HighlyZ-selective synthesis of 1,3-oxathiol-2-ylidenes and 4-methylene-oxazolidine-2-thionesviaatom-specific 5-exo-digcyclization of propargyl alcohol with isothiocyanate

Article abstract of DOI:10.1039/d0ob00083c

DBU mediated 5-exo-digcyclization of isothiocyanate and propargyl alcohol leading to valuable heterocyclic compounds has been accomplished. The different modes of nucleophilicity (eitherS-selective orN-selective) of isothiocyanates were found to depend on

Full text of DOI:10.1039/d0ob00083c

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Antony Savarimuthu, D.G. Leo Prakash, S. Augustine Thomas and T. Gandhi, Org. Biomol. Chem., 2020,
DOI: 10.1039/D0OB00083C.
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Number 47
21 December 2017
Pages 9945-10124
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DOI: 10.1039/D0OB00083C
ARTICLE
Highly Z-selective synthesis of 1,3-oxathiol-2-ylidenes and 4-methylene-oxazolidine-2-thiones via
atom specific 5-exo-dig cyclization of propargyl alcohol with isothiocyanate
S. Antony Savarimuthu,*a D.G. Leo Prakashb S. Augustine Thomas,a Thirumanavelan Gandhic and Mrinal K.
Bera*d
Received 00th January 20xx,
Accepted 00th January 20xx
ABSTRACT: DBU mediated 5-exo-dig cyclization of isothiocyanate and propargyl alcohol leading to valuable heterocyclic
compounds has been accomplished. Different mode of nucleophilicity (either S-selective or N-selective) of isothiocyanates
was found to depend on the substitution pattern of propargyl alcohol. The terminal propargyl alcohol and isothiocyanate
underwent N-nucleophilic attack to afford 3-substituted 4-methylene oxazolidine-2-thiones. On contrary, exclusive S-
nucleophilic cyclization was observed with internal propargyl alcohol to produce (Z)-1,3-oxathiol-2-ylidenes and (Z)-N-(Z)-4-
ethylidene-1,3-oxathiolan-2-ylidenes from secondary and primary propargyl alcohol, respectively. The formation of high Z-
selectivity in imine motif and alkene is the highlight of this new method as the multiple selectivity over C=N and C=C in single
system is synthetically highly challenging. The Z-selectivivity in imine and alkene may be attributed to electronic and steric
factors respectively.
DOI: 10.1039/x0xx00000x
INTRODUCTION: 1,3-oxathiol-2-ylidenes having exocyclic imine and two nucleophilic centers at nitrogen and sulphur. Therefore,
exocyclic C=C bond is an interesting class of heterocyclic compounds different mode of nucleophilic attack by isothiocyanates is almost
with significant biological activities1 yet its synthetic routes are still inevitable under different reaction conditions and with different
limited.2 On contrary, oxazolidine-2-thione units are commonly substrate with which it reacts. The –NCS group predominantly
found in natural products and pharmaceuticals with wide ranging involved in resonance hybrid and so it reacts through either C=S or
bioactivities.3-4 Due to their biological significance and limited the C=N bond. The literature precedence is also in agreement that
number of synthetic routes, developing an efficient method towards different circumstances will determine whether nitrogen or sulphur
1,3-oxathiol-2-ylidenes and oxazolidine-2-thione derivatives5 with atom to act as a nucleophile of isothiocyanate molecule.12 Dethe et
good geometrical selectivity is a matter of interest. In general, the al demonstrated that propargyl amine reacts with isothiocyanates
selectivity around C=C bond is well known and governed by either under basic condition to produce imidazole-2-thiones and spirocyclic
electronic or steric factors. On the other hand, the selectivity around imidazolidine-2-thiones by triggering N-nucleophile (Scheme 1a).13a In
C=N bond is somewhat rare and less studied area. Importantly, the a different instance, Nakka et al reported that S-nucleophile based
multiple selectivities around C=X bond (X= C,N) in a single system cyclization of 2-aminopyridine/amidine13c with isothiacyanates via N-
would be highly challenging and indeed hard to achieve. The S bond formation for the synthesis of N-fused and 3,4-disubstituted
synthetic method with such selectivity would play significant role in 5-imino-1,2,4-thiadiazoles (Scheme 1b).13b Thus, the mode of
all fields of chemistry.
nucleophilic attack of isothiocyanate varies and mainly governed by
In recent years, propargyl alcohol has emerged as a prolific synthon reaction conditions and the reacting partners.
of broad synthetic utility in the context of heterocyclic compounds6
and many more interesting organic transformation.7Strategy for
substituted pyrroles and pyridines from propargyl alcohols with
terminal alkyne under transition metal catalyzed condition is well
established.8 Propargyl alcohol is also known to react with sulphur
dioxide leading to oxathiolene oxide9 while reacting with carbon
dioxide it affords cyclic carbonates under transition metal catalyzed
condition.10 Isothiocyanates, being a higher congener of carbon
dioxide are expected to be more reactive than carbon dioxide and
thus found numerous application in synthesis of heterocyclic
compounds.11 More interestingly, isothiocyanates are equipped with
multiple reaction centers, i.e, one electrophilic centre at carbon and
a. Department of Chemistry, St. Xavier’s College (Autonomous), Palayamkottai,
Tamil Nadu-627 002, India
b. Materials Research Centre, College of Engineering, Swansea University, Swansea
SA2 8PP, UK.
c. Materials Chemistry Division, School of Advanced Sciences, VIT University,
Vellore-632 014, India.
d. Department of Chemistry, Indian Institute of Engineering Science and Technology,
Shibpur, P.O. - Botanic Garden, Howrah-711 103, West Bengal, India
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
Scheme 1 Use of isothiocyanate as potential ambient nucleophilic
reagent in synthesis of novel heterocyclic framework
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
Being inspired by the wide ranging synthetic utility of isothiocyanate
as versatile synthon, we envisioned to employ propargyl alcohol as a [a] Yields of isolated products. DCM = dichloromethane, ACN = acetonitrile,
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DOI: 10.1039/D0OB00083C
DMF = N,N-dimethyl-formamide, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene,
DBN 1,5-diazabicyclo[4.3.0]non-5-ene, DABCO 1,4-
diazabicyclo[2.2.2]octane, DIPEA = di-isopropyl ethyl amine, Et = ethyl, tBu =
tertiary butyl, rt = room temperature, t = time, h = hour, N2 = nitrogen.
synthetic probe to study the isothiocyanate for atom specific
cyclization. Notably, this study would disclose the stereochemical
outcome around the C=X (X = C, N) bonds. Herein, we disclose the
result on DBU assisted coupling and 5-exo-dig cyclization of
isothiocyanate with internal 1o and 2o propargyl alcohol (Scheme 1c)
to access 4-methylene oxazolidine-2-thiones, (Z)-N-(Z)-4-ethylidene-
=
=
The first experiment was carried out were in DCM as solvent with
different organic bases at room temperature under nitrogen
atmosphere. We could able to isolate neither heterocyclic products
nor insignificant amount of cyclized product, which was found to be
N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-2-chloroaniline (4aa)
(Table 1; entries 1-6). In most of the cases a noncyclized linear
product was formed as the major component. In quest of the
optimum condition, keeping the other factors unchanged, the
reaction was further performed with DBU in acetonitrile as solvent
and we were delighted to find that the cyclized product 4aa (Table 1;
entry 7) was afforded exclusively with excellent yield. DMF and
EtOAc were also examined as solvent using DBU as a base. But the
results were not at all encouraging (Table 1, entry 9-10). Experiments
with the inorganic carbonate bases (Na2CO3, K2CO3 and Cs2CO3) and
hydroxides (LiOH, NaOH and KOH) in ACN solvent mostly resulted
with insignificant yield of 4aa and significant yield of the uncyclized
product (3aa) (Table 1; entries 11-16). When the reaction was carried
out in sodium alkoxide bases like NaOMe, NaOEt and NaOtBu, 3aa
was formed as sole product (Table 1; entries 17-19); while the use
of KOtBu and LiOtBu produced 32% and 40% of 4aa (Table 1; entry
20-21), respectively. Here, the best yield for the synthesis of
multisubstituted 1,3-oxathiol-2-ylidenes was accomplished with
the condition mentioned in entry 7 of table 1 and thus considered
as the optimum condition.
1,3-oxathiolan-2-ylidenes
respectively with high Z-selectivity. Further, isothiocyanate
undergoes N-nucleophilic substitution with prop-2-yn-1-ol,
and
(Z)-1,3-oxathiol-2-ylidenes
a
terminal alcohol to afford 4-methylene oxazolidine-2-thiones as
exclusive product.
RESULT AND DISCUSSION: In order to find out the optimum reaction
conditions, 1,3-diphenylprop-2-yn-1-ol (1a) and 1-chloro-2-
isothiocyanatobenzene (2a) were chosen as substrate and reactant,
respectively (Table 1).
Table 1: Study of optimum reaction conditionsa
S
N
O
O
HO
+
HN
solvent, rt
S
N
C S
+
Cl
base
Cl
(1 mmol)
Cl
1 mmol
1mmol
3aa
4aa
1a
2a
Entry Solvent Base
t (h)
% yield of % yield
4aa
15
18
0
of 3aa
50
50
0
1
DCM
DCM
DCM
DCM
DCM
DCM
ACN
DMF
EtOAc
ACN
ACN
ACN
ACN
ACN
ACN
ACN
ACN
ACN
ACN
ACN
DBU
72
72
72
17
20
20
1
2
DBN
Having arrived at the optimum reaction conditions, the scope of
the synthesis was examined with the broad range of
isothiocyanates. The reactions with substituted 1,3-diphenylprop-
2-yn-1-ol (Scheme 2) and the electron-deficient (-Cl14) or electron-
rich (-OMe, -Me and –tBu15) substituted phenyl isothiocyanate
delivered > 80% yield of 4aa-4ae, irrespective of their position.
