Direct transformation of primary nitro compounds into nitriles with sodium-dithionite

Article abstract of DOI:10.1055/s-0033-1370874

A new and practical direct transformation of primary nitro compounds into nitriles with sodium dithionite is described. The reaction is simple, convenient and eliminates the use of expensive and moisture-sensitive reagents. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1370874

PAPER
▌1407
paper
Direct Transformation of Primary Nitro Compounds into Nitriles with
Sodium Dithionite
Transformation of Primary Nitro Compounds into Nitriles
Baris Temelli,* Canan Unaleroglu
Hacettepe University, Department of Chemistry, 06800 Ankara, Turkey
Fax +90(312)2992163; E-mail: temelli@hacettepe.edu.tr
Received: 06.01.2014; Accepted after revision: 06.02.2014
on the direct transformation of aliphatic nitro compounds
into nitriles with sodium dithionite.
Abstract: A new and practical direct transformation of primary ni-
tro compounds into nitriles with sodium dithionite is described. The
reaction is simple, convenient and eliminates the use of expensive
and moisture-sensitive reagents.
Herein, we report a very convenient method for the trans-
formation of primary nitro compounds into nitriles by
Key words: nitriles, sulfur, nitro compounds, synthetic methods, using sodium dithionite as reagent in a water–ethanol sol-
radicals
vent system (Scheme 1). This method eliminates the need
for moisture-sensitive, expensive, and highly toxic re-
agents such as metal cyanides. In addition, using inexpen-
sive reagents with a water–ethanol solvent system instead
of toxic organic solvents gives further advantages in terms
of cost and environmental concerns.
Nitriles are one of the most widely used building blocks in
organic chemistry, and can be used to synthesize many
functional groups such as carbonyl compounds, amines,
and amides.1 Synthetic methods employed for the prepa-
ration of alkyl nitriles include (i) reaction of alkyl halides
with inorganic cyanides,2 (ii) transition-metal-mediated
cyanation,3 (iii) conversion of aldehydes,4 alcohols and
amines,5 (iv) dehydration of aldoximes and amides,6 and
(v) cyanation through C–H bond functionalization.7 The
direct transformation of primary nitro compounds into ni-
triles is an attractive alternative approach for the synthesis
of alkyl nitriles. To date, many methods have been devel-
oped for the conversion of primary nitro compounds into
nitriles by using different systems involving phosphorus
compounds {P2I4,8a (EtO)2PCl,8b and PCl38c,d}, sulfur
compounds (SO29a and Me3SiSSiMe39b), silyl derivatives
such as Me3SiI,10 and radical chemistry.11 Transformation
of optically active nitroalkanes into chiral nitriles by using
benzyl bromide, KOH and nBu4NI was reported by
Carreira et al.12 However, although there are many meth-
ods available for this transformation, there is still a need
for alternative synthetic approaches starting from easily
accessible reagents and using mild reaction conditions.
NO2
CN
R2
EtOH–H2O (1:1)
pH 10, 100 °C
Na2S2O4
+
R1
R2
R1
Scheme 1 Transformation of primary nitro compounds into nitriles
In initial trials, we attempted to transform the nitro group
of 2,2′-(2-nitroethane-1,1-diyl)bis(1H-pyrrole) (1a) into
the corresponding nitrile by the reaction with sodium di-
thionite at different temperatures (Table 1, entries 1–4).
Reactions of compound 1a with four equivalents of sodi-
um dithionite at room temperature and 50 °C in an etha-
nol–water mixture (1:1) did not give any product, even
after 24 hours (Table 1, entries 1 and 2) and starting com-
pound 1a was recovered after the reactions. When the re-
action was carried out at 80 °C, nitrile product 2a was
obtained as the sole product in low yield (20%; Table 1,
entry 3). The yield was increased slightly to 25% by in-
creasing the reaction temperature to 100 °C, and the in-
creased temperature reduced the required reaction time so
that the model reaction was completed in two hours (Ta-
ble 1, entry 4). The reaction was monitored by TLC, and
2,2-di(1H-pyrrol-2-yl)acetonitrile (2a) was purified by
flash column chromatography. Subsequently, the effect of
solvents was investigated on the model reaction at 100 °C
by using several high-boiling-point cosolvents such as di-
oxane, toluene, 1,2-dichloroethane (DCE), 2-propanol
and N,N-dimethylformamide (DMF), however, these sol-
vents gave the product in lower yields than those obtained
by using the ethanol–water solvent system (Table 1, en-
tries 5–9).
