Phys. Org. 529

Nitrosation, Diazotisation, and Deamination. Part X1I.l The Kinetics of N- N it rosat ion of N- M et hylan i I ine

By E. Kalatzis and J. H. Ridd

The rate and kinetic form of the N-nitrosation of N-methylaniline with nitrous acid in aqueous perchloric acid (0.002-6.5~) are similar to those observed for the diazotisation of aniline over the same range of acidity. At acidities below about 1 M. the nitrosation of the free amine by nitrous anhydride provides the most important re- action path but, as the acidity is increased, this is supplanted by a strongly acid-catalysed mechanism which we attribute to the attack of a positive nitrosating agent on the protonated amine. The similarity of the nitrosation results with the diazotisation results shows that N-nitrosation is the rate-determining stage of diazotisation over the whole of this range of acidity.

THE previous Papers in this Series have been mainly concerned with the kinetics and mechanism of diazotis- ation in media of progressively increasing acidity. The initial nitrosation stage has been considered throughout to be rate-determining and, a t low acidities, this has been held to involve attack on the free amine [stage (a), Scheme 11. However, in the last Paper,l the kinetic form and substituent effects for the diazotisation of aniline in 3~-perchloric acid were considered to be in- consistent with a reaction of the free amine, and the direct nitrosation of the protonated amine was held to be rate-determining [stage (b), Scheme 11 through a transition state involving partial bonding of the electro- phile to the aromatic ring. The work in the present two Papers was carried out to provide further evidence on this unusual reaction path; first, by a study of the related N-nitrosation of secondary amines and then (as described in the following Paper) by a more detailed study of substituent effects.

ArNH,

NOX ArNH,.NO d ArNH-NO ArN=NOH

ArNH, ArN, Scheme I

There are few mechanistic studies on the nitrosation of secondary amines: Taylor and Price have examined the nitrosation of dimethylamine a t low acidities and, more recently, Loshkarev and his co-workers 3 have reported on the kinetics of nitrosation reactions involving tropaeoline dyes. Such studies have illustrated some of the expected similarities between diazotisation and N-nitrosation but have not provided a detailed com- parison of the two reactions over a wide range of acidity. Some studies of the nitrosation of N-methylaniline at low acidities are therefore included here.

Low Acidities ([H+] < O.lM).-The results for the re- action of N-methylaniline with nitrous acid at the lowest acidity studied (0.002~) are given in Table 1 ; the

* We retain the convention that a bar over a rate coefficient indicates that i t is calculated with respect to the stoicheio- metric concentrations of the reactants and indicate such con- centration by writing the name of the chemical species within the concentration brackets.

Part XI, B. C. Challis and J. H. Ridd, J . Chem. Soc., 1962, 5208.

N N

reaction rate is independent of the concentration of the amine, and the initial rate varies with the square of the

TABLE 1 Reaction of N-methylaniline and of aniline with nitrous acid

in 0.002~-perchloric acid a t 0" N-Methylaniline

r Aniline * 103[amine] (M) ... 5 10 20 10 20 10 103[nitrous acid] (M) 1 1 1 2 2 1

Time (min.)

10 20 30 40 50 60

3 .... . ....... . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

K,(mole-1 sec.-ll.)

9-2 25.4 39.4 49.1 56.5 62.0 66-3

0.550

Percentage reaction t 9.6 8.5 18.1 17.7 -

25-3 24-9 41.1 40.7 26.0 39.4 39.2 57.9 57-4 41.0 49-2 48.2 67.9 67.8 51.0 56.5 56.2 73.7 74.6 58.0 61.9 61-3 78-5 78.6 63.7 66-2 66-6 81.9 81.6 68.0 0-548 0.545 0.590 0.585 0.583

* Taken from ref. 4. t.Calculated from the concentration of nitrous acid.

initial concentration of nitrous acid. The reaction has therefore the kinetic form of equation* (1); this con- clusion is supported by the constancy of the values of A, for the different kinetic runs.

Rate = A, [nitrous acid]* (1)

Comparison of the results in columns 3 and 7 shows that, under these conditions, the nitrosation of N-methylani- line occurs at the same rate as the diazotisation of aniline. These results are therefore consistent with the expected 5

reaction through the slow formation of nitrous anhydride as outlined in Scheme 2 when Z I - ~ < v2.

