587, 1494, 1360, 1262, 1169, 1081, 1040, 766, 694 cm‐1; H NMR 128.9, 128.2, 126.0, 63.4, 57.5, 50.8, 43.8, 36.9, 21.6; HRMS (ESI):
(500 MHz, CDCl3) δ (ppm) 8.00 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.5 Hz, Calcd for C19H23N2O3S2 (M++H): m/z 391.1150. Found: 391.1151.
2H), 7.27 (t, J = 7.8 Hz, 2H), 7.09 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 7.0 Hz,
2H), 4.36‐4.33 (m, 1H), 4.12‐4.09 (m, 1H), 3.73‐3.65 (m, 3H), 2.48 (s, (Z)‐(2‐(Allylimino)‐3‐tosylthiazolidin‐5‐yl)methanol (16). Epoxy
3H), 2.46 (br, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm) 151.9, 150.0, sulfonamide 1a (0.44 mmol) and allyl isothiocyanate (0.52 mmol)
145.1, 134.4, 129.3, 129.1, 124.4, 120.8, 63.5, 51.4, 43.8, 21.8; HRMS were used. Gummy liquid, yield 0.127 g (89%); Rf = 0.52 (9:1
(ESI): Calcd for C17H19N2O3S2 (M++H): m/z 363.0837. Found: hexane/ethyl acetate); IR (neat) ν 3398, 2927, 1698, 1354, 1214,
363.0840.
1159, 745, 665 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.89‐7.70 (m,
2H), 7.28 (d, J = 6.0 Hz, 2H), 5.82‐5.76 (m, 1H), 5.02‐4.97 (m, 2H), 4.25
(Z)‐(2‐(p‐Tolylimino)‐3‐tosylthiazolidin‐5‐yl)methanol (12). Epoxy‐ (d, J = 8.4 Hz, 1H), 3.98‐3.95 (m, 1H), 3.81‐3.67 (m, 5H), 2.42 (s, 3H);
sulfonamide 1a (0.43 mmol) and p‐tolyl isothiocyanate (0.52 mmol) 13C NMR (100 MHz, CDCl3) δ (ppm) 151.0, 144.7, 134.8, 134.6, 129.2,
were used. Gummy liquid, yield 0.144 g (88%); Rf = 0.50 (9:1 128.8, 115.2, 63.3, 57.9, 51.1, 43.8, 21.6; HRMS (ESI): Calcd for
hexane/ethyl acetate); IR (neat) ν 3426, 2920, 2848, 1634, 1505, C14H19N2O3S2 (M++H): m/z 327.0837. Found: 327.0840.
1
1458, 1355, 1169, 1081, 1040, 808, 668 cm‐1; H NMR (400 MHz,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
(Z)‐(3‐Tosyl‐2‐((4‐(trifluoromethyl)phenyl)imino)thiazolidin‐5‐
(d, J = 8.0 Hz, 2H), 6.83 (br, 1H), 6.65 (d, J = 8.0 Hz, 2H), 4.42‐4.39 (m,
yl)methanol (17). Epoxy‐sulfonamide 1a (0.43 mmol) and 4‐ 1H), 4.31‐4.28 (m, 1H), 4.21‐4.13 (m, 2H), 3.85‐3.80 (m, 1H), 2.47 (s,
(trifluoromethyl)phenyl isothiocyanate (0.52 mmol) were used. 3H), 2.33 (s, 6H); 13C NMR (100 MHz, CDCl3) δ (ppm) 152.8, 150.9,
White solid, yield 0.151 g (80%). Mp 118‐120 oC; Rf = 0.51 (9:1 147.4, 145.0, 134.9, 134.7, 133.9, 133.3, 129.6, 129.3, 129.1, 120.5,
hexane/ethyl acetate); IR (KBr) ν 3397, 3015, 2919, 1642, 1604, 1356, 118.9, 64.9, 51.6, 40.7, 21.7, 20.9, 20.8; HRMS (ESI): Calcd for
1321, 1163, 1104, 1063, 846 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) C26H28N3O4S2 (M++H): m/z 510.1521. Found: 510.1522.
7.98 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H),
6.83 (d, J = 8.0 Hz, 2H), 4.40‐4.37 (m, 1H), 4.18‐4.14 (m, 1H), 3.79‐ (Z)‐((Z)‐2‐(Phenylimino)‐3‐tosylthiazolidin‐5‐yl)methyl hydrogen
3.70 (m, 3H), 2.49 (s, 3H), 1.98 (br, 1H); 13C NMR (100 MHz, CDCl3) δ phenylcarbamate (22). Epoxy‐sulfonamide 1a (0.43 mmol) and
(ppm) 152.8 (d, J = 16.5 Hz), 145.3, 134.2, 129.4, 129.0, 126.30, phenyl isothiocyanate (0.65 mmol) were used. Gummy liquid, yield
126.26, 126.1, 122.9, 121.1, 63.3, 51.6, 43.9, 21.7; 19F NMR (470.6 0.095g (56%); Rf = 0.70 (9:1 hexane/ethyl acetate); IR (neat) ν 3347,
MHz, CDCl3) δ ‐61.9; HRMS (ESI): Calcd for C18H17F3N2O3S2Na 3060, 2924, 1736, 1644, 1596, 1537, 1445, 1356, 1314, 1215, 1089,
(M++Na): m/z 453.0531. Found: 453.0528.
813, 761 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.03 (d, J= 8.0 Hz,
2H), 7.42‐7.31 (m, 8H), 7.11 (br, 3H), .6.76 (d, J = 8.0 Hz, 2H), 4.43 (d,
(2‐Imino‐3‐tosylthiazolidin‐5‐yl)methanol (18). Epoxy‐sulfonamide J = 8.0 Hz, 1H), 4.30 (br, 1H), 4.23‐4.14 (m, 2H), 3.83 (br, 1H), 2.48 (s,
1a (0.43 mmol) and (trimethylsilyl)isothiocyanate (0.52 mmol) were 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 152.7, 151.2, 149.9, 145.1,
used. White solid, yield 0.076 g (61%). Mp 118‐120 oC; Rf = 0.43 (9:1 137.9, 134.6, 129.4, 129.13, 129.10, 129.0, 124.5, 123.8, 120.7, 118.8,
hexane/ethyl acetate); IR (KBr) ν 3466, 3279, 2923, 1790, 1704, 65.1, 51.7, 40.8, 21.7; HRMS (ESI): Calcd for C24H24N3O4S2 (M++H):
1
1598, 1454, 1327, 1158, 1091, 814, 754 cm‐1; H NMR (400 MHz, m/z 482.1208. Found: 482.1209.
