NITRATION OF TOLUENE
NOVEMBER, 1964
3387
The Nitration of Toluene with Alkyl Nitrates and Polyphosphoric Acid' S. M. TSANG, A. P. PAUL, A N D M.P. DIGIAIMO Research and Development Department, Organic Chemicals Division, American Cyanamid Company, Bound Brook, New Jersey Received M a y 20, 1964 The nitration of toluene has been studied with a view to changing the ortho-para (0-p) ratio of the mononitrotoluene product. The system employing neopentyl nitrate in polyphosphoric acid gave a low 0-p ratio of 0.49 as compared with the 1.6 ratio usually obtained with nitronium ion producing reagents. Absolute nitric acid in polyphosphoric acid gave a 0.86 ratio. Amyl nitrate in polyphosphoric acid gave a 0.64 o-p ratio, whereas amyl nitrate in sulfuric acid leads to a high 1.42 ratio. A mechanism is proposed which involves a cyclic complex incorporating a bonded nitronium ion species.
The classical nitration of toluene can be characterized as a reaction in which the isomer distribution of the niononitrotoluene product remains remarkably constant regardless of the reagent employed. The many references to this reaction report only slight variations in the ortho-para (0-p) ratio between 1.41 and 1.62 under a variety of conditions. Several of the pertinent literature references are listed in Table I. TABLE I REPORTED SITRATIONS OF TOLUENE Reagent
Solvent
Temp., OC. '
a-p ratio
Ref.
Sone 0 1.62 a Nitromethane 30 1.58 b 77y0sulfuric acid 30 1.57 C Carbon tetrachloride 0 1,54 d Acetic anhydride 0 1.52 b "0s 90% acetic acid 45 1.41 e a W. H. Gibson, R. Duckham, and R. F. Fairbairn, J . Chem. C. K. Ingold, A. Lapworth, E. Rothstein, Soc., 270 (1922). and D. Ward, ibid., 1959 (1931). W. W. Jones and M. Russel, ibid., 921 (1947). K. Halvarson and L. Melander, Arkiv Kemi, 11, 77 (1957); Chern. Abstr., 51, 15448 (1957). e H . Cohn, E. D. Hughes, X. H. Jones, and M. G. Peeling, Nature, 169,291 (1952). 947, "03 100% HK03 HK03-HON0 Benzoyl nitrate "01
I n all of the systems listed in Table I the m-nitrotoluene content also remained relatively constant fluctuating between 2.5 and 4.4Oj,, except when benzoyl nitrate was employed in carbon tetrachloride at 0" where the meta isomer content reached 6%. I n keeping with the current concept that in a nitration reaction the nitronium ion is the attacking species,2 it follows that when the nitrating reagent serves merely to provide the nitroniuni ion and, especially, a "free" nitroniuni ion, the isomer distribution will be independent of the method of nitrations3 The constancy of the isomer distribution in the nitration of toluene remained as a challenge until some recent results showed that the 0-p ratio can be modified. The use of nitroniuni fluoroborate in a tetraniethylene sulfone solution raised the ratio to 2.05,4awhile the nitraH2SO4)at tion of toluene with mixed acid (HN03 - 1.5' is reported4b t o give an ratio of 0.92. Also nitric acid in the presence of a sulfonated styrene-divinyl-
+
(1) Presented a t the North Jersey-New York Metropolitan Regional Meeting of the American Chemical Society, New York, N. Y., J a n . , 1962. (2) (a) C. K. Ingold, "Structure and Mechanism in Organic Chemistry," Cornell University Press, Ithaca, N. Y., 1952, p. 269 ff: (b) P. l3. D. de la Mare and J. H. Ridd, "Aromatic Substitution, Nitration and Halogenation." Butterworth and Co. (Publishers), Ltd., London, 1959, p. 57 IT. (3) T h e discussion is being limited t o toluene, in which the methyl group does not interact t o a n appreciable extent with the nitrating medium. (4)(a) G. A. Olah, S. J. Kuhn, and S. H. Flood, J . Am. Chem. Sac., 89, 4571 (1961); (b) G . A. Olah and S. J. Kuhn, ibid., 84, 3684 (1962).
