Novel applications of 2-cyanoethylanilines in the synthesis of conjugated primary and secondary anilines

Article abstract of DOI:10.1016/j.tetlet.2003.12.033

2-Cyanoethyl anilines were controllably cleaved by 1equiv of potassium t-butoxide in dry THF with a reaction that can be used in situ with the Wittig reaction to synthesize conjugated primary and secondary anilines.

Full text of DOI:10.1016/j.tetlet.2003.12.033

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1473–1475
Novel applications of 2-cyanoethylanilines in the synthesis
of conjugated primary and secondary anilines
Yi Liao* and Bruce H. Robinson
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA
Received 11 November 2003; revised 8 December 2003; accepted 8 December 2003
Abstract—2-Cyanoethyl anilines were controllably cleaved by 1 equiv of potassium t-butoxide in dry THF with a reaction that can
be used in situ with the Wittig reaction to synthesize conjugated primary and secondary anilines.
Ó 2003 Elsevier Ltd. All rights reserved.
Conjugated aromatic amines are of great interest
because of their potential applications as nonlinear
optical materials,1 as hole transporting materials for
electrophotography, and as electroluminescent materi-
als.2 Preparation of conjugated tertiary anilines is
straightforward and well documented.3 Commonly,
conjugated systems consist of aromatic rings and car-
bon–carbon double bonds. Such structures are generally
synthesized by either a Wittig (or Wittig–Horner) reac-
tion or Heck reaction. The alkene reactant in the Heck
reaction is also usually prepared by a Wittig reaction.
Primary and secondary anilines are important materials.
They are also intermediate materials as precursors for
complicated tertiary anilines. However, preparation of
primary and secondary conjugated anilines is not
straightforward. Direct use of primary and secondary
anilines in a Wittig reaction is impossible because of the
side reaction with aldehyde. So they must be protected
before the reaction. In fact, synthesizing and protecting
amino-aryl-aldehyde is also difficult. For example,
although 4-aminobenzaldehyde can be synthesized in its
monomer form, it polymerizes quickly in organic sol-
vents.4 Thus, protected amino-aryl-phosphonium salts
or phosphates have to be used as one of the reactants in
a Wittig reaction. Such compounds are usually not
commercially available and require multi-step reactions
to prepare.
We discovered that when 2-cyanoethyl anilines were
treated with 1 equiv of potassium t-butoxide in dry THF
at room temperature, the 2-cyanoethyl group was
cleaved nearly quantitatively. To our surprise, this
reaction, though very efficient, does not significantly
interfere with Wittig (or Wittig–Horner) reaction. Thus,
when primary or secondary conjugated anilines are
synthesized by a Wittig reaction, the 2-cyanoethyl group
can be either kept on the product for future cleavage or
cleaved in situ. The 2-cyanoethyl group has been used to
protect carboxylic acid5 and thiouridine,6 but it has
never been reported as a protecting group of aromatic
amines. Plakidin et al. observed the cleavage of a 2-cy-
anoethyl aniline by diethyl amine at 130 °C.7 Babayan
et al. reported thermal and alkaline cleavage of quater-
nary ammonium salts containing the 2-cyanoethyl
group.8 They prepared MeNHR [R ¼ allyl, benzyl,
CH2CHCClCH3, C HCHC(CH3)2] by reacting KOH
2
with the corresponding RNMeCH2CH2CN at 140–
250 °C. Our method of using potassium t-butoxide in
dry THF is more efficient and very convenient for syn-
thesizing conjugated primary and secondary anilines.
2-Cyanoethyl aniline can be prepared easily by reacting
the corresponding aniline with acrylonitrile.9 However,
a more practical way is using commercially available
2-cyanoethyl anilines. More than 1000 commercially
available compounds can be found in the Scifinder
database.
As a demonstration of this reaction, a solution of 4-[(2-
cyanoethyl)methylamino]benzaldehyde and diethyl (2-
thienylmethyl)phosphonate in THF was treated with
1 equiv of 1 N potassium t-butoxide solution in THF, 1
formed (76% yield) together with a small amount of 2
(12% yield). When 2 equiv of potassium t-butoxide were
Keywords: Cleavage; 2-Cyanoethyl aniline; Primary anilines; Second-
ary anilines.
* Corresponding author. Tel.: +1-206-616-1290; fax: +1-206-685-8665;
e-mail: liaoyi@u.washington.edu
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.033

