First catalyst-free CO2 trapping of: N -acyliminium ions under ambient conditions: Sustainable multicomponent synthesis of thia- and oxazolidinyl carbamates

Article abstract of DOI:10.1039/c8ob01865k

The first trapping of N-acyliminium ions by in situ generated carbaminic acid (product of carbon dioxide (CO₂) and amine) is reported. This catalyst-free reaction provides a convenient and feasible approach to prepare N-acyl thia- and oxazolidi

Full text of DOI:10.1039/c8ob01865k

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First catalyst-free CO2 trapping of N-acyliminium ions at ambient
conditions: Sustainable multicomponent synthesis of thia- and
oxazolidinyl carbamates
Received 00th January 20xx,
Accepted 00th January 20xx
Max Franz,a Timo Stalling,a Henning Steinerta and Jürgen Martensa,*
DOI: 10.1039/x0xx00000x
The first trapping of N-acyliminium ions by in situ generated carbaminic acid (product of carbon dioxide (CO2) and amine)
is reported. This catalyst-free reaction provides a convenient and feasible approach to prepare N-acyl thia- and
oxazolidinyl carbamates with good functional-group compatibility and high efficiency under green conditions.
Furthermore, the multicomponent method features broad substrate scope, facile product diversification, smooth scale-up
and notable potential for polymer applications.
www.rsc.org/
keywords: Multicomponent reaction, green conditions, carbon dioxide, carbamate, N-acyliminium ion.
green solvent
O
MCR
mild conditions
simple performance
R'
N
X
O
m
t
Imine
+
Acyl Chloride
a
1
R''
O
N
R'''
- HCl
26 examples
up to 95% yield
Amine
Graphical abstract.
dioxide because of its kinetic intertness and thermodynamic
stability the conversion with amines into carbaminic acids has
been highlighted to be an approved way to get various
carbonyl derivatives.6 Amongst the numerous transformations
of carbamic acids to functional molecules, one of the most
interesting and attractive opportunities is the carbamate
formation.
Introduction
Carbon dioxide (CO2) is a brilliant non-toxic, naturally available,
abundant, and low-cost one-carbon (C1) source and has been
utilized in a multitude of (catalytic) processes1 resulting in the
elegant synthesis of carboxylates2, carbonates3 and
carbamates/oxazolidinones4. Furthermore, due to the
increasing global emissions of carbon dioxide assumed as
mediator of global warming the incorporation of this gas into
small molecules by catalytic and base-promoted procedures
has attracted a great deal of attention in many facets of
modern research.1, 5 In spite of the challenge to convert carbon
Carbamates are ubiquitous in insecticides, herbicides and
fungicides and are widely employed as protecting group in
synthetic chemistry. In addition, the products of
polymerization (= polyurethanes) bear a significant meaning in
materials science. Moreover, the carbamate moiety is often
the essential structural element in drug design and medicinal
chemistry.7 Some medicinally and biologically relevant
compounds containing the carbamate substructure are
depicted in Scheme 1. The first example is Rivastigmine
(Exelon®), which was developed as acetylcholinesterase
inhibitor for the treatment of Alzheimer's disease and
Parkinson's.8 The next representative is Solifenacin (Vesicare®),
a.Institut für Chemie, Carl von Ossietzky Universität Oldenburg, P. O. Box 2503, Carl-
von-Ossietzky-Str. 9–11, 26111 Oldenburg, Germany
E-mail: juergen.martens@uni-oldenburg.de; http://www.martens.chemie.uni-
oldenburg.de.
Electronic Supplementary Information (ESI) available: 1H and 13C NMR spectra of all
new compounds. See DOI: 10.1039/x0xx00000x
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a medicine for the therapy of bladder troubles.9 Capravirine is conform with the sustainable principles of green chemistry.
a transcriptase inhibitor and applicable as Anti-HIV drug10, Accordingly, we concentrated on mild and metal-free
whereas Aldicarb (Temik®) is a cholinesterase inhibitor and conditions with ambient pressure of carbon dioxide, while
therefore used as insecticide.11
using our experience in generation of reactive N-acyliminium
intermediates in MCRs starting from imines by a direct
acylation19 as significant step.20
Scheme
1 Medicinally and biologically active compounds containing carbamate
substructure.
A host of synthetic approaches to the popular class of
carbamates based on carbon dioxide has been reported.12
Along these reactions, a direct and versatile route realized by a
multicomponent reaction (MCR) has been recently described
to productively sequester carbon dioxide as building block.13
Multicomponent reactions offer an impressive alternative to
classical organic reactions, and provide a basis to develop new
reaction manifolds. They serve medicinal and organic chemists
the unique method to link at least three starting materials
simultaneously to a new heavy functional product in an atom
economic, low cost and highly efficient fashion.14 Accordingly,
the smooth elaboration of complex and richly substituted
(heterocyclic) molecules with feasible motifs often results from
MCRs because of their central attribute to reduce a series of
reactions into a single-step operation.15 The design of new
MCRs that take place in a green and experimentally simple
way are attractive goals in diverse fields of research including
carbon dioxide chemistry.16
Scheme 2 Catalyst-free multicomponent reactions (MCRs) using carbon dioxide (CO2) as
C1 building block (simplified).
Results and discussion
To establish the new carbon dioxide based MCR for assembling
heterocyclic carbamates, we started our investigations with an
optimization of the two-step sequence regarding solvents,
stoichiometry and reaction times (Table 1). These studies were
performed by the use of tetramethyl-2,5-dihydro-1,3-thiazole,
acetyl chloride, benzyl amine, carbon dioxide as easily
available model substrates and triethylamine as non-
nucleophilic, well-established base for capturing of hydrogen
chloride. During our preliminary experiments, carbon dioxide
was purged through the reaction mixture via cannula within a
specified time of 30 min (Entries 1–8, Time I, Step b)). Initial
attempts by utilizing DCM as classically used solvent for
additions of acyl chlorides to imines led to the formation of
carbamate 2a in good yields of 53% and 69%, depending on
the reaction time (Entries 1–2). When the total reaction time
of 160 min (Times I–III) was transferred to various solvent
combinations (DCM, MeCN, DMF, Et3N, THF, EtOAc) (Entries 1–
7), we observed that the homogenous systems THF (Entry 6)
and EtOAc (Entry 7) provided the best results. However, we
decided to continue our studies with EtOAc as nearly non-
toxic, green and dry solvent. Due to the sensitivity of chloro
amides produced by Step a) towards moisture we attached
importance to totally dry EtOAc before entering in our process.
This goal was reached by using molecular sieves, a simple and
environmentally friendly method. Furthermore, we
With the privileges of MCRs in hand and the relevance of
carbamates at the back of our mind, our group is highly
interested in a catalyst-free combination of carbon dioxide,
amines and activated bifunctional substrates for the smart
preparation of carbamate units. In the course of these works,
we have recently developed a water mediated carbon dioxide
based MCR that allows an in situ generated carbaminic acid
(product of carbon dioxide and amine) to react with an
activated aldehyde as central building block to furnish a range
of hydroxy oxazolidinones
1
(Scheme 2).17 We extended this
type of MCR to other systems and report herein about the
successfull application of high value N-acyliminium species18 in
an analog CO2 transformation ending in the formation of
heterocyclic carbamates 2. The properties and nature of such
acyl iminium molecules regarding reactivity, stability and
handling (particularly towards moisture) prompted us to find
new conditions that are compatible with all components and
2 | J. Name., 2012, 00, 1-3
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Entry Solv. Ia)
Solv. IIb) Bn-NH2c) Et3Nd) Time Ie) Time IIf) Time IIIg) Yieldh)
simultaneously tested an alternative method to generate an
effective carbon dioxide atmosphere. We figured out that an
easy-to-handle carbon dioxide balloon delivers a reliable
1
2
3
4
5
6
7
DCM / 4 DCM / 20
3
3
3
3
3
3
3
3
3
3
3
3
3
10
10
10
10
30
30
30
30
6
5
30
53%
69%
54%
38%
40%
63%
62%
40%
54%
63%
51%
64%
61%
39%
65%
63%
51%
41%
64%
DCM / 4 DCM / 20
DCM / 4 MeCN / 20
DCM / 4 DMF / 20
DCM / 4 Et3N / 20
120
120
120
120
120
120
120
120
16 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
240
240
5
platform to furnish carbamate
2 in moderate yield of 54%
7
(based on the initially applied DCM system) (Entries 8–9).
Focusing on this carbon dioxide source the yield was increased
to 63% by the employment of EtOAc as solvent and a longer
reaction time (Entry 10). Varying the equivalents of base had a
slight effect on the reaction conversion and we noticed that a
reduced amount of 2.5 equivalents triethylamine gave the
highest yield (64%, Entries 11–13). Reducing the equivalents of
Solv. II 30
7
THF / 4
THF / 20
10
10
30
30
30
30
30
30
30
30
30
30
30
30
10
10
10
6
EtOAc / 4 EtOAc / 20
5
8i) DCM / 4 DCM / 20
9j) DCM / 4 DCM / 20
10j) EtOAc / 4 EtOAc / 20
11j) EtOAc / 4 EtOAc / 20
10
6
10
6
10
5
5
5
benzyl amine provided less product (Entry 14). This negative 12j) EtOAc / 4 EtOAc / 20
2.5
1.5
2.5
2.5
1.5
1.5
1.5
2.5
2.5
6
13j) EtOAc / 4 EtOAc / 20
7
influence could be compensated by a higher amount of
14j) EtOAc / 4 EtOAc / 20 1.5
15j), k) EtOAc / 8 EtOAc / 40 1.5
16j), k) EtOAc / 8 EtOAc / 40 2.0
17j), k) EtOAc / 16 EtOAc / 40 1.0
18j), k) EtOAc / 16 EtOAc / 40 1.0
19j), k) EtOAc / 8 EtOAc / 40 1.5
20j), k) EtOAc / 8 EtOAc / 40 1.5
5
solvents affording carbamate 2 in good yield of 65% (Entry 15).