DMSO‐D6) δ (ppm) 7.72‐7.68 (m, 2H), 7.40 (d, J = 7.6 Hz, 2H), 4.90‐
4.83 (m, 1H), 3.70 (t, J = 10.0 Hz, 1H), 3.47‐3.42 (m, 1H), 3.01‐2.98 (m, (Z)‐((Z)‐2‐((4‐Chlorophenyl)imino)‐3‐tosylthiazolidin‐5‐yl)methyl
3H), 2.38 (s, 3H); 13C NMR (100 MHz, DMSO‐D6) δ (ppm) 188.2, 143.3, hydrogen (4‐chlorophenyl)carbamate (23). Epoxy‐sulfonamide 1a
137.8, 130.2, 127.0, 80.7, 46.3, 45.1, 21.4; HRMS (ESI): Calcd for (0.43 mmol) and 4‐chlorophenyl‐isothiocyanate (0.65 mmol) were
C11H14N2O3S2Na (M++Na): m/z 309.0344. Found: 309.0341.
used. Gummy liquid, yield 0.131 g (67%); Rf = 0.72 (9:1 hexane/ethyl
acetate); IR (neat) ν 3351, 2922, 1736, 1642, 1596, 1533, 1489, 1402,
(Z)‐(2‐(p‐Tolylimino)‐3‐tosyloxazolidin‐5‐yl)methanol (19). Epoxy‐ 1357, 1307, 1214, 1090, 824 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm)
sulfonamide 1a (0.43 mmol) and p‐tolyl isocyanate (0.52 mmol) were 7.98 (d, J = 6.8 Hz, 2H), 7.38‐7.21 (m, 7H), 7.06 (br, 1H), 6.68‐6.66 (m,
used. White solid, yield 0.117 g (74%). Mp 144‐146oC; Rf = 0.48 (9:1 2H), 4.48‐4.45 (m, 1H), 4.34‐4.24 (m, 2H), 4.15‐4.11 (m, 1H), 3.86‐
hexane/ethyl acetate); IR (KBr) ν 3496, 2922, 1597, 1404, 1333, 1164, 3.83 (m, 1H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 152.5,
1093, 815, 662 cm‐1;1H NMR (400 MHz, CDCl3) δ (ppm) 7.98 (d, J = 8.4 151.6, 148.2, 145.2, 136.0, 134.7, 129.7, 129.3, 129.15, 129.13, 129.0,
Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 128.9, 122.1, 119.9, 65.4, 51.7, 41.0, 21.7; HRMS (ESI): Calcd for
Hz, 2H), 4.32‐4.28 (m, 2H), 4.07‐4.03 (m, 2H), 3.74‐3.72 (m, 1H), 3.68‐ C24H22Cl2N3O4S2 (M++H) and (M++H+2): m/z 550.0429, 552.0399.
3.66 (m, 1H), 2.44 and 2.32 (2s, 6H); 13C NMR (100 MHz, CDCl3) δ Found: 550.0428, 552.0396.
(ppm) 152.2, 144.9, 135.9, 135.0, 133.6, 129.9, 129.6, 128.3, 122.6,
60.8, 54.7, 44.2, 21.7, 20.9; HRMS (ESI): Calcd for C18H21N2O4S (Z)‐((Z)‐3‐((4‐Chlorophenyl)sulfonyl)‐2‐(p‐tolylimino)oxazolidin‐5‐
(M++H): 361.1222. Found: 361.1223.
yl)methyl hydrogen p‐tolylcarbamate (24). Epoxy‐sulfonamide 1c
(0.40 mmol) and tolyl isocyanate (0.60 mmol) were used. White solid,
yield 0.126 g (62%). Mp 188‐190 oC; Rf = 0.71 (9:1 hexane/ethyl
(Z)‐(3‐((4‐Chlorophenyl)sulfonyl)‐2‐(p‐tolylimino)oxazolidin‐5‐
yl)methanol (20). Epoxy‐sulfonamide 1c (0.40 mmol) and p‐tolyl acetate); IR (KBr) ν 3339, 2922, 1711, 1514, 1405, 1206, 1171, 1085,
isocyanate (0.48 mmol) were used. White solid, yield 0.102 g (69%). 814, 756, 621 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.05‐8.03 (m,
Mp 152‐154oC; Rf = 0.49 (9:1 hexane/ethyl acetate); IR (KBr) ν 3486, 2H); 7.50‐7.48 (m, 2H), 7.28‐7.12 (m, 8H), 6.85 (br, 1H), 4.46 (t, J =
2922, 1515, 1335, 1162, 1085, 819, 753, 618 cm‐1;1H NMR (400 MHz, 3.4 Hz, 1H), 4.32 (t, J = 4.6 Hz, 1H), 4.12‐4.02 (m, 3H), 2.33 and 2.31
CDCl3) δ (ppm) 7.71 (d, J = 7.2 Hz, 2H), 7.45 (d, J = 6.8 Hz, 2H), 7.29 (s, (2s, 6H); 13C NMR (100 MHz, CDCl3) δ (ppm) 152.7, 151.9, 140.6,
1H), 7.27 (s, 1H), 7.18 (d, J = 6.4 Hz, 2H), 5.07 (t, J = 5.0 Hz, 2H), 4.60‐ 136.4, 136.3, 134.6, 133.2, 130.0, 129.7, 129.6, 129.4, 128.1, 122.9,
4.53 (m, 2H), 4.42‐4.39 (m, 1H), 3.22‐3.07 (m, 2H), 2.36 (s, 3H); 13
C
118.9, 63.0, 53.2, 44.4, 20.9, 20.7; HRMS (ESI): Calcd for
NMR (100 MHz, CDCl3) δ (ppm) 155.6, 139.7, 137.8, 135.9, 133.2, C25H24ClN3O5SNa (M++Na) and (M++Na+2): m/z 536.1023, 538.0993.
