PAPER 2631

Direct Oxidative Conversion of Alcohols, Amines, Aldehydes, and Benzyl

Halides into the Corresponding Nitriles with Trichloroisocyanuric Acid in
Aqueous Ammonia
NitrlesbyDirectOxidativeConversion Veisi*
Hojat
Department of Chemistry, Payame Noor University (PNU), Songhor, Kermanshah, Iran
Fax +98(838)4227463; E-mail: hojatveisi@yahoo.com
Received 18 February 2010; revised 6 April 2010

triles with molecular iodine and 1,3-diiodo-5,5-dimethyl-

Abstract: A new and efficient procedure for the one-pot conversion
of various alcohols, aldehydes and primary amines into the corre-
sponding nitriles in excellent yields was easily achieved by trichloro-
isocyanuric acid (TCCA) as an oxidant and reagent in aqueous
ammonia. Also, various benzylic halides were smoothly and direct-
ly converted into the corresponding aromatic nitriles in high yields
under the same conditions.
Key words: trichloroisocyanuric acid, nitriles, alcohols, amines,
aldehydes, alkyl halides
hydantoin in aqueous ammonia was reported by Togo and
et al.28
Trichloroisocyanuric acid [1,3,5-trichloro-1,3,5-triazine-
2,4,6-(1H,3H,5H)-trione or TCCA] is a stable, homoge-
neous, neutral, nonvolatile, inexpensive, safe, commer-
cially available reagent (used primarily as a disinfectant
and deodorant) that has been used as efficient catalyst, re-
agent, and oxidant in organic synthesis.29–34
Recently, we reported the direct, efficient, practical, and

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Nitriles are very important intermediates in synthetic or- less toxic oxidative conversion of primary alcohols and
ganic chemistry.1 They are important synthetic precur- amines into the corresponding nitriles using poly(N,N¢-
sors, particularly to esters, amides, carboxylic acids, dichloro-N-ethylbenzene-1,3-disulfonamide) (PCBS) and
amines, and nitrogen-containing heterocycles, and they N,N,N¢,N¢-tetrachlorobenzene-1,3-disulfonamide (TCBDA)
have been used as synthetic intermediates for agricultural in aqueous ammonia.35 Herein, as part of our ongoing
chemicals, pharmaceuticals, and functional materials.2,3 study on the application of N-halo reagents in organic
Consequently, there is great interest in finding methods synthesis,36–39 we would like to present the direct oxida-
for their synthesis under mild conditions. A typical meth- tive conversion of alcohols, primary amines, aldehydes,
od is the reaction of alkyl halides with toxic cyanide via a and alkyl halides into the corresponding nitriles using
nucleophilic pathway; the length of the carbon chain is in- trichloroisocyanuric acid as a reagent and oxidant under
creased by one during this process. Due to the toxicity of mild conditions (Scheme 1).
cyanide, nitriles are generally prepared by the dehydration For our initial optimization studies, benzyl alcohol (2a)
of amides with SOCl2, TsCl/pyridine, P2O5, COCl2, was chosen as the model substrate. A mixture of benzyl
(EtO)3P/I2, or Ph3P/CCl4.4 It has been reported that nitriles alcohol (2a) and aqueous ammonia solution was stirred
can be prepared from carboxylic acids or their deriva-
tives,5 amides,6,7 aldehydes,8,9 oximes,10 and nitro com-
pounds.11 Nitrile synthesis from amines is a classical
route. Numerous metal-based oxidants, such as nickel
peroxide,12 silver reagents,13 copper reagents,14 OsO4,15
NaOCl,16 PhIO,17 trichloroisocyanuric acid (TCCA) with
TEMPO18 or triethylamine,19 IBX/I2,20 I2/NH3,21 1,3-di-
iodo-5,5-dimethylhydantoin (DIH) in aqueous ammo-
nia,22,23 and ruthenium reagents24 have been used to
perform this transformation. However, there are only a
few reports on the direct oxidative conversion of alcohols
as starting materials into nitriles in a one-pot procedure,
i.e. using NH4HCO3/(Bu4N)2S2O8/Cu(O2CH)2 (cat.)/
Ni(O2CH)2 (cat.)/aq KOH–i-PrOH,25 MnO2/NH3/MgSO4/
THF–i-PrOH (for benzylic and cinnamic alcohols),25 I2/aq
NH3,26 and DIH/aq NH3,22 and KI/I2/TBHP.27 Recently,
the direct oxidative conversion of alkyl halides into ni-

