Direct synthesis of nitriles from aldehydes using tetrabutylammonium tribromide in aqueous ammonia

Article abstract of DOI:10.1007/s00706-010-0305-5

A convenient method for direct conversion of aldehydes into nitriles has been developed by using tetrabutylammonium tribromide in aqueous ammonia. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-010-0305-5

Monatsh Chem (2010) 141:637–639
DOI 10.1007/s00706-010-0305-5
ORIGINAL PAPER
Direct synthesis of nitriles from aldehydes using tetrabutyl-
ammonium tribromide in aqueous ammonia
Yi-Zhong Zhu Chun Cai
•
Received: 8 December 2008 / Accepted: 17 March 2010 / Published online: 16 April 2010
Ó Springer-Verlag 2010
Abstract A convenient method for direct conversion of
aldehydes into nitriles has been developed by using tetra-
butylammonium tribromide in aqueous ammonia.
HY–zeolite [25], NH OHÁHCl/graphite/MeSO Cl [26],
2
2
NH OHÁHCl/NaI/MeCN [27], NH OHÁHCl/KF–Al O /
2
2
2 3
˚
DMF [28], NH OHÁHCl/DBU/EtOPOCl /MS 3A [29], and
2
2
NH OHÁHCl/KI/ZnO/CH CN [30]. Furthermore, the one-
2
3
Keywords Tetrabutylammonium tribromide Á
pot synthesis of nitriles direct from aldehydes and ammo-
nia water by oxidation of the aldimines formed in situ by
condensation of aldehydes and ammonia is considered as
an expedient method and has been studied with NH /O /
Aqueous ammonia Á Nitriles Á Aldehydes Á Oxidation
3
2
Introduction
CuCl ÁH O/MeONa in MeOH [31], NH /Pb(OAc) in dry
2
2
3
4
benzene [32], NH /I /MeONa in MeOH [33], NH /S /
3
2
3
8
Nitriles are important compounds not only because of their
interesting biological properties, but also their use as ver-
satile starting materials for many important aromatic
compounds, including acids, ketones, oximes, and amines
NaNO [34], NH /H O /CuCl in 2-propanol [35], NH /I
2 3 2 2 3 2
in THF–water [36], NH /CAN [37], NH /NBS [38], NH /
3
3
3
IBX in acetonitrile–water [39], and NH /NaICl [40].
3
2
Although some of these methods present advantages over
other reaction pathways in that the reactions could be
carried out at low temperatures, drawbacks such as the
formation of by-products [33], harsh reaction conditions
[34], production of explosive NI ÁNH [36], or use of
[
1, 2].
Various methods for the synthesis of nitriles have been
reported. Among these methods, the most widely used are
based on the transition-metal-mediated displacement of
aromatic halides and triflates by the cyanide ion [3–18]. On
the other hand, an important alternative for the synthesis of
nitriles is to use aldehydes as substrates. Generally, the
conversion of aldehydes into nitriles was achieved by
dehydration of the corresponding aldoximes by using
reagents such as NH OHÁHCl/NEt /phthalic anhydride
3
3
expensive reagents [32, 39] have extremely limited their
application. The development of this methodology using
new reagents under mild conditions is therefore of interest.
Tetrabutylammonium tribromide (TBATB) is a brominat-
ing agent which is crystalline, easy to handle, and has not
been used for this transformation. Following our interest in
the synthesis of nitriles [41, 42], herein we report a con-
venient method for direct transformation of aldehydes to
nitriles by using TBATB [43] in aqueous ammonia under
mild conditions (Scheme 1).
2
3
[
19],
NH OHÁHCl/peroxymonosulfate–alumina
[20],
2
NH OHÁHCl/N-methylpyrrolidine [21], NH OHÁHCl/
2
2
ammonium acetate [22], NH OH/MgSO /MnO [23],
4
4
2
NH OHÁHCl/dry Al O /MeSO Cl [24], NH OHÁHCl/
2
2
3
2
2
TBATB/aq. NH3
RCHO
RCN
Y.-Z. Zhu Á C. Cai (&)
Chemical Engineering College, Nanjing University of Science
and Technology, Nanjing 210094, People’s Republic of China
e-mail: c.cai@mail.njust.edu.cn
1
2
Scheme 1
123