benzene ion-exchange resin led to the lowering of the o-p ratio to 0.91.5 (An unusually high ratio of 7.33 was reported6 t o result froni the use of acetyl nitrate as the nitrating reagent, but these results are especially surprising in view of those obtained in siniilar systems.'~~) The present work was derived froin a general study of nitration reactions which sought the means by which the 0-p ratio could be lowered drastically. It was felt that the "free" nitronium ion was largely responsible for the constancy of the 0-p ratio and systems were sought in which the nitronium ion would be niade less indiscriminate. I n order to avoid the polar niedia usually employed, the nitration of toluene was carried out in chloroforiii at 0" using absolute nitric acid as the nitrating reagent. A 51.4% yield of niononitrotoluenes was obtained having the usual 1.64 0-p ratio and a 2.5y0 m-nitrotoluene content. Since the water formed froin the nitration reaction would lead to the usual nitrating conditions, an attempt was niade next to remove the water as it formed in the course of the reaction. For this reason dinitrogen pentoxide was substituted for the nitric acid and, although the m-nitrotoluene content remained nearly the same at 2.4%, the yield of mononitrotoluenes was raised to 82.lY0 while the 0 - p ratio was lowered slightly to 1.49. Although dinitrogen pentoxide does serve to remove the water of reaction it also leads to the formation of nitric acid when it reacts with an aromatic substrate. Thus, as the nitric acid is formed it could react with C7H8
+ N205 +C ~ H ~ N O+I HNO,
toluene to generate some water and, thereby, lessen the benefit t o be derived from the use of dinitrogen pentoxide. Since dinitrogen pentoxide can be prepared from the treatment of nitric acid with phosphorus pentoxide, the latter reagent was utilized next to remove nitric acid from the nitration iiiediuni as it was formed. Accordingly, dinitrogen pentoxide was added to a slurry of phosphorus pentoxide, toluene, and chloroforin a t 0'; the 0-p ratio was lowered further to 1.04. To check further on the efficacy of phosphorus pentoxide, absolute nitric acid was added directly to a slurry of phosphorus pentoxide and toluene in chloroform and at rooni temperature instead of 0". These conditions led to a lowering of the 0-p ratio to 0.84. At this point a series of experiments was conducted t o ( 5 ) 0. L. Wright, E. S. Patent 2,948,759 (Aug. 9 1960) (6) A. Pictet and E. Khotinsky, Chem. Ber. 40, 1163 (1937). (7) See Table I. footnote b. (8) See Table I , footnoted.
TSANG, PAUL,AND DIGIAIMO
3388
VOL. 29
TABLE I1 NITRATIOXOF TOLUENE WITH NITRICACID A N D PHOSPHORUS PENTOXIDE AT ROOM TEMPERATURE Solvent
a
ClHn-"Os, moles
PzOs-"Os, moles
CHC1, 3 1.0 CHC13 3 0.5 CHC1, 12 7.9 CHC13" 4 3.2 CH3X0, 3 1.6 The P20swas ball milled in the chloroform for 6 hr.
Time, days
0- P ratio
2
0.84 0.99 0.82 1.07 1.30
1
3 3 1
find the optiniuni requirements of phosphorus pentoxide and nitric acid as well as to determine the effect of substituting nitromethane for chloroform as the solvent. The results of these experiments are listed in Table 11. The results of these experiments can be summarized as follows: (a) chloroform is more effective than njtromethane in lowering the 0-p ratio; ( b ) the toluene-nitric acid ratio does not critically affect the 0-p ratio; (c) a rnininiuni of about 1 molar equiv. of phosphorus pentoxide is required indicating that phosphorus pentoxide is not acting as a true catalyst; (d) 48 hr. is approximately the optiniuni time for the duration of the experiment; and (e) increasing the surface area of the phosphorus pentoxide raises the 0-p ratio to 1.07. The increase in the 0-p ratio due to ball milling of the phosphorus pentoxide is of significance, since the resulting 1.07 ratio is very similar to the 1.04 ratio obtained when dinitrogen pentoxide had been used instead of nitric acid. Increasing the surface area of the phosphorus pentoxide probably causes an increase in the rate of reaction with nitric acid, which produces dinitrogen pentoxide and results in the expected 1.04 ratio. On the other hand, by not ball milling the phosphorus pentoxide the reaction between toluene and nitric acid proceeds to sonie extent initially and the water produced froin the reaction is then taken up by the phosphorus pentoxide. This would indicate that polyphosphoric acid and not phosphorus pentoxide was the essential agent for the para-positional specificity. This was confirmed by a series of experiments using polyphosphoric acid. The results are listed in Table 111.