Sodium dithionite is a readily available, inexpensive re-
ducing agent that is capable of reducing a variety of func-
tional groups, including diazonium salts, imines, oximes,
aldehydes, ketones, and nitroso compounds.13 The use of
sodium dithionite in the reduction of aromatic nitro com-
pounds to produce amines has also been known for a long
time.14 The reduction of tertiary nitro compounds to hy-
droxylamines, and aromatic nitro compounds into amines
was reported by Park et al. with sodium dithionite in the
presence of electron-transfer catalyst octylviologen.14b
However, to the best of our knowledge, there is no report
The reaction was then performed with different amounts
of sodium dithionite in ethanol–water at 100 °C (Table 2).
The yield of the product 2a was increased when the
amount of Na2S2O4 was increased to 20 equivalents (Ta-
ble 2, entries 1–4); it was determined that this amount of
SYNTHESIS 2014, 46, 1407–1412
Advanced online publication: 11.03.2014
DOI: 10.1055/s-0033-1370874; Art ID: SS-2014-T0011-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1408
B. Temelli, C. Unaleroglu
PAPER
Table 1 Optimization of Reaction Temperature and Solventa
Table 2 Optimization of the Reaction Conditionsa
NO2
NO2
CN
CN
EtOH–H2O (1:1)
Na2S2O4
+
+
Na2S2O4
HN
2a
NH
NH
NH
1a
HN
HN
NH
1a
HN
100 °C, 2 h
(4 equiv)
2a
Yield (%)b
Entry
Temp (°C) Solvent (1:1)
Time (h) Yield (%)b
Entry
Na2S2O4 (equiv)
pH
1
2
3
4
5
6
7
8
9
r.t.
50
EtOH–H2O
EtOH–H2O
EtOH–H2O
EtOH–H2O
dioxane–H2O
toluene–H2O
DCE–H2O
24
24
10
2
–
1
2
3
4
5
6
7
8
9
4
10
20
30
20
20
20
20
20
7
7
25
27
30
30
30
35
48
40
41
–
80
100
100
100
100
100
100
20
25
18
10
15
20
15
7
7
2
8
2
9
2
10
11
12
i-PrOH–H2O
DMF–H2O
2
2
a All reactions were performed by using 1 mmol of substrate 1a.
a All reactions were performed by using 1 mmol of substrate 1a.
b Isolated yield after flash chromatography.
b Isolated yield after flash chromatography.
sodium dithionite was sufficient to complete the reaction
when added in portions to minimize decomposition in
aqueous solution. It is known that the pH of the reaction
medium is an important parameter for sodium dithionite
mediated reduction reactions. The reduction of aldehydes
and ketones by sodium dithionite is reported at high pH
values, obtained by using NaHCO3 or buffer solutions, to
prevent rapid decomposition of Na2S2O4, which is sensi-
tive to acid.15 The critical role of pH on sodium dithionite
prompted us to examine the model reaction at higher pH
values (Table 2, entries 5–9) and the highest yield was ob-
tained at pH 10 (48% yield; Table 2, entry 7).
nished nitrile compounds as the main products. All start-
ing materials were consumed in the reactions and no
products other than the expected nitrile compounds could
be identified. The structures of new products were deter-
mined by 1H, 13C NMR, FTIR and HRMS analysis.
Table 3 Transformation of Primary Nitro Compounds into Nitrilesa
Entry Substrate
Product
Yield
(%)b
NO2
CN
To illustrate the applicability of this reaction, a range of
aryl and alkyl substituted primary nitro compounds 1a–p
were treated with sodium dithionite under the optimized
reaction conditions [20 equiv Na2S2O4, pH 10, EtOH–
H2O (1:1), 100 °C]; the results are presented in Table 3.