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Y. Liao, B. H. Robinson / Tetrahedron Letters 45 (2004) 1473–1475
References and notes
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Rebane, A.; Spangler, C. W. Opt. Lett. 2001, 26, 1081;
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Heikal, A. A.; Hess, S. E.; Kogej, T.; Levin, M. D.;
Marder, S. R.; McCord-Maughon, D.; Perry, J. W.;
Rockel, H.; Rumi, M.; Subramaniam, G.; Webb, W. W.;
Wu, X.; Xu, C. Science 1998, 281, 1653–1656.
2. For example: Sato, K.; Yano, M.; Furuichi, M.;
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Katsuma, K.; Shirota, Y. J. Am. Chem. Soc. 1997, 119,
6607; Wienk, M. M.; Janssen, R. A. J. Am. Chem. Soc.
1997, 119, 4492.
Scheme 1.
3. For example: Plater, M. J.; Jackson, T. Tetrahedron 2003,
59, 4673.
4. Campaigne, E. E.; Budde, W. M.; Schaefer, G. F. Org.
Synth. 1951, 31, 6–8.
5. Misra, P. K.; Hashmi, S. A. N.; Haq, W.; Katti, S. B.
Tetrahedron Lett. 1989, 30, 3569; Ogawa, T.;
Hatayama, K.; Maeda, H.; Kita, Y. Chem. Pharm. Bull.
1994, 42, 1579.
6. Adams, C. J.; Murray, J. B.; Arnold, J. R. P.; Stockley, P.
G. Tetrahedron Lett. 1994, 35, 765.
7. Plakidin, V. L.; Vostrova, V. N. J. Org. Chem. USSR
(Engl. Transl.) 1982, 18, 295.
8. Babayan, A. T.; Martirosyan, G. T.; Grigoryan, D. V.;
Grigoryan, E. A. Khimicheskie Nauki 1963, 16, 449;
Grigoryan, D. V.; Kazaryan, A. T.; Martirosyan, G. T.;
Babayan, A. T. Zh. Org. Khim. 1970, 6, 1390.
9. For example: Shawcross, A. P.; Stanforth, S. P. Tetra-
hedron 1989, 45, 7063; Rodriguez, J. G.; Canoira, L.;
Calderon, C. E.; Martinez-Ripoll, M.; Blanco, S. G.
J. Chem. Soc., Perkin Trans. 2 1986, 199; Butskus, P. F.
J. Gen. Chem. USSR 1961, 31, 701; Heininger, S. A. Org.
Synth. 1958, 38, 14.
10. Falicki, S.; Alper, H. Organomet 1988, 7, 2548.
11. Synthetic procedure of 2: To a mixture of 1.88 g (10 mmol)
of 4-[(2-cyanoethyl)methylamino]benzaldehyde and 2.53 g
(11.5 mmol) of diethyl (2-thienylmethyl)phosphonate in
20 mL of dry THF was added 23 mL of 1 N potassium
t-butoxide solution in THF at 0 °C. The mixture was
stirred at room temperature for 24 h. The reaction was
quenched and washed by 20 mL of water. The aqueous
layer was extracted by 20 mL of CH2Cl2 twice. The organic
layers were combined and concentrated under reduced
pressure. The residue was purified by chromatograph on
silica using 1:4 ethylacetate/hexane as the eluant to give
1.83 g of 2 (85% yield). Procedure of 4: To a mixture of
0.684 g (3 mmol) of 3 and 1.37 g (6 mmol) of diethyl
benzylphosphonate in 5 mL of dry THF was added
