L -Proline: An Efficient Organocatalyst for the Synthesis of 5-Substituted 1 H -Tetrazoles via [3+2] Cycloaddition of Nitriles and Sodium Azide

Article abstract of DOI:10.1055/s-0036-1591534

A simple and efficient route for the synthesis of a series of 5-substituted 1 H -tetrazoles using l -proline as a catalyst from structurally diverse organic nitriles and sodium azide is reported. The prominent features of this environmentally benign, cost effective, and high-yielding l -proline-catalyzed protocol includes simple experimental procedure, short reaction time, simple workup, and excellent yields making it a safer and economical alternative to hazardous Lewis acid catalyzed methods. The protocol was successfully applied to a broad range of substrates, including aliphatic and aryl nitriles, organic thiocyanates, and cyanamides.

Full text of DOI:10.1055/s-0036-1591534

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© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–F
letter
A
en
S. B. Bhagat, V. N. Telvekar
Letter
Synlett
L-Proline: An Efficient Organocatalyst for the Synthesis of
5-Substituted 1H-Tetrazoles via [3+2] Cycloaddition of Nitriles and
Sodium Azide
Saket B. Bhagat
0
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Vikas N. Telvekar*
Department of Pharmaceutical Sciences & Technology,
Institute of Chemical Technology, Matunga (E), Mumbai
400 019, India
vikastelvekar@rediffmail.com
Received: 16.11.2017
Accepted after revision: 02.01.2018
Published online: 07.02.2018
O
OH
N
N
N
N
N
N
N
N
N
H
O
DOI: 10.1055/s-0036-1591534; Art ID: st-2017-b0838-l
NH
N
O
N
OH
N
N
N
Abstract A simple and efficient route for the synthesis of a series of 5-
substituted 1H-tetrazoles using L-proline as a catalyst from structurally
diverse organic nitriles and sodium azide is reported. The prominent
features of this environmentally benign, cost effective, and high-yield-
ing L-proline-catalyzed protocol includes simple experimental proce-
dure, short reaction time, simple workup, and excellent yields making it
a safer and economical alternative to hazardous Lewis acid catalyzed
methods. The protocol was successfully applied to a broad range of
substrates, including aliphatic and aryl nitriles, organic thiocyanates,
and cyanamides.
H
O
Candesartan
Valsartan
N
N
N
Bu
N
HO
N
N
H
N
Losartan Cl
N
N
O
N
N
O
NH
N
O
OH
H
N
P
BMS-183920
O
OH
OH
NH
N
Keywords 5-substituted 1H-tetrazoles, organic nitriles, thiocyanates,
cyanamides, sodium azide, L-proline
N
Irbesartan
N
CGS-26303
O
N
N
Tetrazoles are an important class of nitrogen-containing
heterocycles with numerous applications in a wide array of
fields, including organic synthesis, medicinal chemistry,
coordination chemistry, and material science.1 The tetra-
zole functionality is found in anti-inflammatory, antihyper-
tensive, anticancer, anti-allergic, antibiotic, diuretics, and
receptor modulatory agents.2 Tetrazoles serve as a non-
classical bio-isosteres for the carboxylic acid moiety in drug
design owing to their higher lipophilicity, metabolic stabili-
ty, and increased absorption relative to the carboxylic acid.3
The tetrazole structural motif is a part of angiotensin II
receptor antagonist belonging to the sartan family, for
example, losartan, valsartan, candesartan, irbesartan, and
BMS-183920, peptidase inhibitor CGS-26303, anti-arthritic
drug indomethacin derivative, antiasthmatics drug tomelu-
kast and pemirolast, phosphodiesterase inhibitor cilostazol,
and anti-HIV drug candidates (Figure 1).4
N
R
O
N
O
N
H
Cilostazol
NH
N
HN
N
N
N
N
H
N
O
N
N
N
N
O
O
N
Anti-HIV
OH
HO
O
O
OMe
N
Pemirolast
N
HN
N
Tomelukast
Cl
NH
N
N
N
N
O
Indomethacin analogue
Figure 1 Biologically active agents containing the tetrazole moiety
The extensive utility of tetrazoles has prompted signifi-
cant effort toward the development of several sophisticated
strategies for their synthesis, however, the [3+2] cycloaddi-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