3
DABCO
DIPEA
DBU
4
0
43
10
15
0
5
21
24
88
10
30
0
6
DBN
Scheme 2: Scope of the synthesis of 3,4,5-trisubstituted (Z)-1,3-
oxathiol-2-ylidenesa
7
DBU
ACN,
DBU (1 mmol)
O
N
R1
R2
OH
R
R2
+
R
N
C S
9
DBU
1
0
S
R1
rt, 1 to 5 hrs
1 mmol
1 mmol
10
11
12
13
14
15
16
17
18
19
20
21
DBU
1
0
1
4
2
Na2CO3
K2CO3
Cs2CO3
LiOH
15
15
15
15
15
15
15
15
15
1
0
N
O
N
R1
O
R = 2-Cl: 4aa, 88%b
= 2-Me: 4ab, 86%
= 4-tBu: 4ac, 89%b
= 2-OMe: 4ad, 82%
= 3-OMe: 4ae, 80%
R
R
S
S
N
0
32
53
72
60
63
68
82
84
49
30
R2
R = 2-Cl, R1: 5-Br, R2: H: 4ka, 79%
0
Cl
R = 2-Cl, R1: H, R2: 4-F: 4ba, 91%
R = 2-Cl, R1: 2-F, R2: 4-F: 4ca, 86%
R = 2-Cl, R1: 2,5-F, R2: H: 4da, 94%
R = 2-Cl, R1: 2,5-F, R2: 4-F: 4ea, 93%
R = 2-Cl, R1: 4-Cl, R2: 4-F: 4fa, 90%
R = 2-Cl, R1: 2-Cl-5-NO2, R2: H: 4ga, 92%
R = 2-Cl, R1: 4-Br, R2: 4-F: 4ha, 89%
R = 2-Cl, R1: 4-Br, R2: H: 4ia, 77%
R = 2-Cl, R1: 4-iPr, R2: H: 4ja, 75%
N
N
O
O
9
R
S
S
R1
N
O
NaOH
KOH
16
0
F
O
R2
4la, 68%
N
O
R = 4-tBu, R1: 4-Cl, R2: H: 4mc, 73%
R = 4-tBu, R1: 4-Br, R2: 4-F: 4hc, 78%
R
NaOMe
NaOEt
NaOtBu
KOtBu
LiOtBu
0
S
R1
1
2
4hf, 83%
R = 4-OCH2-C6H5, R : 4-Br, R : 4-F:
4aa
0
R2
0
32
40
1
2 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
Prompted by the successful synthesis of multisubstVitieuwteAdrtic(lZe)O-1nl,in3e-
oxathiol-2-ylidenes from secondary propaDrgOyIl: 1a0l.c1o03h9o/lDs,0OthBe00s0a8m3Ce
synthetic procedure was employed with primary propargyl alcohols.
This time N-4-ethylidene-1,3-oxathiolan-2-ylidenes was found to be
the sole product as depicted in Scheme 3. Firstly, 3-phenyl-prop-2-yn-
1-ol was tested separately with six different aromatic
isothiocyanates; for example the ortho substituted (2-Cl or 2-Me)
isothiocyanates yielded 88% of 5na and 82% of 5nb. The gram scale
synthesis from electron rich methoxy substituents attached to ortho
or meta positions of aromatic isothiocyanates were well transformed
to the desired products of 5nd and 5ne with satisfactory yields.
Similarly p-tBu substituted phenyl at C-3 of propargyl alcohols
underwent smooth reaction, affording good to excellent yields of
5nc. This reaction was further applied to six different substituted
phenyl prop-2-yn-1-ols with two isothiocyanates. The 4-nitro and di-
fluoro substituted aromatic propargyl alcohols undergone coupling
and cyclization smoothly with 2-chloro phenyl isothiocyanate and
afforded 90% of 5oa and 87% of 5pa. The disubstituted, substituents
being -Cl and -OMe or -Cl and –Me, propargyl alcohols were
producing very good yields of 5qa and 5ra; the 3-(p-tolyl)prop-2-yn-
1-ol, 3-(5-chloro-2-methylphenyl)prop-2-yn-1-ol and 3-(5-methyl-
pyridin-2-yl) Prop-2-yn-1-ol were equally effective, forming 88% of
5sa , 89% of 5td and 81% of 5ua. The 3-(4-nitrophenyl)prop-2-yn-1-
ol reacting with 1-(tert-butyl)-4-isothiocyanatobenzene gave 92% of
5oc.
[a] Reaction conditions: 1 (4.80 mmol), 2 (4.80 mmol), DBU (4.80
mmol) in 10 volume of ACN wrt 1 under N2 atmosphere. [b]Reactions
were carried out on gram scale.
Subsequently, 2-chloro phenyl isothiocyanate was screened with
differently substituted 1,3-diphenylprop-2-yn-1-ol. 4-fluoro phenyl
propargyl alcohol, explored on gram scale, produced an excellent
yield of 4ba. The other two different positional di-fluoro substituted
propargyl alcohols and three-fluoro substituted propargyl alcohols
were employed and identified as equally good substrates producing
4ca, 4da and 4ea with 86%, 94% and 93% yield, respectively.
Similarly, different halogen (Cl, F, Br) substituted phenyl propargyl
alcohols were successfully coupled with 2-chloro phenyl
isothiocyanate to afford excellent yields of 4fa-4ia, and a propargyl
alcohol with substituents R1= 4-iPr produced 75% of 4ja. In addition,
propargyl alcohols carrying 4-Cl or 4-Br phenyl attached to C-1 and 4-
F phenyl attached to C-3 were also productive when reacted with
electron rich isothiocyanates, delivered moderate yields of 4mc , 4hc
and 4hf. The scope of the methodology was further tested using
Scheme 3: Scope of the synthesis of 3,4-disubstituted (Z)-N-(Z)-4-
disubstituted pyridine propargyl alcohols produced the desired ethylidene-1,3-oxathiolan-2-ylidenesa
products 4ka with good yields. In addition, the Boc protected indole
ACN,
O
substituted phenyl propargyl alcohol delivered the expected product
4la with satisfactory yield.
N
OH
DBU (1 mmol)
R
R1
1 mmol
R N C S
+
S
rt, 1 to 4 hrs
H
1 mmol
R1
It is worth mentioning that our newly synthesized 1,3-oxathiol-2-
ylidene compounds with chloro and bromo substituents could be
considered as potential candidates for different transition metal
catalyzed coupling reaction including Suzuki15 and Sonogashira16 to
generate more complex molecular architecture. Most importantly,
out of all the reactions enlisted in Scheme 2, isothiocyanates reacted
exclusively with S-nucleophilic sites resulting in the formation of 1,3-
oxathiol-2-ylidene as sole product. At this point, what remained
unknown is the stereochemical outcome around C=N bond. In order
to confirm the selectivity in imine, X-ray structure determination was
carried out on the compound 4aa14 which gave good crystal and the
structure determination disclosed the stereochemistry around C=N
bond is Z. This unprecedented selection of Z isomer of imine is
somewhat rare. As shown in figure 1, E-isomer would face severe
electron-electron repulsion between the lone pairs in 2p-lobes of
nitrogen and relatively large 3p-lobes of sulfur and thus highly
disfavoured whereas, the Z-isomer has minimal electron-electron
repulsions between the lone pairs in 2p-lobes of nitrogen and 2p-
lobes of oxygen which results in the exclusive Z-selectivity. Also, this
observation is in line with Gálvez17 et al previous report where they
described that the Z-isomer is indeed more stable than E-isomer.
5
1
2
O
R1 = 4-NO2:
5na
, 88%
R = 2-Cl:
O
5oa
, 90%
N
H
N
5nb
, 82%
= 2-Me:
H
S
5pa
, 87%
= 2,3-F:
S
Cl
5nc
, 86%
= 4-tBu:
= 2-OMe:
= 3-OMe:
5qa
, 77%
= 2-OMe-5-Cl:
b
R1
5nd
, 71%
5ra
, 83%
= 2-Me-5-Cl:
5sa
R
b
5ne
, 73%
= 4-Me:
, 88%
O
S
O
O
N
N
H
N
H
H
S
S
Cl
MeO
N
Cl
NO2
5ua
, 81%
5td
, 89%
5oc
, 92%
5ra
[a] Reaction conditions: 1 (4.80 mmol), 2 (4.8058 mmol), DBU (4.80
mmol) in 10 volume of ACN wrt 1 under N2 atmosphere.
[b]Reaction was carried out on gram scale.
Thus, the reaction was found to be highly successful even with
primary propargyl alcohol. Again we were curious to know the
selectivity around the C=N bond. The careful analysis of NMR spectra
once again, revealed that the reaction is stereoselective since we are
isolating only single isomer. X-ray crystal analysis of 5ra18 revealed
that the stereochemical outcome in alkene is Z as well. This can be
explained as shown in figure 2 where E-isomer is highly disfavoured
due to severe A1,3-strain19 between the hydrogen and aryl group.