10
13
35
35
10
10
However, to improve the conditions further regarding
ecological and economic aspects, we concentrated on the
equivalents and times in more detail. We found that both 1.5
equivalents of benzyl amine, 2.5 equivalents of base and a
total reaction time of seven hours met the intended demands
240 60%l)
forming product
2 in 64% yield (Entries 16–19). Lastly, we
Reactions were performed using the following conditions: "Step a)" 1. imine (1
eq, 1.00 mmol), 2. solvent I, 3. acetyl chloride (1.2 eq, 1.20 mmol); "Step b)" 1.
CO2 (purging via cannula), 2. solvent II, 3. Et3N, 4. Bn-NH2, then stirring (Time I); 5.
addition of "Step a)" (Time II) (purging with CO2 via cannula stopped after 5 min);
then stirring (Time III) (for experimental details, see Experimental Section); a) mL;
b) mL; c) eq; d) eq; e) min; f) min; g) min; h) Yields of isolated products; i) "Step
b)" was performed at 0 °C; j) CO2 atmosphere was generated by a balloon instead
of purging via cannula; k) scale-up: imine (1 eq, 2.00 mmol) and acetyl chloride
(1.2 eq, 2.40 mmol) were used; l) work-up was simplified: Slurry was washed only
with water.
improved the work-up of the reaction identifying a short
process of washing with water as the most efficient option
(60% yield, Entry 20).
Table 1 Optimization.
With the best and greenest reaction conditions in hand, we
turned our attention to the scope of our newly developed MCR
applying gaseous carbon dioxide as essential C1 building block.
Our first target was the incorporation of a representative
collection of primary amines while employing selected acyl
chlorides and 2,5-dihydro-1,3-thiazole derivatives as further
substrates (Scheme 3). We started our investigations with a
number of (hetero-)benzylic amines and isolated carbamates
2a–f in moderate yields (33–65%). The combination of acetyl
chloride derivatives, tetramethyl-2,5-dihydro-1,3-thiazole,
carbon dioxide, triethylamine, and both unsubstituted and
monosubstituted (i. e. 4-OCH3, 2-Br) benzylic amines provided
rapid access to compounds 2a
picolyl, furfuryl, and thiophenemethyl amines was also
successfully applied furnishing carbamates 2d in acceptable
yields (33–60%). The reaction of allylic substrates proceeded
smoothly affording products 2g in good yields (63–83%).
–c (59–65% yield). The use of
–
f
–h
Subsequently, we focused on aniline derivatives and were
surprised that the conversion of aniline failed. However,
several attempts to include this low-priced amine starting
material ended up in trace amounts of the desired carbamate
structure. The inability of aniline to react with carbon dioxide
is not totally understood.21 To overcome this limitation, we
tested 4-anisidine as more electron rich aniline source and
were pleased to note that 4-anisidine underwent clean
conversion to give corresponding carbamate 2i in good yield
(63%). These observations indicate that the nucleophilicity of
the amine is
a
relevant property for
a successful
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transformation with carbon dioxide. Furthermore, our useful intermediate that can be elaborated to a range of cross-
established conditions offered the opportunity to obtain linked heterocyclic structures. In addition to richly
functionalized carbamates 2j
subunits for further derivatizations, such as acetal, ether, and non-demanding (i. e. n-butyl, 2n, 68%) and demanding (i. e. i-
ester motifs, in moderate to good yields (29–84%). Apart from propyl, 2o, 69%; t-butyl, 2p, 38%) alkyl carbamates 2n was
various options to modify 2j , notably, glycine derivative 2m also efficiently promoted.
as a selected example for the class of amino acids represents a
–m bearing powerful structural functionalized amines we found that formation of sterically
–
p
–
l
Scheme 3 Scope of primary amines. Reactions were performed using the following conditions: "Step a)" 1. imine (1 eq, 2.00 mmol), 2. acyl chloride (1.2 eq, 2.40 mmol); "Step b)" 1.
CO2 (balloon), 2. EtOAc, 3. Et3N (2.5 eq, 5.00 mmol), 4. amine (1.5 eq, 3.00 mmol), 5. addition of "Step a)" (for experimental details, see Experimental Section). Yields of isolated
products are shown. a) scale-down: imine (1 eq, 1.00 mmol), acyl chloride (1.2 eq, 1.20 mmol), Et3N (2.5 eq, 2.50 mmol), and amine (1.5 eq, 1.50 mmol) were used; b) scale-up:
imine (1 eq, 10.00 mmol), acyl chloride (1.2 eq, 12.00 mmol), Et3N (2.5 eq, 25.00 mmol), and amine (1.5 eq, 15.00 mmol) were used; c) The substrate methyl glycinate was
introduced as hydrochloride. Additionally, 1.5 eq of Et3N (3.00 mmol) were used.
Next, we extended our scope to the application of secondary Scheme 4. The first examples were implemented into the
amines as building component in our system. Simultaneously, series by means of N-methyl benzyl amine, acetyl chloride,
a variation of the acyl chloride was considered. For these tetramethyl-2,5-dihydro-1,3-thia-/oxazole, triethylamine, and
investigations, we concentrated on remarkable, widely used carbon dioxide to achieve thia- and oxazolidinyl carbamates
and easily available molecules. Our results are shown in 2q
–
r
in up to very good yields (63–91%). Moreover, the range
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of secondary amines was expanded by the employment of secondary amine alkyl carbamate 2u was produced in good
allylic and propargylic starting marterials yielding products 2s yield (80%). In addition, the reaction of (hetero-)cyclic
in good yields (72–86%). Both compounds containing readily secondary amines such as pyrrolidine, tetrahydroisoquinoline,
functionalizable terminal double and triple bonds illustrate the morpholine, and piperazine led to a smooth preparation of
potential for further elaboration of diverse-orientated carbamates 2v (47–73% yield) including various heterocyclic
–
t
a
–y
substance library by simple modifications. In particular, scaffolds. It is worth mentioning that formation of pyrimidyl
palmitic acid derivative 2s completes the green methodology piperazinyl substructure in 2y could be realized in a single-step
of our MCR in a good manner although the generation of 2s process demonstrating the broad substrate compatibility of
required a longer reaction time. As an example for the the carbon dioxide based MCR.
straightforward incorporation of
a sterically demanding
Scheme 4 Scope of secondary amines. Reactions were performed using the following conditions: "Step a)" 1. imine (1 eq, 2.00 mmol), 2. acyl chloride (1.2 eq, 2.40 mmol); "Step b)"
1. CO2 (balloon), 2. EtOAc, 3. Et3N (2.5 eq, 5.00 mmol), 4. amine (1.5 eq, 3.00 mmol), 5. addition of "Step a)" (for experimental details, see Experimental Section). Yields of isolated
products are shown. a) "Step a)" was stirred for 18 h; b) The substrate 1-(2-pyrimidyl)piperazine was introduced as dihydrochloride. Additionally, 3 eq of Et3N (6.00 mmol) were
used.
Finally, we figured out that our environmentally benign Since terminal olefin groups are known to be proper
multicomponent protocol is also applicable for a multi-gram precursors for polymerizations22, we explored the possibility to
scale of carbamates (Scheme 5, Up-scaling). For this purpose, create polymerizable monomers by the new carbon dioxide
we selected isopropyl carbamate structure 2o as model based MCR. In the course of these activities we succeeded in a
compound and were delighted to obtain 2o in almost dimerization reaction providing high-value bis-carbamate 2z
quantitative yield (95%, 5.47 g) after a facile purification by with two allyl units in a moderate yield of 56% (Scheme 5,
crystallization. Notably, we would like to emphasize that we Dimerization). From a synthetic idea, this example and analogs
had already isolated a relatively highly pure crude product thereof illustrate a viable way to prepare potential monomers
after a simple aqueous work-up (for details, see SI).
for polyurethane formation.
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Scheme 5 Examples of up-scaling and dimerization. Reactions were performed using the following conditions: a) "Step a)" 1. imine (1 eq, 20.00 mmol), 2. acyl chloride (1.2 eq,
24.00 mmol); "Step b)" 1. CO2 (balloon), 2. EtOAc, 3. Et3N (2.5 eq, 50.00 mmol), 4. amine (1.5 eq, 30.00 mmol), 5. addition of "Step a)" (for experimental details, see Experimental
Section). b) "Step a)" 1. imine (2 eq, 2.00 mmol), 2. acyl chloride (1 eq, 1.00 mmol); "Step b)" 1. CO2 (balloon), 2. EtOAc, 3. Et3N (5 eq, 5.00 mmol), 4. amine (3 eq, 3.00 mmol), 5.
addition of "Step a)" (for experimental details, see Experimental Section). Yields of isolated products are shown.