SYNTHESIS 2010, No. 15, pp 2631–2635xx. 201

Advanced online publication: 18.06.2010
DOI: 10.1055/s-0029-1218827; Art ID: Z04110SS Scheme 1
© Georg Thieme Verlag Stuttgart · New York
2632 H. Veisi PAPER

under different conditions. The results showed that Table 1 Conversion of Primary Amines, Alcohols, Aldehydes, and
reactions at room temperature provided low yields of Alkyl Halides into Nitriles Catalyzed by Trichloroisocyanuric Acid in
Aqueous Ammonia
benzonitrile (5a), but increasing the amount of trichloro-
TCCA, aq NH3
isocyanuric acid from 0.5 mmol to 0.75 mmol and in- 60 °C
R Y R CN
creasing the temperature from room temperature to 60 °C
1 Y = CH2NH2 5
gave a moderate improvement in the conversion. Typical- 2 Y = CH2OH
ly, benzyl alcohol (2a) in aqueous ammonia (3 mL) in a 3 Y = CHO
4 Y = CH2X
round-bottomed flask was treated with trichloroisocyanu-
ric acid (0.75 equiv) at room temperature and then stirred Entry Amine R X Time Producta Yield
at 60 °C for two hours to provide benzonitrile (5a) in high (h) (%)
yield (Table 1, entry 8). It should be noted that during all
1 1a Ph – 1 5a27 96
reactions care must be taken when adding trichloro-
isocyanuric acid to the substrate/ammonia solution. Add- 2 1b 4-Tol – 1 5b27 98
ing the trichloroisocyanuric acid in one portion would
3 1c 4-MeOC6H4 – 1 5c27 96
result in an explosive reaction. To avoid this problem
trichloroisocyanuric acid was added very careful in sever- 4 1d 4-HOC6H4 – 1.2 5d27 92
al small portions.
5 1e 4-ClC6H4 – 2 5e27 88
Under similar reaction conditions, there was no product
formation in the absence of trichloroisocyanuric acid. The 6 1f 4-H2NCH2C6H4 – 2 5f27 90b
general applicability of this method was further evaluated 7 1g Bn – 1.5 5g27 85
for various primary and benzylic alcohols under opti-
mized reaction conditions using trichloroisocyanuric acid 8 2a Ph – 2 5a27 90

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as an oxidant and reagent (Table 1, entries 8–15). The re-
9 2b 4-Tol – 2.5 5b27 96
activity depends on the nature of alcohol used. Thus, ben-
zylic alcohols 2b–d which contain an electron-donating 10 2c 4-MeOC6H4 – 2.5 5c 27
98
group were smoothly converted into the corresponding ni-
11 2d 4-HOC6H4 – 3 5d27 96
triles 5b–d in good yields (Table 1, entries 9–11), while
benzylic alcohols 2e,h which contain an electron- 12 2h 4-BrC6H4 – 4.5 5h 27
80
withdrawing group gave slightly lower yields (Table 1,
entries 12, 13). 13 2e 4-ClC6H4 – 4 5e27 82
27
A plausible reaction pathway for the conversion of prima- 14 2g Bn – 4 5g 80
ry alcohols into nitriles is shown in Scheme 2. According 15 2i Pr – 5 5i27 75
to this pathway, the initial O-chlorination of the alcohol 2
27
with trichloroisocyanuric acid occurs to form the O-chlo- 16 3a Ph – 2 5a 90
ro compound I, followed by b-elimination of HCl by am-
17 3b 4-Tol – 1.5 5b27 90
monia to form the aldehyde II. This aldehyde reacts with
ammonia to form an aldimine III. Then, the aldimine III 18 3c 4-MeOC6H4 – 1.5 5c 27
92
reacts with trichloroisocyanuric acid in the presence of
19 3e 4-ClC6H4 – 2.5 5e27 88
ammonia to form an N-chloroaldimine IV, followed by b-
elimination of HCl by ammonia to generate the corre- 20 3j 4-O2NC6H4 – 3 5j 27
75
sponding nitrile 5.26
21 3k 1-naphthyl – 2 5k27 85
TCCA 27
R OH R CN 22 3l 2-thienyl – 2 5l 90
2 NH3, 60 °C 5
TCCA 23 3m (E)-CH=CHPh – 5 5m27 75
– HCl
24 3n (CH2)6Me – 5 5n27 70
H Cl
NH3 TCCA
RCHO R-CH=NH R-C=N
R O – HCl – H2O
H
25 4a Ph Br 4 5a28 80
I Cl II III IV
26 4a¢ Ph Cl 3 5a28 85
Scheme 2
27 4a¢¢ Ph I 2.5 5a28 85
The present system was further examined for the direct 28 4b 4-Tol Br 3.5 5b28 85
conversion of aldehydes 3 into nitriles, and the results are
29 4b¢ 4-Tol Cl 3.5 5b28 90
summarized in Table 1 (entries 16–24). We obtained a
very good conversion irrespective of the electronic nature 30 4c 4-MeOC6H4 Br 3 5c28 92
of the aldehyde. Moreover, these reactions were found to
be faster compared to the alcohols. 31 4c¢ 4-MeOC6H4 Cl 3.5 5c28 95