Such strain is not present in the Z-isomer. This attributes to the
exclusive Z-selectivity in the alkene. Further, as anticipated, the
imine remained Z-selective. Thus we have synthesized N-4-
ethylidene-1,3-oxathiolan-2-ylidenes with high dual Z-selectivity.
R
(Z)
(E)
O
N
O
R1
N
R1
R
S
S
R2
R2
B
A
Figure 1: Selectivity in imine
(Z)
(Z)
N
O
H
O
H
N
R
R
H
(Z)
H
S
S
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
R2
(E)
R2
C
D
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
Though a large number of propargyl alcohol werVeiewsuAcrtcicelessOfnulilnlye
employed to synthesize the title compounds, propargyl alcohols with
DOI: 10.1039/D0OB00083C
aliphatic substituents failed to react with isothiocyanate under the
standard reaction condition. A couple of secondary propargyl alcohol
(prepared from pivaldehyde and cyclopropanecarboxaldehyde) were
treated with different isothiocyanate derivatives under optimized
condition but all our attempts remained largely unsuccessful. In none
Figure 2: Selectivity in alkene
Interestingly, either in case of secondary or primary propargyl of the cases, desired compound was obtained for some unknown
reasons.
alcohol, isothiocyanate attack always took place via S-nucleophile
offering 1,3-oxathiol-2-ylidenes 4 and 4-ethylidene-1,3-oxathiolan-2-
ylidenes 5 respectively. The endo- and exo-cyclic C=C in 4 and 5
respectively may be attributed to the corresponding conjugation
effect. In case of 5, the C=C is necessarily exo-cyclic to being in
conjugation with an aromatic ring. Probably, this conjugation is
responsible for the stability of the end product. On the other hand,
C=C bond in 5 is already in conjugation with the aromatic ring even it
is in endo-cyclic position and does not isomerise to exo-cyclic
position.
The possible reaction mechanism has been proposed in Scheme 5.
DBU de-protonates the hydroxyl group in terminal primary propargyl
alcohol and subsequently the corresponding N-anion in
Isothiocyanates attacks the alkyne through a 5-exo-dig mode to get
oxazolidine-2-thiones (6). In internal primary propargyl alcohol, 5-
exo-dig cyclization of S-anion in isothiocyanate attacks the alkyne to
get 5. In case of internal secondary propargyl alcohol, the S-anion led
to the formation of exocyclic olefin which quickly rearranges through
1,3-hydrogen shift to form more substituted endocyclic olefin 4.
Finally, prop-2-yn-1-ol was treated with phenyl isothiocyanates
under optimized reaction condition and the product was found to be
oxazolidine-2-thiones derivative 6a with good yield (Scheme 4). Unlike
the reactions of isothiacyanate with secondary and primary
propargyl alcohols, the nucleophilic attack took place via N-atom to
afford oxazolidine-2-thione. As we said earlier that the relative
nucleophilicity of sulphur and nitrogen atoms of isothiocyanate may
depend on various factors. In case of sterically crowded propargyl
alcohols, the stronger nuclephilic end of isothiocyanate (S-
nucleophile) attacks preferentially. But in case of prop-2-yn-1-ol, N-
nucleophilic attack takes place probably due to the absence of steric
congestion around terminal propargyl alcohol. Subsequently, we
carried out the reaction with differently substituted phenyl
isothiocyantes (4-OBn, 2-Me, 4-tBu and 2-OMe) and delivered
isolated products of oxazolidine-2-thiones derivatives 6b-6e with
moderate to excellent yield. Once again, we were fortunate to have
a suitable crystal of compound 6b20 for crystallographic study which
confirm the structural assignment unambiguously.
Scheme 5: Plausiible reaction mechanism
H
Base
O
S
OH
R1
H
R2
+
R
N
C S
N
R1, R2 = H
R
H
H
Base
6
R1
=
H
O
H
O
H
N
N
R1
O
N
R1
R
R
R
H
S
S
S
R2
R2
4
R2
5
CONCLUSION
A new synthetic protocol have been demonstrated for synthesizing
3,4,5-substituted (Z)-1,3-oxathiol-2-ylidenes, 3,4-disubstituted (Z)-N-
(Z)-4-ethylidene-1,3-oxathiolan-2-ylidenes
and
4-methylene-
oxazolidine-2-thiones by reacting isothiocyanates with internal
secondary, primary and terminal primary propargyl alcohols,
respectively. Interestingly, the site of nucleophilic attack of
isothiocyanate was found to be different, either S-nucleophilic or N-
nucleophilic was achieved depends on the nature of propargyl
alcohol. Moreover, the stereochemical arrangement of various
groups around C=N and C=C were found to be quite significant. The
high Z-selectivity in imine is favored because there is no repulsion
between the lone pairs in sulfur and nitrogen as they are placed far
away around C=N bond. In case of alkene selectivity, the lack of 1,3-
allylic steric strain between hydrogen and aryl group plays an
important role in favoring Z-alkene. It is worth mentioning that the
cyclization is highly atom specific and leading to stereoselectivity
around C=N and C=C bond which is rare and unique outcome of this
study.
Scheme 4: Scope of the synthesis of 3-substituted 4-methylene-
oxazolidine-2-thionesa
ACN,
DBU (1 mmol)
O
S
OH
R N C S
+
N
rt, 1 to 4 hrs
R
H
1 mmol
1 mmol
H
2
6
6a
R = H: , 65%
S
b
O
6b
= 4-Benzyloxy: , 76%
6c
= 2-Me: , 80%
N
b
6d
= 4-tBu: , 70%
R
H
H
6e
= 2-OMe: , 60%
6b
EXPERIMENTAL SECTION
General: 1H and 13C NMR spectra were recorded at 300/ 400
(75/100) MHz spectrometers, respectively and the spectral data
were reported in ppm relative to Tetramethylsilane (TMS) as
the internal standard. Mass spectra were recorded by electron
ionization. IR spectra were recorded on an FT-IR spectrometer,
and major peaks were reported in cm-1. TLC was performed by
[a] Reaction conditions: 1 (4.80 mmol), 2 (4.8058 mmol), DBU (4.80
mmol) in 10 volume of ACN wrt 1 under N2 atmosphere. [b]Reaction
was carried out on gram scale.
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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using commercially available 100-400 mesh silica gel plates (Z)-N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-2-methylaniline
(GF254). Unless and otherwise mentioned, the purchased (4ab): 95 mg, 86% yield; yellow gummy soliDdO; 1I:H10(4.100039VM/ieDwH0zAO,rtBCic0lDe0CO0ln8l)3inCδe
3
chemicals were used without further purification.
7.65-7.61 (m, 2H), 7.43 (dd, J = 5.6, 6.4 Hz, 3H), 7.33-7.25 (m, 3H),
7.22-7.13 (m, 4H), 7.03 (d, J = 7.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 3.96
General procedure for the synthesis of secondary (s, 2H), 2.24 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 161.4, 148.1,
propargyl alcohols (1a-1m). To an oven dried multi-necked 144.0, 137.6, 131.4, 130.7, 129.9, 129.4, 129.3, 128.7, 128.0, 127.8,
round bottom flask (RBF) were added corresponding phenyl 127.5, 125.0, 120.2, 114.0, 33.3, 18.3; IR (KBr) υ max: 2909.9, 2125.4,
acetylene (0.100mol) and tetrahydrofuran (THF), sequentially 1755.8, 1657.9, 1482.9, 1334.3, 1066.7, 843.2, 779.1, 709.3 cm-1; MS
under nitrogen atmosphere. The reaction mixture was cooled (ESI): 358.20 (M+H)+; Anal. Calcd for C23H19NOS: C, 77.28; H, 5.36; N,
to -70 °C. 2.0M solution of n-BuLi in hexane (0.090mol) at -70 °C 3.92. Found: C, 77.32; H, 5.25; N, 3.87.
was added and the reaction mixture was stirred at the same
temperature for about 20 minutes. Then a solution of (Z)-N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-4-(tert-
1
corresponding benzaldehyde (0.067mol) in tetrahydrofuran at - butyl)aniline (4ac): 104 mg, 89% yield; yellow solid; H (400 MHz,
70 °C was added to the reaction mixture which was stirred at CDCl3) δ 7.69-7.67 (m, 2H), 7.40-7.34 (m, 5H), 7.19-7.15 (m, 3H), 6.99
the same temperature for about 10 minutes. The progress of (d, J = 4.8 Hz, 2H), 6.85 (d, J = 2.8 Hz, 2H), 3.90 (s, 2H), 1.32 (s, 9H);
the reaction was monitored by thin layer chromatogram (TLC) 13C {1H} NMR (75 MHz, CDCl3) δ 163.6, 152.9, 144.2, 135.3, 131.9,
and at the completion of the reaction the reaction mixture was 129.0, 128.7, 127.8, 127.3, 127.0, 126.8, 126.5, 125.5, 125.4, 34.8,
quenched with aqueous NH4Cl solution and then extracted with 31.2, 29.7; IR (KBr) υ max: 2729.9, 2159.4, 1785.8, 1677.2, 1425.0,
ethyl acetate. The organic layer washed with aqueous NH4Cl 1313.3, 1286.7, 833.2, 750.1, 715.0 cm-1; MS (ESI): 400.30 (M+H)+;
solution, dried over Na2SO4, filtered and concentrated at Anal. Calcd for C26H25NOS: C, 78.16; H, 6.31; N, 3.51. Found: C, 78.23;
reduced pressure to give a light brown liquid. The crude sample H, 6.27; N, 3.46.
was purified by chromatography on silica gel (petroleum
ether/ethyl acetate = 1/1) to give the desired secondary (Z)-N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-2-methoxyaniline
propargyl alcohols.
