J . Org. C h e m . 1994,59, 5627-5632
6627
A New Route to 4-Aminodiphenylamine via Nucleophilic Aromatic Substitution for Hydrogen: Reaction of Aniline and Azobenzene Michael K. Stern,* Brian K. Cheng, Frederick D. Hileman, and James M. Allman Monsanto Corporate Research, Monsanto Company, St. Louis, Missouri 63167 Received May 2, 1994@
A new example of nucleophilic aromatic substitution for hydrogen is described which encompasses reacting aniline and azobenzene (1) in the presence of base under aerobic conditions to generate 4-(pheny1azo)diphenylamine (2) in high yield. Monitoring the time course of the reaction under anaerobic conditions revealed that hydrazobenzene (9)was formed as an intermediate in the reaction in equal molar amounts a s 2. However, under aerobic conditions 9 was shown not to persist in the reaction mixture. The kinetic effect of isotopic substitution on this reaction was probed by competition experiments utilizing equal molar mixtures azobenzene-dlo and undeuterated material which gave a kH/kD of 4.6 f 0.1. It was concluded from these studies that azobenzene was functioning as both the electrophile and oxidant in this reaction. Catalytic hydrogenation of 2 generates 4-aminodiphenylamine (4-ADPA) (10) and aniline. These reactions form the basis of a novel synthetic route to 4-ADPA which does not utilize halogenated intermediates or reagents and ultimately relies on 0 2 as the terminal oxidant in the system. The development of new environmentally favorable routes for the production of commercially relevant chemical intermediates and products is a n area of considerable interest to the chemical processing industry. These synthetic routes will ideally focus on elimination of waste at the source and will require, in most cases, the discovery of new atomically efficient chemical reactions. In view of these emerging requirements, we have focused our attention on nucleophilic aromatic substitution for hydrogen (NASH) reactions as a means to generate aromatic amines without the need for halogenated materials or intermediates.l Of particular interest was the identification of novel synthetic strategies to 4-aminodiphenylamine (4-ADPA) (10) and its derivatives which are widely used as antioxidants in rubber products. Current processes for the manufacturing of 4-ADPA are heavily dependent on halogenated reagents which ultimately generate waste streams laden with inorganic salts and trace amounts of organic byproducts.2 In pursuit of the these objectives, we recently have shown that the NASH reaction of aniline and nitrobenzene generates high yields of (4-nitrosopheny1)phenylamine and (4nitr0pheny1)phenylamine.~Catalytic hydrogenation of these intermediates produces 4-ADPA in a halogen-free pro~ess.~ The necessity for electron-withdrawing groups (EWG) in the activation of aromatic rings toward nucleophilic substitution is a well-established principle in organic chemistry. In the general case of nucleophilic aromatic substitution for halogen, a wide variety of EWG such as nitro,5 (trifluoromethyl)sulfonyl,6and even phenylazo' have been shown to enhance the rate of S N Areactions. ~ However, in the case of nucleophilic aromatic substitution @Abstractpublished in Advance ACS Abstracts, August 1, 1994. (1) (a) Riley, D. P.; Stern, M. K.; Ebner, J. Industrial Perspectives on the Use of Dioxygen: New Technology to Solve Old Problems in The Activation of Dioxygen and Homogeneous Catalytic Oxidations; Barton, D. H. R., Martell, A. E., Sawyer, D. T., Eds.; Plenum Press: New York, 1993.(b) Stern, M. K.; Cheng, B. K. J. Org. Chem. 1993, 58,6883-6888. (2)(a)Rondestvedt, C. S.J. Org. Chem. 1977,42,1786-1790.(b) A few of the numerous patents are listed: US. Patents 4 187 248, 4 683 332,4 155 936,4 670 595,4 122 118. (3)Stern, M. K.; Hileman, F. D.; Bashkin, J. K. J. Am. Chem. SOC. 1992,114,9237-9238. (4)US.Patent 5 110 763.
for hydrogen, only nitroarenes have been successfully utilized8 with the exception of a recent example where a diazonium salt was used to activate a substituted dicarboxylic acid toward intramolecular nucleophilic aromatic s u b s t i t ~ t i o n .We ~ report here the first example of a nucleophilic aromatic substitution for hydrogen reaction that proceeds with an azo group as the activating electrophile. This reaction forms the basis for a novel route to 4-ADPA that does not require halogenated intermediates or reagents.