We found that the reaction is general with respect to aryl
substituents such as pyrrolyl, thionyl, furyl, phenyl and in-
dolyl (Table 3, entries 1–7). All substrates with aryl
groups furnished the corresponding products in compara-
ble yields (45–60%). The electron-donating or electron-
withdrawing nature of substituents on the phenyl group
did not change the yields of the reaction significantly. As
shown in Table 3 (entries 8–13), the substituents on the ar-
omatic ring had little impact on the yields of the desired
nitrile products, which were obtained in 48–55% yield.
When mono aryl substituted (Table 3, entry 14) and alkyl
substituted nitro compounds were used (Table 3, entries
15 and 16), a small decrease in reaction yield was ob-
served and the corresponding products were isolated in
32–42% yield. All reactions performed at 100 °C fur-
1
1a
2a
48
NH
HN
CN
NH
S
HN
NO2
2
3
1b
1c
2b
2c
54
47
HN
CN
S
HN
NO2
O
HN
CN
O
HN
NO2
4
5
1d
1e
2d
2e
55
52
HN
HN
NO2
CN
Synthesis 2014, 46, 1407–1412
© Georg Thieme Verlag Stuttgart · New York

PAPER
Transformation of Primary Nitro Compounds into Nitriles
1409
Table 3 Transformation of Primary Nitro Compounds into Nitrilesa
(continued)
stopped before all starting material had reacted. The reac-
tion proceeded smoothly and produced the corresponding
product 2g in 30% yield with a minor amount of 2-(1H-
indol-3-yl)-2-phenylacetaldehyde (3) produced in 12%
yield (Scheme 2). Previously, Pojer reported the reaction
of oximes with aqueous sodium dithionite at room tem-
perature that gave a similar type of carbonyl compound.16
Entry Substrate
Product
Yield
(%)b
NO2
CN
6
1f
2f
45
CN
NO2
CN
NO2
HN
7
8
1g
1h
1i
2g
2h
60
50
55
48
2g
EtOH–H2O (1:1)
HN
Na2S2O4
+
HN
+
pH 10, 80 °C
HN
H
O
NO2
(4 equiv)
CN
1g
HN
HN
NO2
HN
MeO
MeO
3
CN
Scheme 2 Transformation reaction at 80 °C
9
2i
2j
HN
HN
Although details of the mechanism remain unclear, based
on the above experimental results, together with reports
on the mechanism of other sodium dithionite reactions,15
a plausible mechanism for the transformation of the nitro
group into a nitrile is tentatively proposed in Scheme 3.
The mechanism of dithionite decomposition and the dis-
tribution of its thermal decomposition products have been
documented extensively. The thermal decomposition of
Na2S2O4 gives the ESR-detectable sulfur dioxide radical
NO2
CN
10
1j
HN
HN
NO2
F3C
F3C
CN
11
12
1k
1l
2k
2l
48
50
·–
HN
anion (SO2 ), which is in equilibrium with dithionite an-
HN
NO2
F
F
ion [Scheme 3, eq. 1].17 The radical anion affords the sul-
fite anion (SO32–) and acts as an electron donor in alkaline
solutions [Scheme 3, eq. 2].18 Nitroso alkyl is a possible
reduction product of nitro compounds.14b In light of the
foregoing precedent, the first step can be assumed to be
the electron-transfer-reduction of diaryl substituted nitro
to give the nitroso compound A, which forms more stable
tautomeric oxime intermediate B.19 Reaction of the latter
intermediate B in the reaction medium affords aldehyde C
and, especially at high temperature, nitrile compound D.20
CN
HN
HN
NO2
Cl
Br
Cl
Br
CN
13
14
1m
1n
2m
2n
55
42
HN
HN
NO2
In summary, we have performed the first direct transfor-
mation of primary nitro compounds into nitriles by the ap-
plication of sodium dithionite. This transformation
allowed the synthesis of a range of novel nitrile com-
pounds. The method operates under mild reaction condi-
tions, in a water-containing solvent system with an
inexpensive, readily available reagent, and is superior to
the existing methodologies because it does not require a
transition-metal catalyst or anhydrous reaction medium.
CN
HN
HN
NO2
CN
15
16
1o
1p
2o
2p
40
32
NO2
CN
a All reactions were performed by using 1 mmol of substrate 1 at
pH 10.
b Isolated yield after flash chromatography.
