Sodium Hydrazide1

NaHNNH2

[16657-57-1]  · H3N2Na  · Sodium Hydrazide  · (MW 54.04)

(capable of nucleophilic addition to alkenes,2 alkynes,3 and nitriles4 to give hydrazines, hydrazones, or amidrazones; reacts by nucleophilic substitution with electrophilic heteroarenes5 to give hydrazines5 or amines6 and with benzene halides7 or benzene sulfonates8 to give hydrazines; reacts with 1,3-dienes in presence of hydrazine to give dehydrogenated hydrazine derivatives;9 further reaction modes include reduction of unsaturated hydrocarbons10 and reductive dehalogenation,11 cleavage of C=C double bonds affording a hydrocarbon and a hydrazone,12 and selective cleavage of tertiary amide bonds13)

Physical Data: IR spectrum.14

Solubility: moderately sol H2NNH2, liquid NH3.

Preparative Methods: obtained as a suspension of pale yellow crystals by action of Sodium Amide on anhydrous Hydrazine under pure N2 at rt in ether or at -33 °C in liquid NH3 in a special apparatus.2a The method of preparation using Na/H2NNH2 often leads to explosion, even if O2 is strictly excluded.15

Handling, Storage, and Precautions: explodes violently and regularly in contact with O2; storage is not recommended. A protective plexiglass screen (thickness 1 cm) is absolutely necessary in front of the apparatus as NaHNNH2 is prepared and reacted. In reactions with organic compounds, moderate heating (max 60 °C) is allowed. Hydrolysis of the reaction mixture is possible by very slow addition (avoidance of local overheating) of water under ice-cooling. Use in a fume hood.

Nucleophilic Addition.

The high tendency of NaHNNH2 to add by a special mechanism2a to unsaturated organic compounds enables the transformation of alkenes such as styrene2 to alkyl hydrazines, of alkynes3 to hydrazones, and of nitriles4 to amidrazones at low temperatures in ether (eqs 1-5). For the reaction of eq 1, only a catalytic amount of NaHNNH2 is necessary.

Nucleophilic Substitution.

NaHNNH2 reacts with electrophilic heteroarenes such as pyridine5a and isoquinoline5b,5c by substitution of hydrogen. In ether, reactions in the presence of H2NNH2 produce mono(heteroaryl)hydrazines, whereas in the absence of H2NNH2, N,N-bis(heteroaryl)hydrazines are generated (eqs 6 and 7). In the case of acridine and phenanthridine the substitution product is an amino heteroarene.6 Treating p-tolyl halides7 with NaHNNH2/H2NNH2 yields tolyl hydrazines by an addition-elimination mechanism (eq 8) or aryne mechanism (eq 9). Sodium p-tolylsulfonate8 reacts under the same conditions to give p-tolylhydrazine.

Oxidative Hydrazination.

Hydrazination with subsequent dehydrogenation to give azines or pyrazoles occurs by simultaneous action of NaHNNH2 and H2NNH2 in ether on 1,3-dienes (eqs 10 and 11).9

Reduction and Reductive Hydrazination.

Treatment of unsaturated hydrocarbons (e.g. stilbene), unsaturated nitrogen compounds, or polycyclic arenes with NaHNNH2/H2NNH2 leads frequently to reduction of the substrate10 (e.g. eq 12). The initially formed NaHNNH2 adduct is believed to eliminate sodium diimide in these cases. Naphthalene is reduced to the 1,2-dihydro derivative, which affords 2-hydrazino-1,2,3,4-tetrahydronaphthaline2b by addition of NaHNNH2 (eq 13). A further type of reduction is reductive dehalogenation.11

Alkene Hydrazidolysis.

NaHNNH2 is capable of cleaving C=C double bonds12 which are activated by an adjacent aryl residue (eq 14). This reaction is analogous to the reaction of aldehydes and ketones with H2NNH2 to give H2O and a hydrazone. By subsequent treatment of the hydrazone of eq 14 with aq acid, a formal hydrolysis (eq 15) of a C=C double bond is achieved. Alternatively, subsequent treatment of the hydrazone with NaOH under Wolff-Kishner conditions gives rise to formal reductive cleavage (eq 16).

A related cleavage reaction (eq 17)12c was observed by reacting 2 equiv NaHNNH2 with b-halogen phenylalkanes in the presence of hydrazine.

Regiospecific or Regioselective Peptide Hydrazidolysis.

In the presence of hydrazine, NaNHNH2 cleaves tertiary amide groups, whereas secondary and primary amide groups (which form mesomeric anions) are stable under these conditions. This allows a quantitative regiospecific hydrolysis of diglycyl-L-proline (eq 18).13 By reacting NaHNNH2/H2NNH2 with insulin, which contains only one tertiary amide bond, selective fission was possible to give the peptide Pro-Lys-Ala-CO2H (ca. 70%).


1. Kauffmann, T. AG 1964, 76, 206; AG(E) 1964, 3, 342.
2. (a) Kauffmann, T.; Kosel, C.; Wolf, D. CB 1962, 95, 1540. (b) Kauffmann, T.; Lötzsch, K.; Rauch, E.; Schoeneck, W. CB 1965, 98, 904.
3. Kauffmann, T.; Sobel, J. CB 1966, 99, 1843.
4. (a) Kauffmann, T.; Spaude, S.; Wolf, D. CB 1964, 97, 3436. (b) Kauffmann, T.; Bán, L. CB 1966, 99, 2600.
5. (a) Kauffmann, T.; Hansen, J.; Kosel, C.; Schoeneck, W. LA 1962, 656, 103. (b) Kauffmann, T.; Hacker, H.; Kosel, C.; Vogt, K. ZN(B) 1959, 14, 601. (c) Kauffmann, T.; Hacker, H.; Kosel, C. ZN(B) 1959, 14, 602.
6. Kauffmann, T.; Hacker, H. CB 1962, 95, 2485.
7. Kauffmann, T.; Henkler, H. CB 1963, 96, 3159.
8. Kauffmann, T.; Burkhardt, W. CB 1969, 102, 3088.
9. Kauffmann, T.; Müller, H. CB 1963, 96, 2206.
10. Kauffmann, T.; Kosel, C.; Schoeneck, W. CB 1963, 96, 999.
11. Kauffmann, T.; Henkler, H.; Zengel, H. AG 1962, 74, 248.
12. (a) Kauffmann, T.; Henkler, H.; Rauch, E.; Lötzsch, K. CB 1965, 98, 912. (b) Kauffmann, T.; Lötzsch, K.; Wolf, D. CB 1966, 99, 3148. (c) Kauffmann, T.; Burkhardt, W.; Rauch, E. AG 1967, 79, 147; AG(E) 1967, 6, 170.
13. Kauffmann, T.; Sobel, J. LA 1966, 698, 235.
14. Goubeau, J.; Kull, U. Z. Anorg. Allg. Chem. 1962, 316, 182.
15. Schlenk, W.; Weichselfelder, T. CB 1915, 48, 669.

Thomas Kauffmann

Universität Münster, Germany



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