Based on literature studies23 and experimental observations, a
mechanistic consideration for the generation of carbamates
2
is depicted in Scheme 6. The proposed reaction mechanism
involves two steps, namely Step a) and Step b), resulting from
the preparative procedure. The reaction starts (Step a) with
the addition of an acyl chloride to an cyclic imine furnishing N-
acyliminium ion
to chloro amide
A
along with the formation of an equilibrium
as intermediate products. Meanwhile, the
B
nucleophilic attack of an amine to carbon dioxide affords
carbaminic acid (Step b). This process might be the reason
C
for a limitation of applying non-electron rich aniline derivatives
in the reported MCR. Then the key addition of the carbaminic
acid to the N-acyliminium ion occurs to give final product 2.
This step is supported by the base triethylamine to trap
liberated hydrogen chloride preventing degradation and hydro
chloride formation of product 2.
Scheme 6 Proposed mechanism.23
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mixture was stirred for 4 h at r.t.. The resulting slurry was
treated with water (10 mL per mmol imine) and the aqueous
phase was extracted with EtOAc (3 x 10 mL per mmol imine).
The combined organic phases were dried (MgSO4) and the
solvent was removed on a rotary evaporator. The crude
product was purified by column chromatography on silica gel
or crystallized from EtOAc/n-hexane.
Conclusions
In conclusion, we have introduced a green multicomponent
approach to form thia- and oxazolidinyl carbamates by the
sustainable utilization of carbon dioxide at ambient pressure.
This inexpensive, non-toxic and readily available C1 unit was
incorporated by trapping of N-acyliminium ions under catalyst-
free and mild reaction conditions. The combination of a broad
substrate scope and a good functional-group tolerance enables
the efficient and practical preparation of derivatizable
heterocycles with valuable scaffold diversity.
(RS)-3-Acetyl-4-benzylcarbamoyloxy-2,2,5,5-tetramethyl-1,3-
thiazolidine (2a): The carbamate 2a was prepared according to
the general procedure using 2,2,5,5-tetramethyl-2,5-dihydro-
1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride (188 mg,
2.40 mmol), triethylamine (506 mg, 5.00 mmol) and
benzylamine (321 mg, 3.00 mmol). The crude product was
purified by column chromatography (n-hexane/EtOAc 3:1, Rf =
0.19) to obtain 406 mg (1.21 mmol) of a colorless solid (yield:
60%).
Furthermore, the environmentally benign multicomponent
reaction was demonstrated to be easily and productively
scalable for gram-scale synthesis and to be a potentially vital
tool for carbon dioxide applications in polymer chemistry.
MP: 117–118 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
298.6 K), major conformer (a double signal set is observed due
to E/Z-isomers, ratio 87:13): δ 1.34 (s, 3 H), 1.58 (s, 3 H), 1.80
(s, 3 H), 1.93 (s, 3 H), 2.21 (s, 3 H), 4.35 (dd, J = 14.8 Hz, J = 5.8
Hz, 1 H), 4.42 (dd, J = 14.8 Hz, J = 6.1 Hz, 1 H), 5.27–5.33 (m, 1
H), 6.37 (s, 1 H), 7.25–7.30 (m, 3 H), 7.31–7.36 (m, 2 H) ppm;
13C NMR (125.8 MHz, CDCl3, 298.5 K), major conformer: δ 23.1,
25.3, 30.65, 30.72, 32.0, 45.2, 52.6, 73.3, 93.8, 127.6, 127.8,
128.9, 138.0, 155.5, 170.2 ppm; IR (ATR): ṽ 3257, 3042, 2995,
2924, 1715, 1646, 1504, 1431, 1401, 1322, 1270, 1226, 1124,
982, 957, 888, 733, 699 cm-1; HRMS (ESI TOF) m/z: calcd for
C17H24N2NaO3S [M + Na]+ 359.1405, found 359.1414.
Experimental
General considerations
Synthetic procedures, performed under argon atmosphere,
were performed on a vacuum line using standard Schlenk
techniques. Preparative column chromatography was carried
out using Grace SiO2 (0.035–0.070 mm, type KG 60), EtOAc and
n-hexane. EtOAc and n-hexane were distilled prior to use. TLC
was performed with Machery-Nagel SiO2 F254 plates on
aluminum sheets. Melting points were obtained on a melting
1
point apparatus (Laboratory Devices) and are uncorrected. H
and 13C NMR spectra were recorded on a Bruker AMX R 500
(measuring frequency: 1H NMR = 500.1 MHz, 13C NMR =
(RS)-3-Chloroacetyl-4-(4-methoxybenzyl)carbamoyloxy-
2,2,5,5-tetramethyl-1,3-thiazolidine (2b): The carbamate 2b
was prepared according to the general procedure using
2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00
mmol), chloroacetyl chloride (271 mg, 2.40 mmol),
1
125.8 MHz), a Bruker Avance III 500 (measuring frequency: H
NMR = 499.9 MHz, 13C NMR = 125.7 MHz) or a Bruker Avance
III HD 500 (measuring frequency: 1H NMR = 500.5 MHz, 13C
NMR = 125.9 MHz) spectrometer in CDCl3 solution. Chemical
shifts are referenced to the residual peaks of the solvent [7.26
ppm (1H NMR), 77.16 ppm (13C NMR)].24 Mass spectra were
obtained with Waters Q-TOF Premier (ESI) and Thermo
Scientific DFS (EI) spectrometers. IR spectra were recorded on
a Bruker Tensor 27 spectrometer fitted with a “Golden Gate”
diamond-ATR (attenuated total reflection) unit. Thiazolines25,
oxazolines25 and acyl chlorides26 were prepared according to
published procedures.
triethylamine
(506
mg,
5.00
mmol)
and
4-
methoxybenzylamine (412 mg, 3.00 mmol). The crude product
was purified by column chromatography (n-hexane/EtOAc 4:1,
Rf = 0.38) to obtain 518 mg (1.29 mmol) of a colorless solid
(yield: 65%).
MP: 113–114 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
299.1 K), major conformer (a double signal set is observed due
to E/Z-isomers, ratio 88:12): δ 1.35 (s, 3 H), 1.59 (s, 3 H), 1.79
(s, 3 H), 1.92 (s, 3 H), 3.79 (s, 3 H), 4.03 (d, J = 12.9 Hz, 1 H),
4.27 (dd, J = 14.6 Hz, J = 5.6 Hz, 1 H), 4.35 (dd, J = 14.6 Hz, J =
6.1 Hz, 1 H), 4.45 (d, J = 12.9 Hz, 1 H), 5.24–5.30 (m, 1 H), 6.45
(s, 1 H), 6.84–6.88 (m, 2 H), 7.16–7.20 (m, 2 H) ppm; 13C NMR
(125.8 MHz, CDCl3, 299.2 K), major conformer: δ 23.0, 30.6,
30.7, 31.3, 43.8, 44.8, 53.1, 55.4, 73.8, 92.1, 114.3, 129.0,
129.9, 155.3, 159.3, 166.1 ppm; IR (ATR): ṽ 3348, 2987, 2927,
2837, 1703, 1668, 1538, 1513, 1398, 1262, 1220, 1119, 984,
940, 892, 799, 689, 594 cm-1; HRMS (ESI TOF) m/z: calcd for
C18H25ClN2NaO4S [M + Na]+ 423.1121, found 423.1124.
General procedure for synthesis of thia- and oxazolidin-4-yl
carbamates 2
Step a): The respective imine (1.0 eq), dissolved in anhydrous
EtOAc (4 mL per mmol imine), was cooled to 0 °C, treated
portionwise with acyl chloride (1.2 eq) and stirred for 3 h at
r.t..
Step b): Meanwhile a three-necked flask, equipped with
dimroth condenser, football bladder (= balloon, for rotary
evaporators) and rubber septum, was purged with carbon
dioxide, before anhydrous EtOAc (20 mL per mmol imine),
anhydrous triethylamine (2.5 eq) and the respective amine
(1.5 eq) were added. After purging with carbon dioxide via
cannula (through solution), the mixture was stirred for 10 min
at r.t. under carbon dioxide atmosphere at ambient pressure.
To the solution of b) the hitherto prepared solution of a) was
added dropwise via syringe within 10 min and the reaction
(RS)-4-(2-Bromobenzyl)carbamoyloxy-3-methoxyacetyl-
2,2,5,5-tetramethyl-1,3-thiazolidine (2c): The carbamate 2c
was prepared according to the general procedure using
2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00
mmol), methoxyacetyl chloride (260 mg, 2.40 mmol),
triethylamine (506 mg, 5.00 mmol) and 2-bromobenzylamine
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(558 mg, 3.00 mmol). The crude product was purified by 1226, 1120, 980, 927, 713, 619 cm-1; HRMS (ESI TOF) m/z:
column chromatography (n-hexane/EtOAc 3:1, Rf = 0.26) to calcd for C15H23N2O4S [M + H]+ 327.1379, found 327.1383.
obtain 524 mg (1.18 mmol) of a colorless solid (yield: 59%).