130.1, 129.6, 128.4, 121.7, 64.6, 55.7, 42.9, 20.9; HRMS (ESI): Calcd Found: 536.1024, 538.0979.
for C17H17ClN2O4SNa (M++Na) and (M++Na+2): m/z 403.0496,
405.0465. Found: 403.0497, 405.0449.
3‐(Phenylsulfonyl)thiazolidine‐2‐thione (26). The procedure was
similar to that for 3. N‐(2‐Bromoethyl)‐sulfonamide 25a (0.38 mmol)
(Z)‐((Z)‐2‐(p‐Tolylimino)‐3‐tosylthiazolidin‐5‐yl)methyl hydrogen p‐ and CS2 (1.9 mmol) were used. Yield 0.086 g (88%, yellow solid);
tolylcarbamate (21). Epoxy sulfonamide 1a (0.43 mmol) and p‐tolyl mp.102‐104 oC; Rf = 0.75 (9:1 hexane/ethyl acetate); IR (KBr) ν 3065,
isothiocyanate (0.65 mmol) were used. White solid, yield 0.133g 2930, 1691, 1572, 1448, 1360, 1283, 1179, 1086, 968, 875, 689 cm‐1;
(60%). Mp 74‐76 oC; Rf = 0.71 (9:1 hexane/ethyl acetate); IR (KBr) ν 1H NMR (400 MHz, CDCl3) δ (ppm) 8.08‐8.06 (m, 2H), 7.72‐7.60 (m,
3349, 2920, 2848, 1720, 1643, 1505, 1463, 1360, 1236, 1164, 1092, 1H), 7.59‐7.55 (m, 2H), 4.72 (t, J = 7.4 Hz, 2H), 3.42 (t, J = 7.4 Hz, 2H);
1
1030, 818 cm‐1; H NMR (500 MHz, CDCl3) δ (ppm) 8.01 (d, J = 8.0 Hz, 13C NMR (100 MHz, CDCl3) δ (ppm) 197.8, 136.6, 134.6, 129.1, 128.8,
2H), 7.36 (d, J = 8.0 Hz, 2H), 7.27 (br, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.07
8 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 9 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
56.9, 29.2; HRMS (ESI): Calcd for C9H9NO2S3Na (M++Na): m/z
281.9693. Found: 281.9690.
3‐((2,4,6‐Triisopropylphenyl)sulfonyl)thiazolidine‐2‐thione (32). N‐
(2‐Bromoethyl)‐sulfonamide 25g (0.25 mmol) and CS2 (1.2 mmol)
3‐Tosylthiazolidine‐2‐thione (27). N‐(2‐Bromoethyl)‐sulfonamide were used. Light yellow solid, yield 0.088 g (90%); Mp.134‐136 oC; Rf
25b (0.36 mmol) and CS2 (1.8 mmol) were used Light yellow solid, = 0.77 (9:1 hexane/ethyl acetate); IR (KBr) ν 2956, 2925, 2868, 1706,
yield 0.083 g (85%). Mp 110‐112 oC; Rf = 0.76 (9:1 hexane/ethyl 1593, 1453, 1422, 1371, 1334, 1278, 1236, 1164, 1076, 1030, 968,
acetate); IR (KBr) ν 2956, 2920, 1593, 1360, 1257, 1164, 1086, 1024, 771 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.18 (s, 2H), 4.73‐4.26
808, 673 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.95 (d, J = 8.0 Hz, (m, 2H), 4.08‐3.97 (m, 2H), 3.45‐3.38 (m, 2H), 2.94‐2.89 (m, 1H), 1.31‐
2H), 7.36 (d, J = 8.0 Hz, 2H), 4.71 (t, J = 7.2 Hz, 2H), 3.41 (t, J = 7.4 Hz, 1.25 (m, 18H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.4, 154.6, 151.6,
2H); 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.9, 145.9, 130.9, 123.9, 55.2, 34.2, 29.7, 24.4, 23.5; HRMS (ESI): Calcd for
133.5, 129.5, 129.2, 57.0, 29.1, 21.8; HRMS (ESI): Calcd for C18H27NO2S3Na (M++Na): m/z 408.1102. Found: 408.1104.
C10H11NO2S3Na (M++Na): m/z 295.9850. Found: 295.9858. Our NMR
shifts are somewhat different from that reported in the literature.17 3‐((4‐Chloro‐2,5‐dimethylphenyl)sulfonyl)thiazolidine‐2‐thione
This compound was crystallized from DCM/ethyl acetate (2:1) (33). N‐(2‐Bromoethyl)‐sulfonamide 25h (0.29 mmol) and CS2 (1.4
mixture at 25 oC. X‐ray structure was determined for this sample.
mmol) were used. Yellow solid, yield 0.078 g (80%). Mp.128‐130 oC;
Rf = 0.78 (9:1 hexane/ethyl acetate); IR (KBr) ν 2925, 1593, 1541,
1
3‐((4‐Methoxyphenyl)sulfonyl)thiazolidine‐2‐thione (28). N‐(2‐ 1484, 1365, 1231, 1164, 1076, 937, 627 cm‐1; H NMR (400 MHz,
Bromoethyl)‐sulfonamide 25c (0.100 g, 0.34 mmol) and CS2 (1.7 CDCl3) δ (ppm) 8.01 (s, 1H), 7.31 (s, 1H), 4.78 (t, J = 7.6 Hz, 2H), 3.47
mmol) were used. Gummy liquid, yield 0.091 g (93%); Rf = 0.73 (9:1 (t, J = 7.4 Hz, 2H), 2.55 and 2.42 (2s, 6H); 13C NMR (100 MHz, CDCl3)
hexane/ethyl acetate); IR (neat) ν 3101, 1680, 1603, 1494, 1365, δ (ppm) 197.3, 140.7, 136.3, 134.8, 134.3, 133.9, 132.6, 56.1, 29.2,
1257, 1159, 1019, 802, 694 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 19.6, 19.5; HRMS (ESI): Calcd for C11H12ClNO2S3 (M++Na) and
8.03‐8.01 (m, 2H), 7.02‐7.00 (m, 2H), 4.70 (t, J = 5.8 Hz, 2H), 3.91 (s, (M++Na+1): m/z 343.9617, 345.9586. Found: 343.9617, 345.9570.
3H), 3.40 (t, J = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 197.7,
164.5, 131.6, 127.8, 114.0, 57.0, 55.8, 29.0; HRMS (ESI): Calcd for 3‐(Naphthalen‐2‐ylsulfonyl)thiazolidine‐2‐thione
(34).
N‐(2‐
C10H11NO3S3Na (M++Na): m/z 311.9799. Found: 311.9797.
Bromoethyl)‐sulfonamide 25i (0.31 mmol) and CS2 (1.6mmol) were
used. Yellow solid, yield 0.078 g (80%). Mp.112‐114 oC; Rf = 0.75 (9:1
N‐(2‐ hexane/ethyl acetate); IR (KBr) ν 2956, 2930, 2863, 1587, 1551, 1458,
3‐((4‐Chlorophenyl)sulfonyl)thiazolidine‐2‐thione (29).