B
S. B. Bhagat, V. N. Telvekar
Letter
Synlett
tion of azide anion to corresponding organic nitriles remain
by far the most direct and convenient method for the
synthesis of 5-substituted 1H-tetrazoles.5 A plethora of syn-
thetic protocols and variations on this general route have
been reported in the literature, which involve the use of
various homogeneous catalytic system such as zinc(II)
salts,6 copper triflates,7 Fe(OAc)2,8 various Lewis acid cata-
lysts such as AlCl3,9 BF3-OEt2,10 FeCl3,11 CdCl2,12 InCl3,13
Sb2O3,14 TBAF,15 I2,16 or heterogeneous catalysts such as
mesoporous ZnS nanospheres,17 nanocrystalline ZnO,18 Cu–Zn
alloy nanopowder,19 CuFe2O4 nanoparticles,20 CoY Zeolite,21
Zn/Al hydrotalcite,22 zeolite/sulfated zirconia,23 phospho-
molybdic acid,24 BaWO4 and other tungstates,25 and
amberlyst-15.26
In spite of many pioneering methodologies explored for
the synthesis of this versatile heterocyclic ring, their wide
application still obviates the need for the development of
alternate routes which eliminate the problems associated
with the use of strong Lewis acids or expensive and toxic
metal catalysts and reagents, stoichiometric amount of cat-
alyst, drastic reaction conditions, water sensitivity, poor
selectivity, or inferior yield of the desired product. This
prompted us to develop a safe, metal-free, and environmen-
tally benign protocol for the synthesis of 5-substituted 1H-
tetrazoles.
Table 1 Optimization of Reaction Conditionsa
N
N
CN
N
L-Proline
NaN3
N
H
1a
2
3a
Entry
L-Proline (mol%) Solvent
Temp (°C)
Yield (%)b
1
2
-
DMF
110
110
110
110
110
80
NDc
70
87
96
94
54
91
47
63
15
10
20
30
50
30
30
30
30
30
DMF
3
DMF
4
DMF
5
DMF
6
DMF
7
DMF
120
110
reflux
reflux
8
DMSO
n-PrOH
EtOH
9
10
a Reaction conditions: benzonitrile (1a, 1mmol), sodium azide (2, 1.25
mmol), and L-proline in solvent (5.0 mL).
b Yields of isolated products.
c ND = no desired product.
entry 2). The yield was improved to 87% when the reaction
was carried out in the presence of 20 mol% of L-proline
(Table 1, entry 3). In an attempt to improve the conversion
and yield, the reaction was repeated using 30 mol% of L-
proline as a catalyst, gratifyingly, this resulted in complete
conversion of benzonitrile into 5-phenyl 1H-tetrazole with-
in 1 h in excellent yield (Table 1, entry 4). A further increase
in the amount of catalyst had no significant effect on the
yield and the reaction time (Table 1, entry 5). Further, a
decrease in temperature to 80 °C had a detrimental influ-
ence on the yield of the product 3a (Table 1, entry 6), while
an increase in temperature from 110 °C to 120 °C gave no
obvious improvement in the reaction (Table 1, entry 7).
Subsequently, the reaction was carried out in different sol-
vents and DMF as solvent provided higher yields than those
using other common solvents, such as DMSO, n-propanol,
and EtOH (Table 1, entries 8–10). Thus, the best result was
achieved by carrying out the reaction with 1:1.25 molar
ratios of benzonitrile and NaN3 in the presence of 30 mol%
L-proline in DMF at 110 °C for 1 h (Table 1, entry 4).
Organocatalysis, use of metal-free small organic mole-
cules as catalyst, has emerged as a rapidly growing research
field for chemical synthesis due to good accessibility, envi-
ronmental friendliness, and high efficiency.27–29 Amongst
them, L-proline is a readily available, safe, easy to handle,
and inexpensive ‘privileged catalyst’ bringing about numer-
ous chemical transformations in a rapid, selective, catalytic,
and atom-economical fashion.30 As a part of our ongoing
research interest aimed at developing green and sustainable
organocatalytic protocols and their subsequent application
to access bioactive compounds, we envisioned the benign
and metal-free L-proline-mediated one-pot synthesis of 5-
substituted 1H-tetrazoles, via [3+2] cycloaddition reaction
between organic nitriles and sodium azide, in high yields
and purity.