1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded in
CDCl3 with a Bruker Ultrashield FT NMR spectrometer. Data for
1H NMR are reported as follows: chemical shift (δ, ppm) and mul-
tiplicity (s = singlet, d = doublet, t = triplet, dd = doublet of dou-
blet, m = multiplet, br s = broad singlet). Coupling constants are
expressed as J values in hertz. Infrared spectra were recorded with
an ATR (Nicolet iS10) instrument and are reported in cm–1; only
We then turned our attention to the mechanism of this in-
teresting transformation. In this context, we repeated the
reaction of 3-(2-nitro-1-phenylethyl)-1H-indole (1g) with
only four equivalents of sodium dithionite at lower tem-
perature (80 °C). The reaction was monitored by TLC and
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1407–1412

1410
B. Temelli, C. Unaleroglu
PAPER
–
2–
(1)
(2)
2SO2
S2O4
–
SO3
e–
2–
2 OH–
SO2
H2O
+
+
+
NO2
R2
NO
R2
NOH
CN
2 e– , 2 H+
Δ
R1
R2
R1
R1
R1
R2
A
D
B
H2O
Na2S2O4
H
O
R1
R2
C
Scheme 3 Proposed mechanism for the transformation
representative absorptions are given. Mass spectra were recorded
with an Agilent Technologies 6224 TOF LC/MS. Flash column
chromatography was performed on silica gel 60 (230–400 mesh).
Reactions were monitored by thin-layer chromatography using 60
F254 silica gel plates. Visualization was accomplished with UV
light, phosphomolybdic acid and/or anisaldehyde. Commercially
available reagents and solvents were used without further purifica-
tion. Buffer solutions were prepared as follows: potassium dihydro-
gen orthophosphate/sodium hydroxide for pH 7, sodium
tetraborate/hydrochloric acid buffer for pH 8, sodium tetrabo-
rate/sodium hydroxide for pH 9 and 10, sodium hydrogen ortho-
phosphate/sodium hydroxide for pH 11. Primary nitro compounds
1a–n were synthesized according to reported procedures.21
IR (ATR): 2203 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.45 (s, 1 H, CHCN), 6.15 (dd,
J = 2.9, 5.9 Hz, 1 H, pyrrole C3-H), 6.22 (br s, 1 H, pyrrole C4-H),
6.67 (br s, 1 H, pyrrole C5-H), 6.91–6.98 (m, 1 H, thiophene C3-H),
7.10–7.11 (m, 1 H, thiophene C4-H), 7.28 (d, J = 5.1 Hz, 1 H, thio-
phene C5-H), 8.18 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 31.7, 108.7, 109.4, 117.6, 119.3,
123.74, 126.6, 126.8, 127.2, 137.3.
HRMS (APCI): m/z [M – H]– calcd for C10H7N2S: 187.0335; found:
187.0339.
2-(Furan-2-yl)-2-(1H-pyrrol-2-yl)acetonitrile (2c)
Yield: 81 mg (47%); brown viscous oil; Rf = 0.45 (EtOAc–hexane,
1:3).
Synthesis of Nitrile Compounds; General Procedure
To a stirred solution of sodium dithionite (0.7 g, 4 mmol) in buffer
solution (3 mL, pH 10) was added a solution of nitro compound
(1 mmol) in EtOH (3 mL) at r.t. and the mixture was heated to
100 °C. Excess sodium dithionite (2.8 g, 16 mmol) was added in
portions during 2 h at this temperature, then the resulting mixture
was cooled to r.t. and EtOAc (10 mL) was added. The aqueous layer
was extracted with EtOAc (3 × 10 mL) and the organic phase was
dried over MgSO4. The solvent was then removed under reduced
pressure and the crude product was purified by flash column chro-
matography on silica gel (EtOAc–hexane).
IR (ATR): 2211 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.25 (s, 1 H), 6.10–6.13 (m, 1 H),
6.18 (br s, 1 H), 6.27–6.31 (m, 2 H), 6.72 (br s, 1 H), 7.35 (s, 1 H),
8.26 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 29.5, 107.3, 107.5, 108.1, 109.8,
116.5, 118.3, 128.9, 142.5, 153.2.
HRMS (APCI): m/z [M – H]– calcd for C10H7N2O: 171.0564; found:
171.0564.
