642
Victor Meyer Reaction
A. GENERAL DESCRIPTION OF THE REACTION
This reaction was first reported by Victor Meyer et al. in 1872.1 It is the formation of a
nitroalkane from the reaction between an alkyl halide and silver nitrite and is known as the
Victor Meyer reaction.2 This reaction is generally carried out in petroleum ether or dialkyl
ether2g in a temperature range from 80◦ to 110◦ C3 , to give a mixture of nitroalkane and
alkylnitrite, due to the bidenate nature of nitrite. The ratio of nitroalkane and alkylnitrite
varies, depending on the nature of alkyl halide and metal nitrite.4 For example, the yields
of nitroalkanes fall progressively when silver nitrite reacts with primary, secondary, and
tertiary halide; whereas the yields of corresponding alkyl nitrite increase in an inverse
order.5 The change of product ratio may arise from both steric and electronic effects. It
is proposed that the formation of the C-N bond in nitroalkane has higher steric hindrance
than the formation of the C-O bond in alkyl nitrite; in parallel, the tertiary halide is less
electrophilic than the primary halide, and the oxygen atom has more negative charge than
the nitrogen atom in silver nitrite; therefore, alkyl nitrite is favored for tertiary halide over
primary halide.5 In spite of the tedious workup process2b and relatively low yield,2b,2g
this reaction is still the most convenient method for the preparation of the homologues of
primary nitroalkanes higher than 1-nitropropane.2g In some cases, alcohol and carbonyl
compounds are also found in the reaction mixtures.2g This reaction has been modified
to make pure nitroalkane by reacting alkyl halide with an excess amount of silver nitrite
and washing the reaction mixture with concentrated sulfuric acid2g,2h or phosphoric acid2h
to remove alkyl nitrite before distillation, because alkyl nitrite is not stable under acidic
conditions.2h In addition, sodium nitrite and potassium nitrite have also been used for the
Comprehensive Organic Name Reactions and Reagents, by Zerong Wang
Copyright © 2010 John Wiley & Sons, Inc.
2868
RELATED REACTIONS 2869
preparation of nitroalkanes from alkyl halides under various conditions.6 It is interesting
that this nucleophilic substitution has been reported to undergo via a transition state of both
SN 1 and SN 2 characters varying with the structure of halide, rather than being the sum of
two simultaneously occurring processes.5
B. GENERAL REACTION SCHEME
R1 R1 R1
R2 X + AgNO2 R2 NO2 + R2 ONO
ether, ∆
R3 R3 R3
R1 = H, alkyl, aryl
R2 = H, alkyl, aryl
R3 = H, alkyl, aryl
X = Cl, Br, I, etc.
C. PROPOSED MECHANISMS
Essentially, this reaction is a nucleophilic substitution, via a transition state of both SN 1
and SN 2 characters, depending on the structure of alkyl halides. However, only the SN 2
mechanism is illustrated here.
Ag Ag
O R1 O R1
R1 R2 NO2 and/or R1 R2 ONO
N N
X R2 O AgX R3 X R2 O AgX R3
R3 R3
D. MODIFICATION
This reaction has been extended to the reaction between an alkyl halide and potassium
nitrite or sodium nitrite.
E. APPLICATIONS
This reaction is very useful for the synthesis of nitroalkanes.
F. RELATED REACTIONS
N/A
2870 VICTOR MEYER REACTION
G. CITED EXPERIMENTAL EXAMPLES
Br + AgNO2 NO2
Petroleum ether
66.6%
45–55°C
Reference 2g.
A mixture of 135 g n-amyl bromide (0.894 mol) and 100 mL petroleum ether (45–55◦ C)
in a 500-mL three-necked flask fitted with a reflux condenser, mercury-sealed Hershberg
stirrer, and thermometer was chilled in an ice bath to 3◦ C. Then 145 g silver nitrite (5%
excess) was added as rapidly as possible, the ice bath was removed, and the temperature
of the well-stirred mixture was allowed to rise to 40◦ C within 30 min. The temperature
of the exothermic reaction was kept at 38–42◦ C for 5.5 h by external cooling. A bro-
mide test on the reaction liquor was negative at the end of this time. The mixture was
filtered, and the silver salts were washed with petroleum ether (7 × 50 mL). Removal
of the solvent and low-boiling by-products (mostly alkyl nitrite) was carried out up to a
bath temperature of 83◦ C (25 mmHg) using a 15-cm Vigreux column. The pale yellow
liquid residue weighed 80.3 grams. The crude product thus obtained was added dropwise
to a stirred solution of 5 g urea in 250 mL conc. H2 SO4 at 0◦ C. The temperature was
kept at 0–2◦ C by the rate of addition and by chilling in an ice-salt bath (20 min for com-
plete addition). The resulting yellow solution was stirred for 10 min longer at 0◦ C, and
then with manual stirring, poured over 500 grams cracked ice to which had been added
200 mL petroleum ether. The container was chilled in an ice-salt bath during this pro-
cess. After separation of the layers, the aqueous layer was extracted with petroleum ether
(2 × 150 mL). The combined organic layers were washed with brine (3 × 800 mL) and
dried over CaCl2 . Removal of the solvent under reduced pressure left 72.0 g of a pale
yellow liquid, which was rectified at 23 mmHg through a Vigreux column. Three frac-
tions were taken, and the combined fractions weighed 69.60 g, corresponding to a 66.6%
yield.