To optimize the reaction conditions and evaluate the
catalytic activity of L-proline for the [2+3] cycloaddition,
the reaction between benzonitrile (1a) and sodium azide
(2) was selected as a model reaction for the synthesis of 5-
phenyl 1H-tetrazole (3a) using different reaction parame-
ters, and the results are summarized in Table 1.
In the absence of catalyst at 110 °C, no reaction occurred
even after 12 h (Table 1, entry 1). However, when benzoni-
trile (1a) was reacted with sodium azide (2) using 10 mol%
L-proline in DMF at 110 °C, the product 5-phenyl 1H-tetra-
zole (3a) was isolated in 70% yield after 6 h (Table 1,
With the optimized conditions in hand, we next investi-
gated the substrate scope and generality of the L-proline
promoted [3+2] cycloaddition reaction to form 5-substitut-
ed 1H-tetrazoles, by employing a variety of structurally
divergent benzonitriles possessing a range of activating and
deactivating functional groups, a few heteroaromatic and
aliphatic nitriles and the results are summarized in Table 2.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

C
S. B. Bhagat, V. N. Telvekar
Letter
Synlett
Table 2 Synthesis of 5-Substituted-1H-tetrazoles under Optimized
Entry
12
Organic nitriles 1
Product 3
Yield (%)b
71
Conditions Using L-Prolinea
H
N
N
N
N
L-Proline (30 mol%)
N
N
N
NaN3
N
R
N
DMF, 110 °C, 1–2 h
N
R
H
N
N
1
2
3
O
O
O
N
13
78
N
O
N
H
Entry
1
Organic nitriles 1
Product 3
Yield (%)b
a Reaction conditions: nitrile (1.0 mmol), sodium azide (1.25 mmol), and
L-proline (30 mol%) in DMF at 110 °C for 1–2 h.
b Isolated yields.
N
N
N
N
96
91
89
N
H
In all cases the conversion was completed within 1–1.5
h with good to excellent yields. The nature of the substitu-
ent on the benzonitrile did not affect the reaction time. In
general, aromatic nitriles containing an electron-withdraw-
ing substituent reacted slightly better than those contain-
ing an electron-donating ring substituent (Table 2, entries
2–6). The benzyl nitriles provided good yields of the corre-
sponding products (Table 2, entries 7 and 8). The hetero-
aromatic nitriles such as 2-thiophenecarbonitrile, 4-pyridine-
carbonitrile, and 2-pyridinecarbonitrile also underwent the
conversion smoothly giving the corresponding tetrazoles in
excellent yields (Table 2, entries 9–11). Among aliphatic
nitriles, valeronitrile as well as ethyl cyanoacetate reacted
under the optimized conditions to afford the corresponding
tetrazoles in moderate yields (Table 2, entries 12 and 13).
Aiming to extend the scope of this protocol, organic thio-
cyanates 4 were subjected to the present reaction condi-
tions (Scheme 1). Gratifyingly, the corresponding thiotetra-
zoles 5 were obtained in excellent yield using n-propanol as
a solvent (Table 3, entries 1 and 2).
N
N
N
N
2
3
N
H
N
N
N
N
N
H
MeO
MeO
N
N
N
N
N
H
4
5
6
90
94
83
O2N
O2N
N
N
N
N
N
H
Cl
Cl
N
N
N
N
N
H
HO
HO
N
N
N
N
N
SCN
n
L-Proline (30 mol%)
N
S
n
N
NaN3
7
8
84
89
H
HN
n-propanol,
110 °C, 1–2 h
N
n = 0,1
n = 0,1
4
2
5
N
N
Scheme 1 A general scheme for the synthesis of thiotetrazoles
N
HN
N
Cl
Cl
Further, to demonstrate the versatility of this protocol,
we undertook the synthesis of arylaminotetrazole deriva-
tives from the corresponding arylcyanamides (Scheme 2).
