Organic Preparations and Procedures International, vol. 20, No. 6, (1988), p 598-9.

Synthesis Of Nitroalkanes From Bromoalkanes By Phase-Thansfer Catalysis

Submitted by Pramodchandra V. Sane and Man Mohan Sharma. (07/30/87)
Department of Chemical Technology, Univ. of Bombay, Matunga, Bombay 400019, India

1-Nitropropane, an intermediate for ethambutol, is usually manufactured by the 
vapour phase nitration of propane, which unfortunately is hazardous and leads to 
the formation of various side-products depending on the reaction conditions.[1] 
The recent use of nitrite form of basic anion exchange resin for the synthesis 
of 1-nitropropane, from the corresponding bromide, involves long reaction periods 
and low selectivity.[2] A number of methods for the nitrite displacement with 
phase-transfer catalyst (PTC), crown ethers, polyethylene glycols and tetraalkyl-
ammonium salts, have been reported; the selectivity for nitrooctane varied 
between 20% and 70% depending upon the reaction conditions and PTC employed.[3-5]

For the synthesis of nitroalkanes from bromoalkanes and sodium nitrite, using 
chloroform as solvent, the liquid-liquid rather than liquid-solid mode of 
operation was required and it was necessary to maintain alkaline conditions by 
the addition of 0.4M sodium carbonate. Several PTC were tried and tetrabutyl-
ammonium hydrogen sulfate (TBAHS) worked best; of a number of solvents tried, 
chloroform was found to be the best. The main by-product formed was the alkyl 
nitrite and hydrolysis to the alcohol was negligible. Thus 6 hrs, with TBAHS as 
PTC, the yield of 1-nitropropane was 62% and 23% of unreacted 1-bromopropane was 
recovered; propyl nitrite was detected to the extent of 14%. Under the same 
conditions as for 1-bromopropane, the yield of 1-nitrobutane was 57% with 26% 
recovery of unreacted 1-bromobutane. By contrast, with 1-chlorobutane, under 
similar conditions as above, no reaction to 1-nitrobutane occurred. 
1-Nitrohexane was obtained in 45% yield and 39% of unreacted 1-bromohexane was 
recovered. Further, with 2-bromopropane the rate was relatively low and the 
yield of 2-nitropropane was 24% and the recovery of unreacted 2-bromopropane 
was 65%.


Experimental Section

1-Nitropropane

The reaction was conducted in a fully baffled mechanically agitated glass 
contactor of 100 mL capacity provided with a glass impeller at 31°. To an 
aqueous phase solution (60 mL) of sodium nitrite (25 g, 0.36 mol) and sodium 
carbonate (2.55 g, 24 mmol), an organic phase consisting of 1-bromopropane 
(10 mL, 0.11 mol) and TBAHS (1.12g, 3.3 mmol) in chloroform (10 mL) was added. 
The reaction mixture was stirred at a constant speed of agitation of 1500 rev/min. 
The progress of the reaction was monitored by analysing samples from the organic 
phase by gas-liquid chromatography; an s.s. column, 3.2 mm dia. x 2 meter long, 
packed with 10% SE-30 on Chromosorb-W, was used with nitrogen, as a carrier, on a 
"Chemito" gas chromatograph. After 6 hrs, the reaction mixture was worked up and 
the residue was distilled to yield 6.0 g (61% yield) of 1-nitropropane, 
bp. 55°/40 mm. The product was structurally confirmed through an FT-IR (Bruker, 
IFS 88) and 1H-NMR (Varian EM-360L, 60 MHz).

References

1. H. B. Hass, E. B. Hodge, B. M. Vanderbilt, Ind. Eng. Chem., 28, 339 (1936); 
   H. B. Hass and H. Shechter, ibid., 39, 817 (1947).
2. G. Gelbard and S Colonna, Synthesis, 113 (1977).
3. J. W. Zubrick, B. I. Dunbar and H. D. Durst, Tetrahedron Lett., 71 (1975).
4. K. Matsunaga and T. Yamashita, Kogyo Kayaku, 41, 3 (1980); CA 94, 3167g (1981).
5. C. Kimura, K. Kashiwaya and K. Murai, Asahi Garasu Kogyo Gijutsu Shoreikai 
   Kenkyu Hokoku, 24, 59 (1974); C. A. 84, 121027 (1976).