MP: 153–154 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3, tetramethyl-1,3-thiazolidine (2f)
(RS)-3-Acetyl-4-(thiophen-2-ylmethyl)carbamoyloxy-2,2,5,5-
The carbamate 2f was
:
300.3 K), major conformer (a double signal set is observed due prepared according to the general procedure using 2,2,5,5-
to E/Z-isomers, ratio 88:12): δ 1.33 (s, 3 H), 1.53 (s, 3 H), 1.82 tetramethyl-2,5-dihydro-1,3-thiazole (143 mg, 1.00 mmol),
(s, 3 H), 1.93 (s, 3 H), 3.38 (s, 3 H), 3.91 (d, J = 13.9 Hz, 1 H), acetyl chloride (94 mg, 1.20 mmol), triethylamine (253 mg,
4.23 (d, J = 13.9 Hz, 1 H), 4.41–4.49 (m, 2 H), 5.36–5.39 (m, 1 2.50 mmol) and 2-thiophenemethylamine (170 mg, 1.50
H), 6.49 (s, 1 H), 7.15 (td, J = 7.7 Hz, J = 1.6 Hz, 1 H), 7.28 (td, J mmol). The crude product was purified by column
= 7.6 Hz, J = 1.3 Hz, 1 H), 7.34 (dd, J = 7.6 Hz, J = 1.4 Hz, 1 H), chromatography (n-hexane/EtOAc 3:1, Rf = 0.40) to obtain 206
7.53–7.56 (m, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 300.1 K), mg (0.60 mmol) of a colorless solid (yield: 60%).
major conformer: δ 23.0, 30.6, 30.8, 31.6, 45.5, 53.3, 59.2, MP: 129–131 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
73.2, 73.8, 91.4, 123.7, 127.8, 129.6, 130.0, 133.1, 137.0, 300.3 K), major conformer (a double signal set is observed due
155.3, 169.0 ppm; IR (ATR): ṽ 3335, 2992, 2928, 1706, 1671, to E/Z-isomers, ratio 87:13): δ 1.34 (s, 3 H), 1.58 (s, 3 H), 1.79
1541, 1301, 1263, 1222, 1112, 983, 931, 887, 741 cm-1; HRMS (s, 3 H), 1.93 (s, 3 H), 2.20 (s, 3 H), 4.53 (dd, J = 15.4 Hz, J = 5.9
(ESI TOF) m/z: calcd for C18H25BrN2NaO4S [M + Na]+ 467.0616, Hz, 1 H), 4.58 (dd, J = 15.4 Hz, J = 6.2 Hz, 1 H), 5.32–5.38 (m, 1
found 467.0627.
H), 6.37 (s, 1 H), 6.92–6.97 (m, 2 H), 7.23 (dd, J = 4.9 Hz, J = 1.4
Hz, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 300.3 K), major
(RS)-3-Acetyl-4-(pyridin-2-ylmethyl)carbamoyloxy-2,2,5,5-
tetramethyl-1,3-thiazolidine (2d): The carbamate 2d was conformer: δ 23.1, 25.3, 30.66, 30.73, 32.0, 40.0, 52.5, 73.3,
prepared according to the general procedure using 2,2,5,5- 93.9, 125.5, 126.0, 127.0, 140.9, 155.2, 170.3 ppm; IR (ATR): ṽ
tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), 3240, 2991, 2926, 1713, 1644, 1543, 1397, 1277, 1226, 1118,
acetyl chloride (188 mg, 2.40 mmol), triethylamine (506 mg, 978, 953, 927, 782, 703, 620 cm-1; HRMS (ESI TOF) m/z: calcd
5.00 mmol) and 2-picolylamine (324 mg, 3.00 mmol). The for C15H22N2NaO3S2 [M + Na]+ 365.0970, found 365.0961.
crude product was purified by column chromatography (n- (RS)-3-Acetyl-4-allylcarbamoyloxy-2,2,5,5-tetramethyl-1,3-
hexane/EtOAc 3:1, Rf = 0.37) to obtain 223 mg (0.66 mmol) of thiazolidine (2g): The carbamate 2g was prepared according to
a colorless solid (yield: 33%).
the general procedure using 2,2,5,5-tetramethyl-2,5-dihydro-
MP: 120–121 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3, 1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride (188 mg,
300.4 K), major conformer (a double signal set is observed due 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and allylamine
to E/Z-isomers, ratio 87:13): δ 1.32 (s, 3 H), 1.55 (s, 3 H), 1.79 (171 mg, 3.00 mmol). The crude product was purified by
(s, 3 H), 1.91 (s, 3 H), 2.18 (s, 3 H), 4.47–4.50 (m, 2 H), 6.21– column chromatography (n-hexane/EtOAc 3:1, Rf = 0.27) to
6.26 (m, 1 H), 6.35 (s, 1 H), 7.16–7.20 (m, 1 H), 7.21–7.25 (m, 1 obtain 360 mg (1.26 mmol) of a colorless solid (yield: 63%).
1
H), 7.64 (td, J = 7.8 Hz, J = 1.8 Hz, 1 H), 8.51–8.54 (m, 1 H) ppm; MP: 84–85 °C (EtOAc/n-hexane); H NMR (500.1 MHz, CDCl3,
13C NMR (125.8 MHz, CDCl3, 300.3 K), major conformer: δ 23.0, 298.8 K), major conformer (a double signal set is observed due
25.3, 30.6, 30.8, 32.1, 46.0, 52.5, 73.3, 93.7, 121.7, 122.6, to E/Z-isomers, ratio 87:13): δ 1.32 (s, 3 H), 1.56 (s, 3 H), 1.80
136.9, 149.3, 155.6, 156.4, 170.3 ppm; IR (ATR): ṽ 3420, 2986, (s, 3 H), 1.92 (s, 3 H), 2.19 (s, 3 H), 3.77–3.85 (m, 2 H), 5.04–
2971, 2932, 1698, 1673, 1504, 1372, 1303, 1230, 1212, 1132, 5.09 (m, 1 H), 5.12–5.22 (m, 2 H), 5.78–5.86 (m, 1 H), 6.33 (s, 1
938, 923, 753, 610 cm-1; HRMS (ESI TOF) m/z: calcd for H) ppm; 13C NMR (125.8 MHz, CDCl3, 298.6 K), major
C16H24N3O3S [M + H]+ 338.1538, found 338.1529.
conformer: δ 23.0, 25.3, 30.66, 30.71, 32.0, 43.5, 52.6, 73.3,
93.6, 116.5, 134.0, 155.3, 170.3 ppm; IR (ATR): ṽ 3329, 2990,
(RS)-3-Acetyl-4-furfurylcarbamoyloxy-2,2,5,5-tetramethyl-
1,3-thiazolidine (2e): The carbamate 2e was prepared 2938, 2868, 1692, 1670, 1522, 1390, 1381, 1273, 1229, 1109,
according to the general procedure using 2,2,5,5-tetramethyl- 975, 937, 917, 777 cm-1; HRMS (ESI TOF) m/z: calcd for
2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride C13H22N2NaO3S [M + Na]+ 309.1249, found 309.1242.
(188 mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and (RS)-3-(4-Methoxyphenyl)acetyl-4-(2-
furfurylamine (291 mg, 3.00 mmol). The crude product was methylallyl)carbamoyloxy-2,2,5,5-tetramethyl-1,3-
purified by column chromatography (n-hexane/EtOAc 3:1, Rf = thiazolidine (2h): The carbamate 2h was prepared according
0.16) to obtain 344 mg (1.05 mmol) of a colorless solid (yield: to the general procedure using 2,2,5,5-tetramethyl-2,5-
53%).
dihydro-1,3-thiazole
(286
mg,
2.00
mmol),
4-
MP: 125–127 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3, methoxyphenylacetyl chloride (443 mg, 2.40 mmol),
298.6 K), major conformer (a double signal set is observed due triethylamine (506 mg, 5.00 mmol) and 2-methylallylamine
to E/Z-isomers, ratio 86:14): δ 1.30 (s, 3 H), 1.55 (s, 3 H), 1.78 (213 mg, 3.00 mmol). The crude product was purified by
(s, 3 H), 1.91 (s, 3 H), 2.18 (s, 3 H), 4.31–4.40 (m, 2 H), 5.33– column chromatography (n-hexane/EtOAc 3:1, Rf = 0.33) to
5.39 (m, 1 H), 6.19–6.21 (m, 1 H), 6.28–6.31 (m, 1 H), 6.34 (s, 1 obtain 672 mg (1.65 mmol) of a colorless solid (yield: 83%).
H), 7.31–7.34 (m, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 298.5 MP: 87–88 °C (EtOAc/n-hexane); H NMR (500.1 MHz, CDCl3,
1
K), major conformer: δ 23.0, 25.2, 30.6, 30.7, 32.0, 38.2, 52.5, 300.3 K), major conformer (a double signal set is observed due
73.3, 93.8, 107.5, 110.5, 142.5, 151.1, 155.3, 170.2 ppm; IR to E/Z-isomers, ratio 87:13): δ 1.05 (s, 3 H), 1.26 (s, 3 H), 1.76
(ATR): ṽ 3266, 2981, 2931, 1712, 1645, 1538, 1399, 1357, (s, 3 H), 1.85 (s, 3 H), 1.90 (s, 3 H), 3.63 (d, J = 15.0 Hz, 1 H),
3.71 (dd, J = 15.9 Hz, J = 5.6 Hz, 1 H), 3.78 (s, 3 H), 3.79–3.87
8 | J. Name., 2012, 00, 1-3
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(m, 2 H), 4.86–4.90 (m, 2 H), 5.11–5.15 (m, 1 H), 6.45 (s, 1 H), Rf = 0.25) to obtain 814 mg (1.56 mmol) of a colorless oil (yield:
6.85–6.87 (m, 2 H), 7.23–7.28 (m, 2 H) ppm; 13C NMR (125.8 78%).