Thus so far, it has been reported in the literature that the
substitution pattern on the aryl ring of arylcyanamides
appears to dictate the course of the reaction.31
N
N
9
92
94
N
S
S
HN
N
N
N
N
N
10
N
N
H
N
H
N
H
N
N
L-Proline (30 mol%)
CN
R1
R1
N
NaN3
N
N
HN
DMF, 110 °C, 1–2 h
N
N
N
6
2
7
11
92
N
N
H
N
Scheme 2 Synthesis of arylaminotetrazoles from arylcyanamides
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

D
S. B. Bhagat, V. N. Telvekar
Letter
Synlett
Table 4 Synthesis of 5-Aryl-1-amino-1H-tetrazolea
Table 3 L-Proline-Catalyzed Synthesis of Thiotetrazolesa
Entry
1
Organic cyanamides 6
Product 7
Yield (%)b
81
Entry
1
Organic thiocyanates 4 Product 5
Yield (%)b
87
H
H
N
N
N
N
S
S
N
N
N
N
HN
HN
S
N
N
H
H
N
N
N
N
N
N
N
2
3
4
86
87
89
N
S
N
N
2
93
N
HN
N
H
H
H
N
N
N
aReaction conditions: thiocyanates (1.0 mmol), sodium azide (1.25 mmol),
L-proline (30 mol%) in n-propanol at reflux for 1–2 h.
b Isolated yields.
N
HN
N
MeO
MeO
Cl
H
H
N
N
N
N
N
HN
N
Cl
Generally, when the substitution on the aryl ring is elec-
tron withdrawing, the formation of 5-aryl-1-amino-1H-
tetrazoles A is favored via guanidine azide intermediate I
and as the electropositivity of substituent increases, the
position of equilibrium shifts toward the isomer 1-aryl-5-
amino-1H-tetrazoles B via guanidine azide intermediate II.
This is due to the rearrangement of the intermediate as
shown in the Scheme 3.32
H
H
N
N
N
N
5
6
91
87
N
HN
N
Cl
Cl
H
H
N
N
N
N
N
HN
N
O2N
O2N
a Reaction conditions: cyanamide (1.0 mmol), sodium azide (1.25 mmol),
and L-proline (30 mol%) in DMF at 110 °C for 1–2 h.
b Isolated yields.
H
H
N
N
N3
N
R1
R1
N
NH
HN
N
H
A
I
N
N
R1 = electron-withdrawing group
NaN3
R1
functionality is activated through hydrogen-bond forma-
tion between L-proline and nitrogen atom of nitrile group
to form the intermediate A. This accelerates the cyclization
step by enhancing the electrophilic character of the cyanide
group. The [3+2] cycloaddition between the C≡N bond of
organic nitrile and azide ion takes place readily to form the
intermediate C. The cycloaddition may be concerted or two
step via formation of an imidoyl azide intermediate B. Fur-
ther, protonation of intermediate C during the acid treat-
ment results in the formation of 5-substituted 1H-tetrazole
product 3. Although the role of the CO2– is not clear, it may
stabilize the transition state of the reaction through elec-
trostatic interaction.
In summary, we have demonstrated an efficient and
atom-economical synthesis of 5-substituted 1H-tetrazoles
using organic nitriles and NaN3 via [3+2] cycloaddition
reaction in the presence of L-proline as an organocatalyst.34
The general protocol described here can be applied to wide
array of substrates including aryl and alkyl organic nitriles
as well as organic thiocyanates and cyanamides affording in
each case the corresponding 5-substituted 1H-tetrazoles in
excellent yields. The selectivity of the protocol to afford 5-
arylamino-1H-tetrazoles as product from aryl cyanamide
irrespective of the substitution pattern is unique to this
protocol. The low cost of reagents, nontoxic and environ-
mentally benign catalyst, milder reaction conditions, short
reaction times, broad substrate scope, good to excellent
N
N
N
N
N3
NH2
N
R1
R1
NH2
II
B
R
1 = electron-donating group
Scheme 3 The possible mechanism involving tautomerism for the
synthesis of different aminotetrazoles
However, under the present reaction conditions, the
electronic effect of the functional group present on the aryl
ring of corresponding cyanamides had no significant im-
pact on the type of product formed. In all the cases, using
our developed protocol, and irrespective of the substitutent
present, 5-aryl-1-amino 1H-tetrazole was formed alone
selectively in excellent yield; no 1-aryl-5-amino-1H-tetra-
zole was observed in the reaction (Table 4, entries 1–6).