"1

v-1

"a

2HN02 N203 + H 2 0

N a 0 3 + ArNHMe ArNH,-NO + HNO, Scheme 2

As the acidity is increased, the reaction rate a t first in- creases (cf. Table 7, Experimental section) presumably because of the increase in the concentration of molecular

a T. W. J. Taylor and L. S. Price, J . Chem. SOC., 1929, 2052. 3 M. A. Loshkarev, S . I. Burmistrov, and R. M. Tsymbal,

Isvest. Vysshikh Ucheb. Zavedenii Khim. i Khim. Tecknol, 1968, No. 2 , 6; M. A. Loshkarev and R. M. Yasyunas, ibid., 1963, No. 2, 236.

4 E. D. Hughes, C. K. Ingold, and J. H. Ridd, J . Chem. Soc., 1958, 65.

5 J. H. Ridd, Quart. Rev., 1961, 15, 418.

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530 J. Chem. SOC. (B), 1966

nitrous acid, but the rate then passes through a maximum and the total reaction order increases from 2 to 3. This order has been calculated from the half-life (t4) for re- action with equal concentrations ( a ) of amine and nitrous acid using the equation

ti = c - (n - 1) log a

The results are given in Table 2 and show that the transition to the third-order form is complete in 0 . 1 ~ - perchloric acid. At this acidity, the results in Table 3 show that the initial reaction rate is doubled by doubling the concentration of the amine and approximately quadrupled by doubling the concentration of the nitrous acid: the kinetic form is therefore as equation (2).

Rate = k, [amine][nitrous acid12 (2) This equation is consistent with the mechanism shown in Scheme 2 providing v - ~ > v2. A similar kinetic transition is observed with aniline at slightly lower acidities .4

TABLE 2

Variation of t h e half-life with t h e initial reactant concen- t ra t ion for t h e nitrosation of N-methylaniline in 0.20- 0- 1M-perchloric acid and t h e calculated reaction order (n )

103 [Reactant]

1 1-5 18.8 2.0 12-8

[HCIO,] (M) tb(min.) n

3'60 } 2.6 0.02 {

0.1 { c ym5 :;Po

0.05 I 1.5 28-0(65-0) *' 2.7

} 3-0

2.0 17-5(35*5) *J 1 108 1.5 45.5 2-0 25-3

* Values in parentheses refer t o the diazotisation of aniline and are taken from ref. 4.

TABLE 3 Nitrosation of N-methylaniline in 0-lw-perchloric acid at 0"

lOS[amine] (M) ......... 1.0 2.0 1.0 103[nitrous acid] (M) ... 1.0 1.0 2.0

Time (min.) 1 05[PhNMeNO] 3 ........................ 4.7 8.7 17.5

10 ........................ 12.1 21.8 40.1 20 ........................ 20-0 34.7 58.1 30 ........................ 28-1 48.5 68.7 40 ........................ 33.5 49.8 75.8 50 ........................ 37.5 54.9 81.1 60 ........................ 40.6 59.1 85.0 &(mole-2 sec.-l l.z) ...... 245 247 269

The increase in acidity also causes the rate of nitros- ation of N-methylanilines to exceed the rate of diazotis- ation of aniline by a factor that increases to -2 in O.O5~-acid (see the results in parentheses in Table 2). This order of relative reactivities was unexpected, for the several determinations of the pK, of N-methyl- aniline agree that the molecule (pK, = 4.85) is more basic than aniline (pK, = 4.6) by a factor of about 1.8. An increase in the basicity of primary amines lowers the rate of diazotisation by nitrous anhydride because the

decrease in the concentration of the free amine is only partly compensated by the increase in the nucleophilicity of the amine. If the measurements of the $Ka are correct, it would appear that N-methylation increases the nucleophilicity of the nitrogen towards nitrous anhydride by a larger factor than its effect on the basicity.

Intermediate Acidities ([H+] = 0-1-6.5~) .-At acidi- ties above O a l ~ , the total reaction order (n) decreases from 3 to' a limiting value of 2, but this order is then divided equally between the reactants. The variation of the total reaction order (n) with acidity is shown in Table 4, the results being calculated from the half-life as

TABLE 4 Variation of t h e half-life w i th the initial reactant con-

centration for t h e nitrosation of N-methylaniline in 0.5-%5~-perchloric acid at 0" and t h e calculated reaction order (n)

103 [Reactant] t i

[HClO,] (M) (min.) n 1.5 192

0.5 { 2 104 } 2.9 2.5 67-4

1.0 { im5 250 145 } 2.8 2.5 98.0 1.5 137

1.5 { 2 102 } 2.2 3.5 80.0 1 106

2.0 { 1-5 68-0 } 2.1 2 49.0

2.5 { i-5 i::: } 2-06 2 23.0

TABLE 5 Nitrosation of N-methylaniline in 3~-pe rch lo r i c acid at 0'