MHz, CDCl3, 299.5 K), major conformer: δ 20.2, 22.9, 29.9, 1H NMR (500.1 MHz, CDCl3, 299.5 K), major conformer (a
30.8, 31.5, 43.4, 46.7, 52.6, 55.4, 73.3, 92.6, 111.1, 114.3, double signal set is observed due to E/Z-isomers, ratio 89:11):
126.8, 129.9, 141.8, 155.6, 158.7, 171.3 ppm; IR (ATR): ṽ 3314, δ 0.99–1.12 (m, 2 H), 1.14–1.20 (m, 2 H), 1.22–1.39 (m, 4 H),
2985, 2934, 1719, 1656, 1510, 1450, 1370, 1246, 1219, 1169, 1.47–1.52 (m, 2 H), 1.53–1.59 (m, 4 H), 1.66–1.70 (m, 1 H),
1013, 979, 821, 731 cm-1; HRMS (ESI TOF) m/z: calcd for 1.72–1.78 (m, 2 H), 1.83–1.91 (m, 1 H), 2.77–2.84 (m, 1 H),
C21H30N2NaO4S [M + Na]+ 429.1824, found 429.1815.
3.07–3.13 (m, 1 H), 3.29–3.36 (m, 2 H), 3.37–3.40 (m, 6 H),
(RS)-3-Chloroacetyl-4-(4-methoxyphenyl)carbamoyloxy-
3.63 (d, J = 15.1 Hz, 1 H), 3.77 (s, 3 H), 3.83 (d, J = 15.1 Hz, 1 H),
2,2,5,5-tetramethyl-1,3-thiazolidine (2i): The carbamate 2i 4.36–4.40 (m, 1 H), 5.05–5.09 (m, 1 H), 6.48 (s, 1 H), 6.83–6.86
was prepared according to the general procedure using (m, 2 H), 7.21–7.24 (m, 2 H) ppm; 13C NMR (125.8 MHz, CDCl3,
2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 299.0 K), major conformer: δ 21.9, 24.1, 24.5, 25.1, 25.4, 25.7,
mmol), chloroacetyl chloride (271 mg, 2.40 mmol), 32.6, 36.8, 37.2, 38.1, 42.6, 43.9, 54.4, 54.5, 55.4, 57.9, 80.0,
triethylamine (506 mg, 5.00 mmol) and 4-methoxyaniline (369 92.3, 102.6, 114.2, 127.0, 129.9, 155.8, 158.7, 171.8 ppm; IR
mg, 3.00 mmol). The crude product was purified by column (ATR): ṽ 3343, 2931, 1717, 1658, 1511, 1449, 1376, 1246,
chromatography (n-hexane/EtOAc 7:2, Rf = 0.50) to obtain 487 1126, 1066, 906, 729 cm-1; HRMS (ESI TOF) m/z: calcd for
mg (1.26 mmol) of a colorless solid (yield: 63%).
C27H40N2NaO6S [M + Na]+ 543.2505, found 543.2509.
MP: 118–119 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3, (RS)-3-Benzoyl-4-(2-methoxyethyl)carbamoyloxy-2,2-
298.0 K): δ 1.41 (s, 3 H), 1.62 (s, 3 H), 1.87 (s, 3 H), 1.96 (s, 3 H), dimethyl-1-thia-3-azaspiro[4.5]decane (2l): The carbamate 2l
3.79 (s, 3 H), 4.04 (d, J = 12.8 Hz, 1 H), 4.49 (d, J = 12.8 Hz, 1 H), was prepared according to the general procedure using 2,2-
6.53 (s, 1 H), 6.78 (s, 1 H), 6.85–6.89 (m, 2 H), 7.28–7.33 (m, 2 dimethyl-1-thia-3-azaspiro[4.5]dec-3-ene (367 mg, 2.00 mmol),
H) ppm; 13C NMR (125.8 MHz, CDCl3, 298.2 K): δ 23.1, 30.7, benzoyl chloride (337 mg, 2.40 mmol), triethylamine (506 mg,
30.8, 31.3, 43.8, 53.1, 55.7, 73.9, 92.1, 114.5, 121.2, 130.0, 5.00 mmol) and 2-methoxylethylamine (321 mg, 3.00 mmol).
152.8, 156.7, 166.1 ppm; IR (ATR): ṽ 3342, 2996, 2935, 1702, The crude product was purified by column chromatography (n-
1677, 1539, 1512, 1398, 1245, 1206, 1169, 1019, 984, 829, 739 hexane/EtOAc 3:1, Rf = 0.10) to obtain 277 mg (0.68 mmol) of
cm-1; HRMS (ESI TOF) m/z: calcd for C17H23ClN2NaO4S [M + Na]+ a colorless solid (yield: 34%).
409.0965, found 409.0966.
MP: 109–110 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
(RS)-3-Acetyl-4-(2,2-dimethoxyethyl)carbamoyloxy-2,2,5,5-
299.2 K), major conformer (a double signal set is observed due
tetramethyl-1,3-thiazolidine (2j): The carbamate 2j was to E/Z-isomers, ratio 88:12): δ 1.10–1.19 (m, 2 H), 1.52–1.62
prepared according to the general procedure using 2,2,5,5- (m, 3 H), 1.64–1.75 (m, 3 H), 1.78–1.87 (m, 1 H), 1.97–2.02 (m,
tetramethyl-2,5-dihydro-1,3-thiazole (1.432 g, 10.00 mmol), 7 H), 3.16–3.23 (m, 2 H), 3.34 (s, 3 H), 3.35–3.39 (m, 2 H),
acetyl chloride (0.942 g, 12.00 mmol), triethylamine (2.530 g, 5.04–5.10 (m, 1 H), 6.29 (s, 1 H), 7.32–7.35 (m, 2 H), 7.36–7.44
25.00 mmol) and 2,2-dimethoxyethylamine (1.577 g, 15.00 (m, 3 H) ppm; 13C NMR (125.8 MHz, CDCl3, 299.1 K), major
mmol). The crude product was purified by recrystallization conformer: δ 22.2, 24.2, 25.4, 31.3, 32.0, 32.7, 38.0, 40.8, 58.9,
(EtOAc/n-hexane) to obtain 2.793 g (8.35 mmol) of a colorless 59.3, 71.2, 72.0, 94.1, 126.2, 128.6, 130.0, 137.8, 154.4, 171.4
solid (yield: 84%).
ppm; IR (ATR): ṽ 3255, 3061, 2979, 2932, 2860, 1721, 1646,
1
MP: 81–83 °C (EtOAc/n-hexane); H NMR (499.9 MHz, CDCl3, 1528, 1449, 1390, 1368, 1332, 1250, 1219, 1128, 1013, 999,
305.0 K), major conformer (a double signal set is observed due 973, 870, 735, 703 cm-1; HRMS (EI, 70 eV) m/z: calcd for
to E/Z-isomers, ratio 90:10): δ 1.31 (s, 3 H), 1.55 (s, 3 H), 1.80 C21H30N2O4S [M]+ 406.1921, found 406.1929.
(s, 3 H), 1.91 (s, 3 H), 2.17 (s, 3 H), 3.28–3.33 (m, 2 H), 3.36 (s, 6 (RS)-Methyl
(((3-benzoyl-2,2,5,5-tetramethylthiazolidin-4-
The carbamate 2m was
H), 4.34–4.37 (m, 1 H), 5.08–5.14 (m, 1 H), 6.31 (s, 1 H) ppm; yl)oxy)carbonyl)glycinate (2m)
:
13C NMR (125.7 MHz, CDCl3, 305.0 K), major conformer: δ 23.0, prepared according to the general procedure using 2,2,5,5-
25.2, 30.66, 30.73, 32.0, 42.6, 52.5, 54.4, 54.5, 73.3, 93.8, tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol),
102.7, 155.6, 170.2 ppm; IR (ATR): ṽ 3330, 2994, 2941, 2903, benzoyl chloride (337 mg, 2.40 mmol), triethylamine (810 mg,
2837, 1718, 1658, 1547, 1444, 1396, 1257, 1222, 1114, 981, 8.00 mmol) and methyl glycinate hydrochloride (377 mg, 3.00
948, 828, 781, 628 cm-1; HRMS (ESI TOF) m/z: calcd for mmol). The crude product was purified by column
C14H26LiN2O5S [M + Li]+ 341.1722, found 341.1713.
(RS)-15-(2,2-Dimethoxyethyl)carbamoyloxy-14-(4-
methoxyphenyl)acetyl-7-thia-14-
chromatography (n-hexane/EtOAc 7:3, Rf = 0.19) to obtain 219
mg (0.58 mmol) of a colorless oil (yield: 29%).
