The first isolation of α-hydroperoxy-N-arylimidoyl cyanides from 2- arylamino-2-alkenenitriles (α-cyanoenamines)

Article abstract of DOI:10.1016/S0040-4039(99)02320-5

Treatment of N-1-(2-chloroalkylidene)arylamines 6 with KCN in CH₃CN at reflux afforded 2-arylamino-2-alkenenitriles 3 (42-58%), which underwent autoxidation, yielding the corresponding α-hydroperoxyimidoyl cyanides (95- 100%). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02320-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1469–1473
The first isolation of α-hydroperoxy-N-arylimidoyl cyanides from
2-arylamino-2-alkenenitriles (α-cyanoenamines)
Sangmin Yun and Kyongtae Kim ∗
Department of Chemistry, Seoul National University, Seoul 151-742, South Korea
Received 26 October 1999; revised 3 December 1999; accepted 10 December 1999
Abstract
Treatment of N-1-(2-chloroalkylidene)arylamines 6 with KCN in CH3CN at reflux afforded 2-arylamino-2-
alkenenitriles 3 (42–58%), which underwent autoxidation, yielding the corresponding α-hydroperoxyimidoyl
cyanides (95–100%). © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: cyano compounds; imines; enamines; peroxides.
N-Alkyl α-cyanoenamines 1 and N-methyl-N-phenyl α-cyanoenamines 2 have received considerable
attention as starting materials for the preparation of a variety of organic compounds.1 Among them,
trialkylketenimines,2 prepared by treatment of 1 with methylmagnesium iodide in ether, followed by
addition of water, reacted with singlet oxygen to give 3-alkylimino-1,2-dioxetanes, exhibiting weak
chemiluminescence upon heating.3 Nevertheless, α-hydroperoxy-N-alkylimidoyl cyanides, which may
act as precursors to the above 1,2-dioxetanes have never been isolated. Furthermore, a survey of the
literature shows that no 3-arylimino-1,2-dioxetanes were detected even under the same conditions as for
the isolation of 3-alkylimino-1,2-dioxetanes.3c
In a continuation of our study on exploiting the synthetic utility of 2,5-diarylisoxazolidine-3-thiones 4,4
we have found that 2,5-diphenyl-4,4-dimethylisoxazolidine-3-thione 4a (R1=R2=Me, Ar=Ar0=Ph)5 reac-
ted with diethylaluminum cyanide (Et2AlCN) in toluene at reflux under a nitrogen atmosphere to give 3-
methyl-2-phenylamino-2-butenenitrile 3a (R1=R2=Me, Ar=Ph) in 41% yield6 (Scheme 1). Interestingly,
compound 3a was slowly converted to α-hydroperoxy-N-phenylimidoyl cyanide 5a (R1=R2=Me, Ar=Ph)
either in crystalline or in a solution state in the air. The results prompted us to investigate the stability of
other N-aryl α-cyanoenamines 3, which could be readily prepared from N-aryl α-chloroaldimines 67 and
KCN in CH3CN at reflux according to the literature method.8 It has been found that all of the compounds
3 prepared undergo autoxidation, yielding hydroperoxides analogous to 5a. Reaction times, yields, and
mps of 2-arylamino-2-alkenenitriles 3 and α-hydroperoxy-N-arylimidoyl cyanides 5 are summarized in
Table 1.
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02320-5
tetl 16248

1470
Scheme 1.
Table 1
Reaction times, yields, and mps of 2-arylamino-2-alkenenitriles 3 and α-hydroperoxy-N-arylimidoyl
cyanides 5
The extent of the conversion of 3a into 5a was determined based on the chemical shifts (CDCl3, 300
MHz) of the methyl protons of 3a at δ 1.86 and 2.12 ppm and those of 5a at δ 1.63 ppm as a single peak.