Br NO2
+ AgNO2
O2N H2O, ∆ O2N
53%
Reference 2b.
To a solution of 0.216 g 4-nitrobenzyl bromide (1 mmol) in 2 mL water was added 0.616 g
silver nitrite (4.0 mmol), and the reaction flask was wrapped with silver paper to protect
the reaction mixture from light. After stirring at 60◦ C for 24 h, the reaction mixture was
filtered, and the filtrate was extracted with EtOAc and dried over Na2 SO4 . Upon removal of
solvent under reduced pressure, the residue was purified by column chromatography using
hexane/EtOAc (95:5) as the eluent to afford 96.5 mg (4-nitro)-nitrotoluene, in a yield of
53%.
Other references related to the Victor Meyer reaction are cited in the literature.7
REFERENCES 2871
H. REFERENCES
1. (a) Meyer, V.; Stuber, O.; Rilliet, A., and Chojnacki, C., Ann., 1872, 171, 1. (b) Meyer, V. and
Stuber, O., Ber., 1872, 5, 203. (c) Meyer, V. and Stuber, O., Ber., 1872, 5, 399. (d) Meyer, V. and
Rilliet, A., Ber., 1872, 5, 1032. (e) Meyer, V. and Chojnacki, C., Ber., 1872, 5, 1037.
2. (a) Adamo, M. F. A.; Duffy, E. F.; Donati, D. and Sarti-Fantoni, P., Tetrahedron, 2007, 63, 2047.
(b) Ballini, R.; Barboni, L. and Giarlo, G., J. Org. Chem., 2004, 69, 6907. (c) Nielsen, A. T.
and Finnegan, W. G., Tetrahedron, 1966, 22, 925. (d) Noble, P.; Borgardt, F. G. and Reed, W.
L., Chem. Rev., 1964, 64, 19. (e) Stille, J. K. and Vessel, E. D., J. Org. Chem., 1960, 25, 478.
(f) Ungnade, H. E. and Smiley, R. A., J. Org. Chem., 1956, 21, 993. (g) Plummer, C. W. and
Drake, N. L., J. Am. Chem. Soc., 1954, 76, 2720. (h) Kispersky, J. P.; Hass, H. B. and Holcomb,
D. E., J. Am. Chem. Soc., 1949, 71, 516.
3. Kornblum, N.; Taub, B. and Ungnade, H. E., J. Am. Chem. Soc., 1954, 76, 3209.
4. Reynolds, R. B. and Adkins, H., J. Am. Chem. Soc., 1929, 51, 279.
5. Kornblum, N.; Smiley, R. A.; Blackwood, R. K. and Iffland, D. C., J. Am. Chem. Soc., 1955, 77,
6269.
6. (a) Kornblum, N., Org. React., 1962, 12, 101. (b) Kornblum, N.; Larson, H. O.; Blackwood, R.
K.; Mooberry, D. D.; Oliveto, E. P. and Graham, G. E., J. Am. Chem. Soc., 1956, 78, 1497.
7. (a) Agrawal, J. P. and Hodgson, R., Organic Chemistry of Explosives, John Wiley & Sons, New
York, 2007. (b) Camps, P.; Muñoz-Torrero, D. and Sánchez, L. S., Tetrahedron: Asymmetry,
2004, 15, 2039. (c) Ono, N., The Nitro Group in Organic Synthesis, Wiley-VCH, New York,
2001. (d) Erden, I.; Keeffe, J. R.; Xu, F.-P. and Zheng, J.-B., J. Am. Chem. Soc., 1993, 115, 9834.
(e) Feuer, H. and Lester, G., Org. Synth., 1963, 4, 368. (f) Toops, E. E., J. Phys. Chem., 1956, 60,
304. (g) Iffland, D. C. and Yen, T.-F., J. Am. Chem. Soc., 1954, 76, 4083. (h) Bothner-By, A. A.
and Vaughan, C. W., J. Am. Chem. Soc., 1952, 74, 4400. (i) Sowden, J. C., J. Biol. Chem., 1949,
180, 55. (j) Kornblum, N.; Patton, J. T. and Nordmann, J. B., J. Am. Chem. Soc., 1948, 70, 746.
(k) Kornblum, N.; Lichtin, N. N.; Patton, J. T. and Iffland, D. C., J. Am. Chem. Soc., 1947, 69,
307. (l) Hass, H. B. and Riley, E. F., Chem. Rev., 1943, 32, 373. (m) Meyer, V., Ber., 1872, 5, 514.
(n) Meyer, V., Ber., 1872, 5, 1029. (o) Meyer, V., Ber., 1872, 5, 1034.