1H NMR (500.1 MHz, CDCl3, 299.0 K), major conformer (a
azadispiro[5.1.58.26]pentadecane (2k): The carbamate 2k was double signal set is observed due to E/Z-isomers, ratio 87:13):
prepared according to the general procedure using 7-thia-14- δ 1.26 (s, 3 H), 1.63 (s, 3 H), 1.99 (s, 3 H), 2.06 (s, 3 H), 3.74 (s, 3
azadispiro[5.1.58.26]pentadec-14-ene (447 mg, 2.00 mmol), 4- H), 3.80–3.83 (m, 2 H), 5.25–5.29 (m, 1 H), 6.18 (s, 1 H), 7.32–
methoxyphenylacetyl chloride (443 mg, 2.40 mmol), 7.42 (m, 5 H) ppm; 13C NMR (125.8 MHz, CDCl3, 299.3 K), major
triethylamine
(506
mg,
5.00
mmol)
and
2,2- conformer: δ 23.0, 31.0, 31.1, 31.8, 42.5, 52.5, 52.9, 73.0, 94.7,
dimethoxyethylamine (315 mg, 3.00 mmol). The crude product 126.0, 128.7, 129.9, 137.7, 154.4, 170.2, 171.1 ppm; IR (ATR): ṽ
was purified by column chromatography (n-hexane/EtOAc 3:1, 3304, 3046, 2982, 2937, 2877, 1730, 1651, 1516, 1445, 1363,
1274, 1204, 1155, 1014, 995, 911, 856, 731, 700, 625 cm-1;
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HRMS (EI, 70 eV) m/z: calcd for C18H24N2O5S [M]+ 380.1400, H) ppm; 13C NMR (125.7 MHz, CDCl3, 305.0 K), major
found 380.1389. conformer: δ 22.9, 25.2, 28.9, 30.6, 30.7, 32.1, 50.8, 52.6, 73.2,
(RS)-3-Acetyl-4-n-butylcarbamoyloxy-2,2,5,5-tetramethyl-1,3- 92.9, 153.6, 170.2 ppm; IR (ATR): ṽ 3254, 2972, 2932, 1728,
thiazolidine (2n): The carbamate 2n was prepared according 1716, 1651, 1542, 1393, 1360, 1213, 1053, 942, 776, 688, 622
to the general procedure using 2,2,5,5-tetramethyl-2,5- cm-1; HRMS (ESI TOF) m/z: calcd for C14H27N2O3S [M + H]+
dihydro-1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride (188 303.1742, found 303.1740.
mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and n- (RS)-3-Acetyl-4-benzylmethylcarbamoyloxy-2,2,5,5-
butylamine (216 mg, 3.00 mmol). The crude product was tetramethyl-1,3-thiazolidine (2q): The carbamate 2q was
purified by column chromatography (n-hexane/EtOAc 3:1, Rf = prepared according to the general procedure using 2,2,5,5-
0.43) to obtain 411 mg (1.36 mmol) of a colorless solid (yield: tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol),
68%).
acetyl chloride (188 mg, 2.40 mmol), triethylamine (506 mg,
1
MP: 71–72 °C (EtOAc/n-hexane); H NMR (500.1 MHz, CDCl3, 5.00 mmol) and N-benzylmethylamine (364 mg, 3.00 mmol).
298.8 K), major conformer (a double signal set is observed due The crude product was purified by column chromatography (n-
to E/Z-isomers, ratio 87:13): δ 0.90–0.94 (m, 3 H), 1.33 (s, 3 H), hexane/EtOAc 3:1, Rf = 0.37) to obtain 635 mg (1.81 mmol) of
1.34–1.38 (m, 2 H), 1.46–1.52 (m, 2 H), 1.57 (s, 3 H), 1.81 (s, 3 a colorless solid (yield: 91%).
H), 1.93 (s, 3 H), 2.20 (s, 3 H), 3.14–3.26 (m, 2 H), 4.84–4.90 (m, MP: 105–106 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
1 H), 6.33 (s, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 298.7 K), 298.7 K), major conformer (a double signal set is observed due
major conformer: δ 13.8, 20.0, 23.0, 25.3, 30.69, 30.73, 32.0, to E/Z-isomers, ratio 56:44): δ 1.33 (s, 3 H), 1.59 (s, 3 H), 1.82
32.0, 40.9, 52.6, 73.3, 93.5, 155.4, 170.3 ppm; IR (ATR): ṽ 3319, (s, 3 H), 1.95 (s, 3 H), 2.22 (s, 3 H), 2.89 (s, 3 H), 4.41–4.46 (m, 1
2961, 2931, 2873, 1706, 1650, 1534, 1441, 1397, 1357, 1378, H), 4.52–4.59 (m, 1 H), 6.43 (s, 1 H), 7.20–7.24 (m, 2 H), 7.25–
1219, 1127, 982, 620 cm-1; HRMS (ESI TOF) m/z: calcd for 7.29 (m, 1 H), 7.30–7.34 (m, 2 H) ppm; minor conformer: δ
C14H27N2O3S [M + H]+ 303.1742, found 303.1747.
1.29 (s, 3 H), 1.57 (s, 3 H), 1.72 (s, 3 H), 1.92 (s, 3 H), 2.21 (s, 3
H), 2.93 (s, 3 H), 4.41–4.46 (m, 1 H), 4.52–4.59 (m, 1 H), 6.42 (s,
(RS)-3-Acetyl-4-isopropylcarbamoyloxy-2,2,5,5-tetramethyl-
1,3-thiazolidine (2o): The carbamate 2o was prepared 1 H), 7.20–7.24 (m, 2 H), 7.25–7.29 (m, 1 H), 7.30–7.34 (m, 2 H)
according to the general procedure using 2,2,5,5-tetramethyl- ppm; 13C NMR (125.8 MHz, CDCl3, 298.8 K), major conformer:
2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride δ 23.3, 25.4, 30.6, 30.7, 32.0, 33.7, 52.5, 52.6, 73.2, 94.3,
(188 mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and 127.7, 127.8, 128.8, 137.1, 155.7, 170.3 ppm; minor
isopropylamine (177 mg, 3.00 mmol). The crude product was conformer: 23.2, 25.3, 30.5, 30.7, 32.0, 34.6, 52.5, 52.6, 73.2,
purified by column chromatography (n-hexane/EtOAc 3:1, Rf = 94.4, 127.5, 127.7, 128.9, 136.8, 155.1, 170.1 ppm; IR (ATR): ṽ
0.24) to obtain 396 mg (1.37 mmol) of a colorless solid (yield: 2992, 2925, 2866, 1700, 1672, 1446, 1390, 1310, 1192, 1122,
69%). After scale-up (factor 10; 20 mmol) the crude product 979, 929, 757, 710 cm-1; HRMS (ESI TOF) m/z: calcd for
was purified by recrystallization (EtOAc/n-hexane) to obtain C18H26N2NaO3S [M + Na]+ 373.1562, found 373.1575.
5.47 g (18.97 mmol) of a colorless solid (yield: 95%).
MP: 125–126 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3, tetramethyl-1,3-oxazolidine (2r)
(RS)-3-Acetyl-4-benzylmethylcarbamoyloxy-2,2,5,5-
The carbamate 2r was
:
298.5 K), major conformer (a double signal set is observed due prepared according to the general procedure using 2,2,5,5-
to E/Z-isomers, ratio 86:14): δ 1.12–1.16 (m, 6 H), 1.29 (s, 3 H), tetramethyl-2,5-dihydro-1,3-oxazole (254 mg, 2.00 mmol),
1.54 (s, 3 H), 1.78 (s, 3 H), 1.90 (s, 3 H), 2.16 (s, 3 H), 3.74–3.83 acetyl chloride (188 mg, 2.40 mmol), triethylamine (506 mg,
(m, 1 H), 4.81 (d, J = 7.7 Hz, 1 H), 6.29 (s, 1 H) ppm; 13C NMR 5.00 mmol) and N-benzylmethylamine (364 mg, 3.00 mmol).
(125.8 MHz, CDCl3, 298.4 K), major conformer: δ 22.87, 22.87, The crude product was purified by column chromatography (n-
22.92, 25.3, 30.6, 30.7, 32.0, 43.3, 52.6, 73.2, 93.3, 154.5, hexane/EtOAc 3:1, Rf = 0.19) to obtain 420 mg (1.26 mmol) of
170.2 ppm; IR (ATR): ṽ 3279, 2973, 2933, 2874, 1712, 1651, a colorless solid (yield: 63%).
1
1539, 1399, 1362, 1220, 1059, 1040, 684, 624 cm-1; HRMS (ESI MP: 76–77 °C (EtOAc/n-hexane); H NMR (500.1 MHz, CDCl3,
TOF) m/z: calcd for C13H24N2NaO3S [M + Na]+ 311.1405, found 299.2 K), major conformer (a double signal set is observed due
311.1405.
to E/Z-isomers, ratio 55:45): δ 1.30 (s, 3 H), 1.39 (s, 3 H), 1.58
(s, 3 H), 1.67 (s, 3 H), 2.15 (s, 3 H), 2.85 (s, 3 H), 4.45 (d, J = 15.1
(RS)-3-Acetyl-4-tert-butylcarbamoyloxy-2,2,5,5-tetramethyl-
1,3-thiazolidine (2p): The carbamate 2p was prepared Hz, 1 H), 4.51–4.55 (m, 1 H), 6.26 (s, 1 H), 7.19–7.22 (m, 2 H),
according to the general procedure using 2,2,5,5-tetramethyl- 7.25–7.29 (m, 1 H), 7.30–7.34 (m, 2 H) ppm; minor conformer:
2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride δ 1.25 (s, 3 H), 1.37 (s, 3 H), 1.52 (s, 3 H), 1.65 (s, 3 H), 2.06 (s, 3
(188 mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and H), 2.96 (s, 3 H), 4.38 (d, J = 15.6 Hz, 1 H), 4.51–4.55 (m, 1 H),
tert-butylamine (219 mg, 3.00 mmol). The crude product was 6.22 (s, 1 H), 7.16–7.18 (m, 2 H), 7.25–7.29 (m, 1 H), 7.30–7.34
purified by column chromatography (n-hexane/EtOAc 3:1, Rf = (m, 2 H) ppm; 13C NMR (125.8 MHz, CDCl3, 299.1 K), major
0.57) to obtain 229 mg (0.76 mmol) of a colorless solid (yield: conformer: δ 22.9, 23.8, 27.0, 27.7, 27.8, 33.7, 52.6, 81.8, 88.6,
38%).