Synthesis 2010, No. 15, 2631–2635 © Thieme Stuttgart · New York

PAPER Nitriles by Direct Oxidative Conversion 2633

Table 1 Conversion of Primary Amines, Alcohols, Aldehydes, and TCCA

CN
N
Alkyl Halides into Nitriles Catalyzed by Trichloroisocyanuric Acid in H 2
aq NH3 (3 mL)
Aqueous Ammonia (continued) 60 °C, 4 h, 90%
TCCA, aq NH3 6 5a
60 °C
R Y R CN
Scheme 4
1 Y = CH2NH2 5
2 Y = CH2OH
3 Y = CHO
4 Y = CH2X Based on these results, a plausible reaction pathway for
the conversion of dibenzylamine (6) into nitrile 5a is
Entry Amine R X Time Producta Yield shown in Scheme 5. Thus, initial N-chlorination of the
(h) (%) amine occurs to give the N-chloro secondary amine VI,
32 4e 4-ClC6H4 Br 8 5e28 80 followed by b-elimination of HCl to form the imino com-
pound VII. Once imino compound VII is formed, it reacts
28
33 4e¢ 4-ClC6H4 Cl 7 5e 80 with aqueous ammonia to form the 1,1-diamino com-
34 4k 1-naphthyl Br 4 5k28 80 pound VIII, which smoothly decomposes to the primary
amine IX and imine III. The primary amine IX reacts with
a
The products were characterized by comparison of their spectro- trichloroisocyanuric acid to form the N-chloroamine V,
scopic and physical data with those of samples synthesized by report-
ed procedures; reference given for known compounds.
followed by n-elimination of HCl to generate imine III.
b
Product was benzene-1,4-dicarbonitrile. Imine III also reacts with trichloroisocyanuric acid to
form the N-chloroimine IV, and finally elimination of HCl
by ammonia occurs to provide the nitrile 5a.21
Furthermore, we used this reaction to prepare nitriles in a
one-pot procedure from amines 1. In this case, the reac- CN
TCCA
tion can be carried out in a single step; under the same N

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H 2
aq NH3 (3 mL)
conditions with trichloroisocyanuric acid (0.75 mmol) in 6 60 °C, 4 h, 90% 5a
aqueous ammonia (30%, 3 mL) at 60 °C, benzylamine
(1a) afforded benzonitrile (5a) within one hour in 96% TCCA
(– HCl)
yield (Table 1, entry 1). Further, we examined the feasi-
bility of this reaction for various substrates, and the results H
Cl
are summarized in Table 1, entries 1–7. R N R
R-C=N
A plausible mechanism for the conversion of a primary VI Cl H H IV
amine 1 into nitrile 5 is shown in Scheme 3. According to (– HCl) R-CH-NH
this mechanism, the initial N-chlorination of the amine V Cl
with trichloroisocyanuric acid occurs to form the N-chlo- R N R TCCA
(– HCl)
roamines V. This is followed by b-elimination of HCl by VII
ammonia, leading to the aldimine III. Then, the aldimine NH3
TCCA
III reacts with trichloroisocyanuric acid in the presence of
NH2
ammonia to form an N-chloroaldimine IV, followed by b-
elimination of HCl by ammonia to generate the corre- R N
H
R R-CH2-NH2
+ R-CH=NH

sponding nitrile 5.26 VIII IX III

We found that under these conditions, dibenzylamine (6) Scheme 5

reacted with trichloroisocyanuric acid in aqueous ammo-
nia to provide benzonitrile (5a) in good yields Based on the results of above study, we planned to per-
(Scheme 4). form the direct oxidative conversion of primary alkyl
halides 4 into the corresponding nitriles using trichloro-
TCCA
isocyanuric acid in aqueous ammonia. Primary alkyl
3 RCH2NH2 3 R CN halides should react with ammonia via an SN2 nucleo-
1 NH3, 60 °C 5
philic pathway to form the corresponding primary amines
O
O
Cl
Cl
– HX that can be smoothly oxidized to corresponding nitriles by
N N
HN NH
Cl
trichloroisocyanuric acid in one-pot. Practically, the reac-
O N O
O N O 3 R-C=N IV
tion was carried out by treating benzyl bromide (4a, 1
H Cl H mmol) in aqueous ammonia (28–30%, 3 mL) with
trichloroisocyanuric acid (1 mmol) at 60 °C in round-
H TCCA bottomed flask to provide benzonitrile (5a) in good yield
3
R NH – HX
3 R-CH=NH
(Table 1, entry 25). 4-Methylbenzyl, 4-methoxybenzyl,
V
Cl
III
and 4-chlorobenzyl halides 4b,c,e could be also converted
into the corresponding nitriles 5b,c,e in good yields under
Scheme 3 the same conditions (Table 1, entries 28–33). 1-Naphthyl-
methyl bromide (4k) could also be converted into corre-