The conversion proceeded faster in non-polar solvents than in polar solvents as shown in Table 2. An
analogous effect of the solvent effect was observed from rapid oxygen uptake of acyl cyanide in non-polar
solvents.3e When R1 and R2 were methyl groups as in 3a–g, it took 44 to 59 h for complete conversions
to the corresponding 5a–g in CHCl3. In contrast, when one of the methyl groups was substituted for ethyl
group as in a mixture of 3i and 3j or both R1 and R2 were ethyl groups as in 3h, it took 240 h and 360
h, respectively, until the spots corresponding to 3 had completely disappeared. The results indicate that
the presence of a bulkier group(s) than the methyl group at the β-position of N-aryl α-cyanoenamines
3 drastically retards the autoxidation. Nevertheless, it is interesting to note that the same reaction times
took the same period (44 h) for the conversion of both 3k (R1-(CH2)5-R2) and 3a to the corresponding
hydroperoxides 5j and 5a, respectively.
Unexpectedly, treatment of 3a with N-chlorosuccinimide (NCS) in CCl4 at room temperature gave 5a
as a major product (67%) along with α-chloro-N-phenylimidoyl cyanide 7 (22%), whereas compound 7
was obtained as a major product (61%) under nitrogen atmosphere (Scheme 2). The result may be due to
no rigorous exclusion of oxygen in view of the formation of α-chloro-N-alkylimidoyl cyanides in almost
quantitative yields under the same conditions.10
Compounds 5a, 5e, 5f, and 5j among the compounds 5 prepared were obtained in crystalline states

1471
Table 2
Percentages for the conversion (3a→5a) for 44 h
Scheme 2.
by recrystallization. However, compounds 5b–d and 5g–i were sticky solids, whose structures were
identified by conversion to the corresponding peroxides 8b–d and 8g–i, respectively (Scheme 3), which
gave satisfactory spectroscopic (NMR, IR) and analytical data.
Scheme 3.
Compounds 5 undergo slow decomposition in the air. For example, compound 5c (R1=R2=Me, Ar=4-
BrC6H4) showed several spots on TLC (Rf=0.35, n-hexane:EtOAc=5:1) in a few days (Scheme 4).
The GC-MS data of the mixture exhibited a fragment with m/z 197, corresponding to the molecular
weight of 4-bromophenylisocyanate, where the retention time was identical to that of the authentic
sample. This result may be rationalized based on an intramolecular cyclization of 5c to give 4,4-
dimethyl-N-(4-bromophenyl)imino-1,2-dioxetane 9, which subsequently undergoes decomposition to
yield 4-bromophenylisocyanate and acetone. Analogous reactions have been reported for the formation
of alkylisocyanates and carbonyl compounds from decomposition of 4-substituted 3-alkylimino-1,2-
dioxetanes.3a,b
Scheme 4.
In summary, apart from 2-alkylamino-2-alkenenitriles, 2-arylamino-2-alkenenitriles undergo slow
autoxidation to give their α-hydroperoxy-N-arylimidoyl cyanides. Some of them are isolable in cryst-
alline states. Since the hydroperoxides undergo slow decomposition via N-arylimino-4,4-dimethyl-
1,2-dioxetanes, they may be useful model compounds for further study of the working of natural
bioluminescent systems.

1472
Acknowledgements
The authors are grateful to KOSEF (project 981-0302-011-2) for financial support of this work.
References
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1979, 28, 2835–2838. (g) De Lombaert, S.; Lesur, B.; Ghosez, L. Tetrahedron Lett. 1982, 28, 4251–4254. (h) Costisella,
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Verhé, R.; De Buyck, L.; Schamp, N. Org. Prep. Proced. Int. 1982, 14, 213–215.
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1993, 115, 11716–11721. (e) Jaroszewski, J. W.; Ettlinger, M. G. J. Org. Chem. 1988, 53, 4635–4637.
4. (a) Seo, Y.; Mun, K. R.; Kim, K. Synthesis 1991, 951–953. (b) Seo, Y.; Mun, K. R.; Lee, Y. Y.; Kim, K. J. Korean Chem.
Soc. 1992, 36, 453–459.
5.
6. Typical procedure: To a solution of 4a (386 mg, 1.36 mmol) in toluene (10 mL) was added Et2AlCN (8.24 mmol, 1 M
solution/toluene, 8.24 mL) under a nitrogen atmosphere. The mixture was heated for 9 h at reflux, followed by addition of
water (1 mL) to the cooled reaction mixture. The white solids formed were filtered and washed with CH2Cl2 (50 mL×3).