6
38
Y.-Z. Zhu, C. Cai
Table 1 Conversion of aldehydes into nitriles using TBATB and aqueous ammonia
b
Entry
RCHO
CHO
RCN
Period (h)
Yield (%)
Mp or bp/p (°C or °C/Torr)
Mp or bp/p (°C or °C/Torr) [Ref.]
1
2
3
4
C
H
6 5
2a
2b
2c
2d
2e
2f
2
3
89
92
93
91
81
82
83
80
84
82
81
3
188–190/760
91–92
187/760 [24]
90 [26]
4-ClC
3-ClC
2-ClC
6
H
6
H
6
H
4
CHO
4
CHO
4
CHO
3
39–40
38–40 [44]
42 [24]
4
42–44
a
5
4-MeC
6
H
4
CHO
CHO
CHO
CHO
5
217–218/760
58–59
216–218/760 [21]
60 [26]
a
6
4-MeOC
6
H
4
6
7
8
9
4-CF
4-FC
3
C
6
H
4
2g
2h
2i
8
37–38
39–41 [45]
188/750 [45]
47 [26]
6
H
4
12
8
186–188/760
47–48
3-Pyridinecarboxaldehyde
1
0
1
CH
CH
3
(CH
(CH
2
)
)
3
CHO
CHO
2j
12
12
139–140/760
186–187/760
138/760 [26]
186/760 [21]
1
3
2
5
2k
Reaction conditions: aldehyde (2 mmol), aqueous ammonia (10 cm ), TBATB (3 mmol), rt
a
TBATB (4 mmol) was used
b
Isolated yields
Results and discussion
Experimental
Benzaldehyde was chosen as a model substrate. After sur-
veying a series of reaction conditions, we found that the
Typical procedure for the conversion of aldehydes
into nitriles
optimal conditions were benzaldehyde (2 mmol), TBATB
3
1.5 equiv.), and ammonia water (10 cm ) at room temper-
3
(
A suspension of an aldehyde (2 mmol) and 10 cm
ature (rt) for 2 h, which provided the desired product 2a in
9% yield. Encouraged by that result, we examined a range of
ammonia water was stirred for 10 min at room tempera-
ture, resulting in formation of a turbid solution. TBATB
(3 mmol), prepared from tetrabutylammonium bromide
according to ref. [43], was added slowly at room temper-
ature to this turbid solution. Then the mixture was stirred
strongly for an appropriate time (see Table 1) as indicated
by TLC. After the reaction was completed, solid products
were collected by simple filtration, whereas liquid products
were obtained by usual work-up through extraction with
8
aldehydes. As shown in Table 1, various aromatic, hetero-
cyclic, and aliphatic aldehydes were efficiently transformed
into their corresponding nitriles in good yields. As expected,
no bromination products were observed in these reactions.
A plausible reaction pathway for the conversion of
aldehydes into the corresponding nitriles with TBATB is
similar to that with molecular iodine suggested by Togo
and co-workers (Scheme 2) [46]. Thus, the reaction pro-
ceeded via oxidation of the aldimine with TBATB to give
an N-bromo aldimine intermediate, which eliminated an
3
ethyl acetate (2 9 25 cm ). The combined organic layer
3
was washed with H O (2 9 15 cm ). Then the organic
2
layer was dried over Na SO , filtered, and concentrated in
4
2
HBr molecule in the presence of NH to afford the nitrile
3
vacuo. If necessary, the product was purified by flash
chromatography on silica gel with EtOAc–petroleum ether
as the eluent. All prepared nitriles are known compounds
and were identified by mp or bp and GC–MS.
product. Here, TBATB may play not only the role of an
oxidant, but also a phase transfer reagent.
In summary, we disclosed a new and efficient one-pot
reaction for the synthesis of nitriles from aldehydes through
oxidation of in situ formed aldimines by using TBATB/aq.
Acknowledgments We are grateful to Nanjing University of Sci-
ence and Technology for financial support.
NH , which offers a useful synthetic method for the prep-
3
aration of nitriles due to its simplicity and good yields.
References
O
TBATB/aq. NH 3
C
R C N
1
2
. Liu KC, Howe RK (1983) J Org Chem 48:4590
. Harris TM, Harris CM, Oster TA, Brown LE, Lee JYC Jr (1988) J
Am Chem Soc 110:6180
. Sundermeier M, Zapf A, Beller M (2003) Eur J Inorg Chem 3513
. Chidambaram R (2004) Tetrahedron Lett 45:1441
R
H
NH3 (-H O)
(-HBr)
2
3
4
TBATB
R CH NH
R CH N Br
5. Marcantonio KM, Frey LF, Liu Y, Chen Y, Strine J, Phenix B,
Wallace DJ, Chen CY (2004) Org Lett 6:3723
6. Collibee SE, Strivastava RR (2004) Tetrahedron Lett 45:8895
Scheme 2
1
23