Run A 10a[amine] = 1.0 Run B lO3[amine] = 0.5

103[nitrous acid] = 0.5 103[nitrous acid] = 1-0

1 05[PhNMe-NO] Time (min.) ...... 3 10 20 40 50 60 80 120 Run A ............... 6.9 17.6 27.5 37.5 40.5 42-6 45.6 47.7 Run B ............... 7.0 17.8 27.4 37.5 40.6 42.6 45.7 48.1

described above. The equal division of this order between the reactants for reaction in 3~-perchloric acid is clear from the two kinetic runs in Table 5, where the concentrations of the reactants are interchanged without any significant effect on the reaction rate. Reactions carried out with various concentrations of reactants a t a given acidity > 3M give consistent rate coefficients when calculated from equation (3) ; this equation is therefore considered as the limiting kinetic form for nitrosation, at acidities above [H+] = 3M.

Rate = k, [amine][nitrous acid] (3) In studying the dependence of k, (equation 3) on

acidity, it is helpful to use the lowest possible concen- 6 D. D. Perrin, I' Dissociation Constants of Organic Bases in

Aqueous Solution," Buttenvorths, London, 1965. 7 L. F. Larkworthy, J . Chem. Soc., 1959, 3116.

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Phys. Org. 53 1

tration of nitrous acid, for this minimises the contribu- for reaction in the presence of perchloric acid alone and tion of nitrosation through nitrous anhydride. With concentrations of nitrous acid below 1 0 - 3 ~ , it has been found possible to retain the second-order form of nitros- ation (equation 3) down to 1M-perchloric acid; this is illustrated by the agreement between the following second-order rate-coefficients for three kinetic runs at this acidity and at 0".

lOS[amine] (M) .................. 2.0 4.0 4-0 104jnitrous acid] (M) ......... 2-0 2.0 4.0 h,(equation 3) (mole-l set.-' 1.) 32.8 32.1 35.3

Values of h2 (equation 3) obtained in this way for nitrosation in the presence of various concentrations of perchloric acid and sodium perchlorate are collected in Table 6. The corresponding values of log h, for con- centrations of perchloric acid up to 3~ are compared in

TABLE 6 Nitrosation of N-methylaniline a t 0"; dependence of K Z

(equation 3) on the concentrations of perchloric acid and sodium perchlorate

[HC104] (M) ... 0.5 1.0 1.5 2-0 2-5 3.0 h,(rnole-lsec.-ll.) 0-0187* 0.0334 0.0737 0.168 0.357 0.769 [HClO,] (M) ... 3.5 4-0 5.0 5-6 6.44 h,(mole-lsec.-ll.) 2.09 4-17 21-4 66-5 401-0

Perchloric acid + sodium fievchlorate to ionic stremgth of 3.0

ii,(mole-lsec.-ll.) 0.136 0.256 0-378 0.519 0.664 0.769

Perchloric acid ( 1 . 0 ~ ) + sodium perchlorate [NaClO,] (M) ... 0.5 1.0 1-5 2.0 2.5 3-0 h,(mole-'sec.-ll.) 0.0521 0-087 0.149 0-256 0-401 0.712

[wHC104] (M) ... 0.5 1.0 1.5 2.0 2.5 3-0

* Nitrosation by the nitrous anhydride mechanism probably contributes significantly to the rate of this kinetic run.

Figure 1 with those obtained for the diazotisation of aniline at 0". The slopes of log h, against acidity for nitrosation and diazotisation are almost identical, both

I L--- 1 8 I I I

I 4 [HC104] or fHC104!+ [NaCI04]

FIGURE 1 Comparison of the values of log k , (equation 3) for the diazotisation of aniline (open circles) and for the N - nitrosation of N-methylaniline (dots). The continuous lines refer to reaction in perchloric acid alone and the broken lines to reactions in 1M-perchloric acid containing varying quantities of sodium perchlorate

for reaction in the-presence of 1M-perchloric acid and various concentrations of sodium perchlorate. The values of log k2 from Table 6 for acidities above 3 . 0 ~ lie on the same linear relationship; a similar plot of log 6,

0.8 c - I 0

u t $ 0 - 6 d

I 1 I 1

0.4 0.6 0.8 1.0 1.2

"0 FIGURE 2 The variation of log k , (equation 3) with the H ,

acidity function for the N-nitrosation of N-methylaniline in mixtures of perchloric acid and sodium perchlorate a t a constant ionic strength of 3.0. The values of H , are taken from ref. 1

for the diazotisation of aniline8 at 2" is also linear for concentrations of perchloric acid up to 6 . 5 ~ . A plot of the values of log k, against -Ho for the solutions with an ionic strength of 3.0 is linear with a slope of almost unity (0.92) (Figure 2); the full kinetic equation for reaction under these conditions is therefore as shown below (equation 4).