10 mL of 1 N potassium t-butoxide solution in THF at
0 °C. The mixture was stirred at room temperature for 24 h.
The reaction was quenched and washed by 20 mL of water.
The aqueous layer was extracted by 20 mL of CH2Cl2
twice. The organic layers were combined and concentrated
under reduced pressure. The residue was purified by
chromatograph on alumina using 7:3 CH2Cl2/hexane as
the eluant to give 0.36 g of 4 (62% yield).
Scheme 2.
used, 1 was cleaved in situ and only 2 formed in 85%
yield. 2 can also be synthesized by treating 1 with 1 equiv
of potassium t-butoxide (Scheme 1).
When bis-2-cyanoethyl aniline is used, primary conju-
gated anilines can be synthesized. Primary conjugated
anilines can be synthesized by reducing the corre-
sponding nitro compounds. For example, 4-aminostil-
bene was prepared by reducing 4-nitrostilbene.10 Our
method provides an alternative route. To demonstrate
this, 4-[di-2-cyanoethyl-amino]benzaldehyde 3 was syn-
thesized from commercially available N,N-bis(cyano-
ethyl)aniline by a Vilsmeier formylation. A mixture of
3and diethyl benzylphosphonate in THF was treated
with 3 equiv of 1 N potassium t-butoxide solution in
THF to give 4-aminostilbene in 62% separated yield
(Scheme 2).
The procedures of preparing 2 and 4, and the charac-
terizations of compounds 1–4 are attached in Ref. 11.
In conclusion, we reported an efficient method to cleave
2-cyanoethyl aniline. This method makes the 2-cyano-
ethyl group a potential protecting group for amines.
More importantly, it can be used in situ with the Wittig
reaction to synthesize secondary and primary conju-
gated anilines.
1, 1H NMR, d (ppm, CDCl3): 7.39 (2H, d, J ¼ 8:9 Hz),
7.15–6.95 (4H, m), 6.84 (1H, d, J ¼ 16:1 Hz), 6.73 (2H, d,
J ¼ 8:9 Hz), 3.73 (2H, t, J ¼ 6:9 Hz), 3.07 (3H, s), 2.61 (2H,
t, J ¼ 6:9 Hz); MS (Electron Spray): 269.1 (M+Hþ). 2, 1H
NMR, d (ppm, CDCl3): 7.32 (2H, d, J ¼ 8:6 Hz), 7.13–6.94
(4H, m), 6.84 (1H, d, 16.1 Hz), 6.62 (2H, d, J ¼ 8:6 Hz),
4.52 (1H, b, NH), 2.87 (3H, s); MS (Electron Spray): 216.1
Acknowledgements
Support from the Air Force Office of Scientific Research
is gratefully acknowledged.
1
(M+Hþ). 3, H NMR, d (ppm, CDCl3): 9.81 (1H, s), 7.81

Y. Liao, B. H. Robinson / Tetrahedron Letters 45 (2004) 1473–1475
1475
(2H, d, J ¼ 9:0 Hz), 6.73 (2H, d, J ¼ 9:0 Hz), 3.90 (4H, t,
J ¼ 6:5 Hz), 2.71 (4H, t, J ¼ 6:5 Hz); MS (Electron Spray):
228.1 (M+Hþ). 4, 1H NMR, d (ppm, CDCl3): 7.46 (2H, d,
J ¼ 7:0 Hz), 7.34–7.18 (5H, m), 7.02 (1H, d, J ¼ 15:0 Hz),
6.90 (1H, d, J ¼ 15:0 Hz), 6.66 (2H, d, J ¼ 8:4 Hz), 3.73 (b,
2H, NH2). MS (Electron Spray): 196.1 (M+Hþ).