m - C ~ H ~ N O% a,
Yield,%
3.7 2.6 2.4
85 49 78 84 73
... ...
results of these experiments, listed in Table IV point to polyphosphoric acid having an 83.0% phosphorus pentoxide content as the optimum choice for yield and lower 0-p ratio. TABLE IV EFFECT OF PHOSPHORIC ACID POLYMER SPECIESON o-p RATIO^ Wt. % of PlOS in HsPOi
Polymer species,* %
0 - p ratio
Yield, %
1.8 0.7 None None Monomer, 49; dimer, 42 1.10 31.7 76.2 Monomer to tetramer, 92 1,04 56.6 80.0 1.01 86.5 83,O Dimer to heptamer, 79 Decamer and higher, 68 1..03 89.5 86.5 a Solvent: anhydrous acetic acid; C7H8-HN03, 3; H,POa-. HNO,, 8; temperature, 2 5 3 0 " . J. R. Parka and J. R Van Wazer, J.Am. Chem. SOC.,79,4890 (1957).
It also became apparent that further work on the polymeric acids would not lead to reduction in the 0-p ratio beyond that already achieved. However, the lowering of the o-p ratio could be explained on the basis that the attacking species in the nitration reaction was not the "free" nitronium ion. Instead, a bonded nitronium ion or an intimate ion pair involving the bulky polymeric acid could be responsible for the observed effect on the o-p ratio. The steric bulk of the species formed from the polymeric acid and the nitric acid together with the bulk of the methyl group of the toluene molecule would favor a pura-positional selectivity. The reaction could be a simple concerted type between toluene and a polyphosphoric acid-nitric acid intermediate, as shown in the equation below, or it could in-
TABLE I11 ACID AND POLYPHOSPHORIC ACID"
NITRATION WITH S I T R I C C.iH8-HKOa. moles
Solvent
Time, days
0 - p ratio
Yield, %
3 CHC13 1 1.16 42 3 Sone 2 0.86 45 2 None 1 0.87 44 a The polyphosphoric acid contained 837, P205; moles of Pz05-H?r'03,2 ; temperature, 24-40'.
In these experiments the nitric acid was added a t a slow and uniform rate while the reaction mixture was vigorously stirred in order to compensate for the high viscosity of the polyphosphoric acid and the high reactivity of the nitric acid. When chloroform was used as a solvent two phases were present in the reaction mixture, and the high 0-p ratio may be due to the competing reaction in the chloroform layer, which, by itself, would have led to an 0-p ratio of 1.64. I n order to assess the type of phosphoric acid responsible for the para-positional selectivity, a series of experiments was conducted in which the phosphorus pentoside content was varied from 0 to 86.5%. The
volve a transient cyclic complex, such as 1. I n either case, it would be the steric effect on the ortho position which leads to a higher yield of the pura isomer. ?Ha
HO, / O * " /P\
/o
0,
I
0-H P H '
HO/pk
0 1
I n order to take advantage of the steric effect, attention was next directed at the alkyl nitrates as a means of achieving even further lowering of the o-p
NOVEMBER, 1964
NITRATION OF TOLUENE
ratio. The use of alkyl nitrates for the nitration of toluene in the presence of sulfuric acid has been reported to give only a slight increase in the para-isomer ~ o n t e n t . ~These conditions probably involve a "free" nitroniuni ion, since the presence of the nitronium ion in a sulfuric acid solution of ethyl nitrate was demonstrated by both cryoscopic and spectral evidence. lo I n the cyclic complex proposed here the use of an alkyl nitrate and polyphosphoric acid should lead to a bound nitronium ion species. I n this way the substitution of a bulky alkyl group for a hydrogen atom a t the position designated by R in the structures, below,
3389
duration of the experiment has an adverse effect on the yield, the cause of which is not immediately apparent. A Raman spectrum of the neopentyl nitrate-polyphosphoric acid mixture showed lines a t 1358 (assigned to the nitrate ion") and a t 1686, 1541, and 1290 em.-' (assigned to molecular nitric acid12); the same lines were observed in the spectrum of potassium nitrate dissolved in polyphosphoric acid. The spectruni was notable for the absence of a line a t 1400 em.-', which could be attributed to the nitronium ion.12 The absence of nitronium ion in the Raman spectra and the low 0-p ratios constitute strong support for the proposal that a bonded nitratiyg species is involved in nitrations utilizing the alkyl nitrate-polyphosphoric acid system.l 3