Bromoethyl)‐sulfonamide 25d (0.33 mmol) and CS2 (1.6 mmol) were 1360, 1236, 1169, 1066, 937, 833, 802, 746 cm‐1; 1H NMR (400 MHz,
used. Light yellow solid, yield 0.086 g (88%). Mp.118‐120 oC; Rf = 0.77 CDCl3) δ (ppm) 8.71‐8.65 (m, 1H), 8.05‐7.94 (m, 3H), 7.72‐7.66 (m,
(9:1 hexane/ethyl acetate); IR (KBr) ν 3091, 2936, 1701, 1582, 1474, 2H), 4.80 (t, J = 7.4 Hz, 2H), 3.44 (t, J = 7.4 Hz, 2H); 13C NMR (100 MHz,
1371, 1288, 1179, 1086, 756 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) CDCl3) δ (ppm) 197.9, 135.7, 133.2, 132 0, 131.6, 129.8, 129.7, 129.2,
8.02‐8.00 (m, 2H), 7.55‐7.53 (m, 2H), 4.71 (t, J = 7.2 Hz, 2H), 3.44 (t, 127.9, 127.8, 122.8, 57.1, 29.2; HRMS (ESI): Calcd for C13H11NO2S3
J= 7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 198.0, 141.4, 130.6, (M++H): m/z 310.0030. Found: 310.0029.
129.9, 129.2, 56.9, 29.2; HRMS (ESI): Calcd for C9H8ClNO2S3Na
(M++Na) and (M++Na+2): m/z 315.9304, 317.9273. Found: 315.9304, 3‐(Thiophen‐2‐ylsulfonyl)thiazolidine‐2‐thione
(35).
N‐(2‐
317.9267.
Bromoethyl)‐sulfonamide 25j (0.37 mmol) and CS2 (1.8 mmol) were
used. Light yellow solid, yield 0.086 g (88%). Mp 134‐136 oC; Rf = 0.74
N‐(2‐ (9:1 hexane/ethyl acetate); IR (KBr) ν 3096, 1510, 1402, 1324, 1221,
3‐((4‐Bromophenyl)sulfonyl)thiazolidine‐2‐thione
(30).
Bromoethyl)‐sulfonamide 25e (0.29 mmol) and CS2 (1.4 mmol) were 1154, 1097, 1019, 849, 740 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm)
used. Yellow solid, yield 0.085 g (87%). Mp 124‐126 oC; Rf = 0.77 (9:1 8.01‐7.99 (m, 1H), 7.77‐7.76 (m, 1H), 7.19‐7.17 (m, 1H), 4.66 (t, J =
hexane/ethyl acetate); IR (KBr) ν3090, 2941, 1696, 1567, 1469, 1365, 7.4 Hz, 2H), 3.42 (t, J = 7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm)
1329, 1272, 1164, 1086, 1004, 968, 823, 746, 694 cm‐1; 1H NMR (400 197.7, 136.7, 135.5, 134.9, 127.3, 56.9, 28.7; HRMS (ESI): Calcd for
MHz, CDCl3) δ (ppm) 7.94‐7.92 (m, 2H), 7.72‐7.70 (m, 2H), 4.70 (t, J = C7H7NO2S4 (M++H): m/z 265.9438. Found: 265.9437.
7.4 Hz, 2H), 3.43 (t, J = 7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm)
197.8, 135.6, 132.2, 130.6, 130.1, 56.9, 29.2; HRMS (ESI): Calcd for Thiazolidine‐2‐thione (36): N‐(2‐Bromoethyl)‐sulfonamide 25k (0.32
C9H8BrNO2S3Na (M++Na) and (M++Na+2): m/z 359.8799, 361.8778. mmol) and CS2 (1.6 mmol) were used. White solid, yield 0.025 g
Found: 359.8795, 361.8775.
(65%,). Rf = 0.58 (9:1 hexane/ethyl acetate); The spectral data are in
accordance with the literature.6i
3‐((4‐(Tert‐butyl)phenyl)sulfonyl)thiazolidine‐2‐thione (31). N‐(2‐
Bromoethyl)‐sulfonamide 25f (0.31 mmol) and CS2 (1.5 mmol) were (Z)‐4‐Methyl‐N‐(3‐tosylthiazolidin‐2‐ylidene)aniline (37): N‐(2‐
used. Light yellow solid, yield 0.080 g (82%). Mp 158‐160 oC; Rf = 0.76 Bromoethyl)‐sulfonamide 25b (0.36 mmol) and p‐tolyl
(9:1 hexane/ethyl acetate); IR (KBr) ν 2961, 2863, 1696, 1593, 1463, isothiocyanate (0.54 mmol) were used. White solid, yield 0.102 g
1371, 1226, 1179, 1081, 632 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) (82%). Mp 114‐116 oC; Rf = 0.78 (9:1 hexane/ethyl acetate); IR (KBr)
7.99 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 4.73‐4.70 (m, 2H), ν 3028, 2923, 2858, 1642, 1503, 1442, 1358, 1170, 1131, 1093, 1018,
3.43‐3.40 (m, 2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ (ppm) 801, 671 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.00 (d, J = 6.0 Hz,
197.9, 158.7, 133.4, 129.1, 125.9, 57.0, 35.4, 31.0, 29.1; HRMS (ESI): 2H), 7.36 (d, J = 7.2 Hz, 2H), 7.08 (d, J = 7.2 Hz, 2H), 6.65 (t, J = 4.0 Hz,
Calcd for C13H18NO2S3 (M++H): m/z 316.0499. Found: 316.0504.
2H), 4.21 (br, 2H), 3.20 (br, 2H), 2.48 and 2.31 (2s, 6H); 13C NMR (100
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 9
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 10 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
MHz, CDCl3) δ (ppm) 152.6, 147.8, 144.9, 134.5, 133.8, 130.1, 129.6, used. White solid, yield 0.092 g (82%). Mp 122‐124 oC; Rf = 0.68 (9:1
129.2, 129.1, 125.5, 120.5, 50.1, 27.1, 21.7, 20.9; HRMS (ESI): Calcd hexane/ethyl acetate); IR (KBr) ν 3255, 3058, 2915, 1640, 1583, 1484,
for C17H19N2O2S2 (M++H): m/z 347.0888. Found: 347.0887.