(4ad): 76 mg, 82% yield; yellow solid; 1H (400 MHz, CDCl3) δ 7.70-7.67
(m, 2H), 7.45-7.35 (m, 4H), 7.16 (dd, J = 4 Hz, 3H), 7.00-6.92 (m, 1H),
General procedure for the synthesis of primary propargyl alcohols 6.90-6.87 (m, 4H), 3.95-3.76 (m, 2H), 3.60 (s, 3H); 13C {1H} NMR (100
(1n-1u). To an oven dried multi-necked RBF were added MHz, CDCl3) δ 164.2, 154.9, 144.0, 135.3, 131.5, 129.8, 129.0, 128.8,
corresponding iodobenzene (0.057mol), prop-2-yn-1-ol (0.085mol), 128.5, 127.9, 127.0, 126.9, 125.9, 125.3, 123.0, 120.9, 112.3, 55.6,
acetonitrile (ACN), Pd(PPh3)2Cl2 (2.844mmol), CuI (2.844 mmol) and 29.7; IR (KBr) υ max: 3020.7, 2023.7, 1950.7, 1599.9, 1498.3, 1396.1,
triethyl amine (0.142mol) were successively added under nitrogen 1328.7, 1426.2, 1210.1, 1067.2, 818.2, 759.1 cm-1; MS (ESI): 374.00
atmosphere at room temperature. The reaction mixture was heated (M+H)+; Anal. Calcd for C23H19NO2S: C, 73.97; H, 5.13; N, 3.75. Found:
to 80 °C and stirred at the same temperature for 2 h. Completion of C, 73.90; H, 5.10; N, 3.66.
the reaction was asserted by TLC and then the reaction mixture was
quenched with aqueous ammonia solution. The reaction mixture was (Z)-N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-3-methoxyaniline
extracted with ethyl acetate, and the organic layer washed with brine (4ae): 54 mg, 80% yield; yellow solid; 1H (400 MHz, CDCl3) δ 7.63-7.61
solution, dried over Na2SO4, filtered and concentrated at reduced (m, 2H), 7.43 (d, J = 7.2 Hz, 3H), 7.32 (dd, J = 4.4, 7.2 Hz, 3H), 7.28-
pressure to give a dark brown liquid. The crude sample was purified 7.21 (m, 3H), 6.67-6.60 (m, 3H), 4.00 (s, 2H), 3.79 (s, 3H); 13C {1H}
by chromatography on silica gel (petroleum ether/ ethyl acetate = NMR (100 MHz, CDCl3) δ 161.1, 150.3, 143.9, 137.6, 130.8, 129.8,
1/1) to give the desired primary propargyl alcohols.
129.4, 129.2, 128.9, 128.7, 127.9, 127.7, 126.4, 113.8, 113.5, 110.8,
107.3, 55.7, 33.2; IR (KBr) υ max: 2979.9, 2095.4, 1725.8, 1667.9,
General procedure for the synthesis of 3,4,5-trisubstituted (Z)-1,3- 1455.9, 1293.3, 1096.7, 850.2, 749.1, 709.0 cm-1; MS (ESI): 374.00
oxathiol-2-ylidenes.
(Z)-N-(4-benzyl-5-phenyl-1,3-oxathiol-2-ylidene)-2-chloroaniline
(4aa): To a solution of 1a (120 mg, 0.576 mmol) in ACN (1.2 mL) was
(M+H)+; Anal. Calcd for C23H19NO2S: C, 73.97; H, 5.13; N, 3.75. Found:
C, 73.90; H, 5.10; N, 3.65.
added successively 1-chloro-2-isothiocyanato-benzene (2a) (97.4 (Z)-2-chloro-N-(4-(4-fluorobenzyl)-5-phenyl-1,3-oxathiol-2-
mg, 0.576 mmol) and DBU (87.7 mg, 0.576 mmol) under nitrogen ylidene)aniline (4ba): 178.2 mg, 91% yield; yellow solid. 1H (400
atmosphere at room temperature. The reaction mixture was stirred MHz, CDCl3) δ 7.66-7.45 (m, 2H), 7.44-7.40 (m, 4H), 7.26-7.16 (m,
for about 1 hr and then quenched into ice-water (25 mL), extracted 3H), 7.07-6.98 (m, 4H), 3.95 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ
with MTBE (25 mL), and the organic layer washed with brine solution 162.5 (244.6Hz), 146.2, 144.3, 133.2, 130.8, 130.3, 130.2, 130.0,
(25 mL), dried over Na2SO4 and filtered. Then the filtrate was stirred 129.3, 128.4, 128.0, 127.2, 126.0, 122.1, 116.4, 116.2, 114.1, 32.5; IR
along with silica gel (500 mg) for 0.5 hr, filtered and concentrated at (KBr) υ max: 2979.1, 2091.4, 1745.6, 1637.9, 1455.9, 1263.3, 1066.2,
a reduced pressure to get 191 mg of 4aa, 88% yield; yellow 850.2, 779.1, 719.0 cm-1; MS (ESI): 396.30 (M+H)+; Anal. Calcd for
amorphous solid. 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 6 Hz, 2H), C22H15ClFNOS: C, 66.75; H, 3.82; N, 3.54. Found: C, 66.83; H, 3.80; N,
7.45-7.21 (m, 7H), 7.20-7.04 (m, 5H), 3.98 (s, 2H); 13C {1H} NMR (100 3.51.
MHz, CDCl3) δ 163.6, 146.2, 144.3, 137.4, 130.8, 129.9, 129.4, 129.2,
128.7, 128.5, 128.3, 128.0, 127.8, 127.3, 125.9, 122.1, 114.2, 33.2; IR (Z)-2-chloro-N-(4-(4-fluorobenzyl)-5-(2-fluorophenyl)-1,3-oxathiol-
(KBr) υ max: 2929.9, 2155.4, 1765.8, 1657.4, 1485.9, 1333.3, 1086.7, 2-ylidene)aniline (4ca): 83 mg, 86% yield; yellow solid; 1H (400 MHz,
853.2, 759.1, 705.3 cm-1; MS (ESI): 378.30 (M+H)+; Anal. Calcd for CDCl3) δ 7.42-7.41 (m, 2H), 7.28-6.95 (m, 10H), 3.74 (s, 2H); 13C {1H}
C22H16ClNOS: C, 69.92; H, 4.27; N, 3.71. Found: C, 69.85; H, 4.18; N, NMR (100 MHz, CDCl3) δ 161.2, 158.7, 146.0, 138.2, 133.0 (3 Hz),
3.76.
132.4 (8.2 Hz), 131.5, 130.8, 130.5 (8 Hz), 130.2 (8.2 Hz), 128.4, 127.2,
126.0, 125.0, 122, 117.7, 116.8 (21.7 Hz), 116.4 (14.1 Hz), 116.1 (22
Hz), 32.5; IR (KBr) υ max: 2939.5, 2045.4, 1705.8, 1647.9.5, 1405.9,
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Journal Name
1253.3, 1056.7, 859.2, 789.1, 721.0 cm-1; MS (ESI): 414.20 (M+H)+; 7.05 (m, 2H), 3.97 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 162.5,
View Article Online
Anal. Calcd for C22H14ClF2NOS: C, 63.85; H, 3.41; N, 3.38. Found: C, 145.7, 142.7, 136.7, 132.0, 131.9, 131.8, 130.4, 130.0, 129.6, 129.4,
DOI: 10.1039/D0OB00083C
63.79; H, 3.37; N, 3.31.
129.0, 128.9, 128.5, 128.2, 127.9, 127.6, 127.5, 126.9, 126.8, 126.5,
125.5, 123.7, 121.6, 115.9, 114.6, 32.8; IR (KBr) υ max: 2999.9, 2095.4,
1725.8, 1467.2, 1455.9, 1303.3, 1076.7, 850.2, 749.8, 700.0 cm-1; MS
(Z)-N-(4-benzyl-5-(2,5-difluorophenyl)-1,3-oxathiol-2-ylidene)-2-
1
chloroaniline (4da): 116 mg, 94% yield; yellow solid; H (400 MHz, (ESI): 456.97 (M+H)+; Anal. Calcd for C22H15BrClNOS: C, 57.85; H, 3.31;
CDCl3) δ 7.40 (dd, J = 1.2 Hz, 1H), 7.31-7.25 (m, 3H), 7.23-7.15 (m, N, 3.07. Found: C, 57.99; H, 3.42; N, 3.14.