Experimental Materials.-Toluene was purified by washing with sulfuric acid followed by fractionation through a Podbielniak column to give material containing less than 0.2% of impurities as determined by vapor phase chromatography using a 12-ft. Apiezon L grease column. Absolute nitric acid was prepared by passing nitrogen gas through a hot mixture of red fuming nitric acid (1800 g.) and fuming nitric acid (453 g.) for 12 hr., then treating the blown would exert a larger inhibiting influence a t the ortho nitric acid with sulfamic acid (20 g.) a t 10" and fractionposition and result in a further lowering of the 0-p ratio. ally distilling with sulfuric acid (680 9.) under nitrogen gas. A small amount of nitrogen dioxide in the distilled nitric acid was The initial results with primary amyl nitrate supported oxidized with ozone a t 5' to nitrogen pentoxide, which was then this approach and are reported in Table V. hydrated with a calculated amount of 70% nitric acid (reagent grade). TABLE V Nitrogen pentoxide was prepared by the dehydration of absolute nitric acid with phosphorus pent0xide.1~ NITRATIONS WITH PRIMARY AMYL NITRATE^ Ethyl nitrate and butyl nitrate were Eastman grade materials; Nitrating reagent 0 - p ratio Yield, % primary amyl nitrate was a commercial material supplied by Amyl nitrate and sulfuric acid 1.42 82.4 Ethyl Corp. Amyl nitrate and polyphosphoric acid sec-Butyl nitrate was prepared by nitrating sec-butyl alcohol (P20acontent, 83%) 0.64 95.3 with 98y0 nitric acid in acetic anhydride at 20-25".16 t-Butyl a Temperature, 50". nitrate was obtained from the reaction of t-butyl alcohol with 98% nitric acid (XZOa-free) in dichloromethane a t -20 to 20".'6 Acetone cyanohydrin nitrate was prepared by R slight modifiThe advantage to be gained from the steric effect of cation of the reported" method by nitrating a 14y0 solution of the alkyl substituent of the alkyl nitrate was extended acetone cyanohydrin in glacial acetic acid with colorless 91 .5y0 further by progressively increasing the size of the subnitric acid (2 moles) and acetic anhydride ( 4 moles), which were stituent. The results, as depicted in Table VI, show added separately but simultaneously to the acetic acid solution. clearly that the lowering of the o-p ratio is directly Neopentyl nitrate was prepared by adding a solution of 88.2 g. ( 1 .0 mole) of neopentyl alcohol in 50 ml. of methylene chloride related to the bulk of the alkyl group. to a mixture of 126.0 g. (2.0 moles) of absolute nitric acid and 50 ml. of 96% sulfuric acid a t 14-16' over a 1.5-hr. period under TABLE VI nitrogen gas. An additional 50 ml. of sulfuric acid was added KITRATION WITH ALKYLNITRATES AND POLYPHOSPHORIC in 15 min. The reaction mixture was drowned in an icewater mixture, and the product was extracted with methylene chloride. ACID" The combined methylene chloride extracts were washed with Temp., Time, 0-p m-isomer, Yield, water. The solvent was removed and the residue was distilled Nitrate OC. hr. ratio % % to yield 105.8 g. (79%) of colorless oil: b.p. 47-49' a t 30-32 Ethyl 45 3 0.76 3.2 53 mm., n Z 41.4066, ~ dZl.8 0.978. n-Butyl 3 0.67 26-35 3.1 60 Anal. Calcd. for C ~ H ~ ~ N OC, B :45.10; H, 8.33; N, 10.52; 4 sec-Butyl 32-40 0.59 3.0 58 0, 36.05. Found: C, 45.2; H, 8.3; N, 10.7; 0, 36.5. &Butyl 25-30 3 . 5 0.50 ... 61 Determination of Isomer Ratios .-The three mononitrotoluene Neopentyl 30-40 24 0.49 .. . 97 isomers were determined by infrared absorption spectra using the Neopen tyl 22-24 72 0.50 2.4 73 characteristic bands a t 8.72 for the ortho isomer, 8.50 for the Acetone cyanohydrin 30-44 120 0,74 1.5 67 a No solvent waa used; the polyphosphoric acid contained 83YGPzo5; the usage of toluene and PZOEwas 3 moles of each (11) J. P. Mathieu and M. Lounsbury, Compt. rend., 118, 1315 (1949); per mole of alkyl nitrate. Discussions Faraday Soc., 9, 196 (1950).