1435, 1230, 1160, 1106, 1104, 895 cm‐1; 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.83‐7.80 (m, 2H), 7.02‐7.00 (m, 2H), 5.59 (br m, J = 8.0 Hz,
2H), 3.88 (s, 3H), 3.35‐3.37 (m, 2H), 3.08 (t, J = 8.0 Hz, 2H); 13C NMR
(Z)‐N‐(3‐((4‐Methoxyphenyl)sulfonyl)thiazolidin‐2‐ylidene)aniline
(38). N‐(2‐Bromoethyl)‐sulfonamide 25c (0.33 mmol) and phenyl (100 MHz, CDCl3) δ (ppm) 163.2, 130.8, 129.2, 114.5, 111.6, 55.7,
isothiocyanate (0.50 mmol) were used. White solid, yield 0.100 g 42.3, 33.8; HRMS (ESI): Calcd for C10H13N2O3S2 (M++H): m/z 273.0367.
(85%). Mp 108‐110 oC; Rf = 0.74 (9:1 hexane/ethyl acetate); IR (KBr) Found: 273.0366.
ν 3064, 1634, 1587, 1546, 1494, 1355, 1267, 1159, 1092, 1014, 833,
792, 761, 694 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.05 (d, J = 7.2 (Z)‐N‐(3‐((4‐Methoxyphenyl)sulfonyl)thiazolidin‐2‐ylidene)‐1‐
Hz, 2H), 7.29‐7.26 (m, 2H), 7.08 (t, J = 6.0 Hz, 1H), 7.03‐7.01 (m, 2H), phenylmethanamine (43). N‐(2‐Bromoethyl) sulfonamide 25c (0.34
6.77‐6.75 (m, 2H), 4.20 (t, J = 5.3 Hz, 2H), 3.91 (s, 3H), 3.18 (t, J = 5.3 mmol) and benzyl isothiocyanate (0.50 mmol) were used. White
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 163.9, 152.8, 150.3, solid, yield 0.105 g (86%). Mp 126‐128 oC; Rf = 0.70 (9:1 hexane/ethyl
131.4, 128.9, 124.2, 120.7, 113.7, 55.7, 50.1, 27.0; HRMS (ESI): Calcd acetate); IR (KBr) ν 3018, 1697, 1353, 1214, 1159, 745, 665 cm‐1; 1H
for C16H17N2O3S2 (M++H): m/z 349.0680. Found: 349.0687.
NMR (400 MHz, CDCl3) δ (ppm) 7.92‐7.90 (m, 2H), 7.28‐7.23 (m, 3H),
7.13 (d, J = 5.2 Hz, 2H), 6.83‐6.81 (m, 2H), 4.15 (t, J = 5.2 Hz, 2H), 3.84
(s, 3H), 3.25 (t, J = 5.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 163.6,
(Z)‐N‐(3‐((4‐Chlorophenyl)sulfonyl)thiazolidin‐2‐ylidene)aniline
(39). N‐(2‐Bromoethyl)‐sulfonamide 25d (0.33 mmol) and phenyl 152.1, 139.4, 131.1, 128.8, 128.1, 127.5, 126.6, 113.7, 59.6, 55.6,
isothiocyanate (0.50 mmol) were used. White solid, yield 0.093 g 49.8, 27.2; HRMS (ESI): Calcd for C17H19N2O3S2 (M++H): m/z 363.0837.
(79%). Mp 168‐170 oC; Rf = 0.79 (9:1 hexane/ethyl acetate); IR (KBr) Found: 363.0838.
ν 2957, 1650, 1593, 1402, 1361, 1237, 1170, 1118, 829, 762 cm‐1; 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.04 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.4 (Z)‐N‐(3‐((4‐(Tert‐butyl)phenyl)sulfonyl)oxazolidin‐2‐
Hz, 2H), 7.26 (t, J = 7.8 Hz, 2H), 7.09‐7.06 (m, 1H), 6.73 (d, J = 8.0 Hz, ylidene)aniline (44): N‐(2‐Bromoethyl)‐sulfonamide 25f (0.31 mmol)
2H), 4.19 (t, J = 6.6 Hz, 2H), 3.20 (t, J = 6.6 Hz, 2H); 13C NMR (100 MHz, and phenyl isocyanate (0.47 mmol) were used. White solid, yield
CDCl3) δ (ppm) 151.5, 148.8, 139.4, 134.9, 129.5, 127.9, 127.8, 123.4, 0.087 g (78%). Mp 194‐196 oC ; Rf = 0.74 (9:1 hexane/ethyl acetate);IR
119.5, 48.9, 26.1; HRMS (ESI): Calcd for C15H14ClN2O2S2 (M++H), (KBr) ν 2910, 2843, 1706, 1644, 1593, 1474, 1402, 1360, 1309, 1267,
(M++H+2): m/z 353.0185, 355.0155. Found: 353.0188, 355.0146.
1226, 1174, 1081, 735 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.04
(d, J = 6.8 Hz, 2H), 7.57 (d, J = 6.8 Hz, 2H), 7.47 (d, J = 6.8 Hz, 2H), 7.34
(t, J = 6.4 Hz, 2H), 7.12 (t, J = 5.8 Hz, 1H), 4.05‐4.01 (m, 2H), 3.91‐3.88
(Z)‐4‐Chloro‐2,5‐dimethyl‐N‐(3‐tosylthiazolidin‐2‐ylidene)aniline
(40). N‐(2‐Bromoethyl)‐sulfonamide 25h (0.30 mmol) and p‐tolyl (m, 2H), 1.35 (s, 9H); 13C NMR (100 MHz, CDCl3) δ (ppm) 157.9, 151.7,
isothiocyanate (0.45 mmol) were used. White solid, yield 0.107 g 138.4, 134.8, 129.0, 128.1, 126.1, 124.4, 118.6, 42.3, 41.2, 35.3, 31.0;
(89%). Mp 158‐160 oC; Rf = 0.80 (9:1 hexane/ethyl acetate); IR (KBr) HRMS (ESI): Calcd for C19H22N2O3S (M++Na): m/z 381.1249. Found:
ν 2951, 2924, 2855, 1643, 1603, 1505, 1439, 1363, 1336, 1279, 1218, 381.1253.
1167, 1137, 1087, 861 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.02
(s, 1H), 7.32 (s, 1H), 7.05 (d, J = 8.0 Hz, 2H), 6.55‐6.53 (m, 2H), 4.35 (t, 1‐(phenylsulfonyl)aziridine (45): This was prepared using a literature
J = 6.6 Hz, 2H), 3.28‐3.24 (m, 2H), 2.61, 2.40 and 2.30 (3s, 9H); 13C method.12c
NMR (100 MHz, CDCl3) δ (ppm) 151.4, 147.1, 139.6, 136.7, 135.2,
134.3, 133.9, 133.8, 132.3, 129.5, 120.5, 49.1, 27.3, 20.9, 19.9, 19.5; 5‐(Chloromethyl)‐3‐tosylthiazolidine‐2‐thione (46).