2-Phenyl-2-(1H-pyrrol-2-yl)acetonitrile (2d)
Yield: 100 mg (55%); colorless viscous oil; Rf = 0.50 (EtOAc–
hexane, 1:3).
IR (ATR): 2230 cm–1.
2,2-Di(1H-pyrrol-2-yl)acetonitrile (2a)
Yield: 82 mg (48%); brown viscous oil; Rf = 0.31 (EtOAc–hexane,
1:3).
IR (ATR): 2243 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.18 (s, 1 H, CHCN), 6.11 (br s,
2 H, pyrrole C3-H, C4-H), 6.68 (br s, 1 H, pyrrole C5-H), 7.32–7.37
(m, 5 H, Ph-H), 8.12 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 36.3, 108.7, 109.3, 118.5, 119.2,
124.3, 127.7, 128.6, 129.3, 134.5.
HRMS (APCI): m/z [M – H]– calcd for C12H9N2: 181.0771; found:
181.0776.
1H NMR (400 MHz, CDCl3): δ = 5.24 (s, 1 H, CHCN), 6.14 (br s,
2 H, C3-H), 6.20 (br s, 2 H, C4-H), 6.67 (br s, 2 H, C5-H), 8.04
(br s, 2 H, NH).
13C NMR (100 MHz, CDCl3): δ = 30.1, 108.5, 109.3, 117.6, 119.4,
122.9.
HRMS (APCI): m/z [M – H]– calcd for C10H8N3: 170.0724; found:
170.0723.
2,2-Diphenylacetonitrile (2e)22
2-(1H-Pyrrol-2-yl)-2-(thiophen-2-yl)acetonitrile (2b)
Yield: 102 mg (54%); orange viscous oil; Rf = 0.39 (EtOAc–
hexane, 1:3).
Yield: 100 mg (52%); yellow solid; mp 73–74 °C (Lit.22 72–73 °C).
1H NMR (400 MHz, CDCl3): δ = 5.14 (s, 1 H, CHCN), 7.30–7.40
(m, 10 H, Ph-H).
Synthesis 2014, 46, 1407–1412
© Georg Thieme Verlag Stuttgart · New York

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Transformation of Primary Nitro Compounds into Nitriles
1411
HRMS (APCI): m/z [M – H]– calcd for C14H10N: 192.0819; found:
192.0822.
2-(4-Fluorophenyl)-2-(1H-pyrrol-2-yl)acetonitrile (2k)
Yield: 96 mg (48%); colorless viscous oil; Rf = 0.48 (EtOAc–
hexane, 1:3).
IR (ATR): 2239 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.15 (s, 1 H, CHCN), 6.05 (br s,
1 H, pyrrole C3-H), 6.09–6.11 (m, 1 H, pyrrole C4-H), 6.68 (br s,
1 H, pyrrole C5-H), 7.00–7.04 (m, 2 H, Ph-H), 7.26–7.29 (m, 2 H,
Ph-H), 8.32 (br s, 1 H, NH).
2-Phenyl-2-p-tolylacetonitrile (2f)22
Yield: 93 mg (45%); yellow solid; mp 60–61 °C (Lit.22 61–62 °C).
1H NMR (400 MHz, CDCl3): δ = 2.22 (s, 3 H, CH3), 4.80 (s, 1 H,
CHCN), 7.10–7.30 (m, 9 H, Ph-H).
HRMS (APCI): m/z [M – H]– calcd for C15H12N: 206.0975; found:
206.0978.
13C NMR (100 MHz, CDCl3): δ = 35.4, 108.7, 109.1, 116.2 (d,
3
2JC–F = 22.0 Hz), 118.6, 119.4, 124.0, 129.5 (d, JC–F = 8.0 Hz),
2-(1H-indol-3-yl)-2-phenylacetonitrile (2g)
Yield: 139 mg (60%); colorless viscous oil; Rf = 0.50 (EtOAc–
hexane, 1:10).
IR (ATR): 2243 cm–1.
130.2 (d, 4JC–F = 3.0 Hz), 162.6 (d, 1JC–F = 247.0 Hz).
HRMS (APCI): m/z [M – H]– calcd for C12H8FN2: 199.0677; found:
199.0674.
