[5,5] sigmatropic shift of N-phenyl-N'-(2-thiazolyl)hydrazines and N,N'- bis(2-thiazolyl)hydrazines into 2-amino-5-(p-aminophenyl)thiazoles and 5,5'- bis(2-aminothiazole) derivatives

Article abstract of DOI:10.1016/S0040-4039(00)00493-7

[5,5] Sigmatropic shift of N-phenyl-N'-(2-thiazolyl)hydrazines and N,N'- bis(2-thiazolyl)hydrazines in acid-catalyzed benzidine-type rearrangement into 2-amino-5-(p-aminophenyl)thiazoles and 5,5'-bis(2-aminothiazole) derivatives is described, respectively. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00493-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3883–3886
[5,5] Sigmatropic shift of N-phenyl-N0-(2-thiazolyl)hydrazines
and N,N0-bis(2-thiazolyl)hydrazines into 2-amino-5-(p-
aminophenyl)thiazoles and 5,50-bis(2-aminothiazole) derivatives†
Boong Won Lee and Seung Dal Lee ∗
Department of Chemistry, Korea Military Academy, Seoul 139-799, South Korea
Received 3 February 2000; revised 16 March 2000; accepted 17 March 2000
Abstract
[5,5] Sigmatropic shift of N-phenyl-N0-(2-thiazolyl)hydrazines and N,N0-bis(2-thiazolyl)hydrazines in acid-
catalyzed benzidine-type rearrangement into 2-amino-5-(p-aminophenyl)thiazoles and 5,50-bis(2-aminothiazole)
derivatives is described, respectively. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: thiazole; hydrazine; thiourea; benzidine-type rearrangement; acid catalyst.
The acid-catalyzed [5,5] sigmatropic shift of hydrazobenzene to 4,40-diaminobiphenyl is well known
and the related studies were published numerously.1 We wish to report examples where N-phenyl-N0-(2-
thiazolyl)hydrazines and N,N0-bis(2-thiazolyl)hydrazines could perform [5,5] sigmatropic shift in acid-
catalyzed benzidine-type rearrangement, respectively.
Because of our interest in the thiazole compounds, we attempted the condensation of N-anilinothiourea
(1)2a and α-chloroacetone to give N-phenyl-N0-[2-(4-methyl)thiazolyl]hydrazine (3a) according to the
Hantzsch method.3 It was found that when the mixture was refluxed in MeOH under neutral conditions,
2-amino-5-(p-aminophenyl)-4-methylthiazole (5a) was obtained in 81% isolated yield. Otherwise, when
it was carried out at room temperature, hydrazine derivative 3a was obtained in 82% isolated yield.
In order to investigate this phenomena stepwise, as illustrated in Scheme 1, a series of hydrazine
derivatives (3) have been prepared in high yield by the treatment of 1 with α-chlorocarbonyl compounds
for 12–15 h at room temperature or 45°C [pathway (A)].
In the next step of pathway (A) in Scheme 1, compound 3 (5 mmol) was refluxed in 0.5 ml of 35%
HCl and 20 ml of H2O solution to rearrange to compound 5 which, otherwise, was prepared by refluxing
directly [pathway (B)] compound 1 and α-chlorocarbonyl compounds in MeOH (refluxed in H+/H2O for
5b). The reactions in Scheme 1 are summarized in Table 1.
∗
†
Corresponding author. Tel: +82-2-2197-2742; fax: +82-2-2197-0197; e-mail: sdlee@kma.ac.kr (S. D. Lee)
Dedicated to Professor T. H. Chan on the occasion of his 60th birthday.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00493-7
tetl 16772

3884
Scheme 1.
Table 1
The reactions of N-anilinothiourea (1) with α-chlorocarbonyl compounds
1
The structure of 5 was evident from H NMR spectroscopic data. After the rearrangement of 3 to 5,
the thiazole 5-H signal in the region δ 6.1–7.4 of 3 disappeared and the pattern of N-phenyl proton peaks
changed to doublet and doublet (J=9.0 Hz) in the region δ 6.60–7.15.
From the fact that 5a and 5c could be directly obtained by refluxing 1 and α-chlorocarbonyl
compounds (chloroacetone and 2-chloroacetophenone) in MeOH under neutral conditions, we assume
that the HCl generated from the first step in Scheme 1, acted as an acid catalyst for the [5,5]-shifts of 3a
and 3c to 5a and 5c, respectively.
On the other hand, we examined the condensation of 2,5-dithiobiurea (2) with α-chlorocarbonyl
compounds according to the same way as shown in Scheme 1. We have also found the condensation of
22b–d with α-chlorocarbonyl compounds at 30–55°C, followed by rearrangement of the resultant N,N0-
bis(2-thiazolyl)hydrazine derivatives (4) under the acidic condition to give 5,50-bis(2-aminothiazole)
derivatives (6), as illustrated in Scheme 2. After the rearrangement of 4 to 6, disappearance of thiazole
5-H signal in the region δ 6.2–7.0 of 4 is characteristic. The overall result of pathway (A) in Scheme 2
was consistent with that of pathway (B) and is summarized in Table 2.
In another interesting Hantzsch synthesis, the reaction of 2,5-dibromo-3,4-hexanedione or 1,4-
dibromo-2,3-butanedione with 2 equiv. of thiourea in refluxing MeOH (Eq. (1)) gave the corresponding
4,40-bis(2-aminothiazole) derivative (7a or 7b).4 Compound 7a or 7b was in contrast to 6d or 6e in
Scheme 2 (Eq. (2)) in terms of site selectivity, respectively.