Synthesis 2010, No. 15, 2631–2635 © Thieme Stuttgart · New York

2634 H. Veisi
sponding naphthalene-1-carbonitrile (5k) in good yield
under the same conditions (Table 1, entry 34).
Clearly, the present reaction is a good method for the di-
rect preparation of aromatic nitriles from benzylic halides.
That means that the use of the Sandmeyer reaction (dia-
zonium with CuCN) or the dehydration of aromatic
amides with dehydrating agents is not required. We have
also examined the preparation of aliphatic nitriles under
the same reaction conditions, but we did not observe any
notable conversions.
A possible reaction pathway for the conversion of benzyl-
ic halides into corresponding aromatic nitriles, with
trichloroisocyanuric acid in aqueous ammonia is shown in
Scheme 6. The initial nucleophilic reaction of ammonia
with the benzylic halide 4 occurs to generate correspond-
ing primary amine IX. N-Chlorination of amine IX with
trichloroisocyanuric acid take place to provide N-chloro
compound V, followed by b-elimination of HCl with am-
monia to provide aldimine III. Then, aldimine III reacts
with trichloroisocyanuric acid to generate N-chloro com-
pound IV, and this is followed by b-elimination of HCl
with ammonia to give the corresponding nitrile 5.
3 RCH2X
TCCA
3 R CN
4 NH3, 60 °C 5
NH3 – HX
3 RCH2NH2 IX
3 R-C=N
O H
Cl
Cl
N N
O
O N O TCCA
HN NH
Cl H
O N O (5) Huber, V. J.; Bartsch, R. A. Tetrahedron 1998, 54, 9281.
3 3 R-CH=NH
H NH
R – HX
V Cl III
Scheme 6
In conclusion, a simple and convenient method has been
developed for the direct conversion of alcohols, alde-
hydes, primary amines, and alkyl halides to their corre-
sponding nitriles in good to high yields in aqueous
ammonia catalyzed by trichloroisocyanuric acid as the ox-
idant and reagent. Prominent advantages of these new
methods are their mild reaction conditions, operational
simplicity, easy reaction work-up, and generality of the
reactions.
All commercially available chemicals were obtained from Merck
and Fluka companies, and used without further purification unless
otherwise stated. 1H NMR spectra were recorded on a Jeol 90 MHz
FT NMR spectrometer using TMS as internal standard. IR spectra
were measured on a Perkin Elmer GX FT-IR spectrophotometer.
All yields refer to isolated products.
Nitriles 5 from Benzyl Halides 4; General Procedure
To a mixture of alkyl halide (1 mmol) and aq NH3 (3.0 mL, 45
mmol) in round bottomed flask was added TCCA (1 mmol) slowly
and very carefully in several small portions at r.t.. The obtained
Synthesis 2010, No. 15, 2631–2635 © Thieme Stuttgart · New York
PAPER
mixture was stirred at 60 °C. When the reaction was complete (TLC
hexane–acetone, 6:1), it was quenched at this temperature with H2O
(10 mL) and it was then was extracted with Et2O (3 × 15 mL). The
combined organic layers were washed with brine and dried
(MgSO4) to give 5 in good yield. If necessary, the product was pu-
rified by column chromatography (silica gel, hexane–EtOAc, 4:1).
Nitriles from Amines 1, Alcohols 2, and Aldehydes 3; General
Procedure
To a mixture of amine, alcohol or aldehyde (1 mmol) and aq NH3
(3.0 mL, 45 mmol) in a round-bottomed flask was added TCCA
(0.75 mmol) slowly and very carefully in several small portions at
r.t. The obtained mixture was stirred at 60 °C. When the reaction
was complete (TLC hexane–acetone, 6:1), it was quenched at this
temperature with H2O (10 mL), and it was then was extracted with
Et2O (3 × 15 mL). The combined organic layers were washed with
brine and dried (MgSO4) to give 5 in good yield. If necessary, the
product was purified by column chromatography (silica gel, hex-
ane–EtOAc, 4:1).
Acknowledgment
We are thankful to Payame Noor University of Songhor, Istanbul
Technical University, and the University of Sheffield for NMR,
Mass spectra and CHN.
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Synthesis 2010, No. 15, 2631–2635 © Thieme Stuttgart · New York