Further, to investigate the application feasibility of the
developed protocol for large-scale synthesis and industry, a
scale-up experiment was carried out. When 5 g benzo-
nitrile (1a) was reacted with sodium azide (2) in DMF under
the standard reaction conditions in the presence of L-proline,
the reaction proceeded smoothly, providing the corre-
sponding 5-phenyl-1H-tetrazole (3a) in 90% yield.
Based on the above findings and in accordance with
previous literature reports,33 a tentative mechanism is pro-
posed as shown in Scheme 4. We presume that the nitrile
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

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S. B. Bhagat, V. N. Telvekar
Letter
Synlett
D. E.; Cleary, K. A.; Grant, S. K.; Wu, J. K.; Kozarich, J. W.;
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N
N
N
N
O
N
NH
R
R
R
N
1
N
N
N
H
H
NaN3
2
OH
3
H+
H
H
H
N+
N+
R
N
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O
–N
–
O
N
[2+3] cycloaddition
N–
N–
+
N
N
O
R
Na+
O
Na+
N
C
A
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H
N+
H
–
O
N–
O
+
N–
Na+
N
R
N
B
Scheme 4 A plausible mechanism for the formation of tetrazoles
yields of the products, and good reproducibility are attrac-
tive features of this protocol. Moreover, in addition to the
above, a simple and clean workup eliminating the need of
sophisticated extraction and column chromatography to
get the product in high purity makes the present method
highly desirable.
Acknowledgment
S.B.B is thankful to the University Grants Commission (UGC, New
Delhi, India) for providing fellowship under UGC-SAP.
Supporting Information
Supporting information for this article (included are experimental
details, 1H NMR and 13C NMR analysis of the synthesised compounds)
is available online at https://doi.org/10.1055/s-0036-1591534.
S
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p
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ortioInfgrmoaitn
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stirring. The solid product was filtered under suction and
washed with sufficient cold water. The solid was air dried to
obtain the pure product.
General Procedure for the Synthesis of 5-Arylamino-1H-
tetrazoles 7
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The mixture of organic cyanamide (1 mmol), NaN3 (1.25 mmol),
and L-proline (30 mol%) in DMF (5 mL) was stirred at 110 °C for
1–2 h. The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was allowed to
cool to room temperature. The cooled reaction mixture was
poured in ice water (15 mL) with stirring. The resulting mixture
was acidified with dilute HCl under vigorous stirring. The solid
product was filtered under suction and washed with sufficient
cold water. The solid was air dried to obtain the pure product.
5-Phenyl-1H-tetrazole (3a, Table 2 Entry 1)
Yield 96%, 140.3 mg; white solid; mp 214–216 °C (lit.6a 215–
216 °C). IR (KBr): νmax = 3207, 3075, 3051, 1610, 1565, 1491,
1466, 688 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 16.8 (br, NH),
8.03–8.01 (m, 2 H), 7.62–7.58 (m, 3 H) ppm. 13C NMR (100 MHz,
DMSO-d6): δ = 155.1, 131.2, 129.5, 126.8, 124.1 ppm. MS (ESI):
m/z = 147 [M + H]+.
5-(4-Pyridyl)-1H-tetrazole (3j, Table 2, Entry 10)
Yield 94%, 138.3 mg; white solid; mp 254–256 °C (lit.21 254–
255 °C). IR (KBr): νmax = 3485, 3264, 3099, 3040, 2966, 1621,
1580, 1450, 1388, 1123, 1096, 1042, 1022, 845, 784 cm–1 1H
.
NMR (400 MHz, DMSO-d6): δ = 16.30 (br s, 1 H), 8.51 (d, J = 7.6
Hz, 2 H), 7.78 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz,
DMSO-d6): δ = 159.1, 149.9, 139.4, 120.9 ppm. MS (ESI): m/z:
148 [M + H]+.
(32) Maham, M.; Khalaj, M. J. Chem. Res. 2014, 38, 502.
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2016, 5, 2. (b) Sinhamahapatra, A.; Giri, A. K.; Pal, P.; Pahari, S.
K.; Bajaj, H. C.; Panda, A. B. J. Mater. Chem. 2012, 22, 17227.