Direct synthesis of nitriles from aldehydes
639
7
8
. Williams JM, Yang CY (2004) Org Lett 6:2837
. Stazi F, Palmisano G, Turconi M, Stantagostino M (2005) Tet-
rahedron Lett 46:1815
29. Zhu J-L, Lee F-L, Wu J-D, Kuo C-W, Shi K-S (2007) Synlett
1317
30. Kivrak A, Zora M (2007) J Organomet Chem 692:2346
31. Brackman W, Smit P (1963) J Recl Trev Chim 82:757
32. Parameswaram KN, Friedman OM (1965) Chem Ind (London)
988
33. Misono A, Osa T, Koda S (1966) Bull Chem Soc Jpn 39:854
34. Sato R, Itoh Y, Itep K, Nihina H, Goto T, Saito M (1984) Chem
Lett 1913
35. Erman MB, Snow JW, Williams MJ (2000) Tetrahedron Lett
41:6749
9
. Hatsuda M, Seki M (2005) Tetrahedron 61:9908
1
1
0. Hatsuda M, Seki M (2005) Tetrahedron Lett 46:1849
1. Jensen ML, Gajare AS, Toyota K, Yoshijuji M, Ozawa F (2005)
Tetrahedron Lett 46:8645
2. Lin LS, Fors BP, Chobanian HR (2006) Tetrahedron Lett 47:3303
3. Whittall J, Cormack PM, Pitts WR (2006) Tetrahedron 62:4705
4. Martin MT, Liu B, Cooley BE Jr, Eaddy JF (2007) Tetrahedron
Lett 48:2555
1
1
1
1
1
5. Polshettiwar V, Hesemann P, Moreau JJE (2007) Tetrahedron
3:6784
6. Littke A, Soumeillant M, Kaltenbach RF III, Cherney RJ, Tarby
CM, Kiau S (2007) Org Lett 9:1711
7. Nandurkar NS, Bhanage BM (2008) Tetrahedron 64:3655
8. Franz AW, Popa LN, Li T, M u¨ ller TJJ (2008) Tetrahedron Lett
36. Talukdar S, Hsu JL, Chou TC, Fang JM (2001) Tetrahedron Lett
42:1103
37. Bandgar BP, Makone SS (2003) Synlett 262
38. Bandgar BP, Makone SS (2006) Synth Commun 36:1347
39. Arote ND, Bhalerao DS, Akamanchi KG (2007) Tetrahedron Lett
48:3651
6
1
1
4
9. Wang EC, Lin GJ (1998) Tetrahedron Lett 39:4047
0. Bose DS, Narsaiah AV (1998) Tetrahedron Lett 39:6533
1. Kumar HMS, Reddy BVS, Reddy PT, Yadav JS (1999) Synthesis
9:3300
40. Telvekar VN, Patel KN, Kundaikar HS, Chaudhari HK (2008)
Tetrahedron Lett 49:2213
1
2
2
41. Zhu Y-Z, Cai C (2007) Eur J Org Chem 2401
42. Zhu Y-Z, Cai C (2008) Aust J Chem 61:581
43. Chaudhuri MK, Khan AT, Patel BK, Deepa D, Kharmawophlang
W, Lakshmiprabha TR, Mandal GC (1998) Tetrahedron Lett
39:8163
44. Manjula K, Pasha MA (2006) Synth Commun 37:1545
45. Online data from product catalog (2009) Sigma-Aldrich. http://
www.sigmaaldrich.com/technical-service-home/product-catalog.
html.
5
86
2
2
2
2
2
2
2
2. Das B, Ramesh C, Madhusudhan P (2000) Synlett 1599
3. Lai G, Bhamare NK, Anderson WK (2001) Synlett 230
4. Sharghi H, Sarvari MH (2002) Tetrahedron 58:10323
5. Srinivas KVNS, Reddy EB, Das B (2002) Synlett 625
6. Sharghi H, Sarvari MH (2003) Synthesis 243
7. Ballini R, Fiorini D, Plamieri A (2003) Synlett 1841
8. Movassagh B, Shokri S (2005) Tetrahedron Lett 46:6923
46. Mori N, Togo H (2005) Synlett 1456
123