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Scheme 2.
Table 2
The reactions of 2,5-dithiobiureas (2) with α-chlorocarbonyl compounds
(1)
(2)

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Those reactions are simple and effective, and also possess interesting potential as a new method in
polythiazole synthesis.
Acknowledgements
This work was supported by Hwarangdae Institute of Korea Military Academy. We would also like to
thank Dr. Kye for his helpful discussion.
References
1. (a) Shine, H. J. In Aromatic Rearrangement; Elsevier: New York, 1967; pp. 126–179. (b) Shine, H. J. In Mechanism of
Molecular Migration; Thyagarajan, B. S., Ed.; Interscience: New York, 1969; Vol. 2, pp. 191–247. (c) Dewar, M. J. S. In
Molecular Rearrangements; de Mayo, P., Ed.; Interscience: New York, 1969; Vol. 1, pp. 323–343. (d) Cox, R. A.; Buncel,
E. In The Chemistry of the Hydrazo, Azo and Azoxy Groups; Patai, S., Ed.; Wiley: New York, 1975; pp. 775–859. (e)
Banthrope, D. V. Chem. Rev. 1970, 70, 295–322. (f) Olah, G. A.; Dunne, K.; Kelly, D. P.; Mo, Y. K. J. Am. Chem. Soc.
1972, 94, 7438–7447. (g) Bunton, C. A.; Rubin, R. J. J. Am. Chem. Soc. 1976, 98, 4236–4246. (h) Park, K. H.; Kang, J. S.
J. Org. Chem. 1997, 62, 3794–3795.
2. (a) The procedure for the synthesis of N-anilinothiourea (1) is as follows: To 20 ml of H2O was dissolved 5 mmol of
phenylhydrazine hydrochloride and 5 mmol of NH4SCN. The mixture was refluxed for 12 h at 120°C and the solvent was
evaporated under reduced pressure. Pale brown solid was recrystallized from H2O. Yield: 88%, 1H NMR (DMSO-d6) δ:
6.7–7.2 (m, Ph), 7.5 (bs, NH), 9.25 (s, NH), 13C NMR (DMSO-d6) δ: 113, 118.7, 128, 147.5, 182. (b) Typical procedure
for the synthesis of 3,4-dimethyl-2,5-dithiobiurea (2a) is as follows: To 20 ml of H2O was dissolved 10 mmol (1.33 g)
of 1,2-dimethylhydrazine dihydrochloride and 20 mmol (1.52 g) of NH4SCN. After the mixture was refluxed for 15 h at
120°C, solid was filtered and washed 3 times with 20 ml of H2O and dried. Yield: 75%, mp=208–210°C (dec.), 1H NMR
(DMSO-d6) δ: 3.3 (s, 6H) 7.7 (bs, NH2), 13C NMR (DMSO-d6) δ: 36.5, 181.5 (c) For 2,5-dithiobiurea (2b), yield: 58%,
1
mp=209–211°C (lit.2d 212°C), H NMR (DMSO-d6) δ: 7.6 (bs, NH2), 9.4 (s, NH), 13C NMR (DMSO-d6) δ: 180. (d)
Compound 2b is also commercially available from Aldrich Chem. Co.
3. (a) Hantzsch, A.; Wever, J. H. Ber. 1887, 20, 3118–3128. (b) Hantzsch, A.; Traumann, V. Ber. 1888, 21, 938–946.
1
4. NMR data for 7a and 7b. (a) 7a; yield: 85%, mp=263–265°C, H NMR (DMSO-d6) δ: 2.35 (s, 6H), 6.60 (s, NH2), 13C
NMR (DMSO-d6) δ: 13.5, 117.5, 141, 163.5. (b) 7b; yield: 88%, mp=246–248°C, 1H NMR (DMSO-d6) δ: 6.62 (s, 2H),
6.95 (s, NH2), 13C NMR (DMSO-d6) δ: 102.5, 146.5, 168.