6H), 7.04 (t, J = 7.2 Hz, 2H), 3.78 (s, 2H); 13C {1H} NMR (100 MHz,
CDCl3) δ 161.5 (288Hz), 155.9 (308Hz), 145.9, 137.1, 136.9, 130.8, (Z)-N-(4-benzyl-5-(4-isopropylphenyl)-1,3-oxathiol-2-ylidene)-2-
129.3, 128.9, 128.4, 127.9, 127.2, 126.0, 121.9, 119.1 (9Hz), 119.0, chloroaniline (4ja): 68 mg, 75% yield; semi yellow solid; 1H (400 MHz,
118.8 (8.6Hz), 118.2 (8.6Hz), 118.0 (8.6Hz), 117.1 (24.8Hz), 33.3 CDCl3) δ 7.61-7.59 (m, 2H), 7.45-7.22 (m, 9H), 7.10-7.05 (m, 1H), 4.01
(4.6Hz); IR (KBr) υ max: 2979.2, 2015.4, 1705.0, 1677.9.5, 1405.0, (s, 2H), 3.02-2.95 (m, 1H), 1.32-1.30(d, J = 6.8 Hz, 6H); 13C {1H} NMR
1253.9, 1066.7, 859.0, 759.1, 711.0 cm-1; MS (ESI): 414.20 (M+H)+; (100 MHz, CDCl3) δ 163.1, 150.4, 145.9, 144.0, 137.1, 130.3, 128.9,
Anal. Calcd for C22H14ClF2NOS: C, 63.85; H, 3.41; N, 3.38. Found: C, 128.2, 127.8, 127.5, 127.2, 126.8, 125.5, 125.3, 121.7, 112.8, 34.0,
63.82; H, 3.37; N, 3.30.
32.7, 23.7; IR (KBr) υ max: 2999.2, 2015.0, 1645.0, 1677.9.5, 1405.0,
1233.9, 1066.7, 859.0, 759.1, 703.0 cm-1; MS (ESI): 420.11 (M+H)+;
Anal. Calcd for C25H22ClNOS: C, 71.50; H, 5.28; N, 3.34. Found: C,
(Z)-2-chloro-N-(5-(2,5-difluorophenyl)-4-(4-fluorobenzyl)-1,3-
oxathiol-2-ylidene)aniline (4ea): 120 mg, 93% yield; yellow solid; 1H 71.68; H, 5.38; N, 3.51.
(400 MHz, CDCl3) δ 7.45-7.30 (m, 2H), 7.25-7.14 (m, 5H), 7.09-6.98
(m, 4H), 3.77 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.3, 160.9, (Z)-N-(4-benzyl-5-(5-bromopyridin-3-yl)-1,3-oxathiol-2-ylidene)-2-
159.7, 136.5, 132.3, 130.4, 130.1, 130.0, 127.9, 126.7, 125.6, 121.4, chloroaniline (4ka): 75 mg, 79% yield; semi yellow solid; 1H (300
118.7, 117.8, 117.7, 117.6, 117.5, 117.2, 115.9, 115.7, 32.1; IR (KBr) MHz, CDCl3) δ 8.78 (s, 1H), 8.70 (s, 1H), 8.17 (s, 1H), 7.40 (d, J = 7.8
υmax: 2929.9, 2109.4, 1755.8, 1670.4, 1405.0, 1313.0, 1286.7, 853.2, Hz, 1H), 7.34-7.32 (m, 3H), 7.26-7.20 (m, 3H), 7.09-7.02 (m, 2H), 3.99
750.1, 705.0 cm-1; MS (ESI): 432.04 (M+H)+; Anal. Calcd for (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 162.0, 150.7, 145.7, 145.4,
C22H13ClF3NOS: C, 61.19; H, 3.03; N, 3.24. Found: C, 62.01; H, 3.20; N, 139.2, 138.2, 136.2, 130.9, 129.6, 128.6, 128.4, 128.2, 127.1, 126.3,
3.22.
121.8, 118.9, 33.2; IR (KBr) υ max: 3029.9, 2009.4, 1755.2, 1670.4,
1445.0, 1313.0, 1286.5, 853.2, 750.1, 709.0 cm-1; MS (ESI): 457.20
(Z)-2-chloro-N-(5-(4-chlorophenyl)-4-(4-fluorobenzyl)-1,3-oxathiol- (M+H)+; Anal. Calcd for C21H14BrClN2OS: C, 55.10; H, 3.08; N, 6.12.
2-ylidene)aniline (4fa): 97 mg, 90% yield; yellow solid; 1H (400 MHz, Found: C, 55.18; H, 3.14; N, 6.17.
CDCl3) δ 7.57-7.53 (m, 2H), 7.46-7.32 (m, 3H), 7.27-7.15 (m, 3H), 7.05- (Z)-tert-butyl 3-(2-((2-chlorophenyl)imino)-4-(4-fluorobenzyl)-1,3-
6.99 (m, 4H), 3.92 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 162.5 oxathiol-5-yl)-1H-indole-1-carboxylate (4la): 65 mg, 68% yield;
(244.7 Hz), 144.6 (282.8 Hz), 136.0, 132.8, 130.8, 130.2, 130.1, 129.6, yellow solid; 1H (400 MHz, CDCl3) δ 8.18 (d, J = 7.2 Hz, 1H), 7.92 (d, J
129.1, 128.4, 127.2, 126.8, 126.0, 122.0, 116.5, 116.3, 114.8, 32.5; IR = 6.4 Hz, 1H), 7.80 (s, 1H), 7.52-7.30 (m, 3H), 7.26-7.17 (m, 3H), 7.07
(KBr) υ max: 2909.9, 2045.4, 1725.1, 1667.9, 1395.1, 1293.3, 1090.6, (d, J = 7.6 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 3.92 (s, 2H), 1.53 (s, 9H);
850.7, 759.1, 709.5 cm-1; MS (ESI): 430.50 (M+H)+; Anal. Calcd for 13C {1H} NMR (100 MHz, CDCl3) δ 161.2, 144.1, 143.1, 137.9, 137.0,
C22H14Cl2FNOS: C, 61.40; H, 3.28; N, 3.25. Found: C, 61.33; H, 3.22; 136.0, 135.5, 134.0, 130.9, 130.2, 128.4, 126.1, 124.0, 122.3, 121.8,
N, 3.22.
116.4, 116.2, 115.7, 59.7, 32.0, 28.6; IR (KBr) υ max: 2979.2, 2015.4,
1705.0, 1677.9, 1405.0, 1253.9, 1066.7, 859.0, 759.1, 717.0 cm-1; MS
(ESI): 535.20 (M+H)+; Anal. Calcd for C29H24ClFN2O3S: C, 65.10; H,
(Z)-N-(4-benzyl-5-(2-chloro-5-nitrophenyl)-1,3-oxathiol-2-ylidene)-
1
2-chloroaniline (4ga): 78 mg, 92% yield; yellow solid; H (400 MHz, 4.52; N, 5.24. Found: C, 65.19; H, 4.58; N, 5.34.
CDCl3) δ 8.41 (s, 1H), 8.27 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.42 (d, J =
3.2 Hz, 1H), 7.31-7.20 (m, 4H), 7.13-7.00 (m, 4H), 3.70 (s, 2H); 13C {1H} (Z)-N-(4-benzyl-5-(4-chlorophenyl)-1,3-oxathiol-2-ylidene)-4-(tert-
1
NMR (100 MHz, CDCl3) δ 163.1, 146.8, 145.7, 142.2, 136.4, 131.8, butyl)aniline (4mc): 76 mg, 73% yield; yellow solid; H (400 MHz,
130.9, 129.7, 129.4, 128.8 (2), 128.4, 128.2, 128.0, 127.8, 126.5, CDCl3) δ 7.55 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.36-7.27 (m,
126.2, 121.9, 33.3; IR (KBr) υ max: 2947.0, 2091.4, 1720.8, 1667.9, 5H), 7.21 (d, J = 6.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 3.95 (s, 2H), 1.30
1455.9, 1293.3, 1096.2, 850.2, 749.1, 04.0 cm-1; MS (ESI): 457.00 (s, 9H); 13C {1H} NMR (75 MHz, CDCl3) δ 161.2, 140.1, 138.5, 137.2,
(M+H)+; Anal. Calcd for C22H14Cl2N2O3S: C, 57.78; H, 3.09; N, 6.13. 136.9, 135.3, 129.0, 128.9, 128.7, 128.1, 127.4, 126.4, 120.5, 113.8,
Found: C, 57.83; H, 3.12; N, 6.19.
34.4, 32.8, 31.4; IR (KBr) υ max: 2079.2, 2015.4, 1705.0, 1779.5,
1405.0, 1293.3, 1066.7, 859.0, 759.1, 701.0 cm-1; MS (ESI): 434.10
(M+H)+; Anal. Calcd for C26H24ClNOS: C, 71.95; H, 5.57; N, 3.23.
(Z)-N-(5-(4-bromophenyl)-4-(4-fluorobenzyl)-1,3-oxathiol-2-
ylidene)-2-chloroaniline (4ha): 103 mg, 89% yield; yellow solid; H Found: C, 71.97; H, 5.51; N, 3.34.
1
(400 MHz, CDCl3) δ 7.59-7.40 (m, 4H), 7.23-7.14 (m, 4H), 7.07-6.98
(m, 4H), 3.92 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.3, 160.9, (Z)-N-(5-(4-bromophenyl)-4-(4-fluorobenzyl)-1,3-oxathiol-2-
142.7, 132.4, 130.4, 129.7, 129.3, 128.9, 127.9, 126.9, 126.7, 125.6, ylidene)-4-(tert-butyl)aniline (4hc): 82 mg, 78% yield; yellow solid;
123.8, 121.5, 116.0, 115.8, 115.6, 32.1; IR (KBr) υ max: 2929.1, 2095.4, 1H (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H),
1725.8, 1667.9, 1459.9, 1293.9, 1066.7, 850.2, 749.6, 719.0 cm-1; MS 7.34 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.00 (dd, J = 8.4 Hz,
(ESI): 474.10 (M+H)+; Anal. Calcd for C22H14BrClFNOS: C, 55.66; H, 4H), 3.91 (s, 2H), 1.30 (s, 9H); 13C {1H} NMR (100 MHz, CDCl3) δ 162.1,
2.97; N, 2.95. Found: C, 55.74; H, 2.91; N, 2.85.