1H NMR (400 MHz, CDCl3): δ = 5.32 (s, 1 H, CHCN), 7.03–7.08
(m, 2 H, Ar-H), 7.16–7.19 (m, 1 H, Ar-H), 7.28–7.36 (m, 4 H, Ar-
H), 7.39–7.41 (m, 3 H, Ar-H), 8.19 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 34.5, 110.9, 111.6, 118.8, 119.7,
120.3, 122.9, 123.2, 125.3, 127.7, 128.1, 129.0, 135.5, 136.6.
HRMS (APCI): m/z [M – H]– calcd for C16H11N2: 231.0928; found:
231.0926.
2-(4-Chlorophenyl)-2-(1H-pyrrol-2-yl)acetonitrile (2l)
Yield: 108 mg (50%); brown viscous oil; Rf = 0.45 (EtOAc–hexane,
1:3).
IR (ATR): 2251 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.18 (s, 1 H, CHCN), 6.13 (br s,
1 H, pyrrole C3-H), 6.15–6.17 (m, 1 H, pyrrole C4-H), 6.73 (br s,
1 H, pyrrole C5-H), 7.26 (d, J = 8.4 Hz, 2 H, Ph-H), 7.34 (d, J =
8.4 Hz, 2 H, Ph-H), 8.17 (br s, 1 H, NH).
2-(4-Methoxyphenyl)-2-(1H-pyrrol-2-yl)acetonitrile (2h)
Yield: 106 mg (50%); yellow viscous oil; Rf = 0.42 (EtOAc–
hexane, 1:3).
13C NMR (100 MHz, CDCl3): δ = 35.5, 108.7, 109.0, 118.4, 119.5,
123.7, 128.9, 129.4, 132.7, 134.6.
HRMS (APCI): m/z [M – H]– calcd for C12H8ClN2: 215.0381;
found: 215.0392.
IR (ATR): 2235 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.80 (s, 3 H, OCH3), 5.14 (s, 1 H,
CHCN), 6.12 (br s, 2 H, pyrrole C3-H, C4-H), 6.70 (br s, 1 H, pyr-
role C5-H), 6.90 (d, J = 8.6 Hz, 2 H, Ph-H), 7.25 (d, J = 8.6 Hz, 2 H,
Ph-H), 7.97 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 35.6, 55.3, 108.5, 109.4, 114.7,
118.6, 119.0, 124.8, 126.3, 128.9, 159.8.
2-(4-Bromophenyl)-2-(1H-pyrrol-2-yl)acetonitrile (2m)
Yield: 144 mg (55%); brown viscous oil; Rf = 0.45 (EtOAc–hexane,
1:3).
IR (ATR): 2242 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.13 (s, 1 H, CHCN), 6.06 (br s,
1 H, pyrrole C3-H), 6.11 (br s, 1 H, pyrrole C4-H), 6.69 (br s, 1 H,
pyrrole C5-H), 7.18 (d, J = 8.3 Hz, 2 H, Ph-H), 7.47 (d, J = 8.3 Hz,
2 H, Ph-H), 8.29 (br s, 1 H, NH).
HRMS (APCI): m/z [M – H]– calcd for C13H11N2O: 211.0877;
found: 211.0882.
2-(1H-Pyrrol-2-yl)-2-p-tolylacetonitrile (2i)
Yield: 108 mg (55%); brown viscous oil; Rf = 0.55 (EtOAc–hexane,
1:3).
13C NMR (100 MHz, CDCl3): δ = 35.7, 108.8, 109.2, 118.2, 119.5,
122.8, 123.6, 129.2, 132.4, 133.5.
HRMS (APCI): m/z [M – H]– calcd for C12H8BrN2: 258.9876;
found: 258.9881.
IR (ATR): 2247 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.36 (s, 3 H, CH3), 5.15 (s, 1 H,
CHCN), 6.11 (br s, 2 H, pyrrole C3-H, C4-H), 6.68 (br s, 1 H, pyr-
role C5-H), 7.17 (d, J = 8.1 Hz, 2 H, Ph-H), 7.23 (d, J = 8.1 Hz, 2 H,
Ph-H), 8.00 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 21.2, 36.0, 108.5, 109.3, 118.6,
119.0, 124.6, 127.6, 130.0, 131.5, 138.4.