96.0, 127.67, 127.74, 128.8, 137.0, 155.6, 169.2 ppm; minor
MP: 137–138 °C (EtOAc/n-hexane); 1H NMR (499.9 MHz, CDCl3, conformer: 22.9, 23.7, 27.1, 27.7, 27.8, 34.9, 52.5, 81.8, 88.7,
304.7 K), major conformer (a double signal set is observed due 95.9, 127.2, 127.8, 128.9, 136.9, 155.1, 169.1 ppm; IR (ATR): ṽ
to E/Z-isomers, ratio 91:9): δ 1.30–1.32 (m, 12 H), 1.55 (s, 3 H), 2980, 2941, 1699, 1670, 1397, 1314, 1259, 1207, 1129, 1002,
1.80 (s, 3 H), 1.91 (s, 3 H), 2.16 (s, 3 H), 4.83 (s, 1 H), 6.27 (s, 1
10 | J. Name., 2012, 00, 1-3
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1
978, 939, 900, 765, 711, 623 cm-1; HRMS (ESI TOF) m/z: calcd MP: 49–50 °C (EtOAc/n-hexane); H NMR (500.1 MHz, CDCl3,
for C18H26N2NaO4 [M + Na]+ 357.1790, found 357.1788.
298.9 K): δ 0.82–0.89 (m, 12 H), 1.29 (s, 3 H), 1.56 (s, 3 H), 1.81
(RS)-4-Diallylcarbamoyloxy-5,5-dimethyl-3-palmitoyl-1,3-
(s, 3 H), 1.93 (s, 3 H), 1.94–2.02 (m, 2 H), 2.14 (s, 3 H), 2.92–
thiazolidine (2s): The carbamate 2s was prepared according to 2.99 (m, 2 H), 3.16–3.25 (m, 2 H), 6.36 (s, 1 H) ppm; 13C NMR
the general procedure using 5,5-dimethyl-2,5-dihydro-1,3- (125.8 MHz, CDCl3, 298.8 K): δ 19.9, 20.0, 20.1, 20.3, 23.2,
thiazole (230 mg, 2.00 mmol), palmitoyl chloride (660 mg, 2.40 25.2, 27.0, 27.5, 30.4, 30.7, 32.1, 52.6, 54.7, 55.2, 73.1, 94.1,
mmol), triethylamine (506 mg, 5.00 mmol) and diallylamine 155.6, 170.2 ppm; IR (ATR): ṽ 2960, 2934, 2872, 1687, 1671,
(291 mg, 3.00 mmol). The crude product was purified by 1470, 1424, 1389, 1310, 1230, 1171, 1074, 764 cm-1; HRMS
column chromatography (n-hexane/EtOAc 7:1, Rf = 0.29) to (ESI TOF) m/z: calcd for C18H34N2NaO3S [M + Na]+ 381.2188,
obtain 847 mg (1.71 mmol) of a colorless oil (yield: 86%).
1H NMR (500.5 MHz, CDCl3, 300.0 K), major conformer (a (RS)-3-Acryloyl-4-pyrrolidinocarbonyloxy-2,2,5,5-tetramethyl-
double signal set is observed due to E/Z-isomers, ratio 95:5): δ 1,3-thiazolidine (2v) The carbamate 2v was prepared
found 381.2188.
:
0.85–0.88 (m, 3 H), 1.23–1.30 (m, 24 H), 1.37 (s, 3 H), 1.42 (s, 3 according to the general procedure using 2,2,5,5-tetramethyl-
H), 1.59–1.64 (m, 2 H), 2.38–2.48 (m, 2 H), 3.80–3.91 (m, 4 H), 2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), acryloyl chloride
4.55 (d, J = 9.7 Hz, 1 H), 4.72 (d, J = 9.7 Hz, 1 H), 5.10–5.18 (m, (217 mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and
4 H), 5.70–5.79 (m, 2 H), 6.33 (s, 1 H) ppm; 13C NMR (125.9 pyrrolidine (213 mg, 3.00 mmol). The crude product was
MHz, CDCl3, 300.0 K), major conformer: δ 14.2, 22.6, 22.8, purified by column chromatography (n-hexane/EtOAc 3:2, Rf =
25.3, 28.7, 29.4, 29.5, 29.55, 29.63, 29.75, 29.78, 29.79, 29.80, 0.46) to obtain 304 mg (0.97 mmol) of a colorless oil (yield:
29.81, 29.82, 32.1, 34.8, 47.6, 48.8, 49.3, 55.6, 89.1, 117.49, 49%).
117.49, 133.01, 133.04, 154.8, 173.4 ppm; IR (ATR): ṽ 2922, 1H NMR (500.1 MHz, CDCl3, 300.3 K): δ 1.30 (s, 3 H), 1.55 (s, 3
2853, 1702, 1671, 1460, 1411, 1286, 1244, 1143, 979, 924, H), 1.84 (s, 3 H), 1.84–1.88 (m, 4 H), 1.98 (s, 3 H), 3.29–3.34 (m,
863, 764 cm-1; HRMS (ESI TOF) m/z: calcd for C28H50LiN2O3S [M 1 H), 3.35–3.39 (m, 2 H), 3.40–3.45 (m, 1 H), 5.69 (dd, J = 1.9
+ Li]+ 501.3702, found 501.3712.
Hz, J = 10.4 Hz, 1 H), 6.33 (dd, J = 1.9 Hz, J = 16.5 Hz, 1 H), 6.50
(s, 1 H), 6.69 (dd, J = 10.4 Hz, J = 16.5 Hz, 1 H) ppm; 13C NMR
(RS)-3-Acetyl-4-methylprop-2-yn-1-ylcarbamoyloxy-2,2,5,5-
tetramethyl-1,3-thiazolidine (2t)
: The carbamate 2t was (125.8 MHz, CDCl3, 300.3 K): δ 23.4, 25.0, 25.7, 30.5, 30.7,
prepared according to the general procedure using 2,2,5,5- 32.2, 46.1, 46.3, 52.7, 73.5, 92.3, 129.3, 129.9, 153.5, 165.7
tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), ppm; IR (ATR): ṽ 2975, 2936, 2882, 1700, 1668, 1408, 1360,
acetyl chloride (188 mg, 2.40 mmol), triethylamine (506 mg, 1284, 1225, 1168, 1074, 980, 862, 763 cm-1; HRMS (ESI TOF)
5.00 mmol) and N-methylpropargylamine (207 mg, 3.00 m/z: calcd for C15H24LiN2O3S [M + Li]+ 319.1668, found
mmol). The crude product was purified by column 319.1666.
chromatography (n-hexane/EtOAc 3:1, Rf = 0.22) to obtain 427 (RS)-3-Acetyl-4-(1,2,3,4-tetrahydroisoquinolin-2-
mg (1.43 mmol) of a colorless oil (yield: 72%).
yl)carbonyloxy-2,2,5,5-tetramethyl-1,3-thiazolidine (2w): The
1H NMR (500.1 MHz, CDCl3, 300.0 K), major conformer (a carbamate 2w was prepared according to the general
double signal set is observed due to E/Z-isomers, ratio 53:47): procedure using 2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole
δ 1.29 (s, 3 H), 1.57 (s, 3 H), 1.82 (s, 3 H), 1.94 (s, 3 H), 2.19 (s, 3 (286 mg, 2.00 mmol), acetyl chloride (188 mg, 2.40 mmol),
H), 2.24–2.26 (m, 1 H), 3.02 (s, 3 H), 4.01 (dd, J = 17.8 Hz, J = triethylamine (506 mg, 5.00 mmol) and 1,2,3,4-
1.7 Hz, 1 H), 4.10–4.16 (m, 1 H), 6.36 (s, 1 H) ppm; minor tetrahydroisoquinoline (400 mg, 3.00 mmol). The crude
conformer: δ 1.31 (s, 3 H), 1.57 (s, 3 H), 1.82 (s, 3 H), 1.94 (s, 3 product was purified by column chromatography (n-
H), 2.19 (s, 3 H), 2.24–2.26 (m, 1 H), 3.00 (s, 3 H), 4.10–4.13 (m, hexane/EtOAc 3:1, Rf = 0.11) to obtain 400 mg (1.10 mmol) of
2 H), 6.36 (s, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 299.3 K), a colorless solid (yield: 55%).
major conformer: δ 23.3, 25.4, 30.7, 30.8, 32.0, 33.5, 38.4, MP: 113–114 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
52.5, 72.6, 73.3, 78.2, 94.6, 155.1, 170.3 ppm; minor 298.5 K), major conformer (a double signal set is observed due
conformer: 23.3, 25.4, 30.7, 30.8, 32.1, 34.3, 38.5, 52.5, 72.6, to E/Z-isomers, ratio 55:45): δ 1.31 (s, 3 H), 1.58 (s, 3 H), 1.86
73.3, 78.2, 94.5, 154.7, 170.3 ppm; IR (ATR): ṽ 2979, 2934, (s, 3 H), 1.96 (s, 3 H), 2.22 (s, 3 H), 2.86–2.90 (m, 2 H), 3.67–
1704, 1676, 1451, 1393, 1379, 1225, 1127, 980, 917, 849, 767 3.82 (m, 2 H), 4.60–4.64 (m, 1 H), 4.66–4.73 (m, 1 H), 6.44 (s, 1
cm-1; HRMS (ESI TOF) m/z: calcd for C14H22LiN2NaO3S [M + Li]+ H), 7.10–7.16 (m, 2 H), 7.17–7.22 (m, 1 H) ppm; minor
305.1511, found 305.1500.