The filtrate was dried over MgSO4. Evaporation of the solvent, followed by chromatography (silica gel, 70–230 mesh, 2×20
cm) of the residue with benzene gave 3-methyl-2-phenylamino-2-butenenitrile 3a (96 mg, 41%): mp 61–63°C (n-hexane);
1H NMR (CDCl3, 300 MHz) δ 1.86 (s, 3H, Me), 2.12 (s, 3H, Me), 4.87 (s, br, 1H, NH), 6.66 (d, 2H, J=8.4 Hz, ArH), 6.84
(t, 1H, J=8.0 Hz, ArH), 7.23 (t, 2H, J=8.4 Hz, ArH); 13C NMR (CDCl3, 75 MHz) δ 19.22, 22.03, 108.76, 114.23, 116.43,
119.98, 129.36, 143.81, 150.02; IR (KBr) 3360, 2208 (CN), 1633 cm−1; MS (EI) m/z 172 (M+, 100), 157 (M+−Me, 89).
Anal. calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.27. Found: C, 76.65; H, 7.12; N, 16.23.
7. Schepin, V. V.; Fotin, V. V.; Russkikh, N. Yu.; Vikent’eva, A. N.; Sinani, S. V. Zh. Org. Khim. 1989, 25, 733–737.
8. De Kimpe, N.; Verhé, R.; De Buyck, L.; Hasma, H.; Schamp, N. Tetrahedron 1976, 32, 3063–3067.
9. Crystalline compound 3a (100 mg, 0.58 mmol) was dissolved in chloroform (10 mL). The conversion was monitored by
1
TLC. The spot corresponding to 3a (Rf=0.45, CH2Cl2) completely disappeared in 44 h. After removal of the solvent, H
1
and 13C NMR spectra of the residue 5a were taken. The H and 13C NMR spectra of 5a–j were recorded at 300 and 75
MHz, respectively, in CDCl3. Compound 5a: mp 53–55°C (n-hexane–CH2Cl2); 1H NMR δ 1.63 (s, 6H, 2Me), 7.09 (d, 2H,
J=7.5 Hz, ArH), 7.32 (t, 1H, J=7.4 Hz, ArH), 7.44 (t, 2H, J=7.4 Hz, ArH), 8.86 (s, br, 1H, OOH); 13C NMR δ 22.17, 84.96,
110.29, 120.05, 127.61, 129.26, 147.59, 147.70; IR (KBr) 3250, 2224 (CN), 1625 cm−1. Anal. calcd for C11H12N2O2: C,
1
64.69; H, 5.92; N, 13.72. Found: C, 64.86; H, 6.13; N, 13.92. Compound 5b: sticky; H NMR δ 1.61 (s, 6H, 2Me), 7.05
(dt, 2H, J=8.7, 2.0 Hz, ArH), 7.40 (dt, 2H, J=8.7, 2.0 Hz, ArH), 8.89 (s, br, 1H, OOH); 13C NMR δ 22.11, 84.95, 110.15,
121.57, 129.43, 133.27, 146.15, 148.26; IR (neat) 3384, 2216 (CN), 1626 cm−1. Compound 5c: sticky; 1H NMR δ 1.60 (s,
6H, 2Me), 6.97 (d, 2H, J=8.6 Hz, ArH), 7.55 (d, 2H, J=8.6 Hz, ArH), 8.93 (s, br, 1H, OOH); 13C NMR δ 22.17, 84.97,

1473
110.18, 121.19, 121.84, 132.44, 146.79, 148.42; IR (neat) 3384, 2216 (CN), 1632 cm−1. Compound 5d: sticky; 1H NMR δ
1.61 (s, 6H, 2Me), 2.38 (s, 3H, Me), 6.81–6.91 (m, 2H, ArH), 7.11 (d, 1H, J=7.8 Hz, ArH), 7.31 (t, 1H, J=7.5 Hz, ArH),
9.04 (s, br, 1H, OOH); 13C NMR δ 21.26, 22.15, 84.87, 110.30, 116.87, 120.63, 128.30, 129.06, 139.23, 147.38, 147.78; IR
