Simple Preparation of Monoalkylhydrazines

Abstract

Alkylation of t-butyl isopropylidene carbazate with alkyl bromides occurs under phase-transfer conditions. Acid hydrolysis of the product completes a simple two-step synthesis of monoalkyl­hydrazines.

Key words

t-butyl carbazate - hydrazine - phase-transfer - alkylation - acid hydrolysis

References

• 1 Kabalka GW. Guchhait SK. Org. Lett.  2003,  5:  4129 
• 2a Zawadzki S. Zwierzak A. Polish J. Chem.  2003,  77:  315 
• 2b Tubrik O. Mäeorg U. Ragnarsson U. Tetrahedron Lett.  2002,  6213 
• 2c Tubrik O. Mäeorg U. Org. Lett.  2001,  3:  2297 
• 3a Smith PAS. The Chemistry of Open Chain Nitrogen Compounds   Vol. 2:  W. A. Benjamin; New York: 1966.  Chap. 9.
• 3b Sidgwick NV. Organic Chemistry of Nitrogen   3rd ed.:  Oxford University Press; London: 1966.  Chap. 15.
• 3c Timberlake JW. Stowell JC. In Chemistry of Hydrazo-, Azo-, and Azoxy Groups   Patai S. Wiley; New York: 1975.  Chap. 4.
• 4 Ghali NI. Venton DL. Hung SC. Le Breton GC.
  J. Org. Chem.  1981,  46:  5413 
• 5 Zawadski S. Osowska-Pacewicka K. Zwierzak A. Synth. Commun.  1987,  485 
• 6 The alkylation conditions described in ref.⁵ have also been used for N-alkylation of N-substitued carboxamides. See: Koziara A. Zawadzki S. Zwierzak A. Synth. Commun.  1979,  527 

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Hydrazine 3c was prepared on 1 mol scale (68% overall yield) without any modification of the experimental procedure. In addition, a differential scanning calorimetry (DSC) test established compound 1 to be chemically stable in the temperature range described in the reaction conditions.

8

Alkylations with allyl and benzyl chlorides were performed under identical conditions as those described for alkyl bromides with comparable yields and purities.

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The stock solutions of hydrazines have been stored in amber vials at room temperature for up to 1 year with no noticeable loss of molarity.

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Experimental Procedure for the Preparation of t -Butyl Isopropylidene Carbazate (1): Added MgSO₄ (ca. 2 g) and 5 drops of HOAc to a solution of tert-butyl carbazate (10 g, 75.6 mmol) in acetone (75 mL). The mixture was heated to reflux for 1 h then cooled, filtered and concd in vacuo to give 12.58 g (97%) of a white solid. Mp 85-87 °C.; lit. mp^2a 85-87 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.46 (br s, 1 H), 1.97 (s, 3 H), 1.77 (s, 3 H), 1.45 (s, 9 H). ¹³C NMR (300 MHz, CDCl₃): δ = 16.1, 25.5, 28.4, 81.0, 150.0, 153.1.

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2a (R = n -propyl): ¹H NMR (300 MHz, CDCl₃): δ = 3.45 (t, J = 7.4 Hz, 2 H), 2.06 (s, 3 H), 1.86 (s, 3 H), 1.48 (m, 2 H), 1.44 (s, 9 H), 0.88 (t, J = 7.4 Hz, 3 H). 2b (R = 2-fluoro-ethyl): ¹H NMR (300 MHz, CDCl₃): δ = 4.56 (t, J = 5.1 Hz, 1 H), 4.40 (t, J = 5.1 Hz, 1 H), 3.86 (t, J = 5.1 Hz, 1 H), 3.78 (t, J = 5.1 Hz, 1 H), 2.07 (s, 3 H), 1.90 (s, 3 H), 1.46 (s, 9 H). 2c (R = cyclopropylmethyl): ¹H NMR (300 MHz, CDCl₃): δ = 3.36 (d, J = 6.9 Hz, 2 H), 2.08 (s, 3 H), 1.91 (s, 3 H), 1.45 (s, 9 H), 0.96 (m, 1 H), 0.43 (m, 2 H), 0.20 (m, 2 H). 2d (R = 2-ethoxyethyl): ¹H NMR (300 MHz, CDCl₃): δ = 3.69 (t, J = 6.3 Hz, 2 H), 3.48 (m, 4 H), 2.06 (s, 3 H), 1.88 (s, 3 H), 1.45 (s, 9 H), 1.16 (t, J = 7.1 Hz, 3 H). 2e (R = 3-propynyl): ¹H NMR (300 MHz, CDCl₃): δ = 4.24 (d, J = 2.3 Hz, 2 H), 2.18 (t, J = 2.3 Hz, 1 H), 2.10 (s, 3 H), 1.92 (s, 3 H), 1.46 (s, 9 H). 2f (R = benzyl): ¹H NMR (300 MHz, CDCl₃): δ = 7.29 (m, 5 H), 4.68 (s, 2 H), 2.03 (s, 3 H), 1.70 (s, 3 H), 1.45 (s, 9 H).

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3a (R = n -propyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 2.84 (t, J = 7.7 Hz, 2 H), 1.57 (m, 2 H), 0.88 (t, J = 7.5 Hz, 3 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 11.1, 18.1, 52.2. 3b (R = 2-fluoroethyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 4.60 (dt, J = 47.2, 4.7 Hz, 2 H), 3.19 (dt, J = 28.0, 4.7 Hz, 2 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 49.6 (d, J = 20 Hz), 80.5 (d, J = 166 Hz). 3c (R = cyclopropylmethyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 2.78 (d, J = 7.5 Hz, 2 H), 1.01 (m, 1 H), 0.52 (m, 2 H), 0.31 (m, 2 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 3.7, 6.4, 55.3. 3d (R = 2-ethoxyethyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 3.56 (t, J = 5.5 Hz, 2 H), 3.45 (q, J = 7.0 Hz, 2 H), 3.05 (t, J = 5.5 Hz, 2 H), 1.12 (t, J = 7.0 Hz, 3 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 15.0, 49.6, 65.7. 3e (R = 3-propynyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 3.68 (d, J = 2.4 Hz, 2 H), 3.40 (t, J = 2.4 Hz, 1 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 39.1, 77.6, 78.8. 3f (R = benzyl): ¹H NMR (300 MHz, d ₆-DMSO): δ = 7.45-7.30 (m, 5 H), 4.06 (s, 2 H). ¹³C NMR (300 MHz, d ₆-DMSO): δ = 54.3, 128.8, 129.1, 130.1, 134.6.