A
general
HRMS (ESI): Calcd for C18H20ClN2O2S2 (M++H), (M++H+2): m/z Mitsunobu protocol was followed (cf. Scheme 11). White solid, yield
395.0654, 397.0625. Found 395.0655, 397.0627. This compound was 0.094 g (89%). Mp 98‐100 oC; Rf = 0.81 (9:1 hexane/ethyl acetate); IR
crystallized from DCM/ethyl acetate (2:1) mixture at room (KBr) ν 2957, 2917, 1592, 1459, 1436, 1366, 1232, 1169, 1091, 1060,
temperature. X‐ray structure was determined for this sample.
807, 705 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.96 (d, J = 8.4 Hz,
2H), 7.38 (d, J = 8.0 Hz, 2H), 4.99‐4.95 (m, 1H), 4.63‐4.58 (m, 1H),
(Z)‐N‐(3‐(Thiophen‐2‐ylsulfonyl)thiazolidin‐2‐ylidene)aniline (41). 3.86‐3.80 (m, 1H), 3.74‐3.63 (m, 2H), 2.48 (s, 3H); 13C NMR (100 MHz,
N‐(2‐Bromoethyl)‐sulfonamide 25j (0.37 mmol) and phenyl CDCl3) δ (ppm) 195.3, 146.4, 133.5, 129.8, 129.4, 59.2, 45.2, 44.4,
isothiocyanate (0.55 mmol) were used. White solid, yield 0.104 g 22.0; LC/MS: m/z 322 [M+1 (35Cl)]+; Anal. Calcd. for C11H12ClNO2S3: C,
(87%). Mp 120‐122 oC; Rf = 0.76 (9:1 hexane/ethyl acetate); IR (KBr) 41.05; H, 3.76; N, 4.35. Found: C, 41.13; H, 3.79; N, 4.28.
ν 3085, 1639, 1587, 1536, 1494, 1365, 1221, 1164, 1133, 1097, 1019,
859, 735 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.95‐7.94 (m, 1H), 5‐Methylene‐3‐tosylthiazolidine‐2‐thione
(47).
A
general
7.75‐7.73 (m, 1H), 7.33‐7.29 (m, 2H), 7.19‐7.17 (m, 1H), 7.14‐7.09 (m, Mitsunobu protocol was followed (cf. Scheme 11). White solid, yield
1H), 6.87‐6.84 (m, 2H), 4.19 (t, J = 6.6 Hz, 2H), 3.23 (t, J = 6.6 Hz, 2H); 0.079 g (85%). Mp 134‐136 oC; Rf = 0.82 (9:1 hexane/ethyl acetate);
13C NMR (100 MHz, CDCl3) δ (ppm) 152.9, 150.2, 135.3, 134.0, 129.0, IR (KBr) ν 3094, 3050, 2921, 1627, 1595, 1454, 1363, 1235, 1167,
127.0, 124.5, 120.8, 50.2, 26.9; HRMS (ESI): Calcd for C13H12N2O2S3 1071, 874 cm‐1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.95 (d, J = 8.4 Hz,
(M++H): m/z 325.0139. Found: 325.0133.
2H), 7.36 (d, J = 8.4 Hz, 2H), 5.32‐5.30 (m, 1H), 5.28‐5.09 (m, 3H), 2.46
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 194.6, 146.3, 134.8, 133.5,
3‐Tosylthiazolidin‐2‐imine (42). N‐(2‐Bromoethyl)‐sulfonamide 25c 129.6, 129.3, 106.3, 62.2, 21.8; LC/MS: m/z 286 [M+1]+; Anal. Calcd.
(0.34 mmol) and (trimethylsilyl) isothiocyanate (0.50 mmol) were
10 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 11 of 13
View Article Online
DOI: 10.1039/C7OB02915B
Journal Name
ARTICLE
J. Org. Chem. 2016, 81, 11508; (d) R. A. Craig II, N. R. O’Connor,
A. F. G. Goldberg and B. M. Stoltz, Chem. Eur. J. 2014, 20, 4806;
(e) M. Sengoden and T. Punniyamurthy, Angew. Chem. Int. Ed.
2013, 52, 572; (f) J‐Y. Wu, Z‐B. Luo, L‐X. Dai and X‐L. Hou, J. Org.
Chem. 2008, 73, 9137; (g) M. D’hooghe, A. Waterinckx and N. D.
Kimpe, J. Org. Chem. 2005, 70, 227.
for C11H11NO2S3: C, 46.29; H, 3.88; N, 4.91. Found C, 46.15; H, 3.83;
N, 5.02.
(Z)‐N‐(1‐(5,5‐dimethyl‐2‐oxido‐1,3,2‐dioxaphosphinan‐2‐yl)‐1‐(p‐
tolyl)prop‐1‐en‐2‐yl)‐4‐methylbenzenesulfonamide
(49).
The
3. (a) O. Devinyak, B. Zimenkovsky and R. Lesyk, Curr. Top. Med.
Chem. 2012, 12, 2763 (b) T. Tomasic and L.P. Masic Curr. Med.
Chem. 2009, 16, 1596; (c) M. A. Ramirez and N. L. Borja,
Pharmacotherapy 2008, 28, 646; (d) N. Hotta, Y. Akanuma, R.
Kawamori, K. Matsuoka, Y. Oka and M. Shichiri, Diabetes Care
2006, 29, 1538; (e) P. Vicini, A. Geronikaki, K. Anastasia, M. Incerti
and F. Zani, Bioorg. Med. Chem. 2006, 14, 3859; (f) R. Ottana`, R.
Maccari, M. L. Barreca, G. Bruno, A. Rotondo, A. Rossi, G.
Chiricosta, R. D. Paola, L. Sautebin, S. Cuzzocrea and M. G.
Vigorita, Bioorg. Med. Chem. 2005, 13, 4243; (g) M. Takagi, K.
Ishimitsu and T. Nishibe, Oxa(thia)zolidine Derivative and Anti‐
Inflammatory Drug. U.S. Patent 6,762,200, July 13, 2004; (h) B. R.
Dixon, C. M. Bagi, C. R. Brennan, D. R. Brittelli, W. H. Bullock, J.
Chen, W. L. Collibee, R. Dally, J. S. Johnson and H. C. E. Kluender,
Substituted 2‐Arylimino Heterocycles and Compositions
Containing Them, for Use as Progesterone Receptor Binding
Agents. U.S. Patent 6, 353, 006, March 5, 2002; (i) R. B.
