Synthesis of F-alkylated hydrazinoalcohols

Journal of Fluorine Chemistry 108 (2001) 121±123

Synthesis of F-alkylated hydrazinoalcohols I. Mastouri, A. Hedhli, A. Baklouti* Faculte des Sciences de Tunis, DeÂpartement de Chimie, Laboratoire de Chimie Structurale Organique, Campus Universitaire, 1060 Tunis, Tunisia Received 16 June 2000; accepted 7 November 2000

Abstract The ring opening reaction of F-alkylepoxides by hydrazine takes place regiospeci®cally on the primary carbon atom, to furnish the corresponding F-alkylated hydrazinoalcohols. # 2001 Elsevier Science B.V. All rights reserved. Keywords: F-alkyloxirane; Hydrazine; Hydrazinoalcohol

1. Introduction The hydrazinoalcohols, which may have interesting medical properties [1], are generally prepared from halohydrins [2] or epoxides [1,3±10] by the action of hydrazine. We reported previously the substitution of a O-tosyl group by hydrazine in the case of 2-¯uorotosylates [11] and we wish herein to describe the action of hydrazine on F-alkylated epoxides. 2. Results and discussion When the action of hydrazine hydrate on F-alkylated epoxides (1) was carried out at low temperature ( 108C), only 1 mol equivalent epoxide/hydrazine product (2) was formed according to Scheme 1. At room temperature, this derivative is the major one among the obtained complex mixture of products. The synthesized F-alkylated hydrazinoalcohols are detailed in Table 1. The reaction was conducted at 108C to avoid polyalkylation of hydrazine. The complex mixture mentioned above was probably, in part at least, the result of hydrazine polyalkylation since, when working at 08C on epoxide (1b), for example, 8% of bis(F-alkylated) hydrazinoalcohol (2b0 ), m/z 756.8 (9.01%) was obtained beside the monoalkylated product (2b) (Scheme 2). We reported previously the synthesis of bis(F-alkylated) aminodiols (2 mol F-alkyloxirane/1 mol ammonia), via ring *

Corresponding author. Fax: ‡216-1-885-008.

opening reaction of F-alkyloxiranes with ammonia at room temperature [12]. In the case of hydrazine when compared with ammonia, the major product is still the monoalkylated one even when the reaction is carried out at room temperature. 3. Experimental IR spectra were recorded on Perkin-Elmer Paragon 1000 PC. The 1H, 19F, 13C NMR were recorded on BruÈker AC 300 at 300 MHz for proton, 282 MHz for ¯uorine and 75 MHz for carbon atoms. TMS was used as standard reference for 1 H and 13C NMR spectra and CFCl3 for 19F NMR spectra. HRMS spectra were obtained from MAT 95 SBE. Starting epoxides were prepared according to standard methods [13,14]. 3.1. Preparation of F-alkylated hydrazinoalcohols: general procedure Hydrazine hydrate (7 ml, 140 mmol) was put into a N2®lled ¯ask and cooled at 108C, then epoxide (1, 14 mmol) dissolved in chloroform (30 ml) was added. After 24 h of stirring, the whole mixture was diluted with chloroform and decanted. The organic layer was washed with water and dried on Na2SO4. The solvent was removed under vacuum and the product (2) was recrystalized from chloroform to give compound 2. 2a: IR (®lm, cm 1) nN H ˆ 3460±3560, nO H ˆ 3400± 3420, nC F ˆ 1108, dN H ˆ 1600. 1H NMR (CD3OD): d: 3.21 (m, 2H, CH2N), 4.4 (m, 1H, CHOH), 4.92 (s, NHNH2,

0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 3 9 9 - 7

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I. Mastouri et al. / Journal of Fluorine Chemistry 108 (2001) 121±123

Table 1 Hydrazinoalcohols prepared Epoxide

a

Hydrazinoalcohol

Melting point (8C)

Yield (%)a

Viscous oil

49

52

55

53

68

53

60

55

63

Based on starting epoxide.

Scheme 1.