(neat) 3384, 2216 (CN), 1626 cm−1. Compound 5e: mp 61–63°C (n-hexane–CH2Cl2); 1H NMR δ 1.59 (s, 6H, Me), 2.35 (s,
3H, Me), 7.03 (d, 2H, J=8.3 Hz, ArH), 7.20 (d, 2H, J=8.3 Hz, ArH), 9.24 (s, br, 1H, OOH); 13C NMR δ 21.08, 22.18, 84.87,
110.58, 120.35, 129.80, 137.83, 145.19, 146.71; IR (KBr) 3408, 2208 (CN), 1626 cm−1. Anal. calcd for C12H14N2O2: C,
1
66.04; H, 6.47; N, 12.84. Found: C, 66.01; H, 6.41; N, 12.89. Compound 5f: mp 54–57°C (n-hexane–CH2Cl2); H NMR
δ 1.62 (s, 6H, 2Me), 2.19 (s, 3H, ArMe), 6.86–6.92 (m, 1H, ArH), 7.15–7.29 (m, 3 H, ArH), 8.98 (s, br, 1H, OOH); 13C
NMR δ 17.62, 22.22, 84.93, 110.25, 117.72, 126.69, 127.36, 129.52, 130.72, 147.01, 147.83; IR (KBr) 3384, 2216 (CN),
1
1634 cm−1. Anal. calcd for C12H14N2O2: C, 66.04; H, 6.47; N, 12.84. Found: C, 65.98; H, 6.43; N, 12.81. 5g: sticky; H
NMR δ 1.60 (s, 6H, 2Me), 3.82 (s, 3H, OMe), 6.94 (dt, 2H, J=9.0, 2.1 Hz, ArH), 7.22 (dt, 2H, J=9.0, 2.1 Hz, ArH), 9.20
(s, br, 1H, OOH); 13C NMR δ 22.22, 55.44, 84.91, 111.04, 114.31, 122.74, 140.31, 144.48, 159.48; IR (neat) 3441, 2214
(CN), 1622 cm−1. Compound 5h: sticky; 1H NMR δ 0.97 (t, 6H, J=7.5 Hz, 2Me), 1.88–2.12 (m, 4H, 2CH2), 7.05 (t, 2H,
J=7.8 Hz, ArH), 7.27 (t, 1H, J=7.5 Hz, ArH), 7.41 (t, 2H, J=7.6 Hz, ArH), 9.23 (s, br, 1H, OOH); 13C NMR δ 7.00, 23.94,
1
89.43, 110.43, 119.83, 127.23, 129.14, 148.03, 148.12; IR (neat) 3360, 2208 (CN), 1622 cm−1. Compound 5i: sticky; H
NMR δ 1.00 (t, 6H, J=7.5 Hz, 2Me), 1.58 (s, 6H, 2Me), 1.80–2.05 (m, 4H, 2CH2), 2.36 (s, 6H, 2ArMe), 7.02 (d, 4H, J=8.3
Hz, 2ArH), 7.21 (d, 4H, J=8.3 Hz, 2ArH), 9.06 (s, br, 2H, 2OOH); 13C NMR δ 7.42, 18.87, 21.02, 28.32, 87.33, 110.68,
120.25, 129.76, 137.74, 145.28, 146.81; IR (neat) 3360, 2208 (CN), 1616 cm−1. Compound 5j: mp 85–86°C (n-hexane); 1H
NMR δ 1.23–1.44 (m, 1H, CHH), 1.52–1.75 (m, 5H, methylene), 1.76–1.96 (m, 2H, CH2), 2.02–2.20 (m, 2H, CH2), 7.06
(d, 2H, J=8.1 Hz, ArH), 7.27 (t, 1H, J=7.5 Hz, ArH), 7.40 (t, 2H, J=7.7 Hz, ArH), 9.38 (s, br, 1H, OOH); 13C NMR δ 20.99,
24.85, 30.30, 85.60, 110.30, 119.93, 127.36, 129.13, 147.95, 148.17; IR (KBr) 3352, 2216 (CN), 1626 cm−1. Anal. calcd
for C14H16N2O2: C, 68.83; H, 6.60, N, 11.47. Found: C, 68.80; H, 6.62; N, 11.43.
10. (a) De Kimpe, N.; Verhé, R.; De Buyck, L.; Schamp, N. Synth. Commun. 1979, 9, 901–913. (b) De Kimpe, N.; Verhé, R.;
De Buyck, L.; Chys, J.; Schamp, N. Bull. Soc. Chim. Belg. 1979, 88, 695–717.