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Org. Synth. 1957, 37, 63
DOI: 10.15227/orgsyn.037.0063
NICOTINAMIDE-1-OXIDE
Submitted by E. C. Taylor, Jr.1 and Aldo J. Crovetti2.
Checked by Charles C. Price and Walter A. Schroeder.
1. Procedure
In a 2-l. round-bottomed flask with ground-glass joint (Note 1) are placed 100 g. (0.82 mole) of powdered nicotinamide (Note 2) and 1 l. of C.P. glacial acetic acid, and the mixture is warmed with occasional shaking on a steam bath until a clear solution is obtained. To this mixture is added 160 ml. (1.39 moles) of cold 30% hydrogen peroxide. An air condenser is attached to the reaction flask, and the mixture is heated on a steam bath for 3.5 hours.
The reaction mixture is then distilled under reduced pressure (80–100 mm.) (Note 3). After 600–700 ml. has distilled, the mixture is diluted with 150–200 ml. of distilled water and the distillation is continued. The product separates near the end of the distillation, causing somewhat vigorous bumping for a short period. When the bumping has almost ceased, the pressure is reduced to 20 mm. and the distillation continued almost to dryness (Note 4).
The major portion of wet solid is removed from the flask and transferred to a 1-l. Erlenmeyer flask. The remaining solid is washed out with a little distilled water, and the washings are transferred to the flask. The solid is dissolved in the smallest amount of boiling water required, the flask removed from the heat source, and 50 ml. of ethyl alcohol added (Note 5). The flask is allowed to cool slowly, and, after the major portion of the product has separated, the flask is cooled to 5° overnight. The solid is removed by filtration and washed with cold alcohol, then acetone, and finally ether. The white, crystalline, air-dried product weighs 82–93 g. (73–82%), m.p. 291–293° dec. (rapid heating); the compound starts to turn brown at about 280–285° (Note 6).
2. Notes
1. Since hydrogen peroxide attacks rubber stoppers, glass-jointed equipment is recommended.
2. U.S.P. Niacinamide (Mallinckrodt) was used.
3. For the distillation, the still head consisted of a Claisen-type adapter with a parallel side arm (24/40 standard taper joints), 21 cm. high and 10.5 cm. wide. An ordinary straight still head is attached to the parallel side arm. This large still head prevents any bumping solid from entering the condenser.
4. Distilling to complete dryness exposes the solid to prolonged heating and causes oxidation of the product, which is obtained colored and in lower yield.
5. The alcohol serves to retain the brown color upon recrystallization and to decompose any excess hydrogen peroxide.
6. Because of the questionable value of the melting point as a criterion of purity, the checkers analyzed two samples of the product: Calcd. for C6H6N2O: C, 52.17; H, 4.34. Found (Sample 1): C, 52.34; H, 4.44. Found (Sample 2): C, 52.61, 52.63; H, 4.46, 4.53.
3. Discussion
The procedure given is essentially that described by Taylor and Crovetti.3 Nicotinamide-1-oxide (m.p. 275–276° dec.) has also been prepared by the alkaline hydrolysis of nicotinonitrile-1-oxide4 and by the action of ammonium hydroxide on methyl nicotinate-1-oxide.5 The melting point of the product prepared by the latter synthesis is reported to be 282–284° dec.
This preparation is referenced from:

References and Notes
  1. Princeton University, Princeton, New Jersey.
  2. University of Illinois, Urbana, Illinois.
  3. Taylor and Crovetti, J. Org. Chem., 19, 1633 (1954).
  4. Jujo, J. Pharm. Soc. Japan, 66, 21 (1946) [C. A., 45, 6200 (1951)].
  5. Shimizu, Naito, Ohta, Yoshikawa, and Dohmori, J. Pharm. Soc. Japan, 72, 1474 (1952) [C. A., 47, 8077 (1953)].

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

Niacinamide

ethyl alcohol (64-17-5)

acetic acid (64-19-7)

ether (60-29-7)

acetone (67-64-1)

hydrogen peroxide (7722-84-1)

ammonium hydroxide (1336-21-6)

nicotinamide (98-92-0)

nicotinamide-1-oxide (1986-81-8)

nicotinonitrile-1-oxide (14906-64-0)

methyl nicotinate-1-oxide