conformer: δ 1.28 (s, 3 H), 1.58 (s, 3 H), 1.87 (s, 3 H), 1.96 (s, 3
(RS)-3-Acetyl-4-diisobutylcarbamoyloxy-2,2,5,5-tetramethyl-
H), 2.21 (s, 3 H), 2.86–2.90 (m, 2 H), 3.67–3.82 (m, 2 H), 4.60–
1,3-thiazolidine (2u): The carbamate 2u was prepared 4.64 (m, 1 H), 4.66–4.73 (m, 1 H), 6.44 (s, 1 H), 7.10–7.16 (m, 2
according to the general procedure using 2,2,5,5-tetramethyl- H), 7.17–7.22 (m, 1 H) ppm; 13C NMR (125.8 MHz, CDCl3, 298.7
2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), acetyl chloride K), major conformer: δ 23.4, 25.4, 29.1, 30.7, 30.8, 32.0, 42.0,
(188 mg, 2.40 mmol), triethylamine (506 mg, 5.00 mmol) and 45.9, 52.7, 73.2, 94.1, 126.5, 126.6, 126.8, 128.8, 133.1, 134.3,
diisobutylamine (388 mg, 3.00 mmol). The crude product was 154.3, 170.3 ppm; minor conformer: 23.3, 25.4, 28.8, 30.7,
purified by column chromatography (n-hexane/EtOAc 3:1, Rf = 30.8, 32.0, 41.7, 45.9, 52.7, 73.2, 94.2, 126.4, 126.6, 126.9,
0.56) to obtain 573 mg (1.60 mmol) of a colorless solid (yield: 128.9, 132.6, 134.5, 154.5, 170.3 ppm; IR (ATR): ṽ 3014, 2973,
80%).
2933, 2890, 1693, 1673, 1439, 1388, 1306, 1210, 1084, 975,
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918, 740, 642 cm-1; HRMS (ESI TOF) m/z: calcd for IR (ATR): ṽ 3343, 2987, 2936, 2872, 1714, 1661, 1519, 1468,
C19H26N2NaO3S [M + Na]+ 385.1562, found 385.1571.
1392, 1378, 1259, 1220, 1143, 1011, 979, 944, 915, 771, 730
cm-1; HRMS (ESI TOF) m/z: calcd for C28H46N4NaO6S2 [M + Na]+
(RS)-4-Morpholinocarbonyloxy-3-(4-nitrobenzoyl)-2,2,5,5-
tetramethyl-1,3-thiazolidine (2x)
: The carbamate 2x was 621.2756, found 621.2766.
prepared according to the general procedure using 2,2,5,5-
tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00 mmol), 4-
nitrobenzoyl chloride (445 mg, 2.40 mmol), triethylamine (506
mg, 5.00 mmol) and morpholine (261 mg, 3.00 mmol). The
crude product was purified by column chromatography (n-
hexane/EtOAc 2:1, Rf = 0.42) to obtain 616 mg (1.45 mmol) of
a colorless solid (yield: 73%).
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
MP: 180–181 °C (EtOAc/n-hexane); 1H NMR (500.1 MHz, CDCl3,
299.4 K): δ 1.24 (s, 3 H), 1.65 (s, 3 H), 1.96 (s, 3 H), 2.06 (s, 3 H),
3.25–3.37 (m, 2 H), 3.44–3.55 (m, 2 H), 3.60–3.68 (m, 4 H),
6.10 (s, 1 H), 7.48–7.52 (m, 2 H), 8.24–8.28 (m, 2 H) ppm; 13C
NMR (125.8 MHz, CDCl3, 299.4 K): δ 23.1, 30.9, 31.0, 31.6,
44.0, 44.6, 53.2, 66.6, 66.7, 73.2, 94.4, 124.1, 127.3, 143.3,
148.5, 153.1, 168.8 ppm; IR (ATR): ṽ 2988, 2932, 2858, 1703,
1660, 1520, 1371, 1341, 1219, 1114, 1077, 979, 860, 836, 766
cm-1; HRMS (ESI TOF) m/z: calcd for C19H25N3NaO6S [M + Na]+
446.1362, found 446.1354.
We are thankful to the Central analytic section of the
University of Oldenburg for retrieving NMR and MS data.
Notes and references
1
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107, 2365; (b) D. J. Darensbourg, Inorg. Chem., 2010, 49,
10765.
(a) A. Correa and R. Martín, Angew. Chem. Int. Ed., 2009, 48
2
,
6201; (b) D. Yu, S. P. Teong and Y. Zhang, Coord. Chem. Rev.,
2015, 293–294, 279.
(RS)-3-Acetyl-4-(4-pyrimidin-2-ylpiperazin-1-yl)carbonyloxy-
2,2,5,5-tetramethyl-1,3-thiazolidine (2y): The carbamate 2y
was prepared according to the general procedure using
2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole (286 mg, 2.00
mmol), acetyl chloride (188 mg, 2.40 mmol), triethylamine
(1.113 g, 11.00 mmol) and 1-(2-pyrimidyl)piperazine
dihydrochloride (711 mg, 3.00 mmol). The crude product was
purified by column chromatography (n-hexane/EtOAc 3:7, Rf =
0.35) to obtain 372 mg (0.95 mmol) of a colorless oil (yield:
47%).
1H NMR (500.1 MHz, CDCl3, 300.2 K): δ 1.32 (s, 3 H), 1.59 (s, 3
H), 1.83 (s, 3 H), 1.95 (s, 3 H), 2.23 (s, 3 H), 3.49–3.68 (m, 4 H),
3.73–3.96 (m, 4 H), 6.42 (s, 1 H), 6.53 (t, J = 4.7 Hz, 1 H), 8.32
(d, J = 4.7 Hz, 2 H) ppm; 13C NMR (125.8 MHz, CDCl3, 299.2 K):
δ 23.3, 25.4, 30.7, 30.8, 32.0, 43.66, 43.66, 43.71, 44.1, 52.7,
73.3, 94.3, 110.7, 154.3, 157.9, 161.7, 170.3 ppm; IR (ATR): ṽ
2991, 2935, 2858, 1698, 1676, 1584, 1495, 1427, 1377, 1212,
1071, 798 cm-1; HRMS (EI 70 eV) m/z: calcd for C18H27N5O3S
[M]+ 393.1829, found 393.1834.
3
4
D. J. Darensbourg, Chem. Rev., 2007, 107, 2388.
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X. Guo, C.-L. Zhong, L.-N. He, Y.-N. Zhao, Q.-W. Song, A.-H.
Liu and J.-Q. Whang, Green Chem., 2013, 15, 2401; (d) A. A.
Sathe, D. R. Hartline and A. T. Radosevich, Chem. Commun.,
2013, 49, 5040; (e) O. Jacquet, C. Das Neves Gomes, M.
Ephritikhine and T. Cantat, ChemCatChem., 2013, 5, 117; (f)
Q.-W. Song, B. Yu, X.-D. Li, R. Ma, Z.-F. Diao, R.-G. Li, W. Li
and L.-N. He, Green Chem., 2014, 16, 1633; (g) Z. Xin, C.
Lescot, S. D. Friis, K. Daasbjerg and T. Skrydstrup, Angew.
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(R*,S*)-
and
(R*,R*)-Adipoylbis(2,2,5,5-
tetramethylthiazolidine-3,4-diyl) bis(allylcarbamate) (2z): The
carbamate 2z was prepared according to the general
procedure using 2,2,5,5-tetramethyl-2,5-dihydro-1,3-thiazole
(286 mg, 2.00 mmol), adipoyl chloride (183 mg, 1.00 mmol),
triethylamine (506 mg, 5.00 mmol) and allylamine (171 mg,
3.00 mmol). The crude product was purified by column
chromatography (n-hexane/EtOAc 7:3, Rf = 0.17) to obtain 336
mg (0.56 mmol) of a colorless oil (yield: 56%).
Choi, ACS Sustainable Chem. Eng., 2018, 6, 6675.
6
J. Paz, C. Pérez-Balado, B. Iglesias and L. Muñoz, J. Org.
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739.
7
8
,
1H NMR (500.5 MHz, CDCl3, 300.0 K): δ 1.33 (s, 6 H), 1.56 (s, 6
H), 1.61–1.69 (m, 4 H), 1.80 (s, 6 H), 1.92 (s, 6 H), 2.33–2.41 (m,
2 H), 2.46–2.55 (m, 2 H), 3.73–3.89 (m, 4 H), 4.96–5.03 (m, 2
H), 5.12–5.22 (m, 4 H), 5.78–5.88 (m, 2 H), 6.39 (s, 2 H) ppm;
13C NMR (125.9 MHz, CDCl3, 300.0 K): δ 23.07, 23.07 24.6,
24.7, 30.75, 30.75, 30.76, 30.76, 32.11, 32.11, 36.1, 36.2,
43.54, 43.54, 52.74, 52.74, 73.39, 73.39, 92.59, 92.61, 116.62,
116.62, 134.07, 134.07, 155.26, 155.26, 172.42, 172.42 ppm;
9
D. Luo, L. Liu, P. Han, Q. Wei and H. Shen, Int. Urogynecol. J.,
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Ware, Eds.; Springer: New York, 1988, 105, 1.
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12 | J. Name., 2012, 00, 1-3
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ARTICLE
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22 A. Sehlinger, T. Stalling, J. Martens and M. A. R. Meier,
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24 G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb, A.
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26 All acyl chlorides were obtained by the conversion of the
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