Rate = k3 [amine][nitrous acidlh,

This can also be written as equation (5), for a t these acidities the s t oicheiome t ric concent rat ions of the reactants are effectively equal to the concentrations of the chemical species shown in the equation.

(4)

Rate = K,[PhmhH,Me] [HNO,]h,

A similar kinetic equation has been reported for the diazotisation of aniline under these c0nditions.l

The change in the order with respect to nitrous acid as the acidity is increased, and the rapid increase in the values of h, (equation 3) with acidity, point to the replacement of nitrous anhydride by a positive nitrosat- ing agent formed from one molecule of nitrous acid. By analogy 1 with the diazotisation of aniline, we consider that this nitrosating agent attacks the protonated amine ; the justification for this interpretation of equation (5) is discussed in detail in the following Paper. The course of N-nitrosation under these conditions can therefore then be represented by the reactions in Scheme 3. In this Scheme, the nitrosating agent is shown as the nitrous acidium ion (or monohydrated nitrosonium ion)

* E. C. R. de Fabrizio, Ph.D. Thesis, London, 1964; cf. following Paper.

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532 J. Chem. SOC. (B), 1966

but the effective degree of hydration of the nitrosoniurn ion in these reactions may well depend on the acidity.

HNOs + H+ __ H,NO,+

+ slow c H,NO,+ + ArNMeH, _.+ H,Of + ArNMeH-NO

fast ArNfMeH-NO __t ArNMeNO + H+

Scheme 3

Some work has been carried out a t acidities above 6.5~-perchloric acid but the yield of N-methyl-N- nitrosoaniline is then less than expected from the initial concentrations of the reactants. It is possible that the rate of denitrosation of the nitrosamine is then becoming significant. Nitrosations in this region of acidity are under further investigation.

Conclusions.-The kinetic forms observed in the nitrosation of N-methylaniline are the same as those observed in the diazotisation of aniline and the transi- tions between these kinetic forms occur a t similar acidities in nitrosation and diazotisation. The de- pendence of the corresponding rate-coefficients on acidity is the same in nitrosation and diazotisation and this also applies to the effect of added sodium perchlorate. The magnitudes of the rate coefficients for the two reactions are also similar. Thus, all the kinetic characteristics of the diazotisation of aniline in aqueous perchloric acid can be found in the nitrosation of N-methylaniline.

We conclude from this that the N-nitrosation stage of diazotisation determines the reaction rate over the whole of the range 0-002-6-5~-perchloric acid. The earlier studies lo had already given good reasons for expecting this result for diazotisation at the lower acidities but it appeared important to establish this result also for diazotisation in 3~-perchlonc acid, since it enables the anomalous substituent effects observed in diazotisation at this acidity to be interpreted in terms of the electronic requirements of the transition state leading to N - nitrosation. The discussion of these substituent effects is given in the following Paper.

EXPERIMENTAL

Materials.-The perchloric acid and sodium hydroxide were AnalaR reagents and were used to prepare the sodium perchlorate. AnalaR sodium nitrite was dried over phosphorus pentoxide before use. N-Methylaniline (B.D.H. reagent grade) was dried over potassium hydroxide and distilled twice over zinc dust in an atmosphere of nitrogen. N-Methyl-N-nitrosoaniline was prepared as described by Vogel l1 and distilled three times under reduced pressure (b. p. 119-120"/12 mm.).

Kinetic Studies.-The reaction was followed from the absorption maximum of N-methyl-N-nitrosoaniline a t 2690 A ( E = 7.45 x lo3) in mildly acidic media. The spectrum is not sensitive to the acidity over the range studied (0-0.4~-perchloric acid). The contribution of the reactants to the optical density a t this wavelength is very slight except a t the lowest acidity studied. The technique

0 E. Kalatzis, Ph.D. Thesis, London, 1964. lo E. D. Hughes, C. K. Ingold, and J. H. Ridd, J . Chem. SOL,

1958, 88.

used depended on the acidity. For the kinetic runs at the lower acidities, the reaction was started by adding an aqueous solution of sodium nitrite to a solution of the amine in aqueous perchloric acid, both solutions being a t 0". Samples were extracted a t suitable intervals and were diluted by a factor of 10-50; the optical density a t 2690 A was then measured immediately against a similar solution of the amine in perchloric acid as a blank. A slight correction was applied to these readings to allow for the change in the concentration of the amine and the nitrous acid in the reactant solution.