(c) Nandre, K. P.; Salunke, J. K.; Nandre, J. P.; Patil, V. S.; Borse, A.
U.; Bhosale, S. V. Chin. Chem. Lett. 2012, 23, 161.
5-(Benzylsulfanyl)-1H-tetrazole (5b, Table 3, Entry 2)
Yield 93%, 178.8 mg; white solid; mp 133–135 °C (lit.35 134–
135 °C). IR (KBr): νmax = 3061, 2900, 2812, 2653, 2545, 2490,
1532, 1493, 1454, 1433, 1362, 1318, 1236, 1079, 1037, 980,
776, 704 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 16.45 (br s, 1
(34) Typical Procedure for the Synthesis of 5-Substituted 1H-
tetrazoles 3, 5, 7
H), 7.40–7.38 (m, 2 H), 7.32–7.28 (m, 3 H), 4.50 (s, 2 H) ppm. 13
C
NMR (100 MHz, DMSO-d6): δ = 154.2, 137.2, 129.5, 129.1, 128.2,
General Procedure for the Synthesis of 5-Aryl/Alkyl 1H-
Tetrazoles 3
36.5 ppm. MS (ESI): m/z = 193 [M + H]+.
5-(p-Tolyl)amino-1H-tetrazole (7b, Table 4, Entry 2)
Yield 86%, 150.7 mg; coffee colored solid; mp 200–202 °C (lit.35
201–203 °C). IR (KBr): νmax = 3268, 3210, 3135, 3091, 1626,
1578, 1545, 1470, 1440, 1256, 1134, 1090, 1060, 835, 782, 730,
The mixture of organic nitrile (1 mmol), NaN3 (1.25 mmol), and
L-proline (30 mol%) in DMF (5 mL) was stirred at 110 °C for 1–2 h.
The progress of the reaction was monitored by TLC. After com-
pletion of the reaction, the reaction mixture was allowed to cool
to room temperature. The cooled reaction mixture was poured
in ice water (15 mL) with stirring. The resulting mixture was
acidified with dilute HCl under vigorous stirring. The solid
product was filtered under suction and washed with sufficient
cold water. The solid was air dried to obtain the pure product.
General Procedure for the Synthesis of 5-(Substituted
Sulfanyl)-1H-tetrazoles 5
The mixture of appropriate thiocyanate (1 mmol), NaN3 (1.25
mmol), and L-proline (30 mol%) in n-propanol (5 mL) was
refluxed for 1–2 h. The progress of the reaction was monitored
by TLC. After completion of the reaction, the reaction mixture
was allowed to cool to room temperature. The cooled reaction
mixture was poured in ice water (15 mL) with stirring. The
resulting mixture was acidified with dilute HCl under vigorous
503 cm–1 1H NMR (400 MHz, DMSO-d6): δ = 15.21 (br s, 1 H),
.
9.66 (s, 1 H), 7.38 (d, J = 8.4 Hz, 1 H), 7.12 (d, J = 8.4 Hz, 1 H), 2.24
(s, 1 H) ppm. 13C NMR (100 MHz, DMSO-d6): δ = 155.8, 138.1,
130.2, 124.0, 117.8, 20.3 ppm. MS (ESI): m/z = 176 [M + H]+.
5-(4-Chlorophenyl)amino-1H-tetrazole (7d, Table 4, Entry 4)
Yield 89%, 174.1 mg; white solid; mp 227–229 °C (lit.35 226–
228 °C). IR (KBr): νmax = 3268, 3210, 3135, 3091, 1626, 1578,
1545, 1470, 1440, 1256, 1134, 1090, 1060, 835, 782, 730, 503
cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 15.43 (br s, 1 H), 9.97 (s,
1 H), 7.56–7.53 (d, J = 11.9 Hz, 1 H), 7.38–7.35 (d, J = 11.9 Hz, 1
H) ppm. 13C NMR (100 MHz, DMSO-d6): δ = 156.1, 139.8, 129.3,
125.1, 118.7 ppm. MS (ESI): m/z = 196 [M + H]+.
(35) (a) Lieber, E.; Enkoji, T. J. Org. Chem. 1961, 26, 4472. (b) Habibi,
D.; Nasrollahzadeh, M. Monatsh. Chem. 2012, 143, 925.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F