3-Methyl-2-(1H-pyrrol-2-yl)butanenitrile (2n)
Yield: 62 mg (42%); yellow viscous oil; Rf = 0.45 (EtOAc–hexane,
1:6).
IR (ATR): 2235 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.99 (d, J = 4.9 Hz, 3 H, CH3),
1.01 (d, J = 4.9 Hz, 3 H, CH3), 2.03–2.11 [m, 1 H, CH(CH3)2], 3.72
(d, J = 5.9 Hz, 1 H, CHCN), 6.04 (br s, 1 H, pyrrole C3-H), 6.09–
6.13 (m, 1 H, pyrrole C4-H), 6.69 (br s, 1 H, pyrrole C5-H), 8.14 (br
s, 1 H, NH).
HRMS (APCI): m/z [M – H]– calcd for C13H11N2: 195.0928; found:
195.0936.
2-(1H-Pyrrol-2-yl)-2-[4-(trifluoromethyl)phenyl]acetonitrile
(2j)
Yield: 120 mg (48%); brown viscous oil; Rf = 0.58 (EtOAc–hexane,
13C NMR (100 MHz, CDCl3): δ = 19.1, 20.4, 33.0, 38.6, 107.8,
1:3).
109.1, 118.1, 119.0, 123.9.
IR (ATR): 2243 cm–1.
HRMS (APCI): m/z [M – H]– calcd for C9H11N2: 147.0928; found:
147.0931.
1H NMR (400 MHz, CDCl3): δ = 5.27 (s, 1 H, CHCN), 6.11 (br s,
1 H, pyrrole C3-H), 6.14–6.16 (m, 1 H, pyrrole C4-H), 6.75 (br s,
1 H, pyrrole C5-H), 7.49 (d, J = 8.2 Hz, 2 H, Ph-H), 7.66 (d, J =
8.2 Hz, 2 H, Ph-H), 8.09 (br s, 1 H, NH).
13C NMR (100 MHz, CDCl3): δ = 36.2, 109.3, 109.7, 117.8, 119.7,
119.7 (q, 1JC–F = 271.0 Hz), 126.4 (q, 3JC–F = 3.7 Hz), 128.1, 128.8,
131.3 (q, 2JC–F = 33.0 Hz), 138.5.
Acetonitrile (2o)
Yield: 16 mg (40%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H, CH3).
Pentanenitrile (2p)23
Yield: 27 mg (32%); colorless liquid.
HRMS (APCI): m/z [M – H]– calcd for C13H8F3N2: 249.0645;
found: 249.0657.
1H NMR (400 MHz, CDCl3): δ = 1.02 (t, J = 5.9 Hz, 3 H, CH3),
1.47–1.54 (m, 2 H, CH2CH3), 1.64–1.74 (m, 2 H, CH2CH2CH2),
2.30 (t, J = 5.9 Hz, 2 H, CH2CN).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1407–1412

1412
B. Temelli, C. Unaleroglu
PAPER
HRMS (APCI): m/z [M – H]– calcd for C5H8N: 82.0662; found
82.0663.
Zhu, J.-L.; Wu, J.-D.; Chu, C.-M.; Yao, C.-F.; Shia, K.-S.
Chem. Commun. 2007, 301. (f) Choi, E.; Lee, C.; Na, Y.;
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2-(1H-Indol-3-yl)-2-phenylacetaldehyde (3)
Yield: 28 mg (12%); colorless viscous oil; Rf = 0.55 (EtOAc–
hexane 1:10).
IR (ATR): 1712 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.08 (s, 1 H, CHCO), 7.02–7.35
(m, 10 H, Ar-H), 8.13 (br s, 1 H, NH), 9.90 (s, 1 H, CHO).
13C NMR (100 MHz, CDCl3): δ = 56.1, 110.9, 111.1, 119.1, 119.9,
122.5, 122.9, 126.6, 127.4, 128.7, 128.9, 136.0, 136.2, 197.1.
HRMS (APCI): m/z [M – H]– calcd for C16H12NO: 234.0924; found:
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Acknowledgment
This work was financially supported by Hacettepe University (BAP
Project 010D05601004). We wish to thank Prof. Dr. Metin Balci for
helpful discussion.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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