145.4, 133.0, 132.9, 132.5, 130.2, 130.1, 129.3, 127.5, 126.9, 124.1,
120.9, 116.5, 116.2, 114.2, 34.9, 32.5, 31.8; IR (KBr) υ max: 3079.2,
2015.4, 1745.0, 1679.5, 1385.0, 1253.2, 1066.7, 859.0, 709.1, 711.0
(Z)-N-(4-benzyl-5-(4-bromophenyl)-1,3-oxathiol-2-ylidene)-2-
chloroaniline (4ia): 83 mg, 77% yield; yellow solid; 1H (400 MHz, cm-1; MS (ESI): 496.10 (M+H)+; Anal. Calcd for C26H23BrFNOS: C,
CDCl3) δ 7.62-7.45 (m, 4H), 7.43-7.28 (m, 4H), 7.22-7.22 (m, 3H), 7.09- 62.90; H, 4.67; N, 2.82. Found: C, 62.97; H, 4.71; N, 2.76.
6 | J. Name., 2012, 00, 1-3
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3005.2, 2859.1, 1729.1, 1787.4, 1265.0, 1060.4, 1019.7, 853.2, 738.8,
View Article Online
(Z)-4-(benzyloxy)-N-(5-(4-bromophenyl)-4-(4-fluorobenzyl)-1,3-
687.0, 502.9 cm-1; MS (ESI): 298.20 (M+H)+; Anal. Calcd for
DOI: 10.1039/D0OB00083C
1
oxathiol-2-ylidene)aniline (4hf): 96 mg, 83% yield; yellow solid; H C17H15NO2S: C, 68.66; H, 5.08; N, 4.71. Found: C, 68.55; H, 5.01; N,
(400 MHz, CDCl3) δ 7.62-7.59 (m, 2H), 7.58-7.49 (m, 2H), 7.48-7.45 4.65.
(m, 3H), 7.43-7.39 (m, 3H), 7.19-6.96 (m, 2H), 6.88-6.82 (m, 4H), 5.05
(d, J = 14.4 Hz, 2H), 3.90 (d, J = 26 Hz, 2H); 13C {1H} NMR (100 MHz, (Z)-N-((Z)-4-benzylidene-1,3-oxathiolan-2-ylidene)-3-
CDCl3) δ 158.2, 142.8, 137.4, 136.6, 132.7, 131.0, 130.2, 129.7, 129.3, methoxyaniline (5ne): 79 mg, 73% yield; yellow solid; 1H (400 MHz,
128.7, 128.4, 128.0, 127.9, 127.3, 126.2, 124.1, 123.1, 116.3, 114.2, CDCl3) δ 7.35-7.24 (m, 6H), 6.70 (dd, J = 2.0, 1.6 Hz, 1H), 6.60-6.56 (m,
32.5, 29.5; IR (KBr) υ max: 2959.2, 2015.4, 1755.0, 1677.3, 1385.0, 2H), 6.55 (s, 1H), 5.20 (d, J = 1.6 Hz, 2H), 3.80 (s, 3H); 13C {1H} NMR
1253.9, 1066.7, 889.0, 759.1, 701.5 cm-1; MS (ESI): 546.20 (M+H)+; (100 MHz, CDCl3) δ 160.5, 149.6, 153.0, 130.1, 129.6, 129.0, 127.9,
Anal. Calcd for C29H21BrFNO2S: C, 63.74; H, 3.87; N, 2.56. Found: C, 120.3, 115.3, 113.6, 110.5, 108.7, 107.1, 75.1, 55.4; IR (KBr) υ
:
max
63.64; H, 3.75; N, 2.50.
3055.2, 2899.4, 1869.1, 1487.4, 1225.0, 1062.4, 1045.7, 853.2, 768.8,
667.0, 502.6 cm-1; MS (ESI): 298.20 (M+H)+; Anal. Calcd for
General procedure for synthesis of 3,4-disubstituted (Z)-N-(Z)-4- C17H15NO2S: C, 68.66; H, 5.08; N, 4.71. Found: C, 68.55; H, 5.01; N,
ethylidene-1,3-oxathiolan-2-ylidenes.
4.65.
(Z)-N-((Z)-4-benzylidene-1,3-oxathiolan-2-ylidene)-2-chloroaniline
(Z)-4-(tert-butyl)-N-((Z)-4-(4-nitrobenzylidene)-1,3-oxathiolan-2-
(5na): To a solution of 1n (125 mg, 0.946 mmol) in ACN (1.2 mL) was ylidene)aniline (5oc): 117 mg, 92% yield; yellow solid; 1H (400 MHz,
added successively 1-chloro-2-isothiocyanato-benzene (2a) (160 mg, CDCl3) δ 8.22-8.20 (d, J = 8.4 Hz, 2H), 7.45-7.35 (m, 4H), 6.97-6.95 (d,
0.946 mmol) and DBU (144 mg, 0.946 mmol) under nitrogen J = 8.4 Hz, 2H), 3.84 (s, 2H), 1.32 (s, 9H); 13C {1H} NMR (100 MHz,
atmosphere at room temperature. The reaction mixture was stirred CDCl3) δ 156.8, 142.6, 142.3, 140.5, 138.9, 127.8, 124.4, 121.4, 119.0,
for about 1 hr and then quenched into ice-water (25 mL), extracted 115.3, 112.5, 29.4, 27.5, 26.4; IR (KBr) υ max: 3015.2, 2659.4, 1969.1,
with MTBE (25 mL), and the organic layer washed with brine solution 1487.4, 1205.1, 1062.4, 1023.7, 853.0, 768.8, 681.0, 512.9 cm-1; MS
(25 mL), dried over Na2SO4 and filtered. Then the filtrate was stirred (ESI): 369.12 (M+H)+; Anal. Calcd for C20H20N2O3S: C, 65.20; H, 5.47;
along with silica gel (500 mg) for 0.5 hr, filtered and concentrated at N, 7.60. Found: C, 55.56; H, 3.57; N, 4.15.
a reduced pressure to obtain 250.7 mg, 88% yield; pale yellow solid. General procedure for synthesis of 3,4-disubstituted (E)-N-(Z)-4-
1H (400 MHz, CDCl3) δ 7.42-7.38 (m, 2H), 7.36-7.30 (m, 2H), 7.28-7.23 ethylidene-1,3-oxathiolan-2-ylidenes.
(m, 3H), 7.10 (t, J = 8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.61 (s, 1H), 5.27
(s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 164.0, 145.8, 135.3, 130.6, (Z)-2-chloro-N-((Z)-4-(4-nitrobenzylidene)-1,3-oxathiolan-2-
130.0, 129.2, 128.4, 128.3, 128.1, 127.0, 126.0, 122.8, 120.9, 76.2; IR ylidene)aniline (5oa): To a solution of 1o (120 mg, 0.799 mmol) in
(KBr) υ max: 3025.2, 2859.4, 1669.1, 1487.4, 1205.0, 1062.4, 1015.7, ACN (1.2 mL) was added successively 1-chloro-2-isothiocyanato-
853.2, 768.8, 687.0, 512.2 cm-1; MS (ESI): 302.10 (M+H)+; Anal. Calcd benzene (2a) (135.1 mg, 0.799 mmol) and DBU (121.7 mg, 0.799
for C16H12ClNOS: C, 63.68; H, 4.01; N, 4.64. Found: C, 63.76; H, 4.11; mmol) under nitrogen atmosphere at room temperature. The
N, 4.76.
reaction mixture was stirred for about 1 hr and then quenched into
ice-water (25 mL), extracted with MTBE (25 mL), and the organic
(Z)-N-((Z)-4-benzylidene-1,3-oxathiolan-2-ylidene)-2-methylaniline layer washed with brine solution (25 mL), dried over Na2SO4 and
(5nb): 96 mg, 82% yield; white solid; 1H (300 MHz, CDCl3) δ 7.40-7.25 filtered. Then the filtrate was stirred along with silica gel (500 mg) for
(m, 2H), 7.25-7.12 (m, 4H), 7.10-7.00 (m, 2H), 6.90-6.83 (m, 1H), 6.58 0.5 hr, filtered and concentrated at a reduced pressure to give 229.6
(s, 1H), 5.21 (s, 2H), 2.21 (s, 3H); 13C {1H} NMR (75 MHz, CDCl3) δ mg, 90% yield; yellow solid. H (400 MHz, CDCl3) δ 8.22-8.20 (d, J =
1
161.1, 147.0, 130.7, 130.4 (31.5 Hz), 129.5 (52.5 Hz), 128.6 (31.5 Hz), 8.4 Hz, 2H), 7.43-7.39 (m, 3H), 7.28-7.21 (m, 1H), 7.09-7.00 (m, 2H),
127.8 (48.8 Hz), 126.6 (44.3 Hz), 124.6, 120.4, 120.0, 100.8, 75.2, 6.78 (s, 1H), 3.85 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 164.1,
17.8; IR (KBr) υ max: 3005.2, 2859.9, 1599.1, 1457.4, 1205.0, 1062.4, 147.4, 145.5, 143.7, 133.2, 130.4, 129.4, 127.9, 126.5, 125.6, 124.1,
1015.0, 855.2, 768.8, 657.7, 502.2 cm-1; MS (ESI): 281.70 (M+H)+; 121.4, 118.3, 32.3; IR (KBr) υ max: 3022.2, 2859.0, 1669.1, 1481.4,
Anal. Calcd for C17H15NOS: C, 72.57; H, 5.37; N, 4.98. Found: C, 72.52; 1205.0, 1102.4, 1195.7, 853.2, 768.8, 667.0, 509.2 cm-1; MS (ESI):
H, 5.43; N, 5.08.