Greenwald, A. Pendri, A. Martinez, C. Gilbert and P. Bradley,
Bioconjugate Chem. 1996, 7, 638.
method involves straightforward reaction using 0.32 mmol each of
3/48 (cf. Scheme 12) in DMSO (ca 1 mL) and K2CO3 (1 equiv). White
solid, yield 0.118 g (80%). Mp 152‐154 oC; Rf = 0.53 (9:1 hexane/ethyl
acetate);IR (KBr) ν 2966, 2887, 1600, 1471, 1441, 1380, 1342, 1304,
1163, 1051, 1004, 816 cm‐1; 1H NMR (500 MHz, CDCl3) δ (ppm) 11.4
(br, 1H), 7.84 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 7.10 (d, J =
8.0 Hz, 2H), 6.97‐6.95 (m, 2H), 4.15‐4.12 (m, 2H), 3.53‐3.47 (m, 2H),
2.42 (s, 3H), 2.33 (s, 3H), 1.80 (d, J = 1.0 Hz, 3H), 0.87 (s, 3H), 0.50 (s,
3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 153.0 (d, J = 7.1 Hz), 143.8,
137.5 (d, J = 20.3 Hz), 137.4, 131.3 (d, J = 4.6 Hz), 131.3, 131.2, 129.8,
129.11, 129.10, 127.3, 104.0 (d, J = 149.1 Hz), 75.6 (d, J = 5.1 Hz), 32.1
(d, J = 5.6 Hz), 21.6, 21.4, 21.2, 20.9, 17.4 (d, J = 11.4 Hz); 31P NMR
(162 MHz, CDCl3) δ (ppm) 15.16; LC/MS: m/z 450 [M+1]+; Anal. Calcd.
For C22H28NO5PS: C, 58.78; H, 6.28; N, 3.12. Found C, 58.76; H, 6.28;
N, 3.12.
4. (a) A. O. Lozada and H. F. Olivo, Org. Lett. 2008, 10, 617; (b) M. T.
Crimmins and M. Shamszad, Org. Lett. 2007, 9, 149; (c) D. A.
Evans, C. W. Downey and J. L. Hubbs, J. Am. Chem. Soc. 2003,
125, 8706; (d) F. Velázquez and H. F. Olivo, Curr. Org. Chem.
2002, 6, 303; (e) D. A. Evans, C. W. Downey, J. T. Shaw and J. S.
Tedrow, Org. Lett. 2002, 4, 1127; (f) M. T. Crimmins, B. W. King,
E. A. Tabet and K. Chaudhary, J. Org. Chem. 2001, 66, 894; (g) M.
T. Crimmins and K. Chaudhary, Org. Lett. 2000, 2, 775.
5. (a) M. Ferreira and M. M. Sa, Adv. Synth. Catal. 2015, 357, 829;
(b) M. D’hooghe and N. D. Kimpe, Tetrahedron 2006, 62, 513; (c)
S. Kasmi‐Mir, A. Djafri, L. Paquin, J. Hamelin and M. Rahmouni,
Molecules 2006, 11, 597.
Acknowledgments
We thank the Department of Science & Technology (DST, New Delhi)
and University Grants Commission (UGC, New Delhi) for equipment
under FIST/PURSE and UPE programmes, respectively. We thank
ACRHEM‐University of Hyderabad for recording some IR spectra. KCK
thanks CSIR (New Delhi) for funding and DST for the J. C. Bose
fellowship. MA thanks UGC (New Delhi) for a fellowship.
6. (a) M. D’hooghe and H. ‐J. Ha, (Eds). Synthesis of 4‐ to 7‐
membered heterocycles by Ring Expansion Aza‐, oxa‐ and
thiaheterocyclic small‐ring systems. Topics in Heterocyclic
Chemistry‐41, Springer, Cham (Switzerland) 2016, DOI
10.1007/978‐3‐319‐24960‐5 (b) S. U. Dighe, V. D. Yadav, R.
Srivastava, A. Mishra, S. Gautam, A. K. Srivastava, V. M.
Balaramnavar, A. K. Saxena and S. Batra, Tetrahedron 2014, 70,
6841; (c) T. Stalling, W. Saak and J. Martens, Eur. J. Org. Chem.
2013, 8022; (d) A. ‐Z. Halimehjani, K. Marjani and A. Ashouri,
Tetrahedron Lett. 2012, 53, 3490; (e) A. M. Jacobine and G. H.
Posner, J. Org. Chem. 2011, 76, 8121; (f) A. Alizadeh, N. Zohreh,
H. Sabahnoo and Z. Noaparast, Tetrahedron 2011, 67, 1709; (g)
S.‐F. Gan, J. ‐P. Wan, Y.‐J. Pan and C.‐R. Sun, Synlett 2010, 6, 973;
(h) N. Chen, W. Jia and J. Xu, Eur. J. Org. Chem. 2009, 5841; (i) J.
Baiget, A. Cosp, E. Gálvez, L. Gómez‐Pinal, P. Romea and F. Urpí,
Tetrahedron 2008, 64, 5637; (j). S. Gabillet, D. Lecercle, O. Loreau,
M. Carboni, S. Dézard, J.‐M. Gomis and F. Taran, Org. Lett. 2007,
9, 3925; (k) D. Delaunay, L. Y. Toupet and M. L. Corre, J. Org.
Chem. 1995, 60, 6604.
Notes and references
1. (a). P. Mukherjee and A. R. Das, J. Org. Chem. 2017, 82, 2794; (b).
H.‐W. Zhao, Y.‐D. Zhao, Y.‐Y. Liu, J. Du, H.‐L. Pang, X.‐Q. Chen, X.‐
Q. Song and N.‐N. Feng, Eur. J. Org. Chem. 2017, 3466; (c). H.‐W.
Zhao, X.‐Q. Chen, Y.‐D. Zhao, Y.‐Y. Liu, H.‐L. Pang, X.‐Q. Song, T.
Tian, B. Li, Z. Yang, J. Du and N.‐N. Feng, Eur. J. Org. Chem. 2017,
3139; (d) A. A. Nechaev, A. A. Peshkov, K. V. Hecke, V. A. Peshkov
and E. V. Van der Eycken, Eur. J. Org. Chem. 2017, 1063; (e) H.‐
W. Zhao, T. Tian, H.‐L. Pang, B. Li, X.‐Q. Chen, Z. Yang, W. Meng,
X.‐Q. Song, Y.‐D. Zhao and Y.‐Y. Liu, Adv. Synth. Catal. 2016, 358,
2619; (f) A. Bongers, I. Ranasinghe, P. Lemire, A. Perozzo, J.‐F.