It is apparent that the neopentyl nitrate-polyphosphoric acid system affords the lowest 0-p ratio and the best yields of mononitrotoluene. Temperature does not appear to affect the 0-p ratio but increasing the (9) H. 4 , 1947).
R . Wright and W. J. Donaldson, U. S. Patent 2,416,974 (lMarch
(10) L. P. Kuhn, J . Am. Chem. Soc., 69, 1974 (1947).
(12) C. K. Ingold. D. J. Millen, and H. G. Poole, J . Chem. Soc., 2576 (1950). (13) We are indebted to one of the referees for pointing o u t that G . A. Olah, et 02. [ J . Am. Chem. Soc., 84, 3687 (1962)], propose solvated ion pairs
as the active species in other systems, which lends support to the present proposal concerning the polyphosphoric acid system. (14) N. S. Gruenhut, M. Goldfrank, M. L. Cushing, and G . V. Ceasar, Inorg. Syn., 3, 78 (1950). (15) J. E. Lufkin, U. S. Patent 2,396,330 (March 12, 1946). (16) A. Michael and G . H. Carlson, J . Am. Chem. Soc., 67, 1268 (1935). (17) W. D . Emmons and J. P. Freeman, ibid.. 77, 4387 (1955).
3390
NEALE,SCHEPERS, AND WALSH
para isomer, and 11.05 p for the meta isomer.18 The deviation for the G-p ratio in the range of 0.4 to 2.0 was 0.05 (2 q), while the deviation for the meta isomer content in the O-lOyo range was 0.3 (2 u ) . For these analyses the samples were distilled to remove small amounts of the dinitrotoluene isomers, which interfered with the determination. I n general, dinitration was negligible. Some of the analyses were also determined by a V.P.C. methodlg using a 12-ft. Apiezon L grease column. General Procedure for Nitration.-In the general procedure the nitrating reagent was added slowly with stirring to the toluene which was either dissolved in a solvent or mixed with an acid, under anhydrous conditions. The reaction mixture was stirred for the indicated periods, drowned in ice-water, and extracted four to five times with chloroform. The combined chloroform extracts were washed with a dilute sodium carbonate solution, dried over anhydrous magnesium sulfate or sodium sulfate, and distilled to remove the solvent. When the analysis utilized the V.P.C. method, the pot residue was used directly and without further treatment; when the analysis utilized the infrared spectral procedure, the pot residue was fractionated to obtain the isolated mononitrated products, boiling a t 96' a t 10 mm. Nitration of Toluene with Neopentyl Nitrate in Polyphosphoric Acid.-To a mixture of 55.3 g. of toluene and 71.0 g. of poly(18) F. Pristera and M. Halik [Anal. Chem., 97, 217 (1955)l determined the meta isomer using the 12.49-p absorption band, b u t this is interfered with by the equally strong 12.7-p band of the ortho isomer. (19) J. S. Parsons, S. M. Tsang, M. P. DiGiaimo. R. Feinland, and R. A . L. Paylor, ibid., 88, 1858 (1961).