347.02 (M+H)+; Anal. Calcd for C16H11ClN2O3S: C, 55.41; H, 3.20; N,
8.08. Found: C, 55.82; H, 3.51; N, 8.42.
(Z)-N-((Z)-4-benzylidene-1,3-oxathiolan-2-ylidene)-4-(tert-
butyl)aniline (5nc): 82 mg, 86% yield; yellow solid; 1H (400 MHz, (Z)-2-chloro-N-((Z)-4-(2,3-difluorobenzylidene)-1,3-oxathiolan-2-
1
CDCl3) δ 7.36-7.33 (m, 5H), 7.28-7.24 (m, 2H), 6.92 (d, J = 8.4 Hz, 2H), ylidene)aniline (5pa): 94 mg, 87% yield; light brown solid; H (400
6.60 (s, 1H), 5.18 (d, J = 1.6 Hz, 2H), 1.33 (s, 9H); 13C {1H} NMR (75 MHz, CDCl3) δ 7.41 (d, J = 7.6 Hz, 1H), 7.26-7.22 (m, 1H), 7.11-7.00
MHz, CDCl3) δ 161.2, 147.4, 145.3, 135.0, 130.4, 128.5, 127.8, 127.0, (m, 5H), 6.75 (s, 1H), 5.32 (s, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ
125.7, 120.8, 120.0, 74.7, 34.4, 31.4; IR (KBr) υ max: 3025.2, 2859.2, 162.7, 152.0, 149.4, 146.8, 145.3, 134.0, 130.0, 127.2, 125.8, 125.3,
1669.1, 1457.4, 1205.2, 1062.4, 1065.7, 851.2, 768.8, 697.0, 512.2 124.3, 123.1, 122.5, 116.7, 111.5, 75.8; IR (KBr) υ max: 3029.2, 2959.4,
cm-1; MS (ESI): 324.30 (M+H)+; Anal. Calcd for C20H21NOS: C, 74.27; H, 1769.1, 1487.4, 1185.0, 1062.4, 1015.7, 853.1, 768.5, 687.0, 522.2
6.54; N, 4.33. Found: C, 74.31; H, 6.50; N, 4.27.
cm-1; MS (ESI): 338.10 (M+H)+; Anal. Calcd for C16H10ClF2NOS: C,
56.89; H, 2.98; N, 4.15. Found: C, 56.96; H, 2.91; N, 4.05.
(Z)-N-((Z)-4-benzylidene-1,3-oxathiolan-2-ylidene)-2-
1
methoxyaniline (5nd): 76 mg, 71% yield; pale yellow solid; H (400 (Z)-2-chloro-N-((Z)-4-(5-chloro-2-methoxybenzylidene)-1,3-
MHz, CDCl3) δ 7.33-7.27 (m, 2H), 7.26-7.10 (m, 4H), 6.95-6.93 (m, oxathiolan-2-ylidene)aniline (5qa): 79 mg, 77% yield; yellow solid;
3H), 6.57 (s, 1H), 5.23 (d, J = 1.6 Hz, 2H), 3.83 (s, 3H); 13C {1H} NMR 1H (400 MHz, CDCl3) δ 7.40 (d, J = 6 Hz, 1H), 7.26-7.10 (m, 4H), 7.10-
(100 MHz, CDCl3) δ 163.1, 151.7, 137.8, 135.5, 130.7, 129.2, 128.3, 6.97 (m, 1H), 6.78 (d, J = 8 Hz, 2H), 5.26 (s, 2H), 3.82 (s, 3H); 13C {1H}
126.0, 122.6, 121.4, 120.3, 119.8, 112.2, 75.8, 56.2; IR (KBr) υ
:
NMR (75 MHz, CDCl3) δ 179.5, 155.8, 133.1, 132.9, 132.2, 131.4,
max
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131.0, 130.8, 130.5, 130.1, 128.6, 128.1, 125.2, 124.3, 111.6, 55.6, (300 MHz, CDCl3) δ 7.57-7.47 (m, 3H), 7.33-7.26 (m, 2H), 5.29 (t, J =
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24.1; IR (KBr) υ max: 3005.2, 2009.4, 1869.1, 1487.4, 1205.0, 1062.4, 5.1 Hz, 2H), 4.28 (q, J = 2.7 Hz, 1H), 4.09 (qD, JO=I: 120.7.10H3z9,/1DH0O);B103C00{813HC}
1015.7, 853.2, 768.8, 687.6, 504.2 cm-1; MS (ESI): 366.20 (M+H)+; NMR (75 MHz, CDCl3) δ 188.7, 143.9, 135.0, 129.9, 129.4, 128.1, 84.4,
Anal. Calcd for C17H13Cl2NO2S: C, 55.75; H, 3.58; N, 3.82. Found: C, 71.6; IR (KBr) υ max: 3013.2, 2859.4, 1869.1, 1407.4, 1185.0, 1062.4,
55.83; H, 3.69; N, 3.92.
1015.7, 833.1, 768.5, 687.0, 512.2 cm-1; MS (ESI): 192.00 (M+H)+;
Anal. Calcd for C10H9NOS: C, 62.80; H, 4.74; N, 7.32. Found: C, 61.70;
H, 4.42; N, 7.42.
(Z)-2-chloro-N-((Z)-4-(5-chloro-2-methylbenzylidene)-1,3-
oxathiolan-2-ylidene)aniline (5ra): 89 mg, 83% yield; pale yellow
solid; 1H (400 MHz, CDCl3) δ 7.40 (d, J = 8 Hz, 1H), 7.26-7.20 (m, 1H), 3-(4-(benzyloxy)phenyl)-4-methyleneoxazolidine-2-thione (6b): 72
1
7.14-7.05 (m, 4H), 6.96 (d, J = 7.6 Hz, 1H), 6.61 (s, 1H), 5.26 (d, J = 1.2 mg, 76% yield; semi solid; H (300 MHz, CDCl3) δ 7.46-7.35 (m, 5H),
Hz, 2H), 2.25 (s, 3H); 13C {1H} NMR (75 MHz, CDCl3) δ 161.1, 147.2, 7.26-7.7.20 (m, 2H), 7.13-7.10 (m, 2H), 5.27 (t, J = 5.1 Hz, 2H), 5.10 (s,
136, 134.6, 133.3, 131.8, 131.6, 130.1, 128.0, 127.7, 126.9, 126.5, 2H), 4.27 (q, J = 2.5 Hz, 1H), 4.10 (q, J = 2.5 Hz, 1H); 13C {1H} NMR (75
125.7, 122.2, 117.7, 74.6, 19.3; IR (KBr) υ max: 3033.2, 2599.0, 1669.1, MHz, CDCl3) δ 185.0, 159.3, 144.1, 136.4, 129.2, 128.7, 128.2, 127.6,
1481.4, 1205.0, 1092.4, 1095.7, 853.2, 768.1, 667.0, 500.2 cm-1; MS 116.0, 84.3, 71.5, 70.4; IR (KBr) υ max: 3023.2, 2019.4, 1969.1, 1407.4,
(ESI): 350.40 (M+H)+; Anal. Calcd for C17H13Cl2NOS: C, 58.29; H, 3.74; 1195.0, 1062.0, 1015.7, 853.2, 768.2, 687.6, 500.2 cm-1; MS (ESI):
N, 4.00. Found: C, 58.33; H, 3.79; N, 4.10.
298.20 (M+H)+; Anal. Calcd for C17H15NO2S: C, 68.66; H, 5.08; N, 4.71.
Found: C, 68.55; H, 5.17; N, 4.76.
(Z)-2-chloro-N-((Z)-4-(4-methylbenzylidene)-1,3-oxathiolan-2-
ylidene)aniline (5sa): 71.9 mg, 88% yield; yellow solid; 1H (400 MHz, 4-methylene-3-(o-tolyl)oxazolidine-2-thione (6c): 75 mg, 80% yield;
CDCl3) δ 7.45-7.43 (m, 1H), 7.28-7.01 (m, 7H), 6.61 (s, 1H), 5.28 (s, semi yellow solid; 1H (300 MHz, CDCl3) δ 7.40-7.34 (m, 3H), 7.16 (m,
2H), 2.35 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 130.9, 125.1, 1H), 5.31 (t, J = 4.8 Hz, 2H), 4.26 (t, J = 4.8 Hz, 1H), 3.90 (t, J = 4.8 Hz,
123.1, 122.4, 121.5, 120.9, 120.6, 119.6, 118.5, 115.4, 113.4, 68.7, 1H), 2.21 (s, 3H); 13C {1H} NMR (75 MHz, CDCl3) δ 188.0, 143.0, 136.4,
14.2; IR (KBr) υ max: 3092.2, 2659.0, 1969.1, 1501.4, 1205.0, 1082.4, 133.4, 131.8, 131.6, 130.3, 129.9, 128.4, 127.9, 127.6, 127.5, 84.3,
1195.5, 893.2, 748.8, 667.0, 529.2 cm-1; MS (ESI): 316.10 (M+H)+; 71.7, 17.4; IR (KBr) υ max: 3025.2, 2009.4, 1669.1, 1487.4, 1205.0,
Anal. Calcd for C17H14ClNOS: C, 64.65; H, 4.47; N, 4.44. Found: C, 1062.1, 1015.7, 853.2, 798.8, 657.6, 509.9 cm-1; MS (ESI): 206.10
65.02; H, 4.56; N, 4.76.