Vincent‐Rocan and A. M. Beauchemin, Org. Lett. 2016, 18, 3778;
(g) W. Hao, J. Huang, S. Jie and M. Cai, Eur. J. Org. Chem. 2015,
6655; (h) H.‐W. Zhao, T. Tian, B. Li, Z. Yang, H.‐L. Pang, W. Meng,
X‐Q. Song and X.‐Q. Chen, J. Org. Chem. 2015, 80, 10380; (i) L.
Wang, D. Yang, D. Li, X. Liu, Q. Zhao, R. Zhu, B. Zhang and R.
Wang, Org. Lett. 2015, 17, 4260; (j) D. Cantillo, M. Ávalos, R.
Babiano, P. Cintas, J. L. Jiménez, M. E. Light, J. C. Palacios and R.
Porro, J. Org. Chem. 2014, 79, 4201; (k) S. Chuprakov, S. W. Kwok
and V. V. Fokin, J. Am. Chem. Soc. 2013, 135, 4652; (l) A. F. G.
Goldberg, N. R. O. Connor, R. A. Craig II and B. M. Stoltz, Org. Lett.
2012, 14, 5314; (m) Y. Takeda, S. Okumura, S. Tone, I. Sasaki and
S. Minakata, Org. Lett. 2012, 14, 4874; (n) G. Fiorani, W. S. Guo
and A. W. Kleij, Green Chem. 2015, 17, 1375; (o) J. Fabian, J. Org.
Chem. 2000, 65, 8940.
7. (a) J. Rintjema, R. Epping, G. Fiorani, E. Martin, E. C. Escudero‐Ad
n and A. W. Kleij, Angew. Chem. Int. Ed. 2016, 55, 3972.
8. (a) A. Leela Siva Kumari, A. Siva Reddy and K. C. Kumara Swamy,
Org. Lett. 2016, 18, 5752; (b) C. Wang and H. Yamamoto, Angew.
Chem. Int. Ed. 2015, 54, 8760; (c) C. Wang and H. Yamamoto, J.
Am. Chem. Soc. 2014, 136, 6888; (d) C. Wang and H. Yamamoto,
Org. Lett. 2014, 16, 5937; (e) J. M. Schomaker, S. Bhattacharjee,
J. Yan and B. Borhan J. Am. Chem. Soc. 2007, 129, 1996; (f) D. M.
Hodgson, M. J. Fleming, Z. Xu, C. Lin and S. J. Stanway, Chem.
Commun. 2006, 3226; (g) D. Leca, K. Song, M. Albert, M. G.
Gonçalves, L. Fensterbank, E. Lacôte and M. Malacria, Synthesis
2005, 1405.
2. (a) L. Gao, K. Fu and G. Zheng, RSC Adv. 2016, 6, 47192; (b) A.
Bhattacharyya, C. V. Kavitha and M. K. Ghorai, J. Org. Chem.
2016, 81, 6433; (c). M. Sengoden, R. Irie and T. Punniyamurthy,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 11
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 12 of 13
View Article Online
DOI: 10.1039/C7OB02915B
ARTICLE
Journal Name
9. (a). X‐B. Lu and D. Darensbourg, Chem. Soc. Rev. 2012, 41, 1462;
(b) F. Fontana, C. C. Chen and V. K. Aggarwal, Org. Lett. 2011, 13,
3454; (c). J. Diebler, A. Spannenberg and T. Werner,
ChemCatChem. 2016, 8, 2027; (d). J. Diebler, A. Spannenberg and
T. Werner, Org. Biomol. Chem. 2016, 14, 7480; (e). S. Motokucho,
D. Takeuchi, F. Sanda and T. Endo, Tetrahedron 2001, 57, 7149;
(f) A. Modi, W. Ali and B. K. Patel, Org. Lett. 2017, 19, 432; (g). G.
M. T. Smith, P. M. Burton and C. D. Bray Angew. Chem. Int. Ed.
2015, 54, 15236; (h) T. L. Church, C. M. Byrne, E. B. Lobkovsky
and G. W. Coates, J. Am. Chem. Soc. 2007, 129, 8156.
10. (a) Y. Yin, H. Zhou, G. Sun and X. Liu. J. Heterocyclic Chem. 2015,
52, 1337; (b) J. Wei, Z. Chen, Y. Gao, P. Zhang, C. Wang, P. Zhao,
Y. Wang and X. Shi, Chin. J. Chem. 2012, 30, 391.
11. (a) K. Inamoto, M. Shiraishi, K. Hiroya and T. Doi, Synthesis 2010,
3087; (b) F. Shibahara, A. Suenami, A. Yoshida and T. Murai,
Chem. Commun. 2007, 2354.
12. (a) M. Anitha, G. Gangadhararao and K. C. Kumara Swamy, Org.
Biomol. Chem. 2016, 14, 3591; (b) D. Basavaiah, S. Pal, G.
Veeraraghavaiah and K. C. Bharadwaj, Tetrahedron 2015, 71,
4659; (c) M. P. Lowe, D. Parker, O. Reany, S. Aime, M. Botta, G.
Castellano, E. Gianolio and R. Pagliarin, J. Am. Chem. Soc. 2001,
123, 7601.
13. K. C. Kumara Swamy, N. N. Bhuvan Kumar, E. Balaraman and K.
V. P. Pavan Kumar, Chem. Rev. 2009, 109, 2551.
14. D. D. Perrin, W. L. F. Armarego and D. R. Perrin, Purification of
Laboratory Chemicals; Pergamon: Oxford, UK, 1986.
15. (a) M. Sova, A. Kovaĉ, S. Turk, M. Hrast, D. Blanot and S. Gobec,
Bioorg. Chem. 2009, 37, 217; (b) S. Yahiaoui, K. Hamidouche, C.
Ballandonne, A. Davis, J. S. O. Santos, T. Freret, M. Boulouard, C.
Christophe Rochais and P. Dallemagne, Eur. J. Med. Chem. 2016,
121, 283.
16. (a) G. M. Sheldrick, SADABS, Siemens Area Detector Absorption
Correction; University of Göttingen: Göttingen, Germany, 1996.
(b) G. M. Sheldrick, SHELX‐97, A Program for Crystal Structure
Solution and Refinement; University of Göttingen, Göttingen,
Germany, 1997. (c) G. M. Sheldrick, SHELXTL NT Crystal Structure
Analysis Package; Bruker AXS, Analytical X‐ray System, Madison,
WI, 1999; version 5.10.
17. M. Ghazanfarpour‐Darjani and A. Khodakarami, Monatsh Chem.
2016, 147, 829.
12 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 13 of 13
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB02915B