OH). 19F NMR (CD3OD) d: 79.43 (t, 3F, CF3, 3 JF F ˆ 8:51 Hz), 121.72 (q, 2F, CF2a, 2 JF F ˆ 290:17 Hz), 119.80 (m, 2F, CF2b), 123.02 (m, 2F, CF2o). 13C NMR (CD3OD) d: 53.30 (s, 1C, CH2N), 68.56 (dd, 1C, CHOH, 2 JC F…A† ˆ 22:6 Hz, 2 JC F…B† ˆ 26 Hz). HRMS (CI): (M‡H)‡. Calc.: 295.06314; found: 295.06335, D…mmu† ˆ 0:2. 2b: IR (®lm, cm 1) nN H ˆ 3450±3560, nO H ˆ 3400± 3420, nC F ˆ 1010, dN H ˆ 1600. 1H NMR (CD3OD): d: 3.00 (m, 2H, CH2N), 4.40 (m, 1H, CHOH), 4.89 (s, NHNH2, OH). 19F NMR (CFCl3) d: 79.62 (t, 3F, CF3, 3 JF F ˆ 9:75 Hz), 121.16 (q, 2F, CF2a, 2 JF F ˆ 285:50 Hz), 119.70 (m, 2F, CF2b), 120.13 (m, 2F, CF2g), 123.63 (m, 2F, CF2d), 124.42 (m, 2F, CF2o). 13C NMR (CD3OD) d: 53.00 (s, 1C, CH2N), 68.52 (dd, 1C, CHOH, 2 JC F…A† ˆ 84:28 Hz, 2 JC F…B† ˆ 99:15 Hz). HRMS (CI): (M‡H)‡. Calc.: 395.04278; found: 395.04290, D…mmu† ˆ 0:1. 2c: IR (®lm, cm 1) nN H ˆ 3450±3560, nO H ˆ 3400± 3420, nC F ˆ 1010, dN H ˆ 1600. 1H NMR (CD3OD): d:

3.25 (m, 2H, CH2N), 4.30 (m, 1H, CHOH), 4.85 (s, NHNH2, OH). 19F NMR (CFCl3) d: 79.45 (t, 3F, CF3, 3 JF F ˆ 9:65 Hz), 119.50 (q, 2F, CF2a, 2 JF F ˆ 291:00 Hz), 120.84 (m, 8F, CF2e, CF2d, CF2g, CF2b), 123.07 (m, 2F, CF2x), 124.39 (m, 2F, CF2o). 13C NMR (CD3OD) d: 50.00 (s, 1C, CH2N), 68.64 (dd, 1C, CHOH, 2 JC F…A† ˆ 22:40 Hz, 2 JC F…B† ˆ 26:13 Hz). HRMS (CI): (M‡H)‡. Calc.: 495.03638; found: 495.03649, D…mmu† ˆ 0:1. 2d: IR (®lm, cm 1) nN H ˆ 3450±3550, nO H ˆ 3400± 3420, nC F ˆ 1000, dN H ˆ 1600. 1H NMR (CD3OD) d: 2.30 (m, 2H, CH2CF2), 3.52 (m, 2H, CH2N), 4.26 (m, 1H, CHOH), 4.80 (s, NHNH2, OH). 19F NMR (CFCl3) d: 79.02 (t, 3F, CF3, 3 JF F ˆ 9:75 Hz), 111.38 (q, 2F, CF2a, 2 JF F ˆ 287:80 Hz), 119.68 (m, 2F, CF2b), 120.56 (m, 2F, CF2g), 121.45 (m, 2F, CF2d), 124.09 (m, 2F, CF2o). HRMS (CI): (M‡H)‡. Calc.: 409.05769; found: 409.05830, D…mmu† ˆ 0:6. 2e: IR (®lm, cm 1) nN H ˆ 3450±3560, nO H ˆ 3400± 3420, nC F ˆ 1010, dN H ˆ 1600. 1H NMR (CD3OD) d: 2.32 (m, 2H, CH2CF2), 3.41 (m, 2H, CH2N), 4.26 (m, 1H, CHOH), 4.78 (s, NHNH2, OH). 19F NMR (CFCl3) d: 79.02 (t, 3F, CF3, 3 JF F ˆ 9:75 Hz), 111.38 (q, 2F, CF2a, 2 JF F ˆ 291:00 Hz), 119.58 (m, 2F, CF2b), 120.56 (m, 2F, CF2g), 121.45 (m, 2F, CF2d), 122.64 (m, 4F, CF2e, CF2x), 124.09 (m, 2F, CF2o). HRMS (CI): (M‡H)‡. Calc.: 509.05129; found: 509.05216, D…mmu† ˆ 0:8.

Scheme 2.

I. Mastouri et al. / Journal of Fluorine Chemistry 108 (2001) 121±123

Acknowledgements The authors are grateful to Prof. J. Courtieu and F. Perez for HRMS measurements. References [1] M. Tichniouin, J. Sauleau, A. Sauleau, Eur. J. Med. Chem. 20 (1985) 181. [2] G. Gever, J. Am. Chem. Soc. 76 (1954) 1283. [3] G. Benoit, Bull. Soc. Chim. Fr. (1939) 709.

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