(M+H)+; Anal. Calcd for C11H11NOS: C, 64.36; H, 5.40; N, 6.82. Found:
C, 64.25; H, 5.32; N, 6.91.
(Z)-N-((Z)-4-(5-chloro-2-methylbenzylidene)-1,3-oxathiolan-2-
1
ylidene)-2-methoxyaniline (5td): 88 mg, 89% yield; yellow solid; H 3-(4-(tert-butyl)phenyl)-4-methyleneoxazolidine-2-thione (6d): 85
(400 MHz, CDCl3) δ 7.16-7.09 (m, 4H), 6.92 (t, J = 6, 2.4 Hz, 3H), 6.57 mg, 70% yield; semi yellow solid; 1H (400 MHz, CDCl3) δ 7.54 (dd, J =
(s, 1H), 5.22 (d, J = 1.6 Hz, 2H), 3.83 (s, 3H), 2.24 (s, 3H); 13C {1H} NMR 2 Hz, 2H), 7.24 (dd, J = 2 Hz, 2H), 5.27 (t, J = 4.8 Hz, 2H), 4.26 (t, J =
(100 MHz, CDCl3) δ 146.1, 151.1, 137.1, 136.2, 134.6, 133.9, 131.8, 5.2 Hz, 1H), 4.13 (t, J = 5.2 Hz, 1H), 1.36 (s, 9H); 13C {1H} NMR (75
131.5, 127.9, 126.9, 125.7, 121.8, 121.0, 117.1, 111.8, 74.7, 55.7, MHz, CDCl3) δ 188.8, 152.4, 144.1, 132.2, 127.4, 126.8, 84.4, 71.5,
19.3; IR (KBr) υ max: 3059.2, 2759.4, 1589.1, 1407.4, 1185.0, 1062.4, 31.3; IR (KBr) υ max: 3020.2, 2009.4, 1839.1, 1497.4, 1205.0, 1022.1,
1015.7, 853.1, 778.5, 687.0, 505.5 cm-1; MS (ESI): 346.10 (M+H)+; 1015.7, 856.1, 768.8, 687.6, 510.7 cm-1; MS (ESI): 248.20 (M+H)+;
Anal. Calcd for C18H16ClNO2S: C, 62.51; H, 4.66; N, 4.05. Found: C, Anal. Calcd for C14H17NOS: C, 67.98; H, 6.93; N, 5.66. Found: C, 68.08;
62.42; H, 4.56; N, 4.01.
H, 7.02; N, 5.71.
(Z)-2-chloro-N-((Z)-4-((5-methylpyridin-2-yl)methylene)-1,3-
3-(2-methoxyphenyl)-4-methyleneoxazolidine-2-thione (6e): 70
oxathiolan-2-ylidene)aniline (5ua): 79 mg, 81% yield; semi yellow mg, 60% yield; semi yellow solid; 1H (400 MHz, CDCl3) δ 7.48-7.44 (m,
solid; 1H (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.24- 1H), 7.26-7.22 (m, 1H), 7.11-7.07 (m, 2H), 5.34-5.24 (m, 2H), 4.22 (q,
7.23 (m, 1H), 7.10-7.00 (m, 3H), 6.56 (s, 1H), 5.32 (s, 2H), 2.29 (s, 3H); J = 7.2 Hz, 1H), 3.95 (q, J = 7.2 Hz, 1H), 3.84 (s, 3H); 13C {1H} NMR (100
13C {1H} NMR (100 MHz, CDCl3) δ 167.0, 150.6, 149.6, 145.9, 137.5, MHz, CDCl3) δ 188.9, 155.1, 143.2, 131.2, 129.9, 123.2, 121.4, 112.9,
134.8, 131.4, 130.4, 128.0, 127.1, 125.6, 123.6, 123.0, 116.8, 75.2, 83.7, 71.8, 55.9; IR (KBr) υ max: 3031.2, 2079.4, 1869.0, 1527.4,
18.7; IR (KBr) υ max: 3019.2, 2959.4, 1769.7, 1467.4, 1085.0, 1042.4, 1205.0, 1032.4, 1002.7, 873.2, 768.8, 685.6, 501.0 cm-1; MS (ESI):
1005.7, 823.1, 768.5, 687.8, 500.2 cm-1; MS (ESI): 317.30 (M+H)+; 222.10 (M+H)+; Anal. Calcd for C11H11NO2S: C, 59.71; H, 5.01; N, 6.33.
Anal. Calcd for C16H13ClN2OS: C, 60.66; H, 4.14; N, 8.84. Found: C, Found: C, 59.88; H, 5.18; N, 6.39.
60.77; H, 4.21; N, 8.91.
General procedure for the synthesis of secondary propargyl
General procedure for synthesis of 3-substituted 4-methylene- alcohols (1v-1w).
oxazolidine-2-thiones (6a-6e).
A solution of acetylene (1.2 equiv.) in 1,4-dioxane (10 volume),
sodium tertiary pentoxide (NaOtP) (30% in THF) (1.2 equiv.) at
4-methylene-3-phenyloxazolidine-2-thione (6a): To a solution of room temperature was added under nitrogen atmosphere for 5
prop-2-yn-1-ol (180 mg, 0.321 mmol) in ACN (1.2 mL) was added minutes and stirred the reaction mixture for 10 minutes. A
successively 1-chloro-2-isothiocyanato-benzene (2a) (433 mg, 0.321 solution of aliphatic aldehyde (1.0 equiv.) in 1,4-dioxane (5
mmol) and DBU (500 mg, 0.321 mmol) under nitrogen atmosphere volume) was added into the reaction mixture at room
at room temperature. The reaction mixture was stirred for about 1 temperature for 5 minutes and stirred for 30 minutes. The
hr and then quenched into ice-water (25 mL), extracted with MTBE progress of the reaction was monitored by thin layer
(25 mL), and the organic layer washed with brine solution (25 mL), chromatography (TLC). The reaction mixture was quenched by
dried over Na2SO4 and filtered. Then the filtrate was stirred along adding sat. NH4Cl solution and extracted twice with ethyl
with silica gel (500 mg) for 0.5 hr, filtered and concentrated at a acetate. The combined ethyl acetate layer was washed with
1
reduced pressure to give 400 mg, 65% yield; semi yellow solid; H brine solution, dried over anhydrous Na2SO4, filtered and
8 | J. Name., 2012, 00, 1-3
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concentrated completely under reduced pressure. The crude
sample was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 1/1) to give the desired
secondary propargyl alcohols as light brown oil.
f) R. Morales-Nava, M. Fernández-ZertucheV,ieMw.ArOticrldeóOñnleinze.
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1-(4-fluorophenyl)-4,4-dimethylpent-1-yn-3-ol (1v): light brown oil;
1H (400 MHz, CDCl3) δ 7.43-7.39 (m, 2H), 7.02-6.98 (m, 2H), 4.22 (s,
1H), 1.24 (s, 1H), 1.06 (s, 9H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.8,
161.4, 133.7, 133.6, 118.8, 118.9, 115.7, 115.5, 88.7, 84.8, 36.2, 27.1,
25.4.
6
1-cyclopropyl-3-(4-fluorophenyl)prop-2-yn-1-ol (1w): light brown
1
oil; H (400 MHz, CDCl3) δ 7.41-7.38 (m, 2H), 7.02-6.97.22 (m, 2H),
7
4.41 (t, J = 6.4 Hz, 1H), 2.0 (d, J = 6 Hz, 1H), 1.34- 1.30(m, 1H), 0.63-
0.49 (m, 4H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.9, 161.4, 133.8,
133.7, 118.7, 118.6, 115.7, 115.5, 87.6, 84.0, 66.3, 17.3, 3.4, 1.7.
Conflicts of interest
There are no conflicts to declare.
8
9
Acknowledgements
Authors would like to sincerely thank Sophisticated Analytical
Instruments Facility (SAIF), Indian Institute of Engineering Science
and Technology (IIEST) Shibpur for single crystal X-ray analysis of
compounds 4aa and 5ra. M.K.B. would like to thank Council of
Scientific and Industrial Research (CSIR), New Delhi for financial
support (Grant No. 02(0270)/16/EMR-II).
M. Ying, M. G. Smentek, R. Ma, C. S. Day, S. V. Torti, M. E.
Welker. Lett. Org. Chem. 2009, 6, 242-251.
10 K. Sekine, T. Yamada. Chem. Soc. Rev., 2016, 45, 4524-
4532.
Notes and references
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2
3
4
5
14 CCDC1879214 (4aa) contains the supplementary
crystallographic data for this paper. These data can be
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Crystallographic
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Journal Name
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18 CCDC1879222 (5ra) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic
www.ccdc.cam.ac.uk/data_request/cif
19 R. W. Hoffmann. Chem. Rev., 1989, 89, 1841–1860.
Data
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20 CCDC1870970 (6b) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic
Data
Center
via
www.ccdc.cam.ac.uk/data_request/cif.
Graphical Abstracts
(Z)
If R1 = H
O
N
R
S
(z)
H
HO
O
S
R2
R2
O
If R1, R2 = H
R1
N
+
R
H
If R1 = aryl /
alkyl
(z)
H
N
R
N
C
S
R1
R2
R
S
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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