VQL. 29
phosphoric acid in a 250-ml., three-necked, round-bottomed flask fitted with a stirrer, thermometer, and dropping funnel was added 20.0 g. of neopentyl nitrate over 3 hr. and 38 min. During the addition the temperature ranged from 30 to 31.5", and a t the end of the addition the reaction mixture was allowed to stir overnight a t 30". Finally, the reaction mixture was heated to 40" and stirred a t 40" for 1 hr. Infrared absorption spectra of both the polyphosphoric acid and toluene layers showed the presence of nitrotoluenes and the absence of neopentyl nitrate by the failure to observe a band a t 13.2 p . The reaction mixture was then drowned in 300 g. of ice-water and extracted with chloroform. The combined chloroform extracts were washed with 50 ml. of 594 sodium bicarbonate solution and water and dried over anhydrous sodium sulfate. The solvent was removed by distillation until the pot temperature reached 130", and the residue was distilled to give two fractions: (a) 12.94 g. boiling a t 8489" a t 10 mm., and (b) 14.74 g. boiling a t 94-102" a t 8-10 mm. Analysis showed fraction a to contain 5.16g. of mononitrotoluenes and fraction b to be all mononitrotoluenes; total yield of mononitrotoluenes was 19.90 g. (97y0), having an 0-p ratio of 0.49, determined by infrared absorption data.
Acknowledgment.-We are indebted to Professor H. C. Brown for helpful discussions, to Dr. J. L. Gove for the infrared spectral analyses, to Dr. R. L. Anister for the Raman spectral data, and to Miss I. H. Prokul for the microanalyses.
The Chlorination of Reactive Anilines R. S. NEALE,R. G. SCHEPERS, .4ND 31. R. WALSH Unzon Carbade Research Institute, Tarrytown, New York Received June 15, 1964 Chlorination of aniline and N-alkylanilines with N-chlorosuccinimide in hot benzene afforded 65-95y0 of mixtures of o- and p-chloroanilines. Very little tar or dichlorinated material was produced, and the 0-p ratio usually exceeded 2, even in the case of N-t-butylaniline. The products appear to arise mainly from a facile rearrangement of intermediate N-chloro isomers.
As a result of our studying the chemistry of aminium radicals >N+,we wished to prepare some representative alkylaryl-K-chloraniines, ArN(Cl)R, a class of compounds not represented in the literature. Treatment of various anilines with N-chlorosuccinimide (NCS) in hot benzene, however, yielded only mixtures of mono-o- and -p-chloroanilines in 65-95% yield (Table I), instead of the desired N-chloro isomers. This reaction therefore affords a convenient method for the direct monochlorination of reactive anilines under mild conditions without the use and subsequent removal of protecting groups. These mild conditions may also be generally suitable for the monochlorination of other reactive aromatic compounds, if specific effects due to the presence of the nitrogen atom in the anilines studied are not important to the prevention of polychlorination. The 0-p ratio of the product mixture was high, usually greater than 2 : 1, and could be increased t o some extent by employing an excess of the aniline relative to NCS. The method is therefore particularly suited to the preparation of o-chloroanilines, which may be obtained free of the para isomers by simple fractional distillation. I n the only previous report of synthetically useful procedures for the chlorination of anilines, which was limited to N,N-dimethylaniline, the 0 - p ratio and yield were shown to depend heavily on the chlorination system; our study not only (1) T. H. Chao and L. P. Cipriani, J. Org. Chem., 96, 1079 (1961).
discloses the generality of chlorination by XCS in an inert solvent, but provides strong circumstantial evidence for the formation of the desired N-chloroanilines as intermediates in these reactions. Discussion The results presented in Table I favor a chlorination mechanism whereby at least a niajor part of the reactions proceeds through N-chloro intermediates. The 0-p ratio observed in most cases slightly exceeded the statistically possible 2 : 1 distribution, and decisively exceeded the 1.8 (or less) to 1 distribution normally expected from electrophilic substitution by a very small, reactive species such as YO2+ or Clz in a polar ~ o l v e n t . ~The high 0-p ratios appear to support an intramolecular rearrangement of intermediate X-chloroanilines to ring-chlorinated products, for the following reasons. By analogy to the direct electrophilic chlorination of toluene3 one might predict for the possibility of uncatalyzed chlorination by free chlorine, formed in situ, maximum 0-p ratios on the order of 1.5 in hydroxylic solvents, but ratios considerably less than unity in a nonhydroxylic solvent. The 0-p ratios obtained now in benzene obviously contrast markedly with this; this suggests that free chlorine is not the (2) R. Ketcham, R. Cavestri, and D. Jambotkar, zbzd., 98, 2139 (1963). (3) L. M. Stock and .4.Himoe, Tetrahedron Lettere. No. 18, 9 (1960).