With the faster kinetic runs, i t became impracticable to measure the optical density of each solution immediately after sampling. The samples were then run into a solution of sodium hydroxide and borax, the concentrations being adjusted so that the final pH was -8. A t this acidity, the N-nitroso-compound is stable but the nitrosation ceases. At the end of the kinetic run, these solutions were made slightly acid,* brought to a known volume, and the optical densities measured against an equivalent blank.

The rate of the reaction at acidities above 5~-perchloric acid did not permit the extraction of samples and the kinetic points were then determined from separate reaction mixtures using three-limbed reaction vessels of the type shown (Figure 3); this incorporates a B29 joint with a teflon sleeve. Limbs A and B contained the reactants and the bulb C contained the quenching solution (sodium

TABLE 7 Examples of kinetic runs

(A) Sampling technique (Run No. 100) [amine] = 0 . 0 1 ~ ; [nitrous acid] = 0 . 0 0 1 ~ ; [HClO,] = 0 . 0 1 ~

Reac- k, $ Reac- k, t Time tion (eqn. Time tion (eqn. (min.) O.D. * (%) 1) (min.) O.D. * (yo) 1)

3 0.091 15.2 - 30 0-363 60-7 0-859 10 0-208 34.7 0.886 40 0.403 67.5 0-864 15 0.261 43.7 0.862 50 0.433 72.4 0.862 20 0.305 51.0 0.868 60 0.452 75.5 0-860 * Optical density of a 2-ml. sam le diluted to 100 ml. and

measured in a 4 cm. cell at 2690 f A slight correction has been applied (-1% of the optical density) t o allow for the difference in the amine concentration between the reaction mixture and the reference solution. t Integrated from the time of the first reading. Units are mole-l sec.-l 1.

(B) Use of three-limbed tube (Run No. 173) Limb A 7.7 ml. of 2 x lO-,~-arnine perchlorate in 5 -6~-pe r -

chloric acid ,, B 7.7 ml. of 1.37 x lO-*~-nitrous acid in 5*6~-perchloric

acid ,, C 8.60 ml. of 10N-sodium hydroxide & I 0 ml. of 0 . 1 ~ -

borax

Time Reaction (mole-' (sec.) O.D. $ (%) sec.-l 1.) 30 0.152 17.9 70.2 60 0-257 30.2 67.8 90 0.342 40.2 67-9

120 0.397 46-7 64.6 180 0.497 58.5 64.8 600 0.748 88.0 63.5

h, (eqn. 3)

$ Optical density of reaction mixture after quenching and final addition of 2 ml. of lxf-perchloric acid giving a volume of 37-1 ml.

* To reduce absorption by the free amine. l1 A. I. Vogel, " Textbook of Practical Organic Chemistry,"

Longmans, London, 1948, p. 547.

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Phys. Org. 533

hydroxide + borax). The solutions were cooled to 0" and the reaction was started by partial rotation of the reaction vessel, thus mixing the solutions of amine and nitrous acid. The reaction was later stopped by rotating the reactant limbs through 180" and shaking; thereby mixing the

u FIGURE 3

reactant solution and the quenching solution. The optical density of the final solution at 2690 A was then determined after slightly acidifying the solution as described above. In calculating the concentration of the N-nitroso-compound in the reactant solution it is necessary to allow for the non- additivity of the volumes during quenching; the slight correctien required was determined in ancillary experiments.

For these experiments solutions of amine perchlorate and nitrous acid were both initially made up in perchloric acid of

the required concentration so as to eliminate the heat of dilution of perchloric acid. Unfortunately, the addition of aqueous sodium nitrite to fairly strong solutions of perchloric acid leads to significant decomposition and the nitrous acid content of the solutions used in the kinetic runs was there- fore determined after mixing using the modified Griess- Ilosva method. This determination was carried out for each kinetic point using a sample prepared in exactly the same way as that used in the kinetic run and kept for the same period of time before analysis. Fortunately, the greater part of the decomposition appears to occur during or soon after mixing of the sodium nitrite and the perchloric acid, for the samples of a solution used for different points of a kinetic run were found to contain almost equal con- centrations of nitrous acid.

The relevant calculations are illustrated by the two kinetic runs in Table 7; the first was carried out using the sampling technique and the second using the three-limbed reaction vessel. Further details of this work are given else- where.g

WILLIAM RAMSAY AXD RALPH FORSTER LABORATORIES, UNIVERSITY COLLEGE, GOWER ST., LONDON W.C. 1 .

[5/1311 Received, December 9tA, 19651

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