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Synlett 2005(12): 1939-1941  
DOI: 10.1055/s-2005-871928
LETTER
© Georg Thieme Verlag Stuttgart · New York

Increasing the N-H Acidity: Introduction of Highly Electronegative Groups into the Hydrazine Molecule

Aleksei Bredikhina, Olga Tšubrika, Rannar Sillardb, Uno Mäeorg*a
a Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia
Fax: +372(7)375245; e-Mail: uno.maeorg@ut.ee;
b Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171-77 Stockholm, Sweden
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Publication History

Received 21 April 2005
Publication Date:
07 July 2005 (online)

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Abstract

Various hydrazine derivatives containing combinations of trifluoroacetyl, trifluoromethanesulfonyl, and 2,4-dinitrophenyl groups were prepared. Synthetic strategy is studied in terms of using protecting groups and direct acylation.

Key words

acylations - hydrazines - neighboring-group effects - protecting groups - sulfonamides

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An oven-dried flask was charged with 224 mg of the compound 1 (1 mmol), then evacuated and backfilled with argon. Then, 8 mL of Et2O was added to dissolve the solid and the solution was cooled down to -80 °C. A 1.6 M solution of n-BuLi in hexane (2 equiv, 1.26 mL) was added dropwise and the obtained mixture stirred for 30 min. In the other flask, 6 mL of trifluoroacetylanhydride was added to the solution of pyridinium chloride (10 equiv) in minimum quantity of TFA. The emerging gaseous CF3COCl was passed into the solution of metallated compound 1. The mixture was stirred for 30 min at -80 °C and then let to warm up to r.t. LiCl was filtered off and solvents were evaporated in vacuo, yielding 271 mg of 2 (mp 148-150 °C). The ESI molecular ion does not exist due to the rapid decomposition to 1. 13C NMR (DMSO-d 6): δ = 116.1 (q, J CF = 286 Hz, CF3CONH), 117.1 [q, J CF = 294 Hz, (CF3CO)2N], 155.8 (q, J CF = 37 Hz, CF3CONH), 159.2 [q, J CF = 33, (CF3CO)2N]. Compound 3 was obtained in the same way in THF using 1 equiv n-BuLi for the first deprotonation of 1. After the reaction with CF3COCl the addition of 1 equiv n-BuLi and CF3COCl was repeated. THF was removed using rectifi-cation, furnishing 3 as a colorless oil. ESI-HRMS: m/z calcd for C8HF12N2O4: 416.9739; found: 416.9745 [MH]+. 13C NMR (DMSO-d 6): δ = 116.9 [q, J CF = 293 Hz, (CF3CO)2N], 160.2 [q, J CF = 34, (CF3CO)2N].

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Compound 4a: mp 130-132 °C. 1H NMR (DMSO-d 6): δ = 1.42 (s, 9 H, Boc), 9.31 (s, 1 H, NH), 11.27 (s, 1 H, NH). 13C NMR (DMSO-d 6): δ = 27.9 (Me, Boc), 80.1 (Cq, Boc), 115.9 (q, CF3, J CF = 287 Hz), 154.4 (CO, Boc), 156.2 (q, CF3CO, J CF = 36 Hz). IR: 3294, 3192 (NH), 1740, 1696 (C = O) cm-1. Anal. Calcd for C7H11F3N2O3: C, 36.85; H, 4.86; N, 12.28. Found: C, 37.14; H, 4.77; N, 12.03.
Compound 4b: mp 106-108 °C. 1H NMR (CDCl3): δ = 5.150 (s, 2 H, PhCH2), 4.341 (s, 5 H, CHarom), 9.096 (s, 1 H, NH-Z), 10.926 (s, 1 H, NHCOCF3). 13C NMR (CDCl3): δ = 67.4 (PhCH2), 116.0 (q, J CF = 286 Hz, CF3), 128.1, 128.3, 128.5, 136.0 (Carom), 155.8 (CO, Z), 157.1 (q, J CF = 38 Hz, CF3CO). ESI-MS: m/z calcd for C10H8F3N2O3: 261.049; found: 261.096 [M-].

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Compound 4d: mp 140-141 °C. 1H NMR (DMSO-d 6): δ = 5.15 (s, 2 H, PhCH2), 7.38 (s, 5 H, Ph), 10.12 (s, 1 H, NH-Z), 11.66 (s, 1 H, NHSO2CF3). 13C NMR (DMSO-d 6): δ = 66.9 (s, PhCH2), 119.2 (q, J CF = 321 Hz, CF3SO2), 127.9, 128.2, 128.4, 136.0 (Carom), 156.1 (CO). ESI-MS: m/z calcd for C9H8F3N2O4S: 297.016; found: 297.083 [M-].
Compound 4e: mp 161-163 °C. 1H NMR (DMSO-d 6): δ = 7.29 (d, J CH = 9.6 Hz, 1 H, Ar), 8.39 (m, 1 H, Ar), 8.90 (d, J CH = 2.6 Hz, 1 H, Ar), 10.41 (s, 1 H, NH). 13C NMR (DMSO-d 6): δ = 115.1 (Carom), 115.9 (J CF = 286 Hz, COCF3), 123.1, 130.5, 137.6, 147.1 (Carom), 156.4 (J CF = 36 Hz, CO). ESI-MS: m/z calcd for C8H4F3N4O5: 293.013; found: 293.071 [M-].