Results The addition of strong bases, such as potassium tertbutoxide/l8-crown-6 or tetramethylammonium hydroxide dihydrate ((CH&N+OH-*2H20) to mixtures of azobenzene (1) and aniline results in the formation of a dark purple solution. This reaction was allowed to stir for 12 h a t 60-70 "C under a nitrogen blanket without the rigorous exclusion of 02. Subsequent analysis of the reaction mixture by reverse phase HPLC indicated the single major product to be 4-(phenylazo)diphenylamine (2). Quenching of the reaction with methanollwater resulted in the precipitation of an orange solid which was recrystallized to give 2 in 96% yield on the basis of moles of 1 charged. Monitoring the time course of this reaction by HPLC revealed the intermediacy of hydrazobenzene ( 9 )in the formation of 2 from aniline and azobenzene. It was evident from the analysis that as the reaction ( 5 ) Terrier, F. Nucleophilic Aromatic Displacement: The Influence of the Nitro Group in Organic Nitro Chemistry Series; Feuer, H., Ed.; VCH Publishers, Inc.: 1991. (6) Shein, S. M.; Ignatov, V. A.; Kozorez. L. A.; Chervatyuk, L. F. Zh. Obshch. Khim. 1967,37,114. (7)Miller, J.Aromatic Nucleophilic Substitution; Elsevier: Amsterdam, 1968. (8) (a) Traynelis, V. J.; McSweeney, J. V. J. Org. Chem. 1966,31, 243-247. (b) Makosza, M.;Winiarski, J. Acc. Chem. Res. 1987,20, 282-289,and references therein. (c) Makosza, M.; Bialecki, M. J.Org. Chem. 1992,57,4784-4785. (d) Katritzky, A. R.; Laurenzo, K. S.J. Org. Chem. 1986,51, 5039. (e) Katritzky, A. R.; Laurenzo, K. S. J. Org. Chem. 1988,53,3978. (0Ayyangar, N. R.; Naik,S.N.; Srinivasan, K. V. Tetrahedron Lett. 1990, 3217. (g) Davis, R. B.; Pizzini, L. C.; Benigni, J. D. J.Am. Chem. SOC.1960,82,2913-2915. (h) Davis, R. B.; Pizzini, L. C. J. Org. Chem. 1960,25,1884-1888. (9)Panetta, C. A.; Fang, Z.; Heimer, N. E. J. Org. Chem. 1993,58, 6146-6147.
0022-3263/94/1959-5627$04.50/00 1994 American Chemical Society
J. Org. Chem., Vol. 59, No. 19, 1994
5628
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Stern et al.
Scheme 1
A
Azobenzene
0 0
4-(Pheny1azo)diphenylamine Hydrazobenzene
4-
-
c n . 0
2E
A '
A
2.000 I
0 0
2b
A
'1 -
-
QNH~+QN=N-Q
3-
20
40 Time (min)
60
80
c I
Figure 1. Time course of the reaction under anaerobic conditions monitoring the production of 2 and 9 and the consumption of 1 by HPLC chromatography. Table 1. Effect of Water on the Yield of 4-(Phenylazo)diphenylamine(2) mole ratio water:tert-butoxide % yieldo 2 10 3 1 0.5
0 1 7 50
Yields are based on moles of azobenzene charged and were determined by reverse-phase HPLC analysis as described in the Experimental Section. Reaction conditions: aniline (1.25 g), azobenzene (0.45 g), potassium tert-butoxide (0.55 g), and 18crown-6 (0.65 g) were mixed with various amounts of water. The reactions were stirred at 80 "C for 2 h aRer which time they were analyzed by HPLC.
350
420.0
490.0
560.0
630.0
700
Wavelength (nm)
0.
progressed, both hydrazobenzene and azobenzene were steadily consumed, generating 2 as the only major product. However, when an identical reaction was run under strictly anaerobic conditions, hydrazobenzene persisted in the reaction mixture and was formed concomitantly with 2 in equal molar amounts (Figure 1). As we have observed in other NASH reactions, the amount of water present in this reaction has a significant effect on the yield of 2 (Table l).lbb For optimal production of 2, nearly anhydrous conditions must be maintained. That 2 was indeed formed via a NASH reaction and not by condensation of aniline with (4-nitrosopheny1)phenylamine, as recently observed by Marletta,lo was confirmed by a series of deuterium-labeling experiments (Scheme 1). Thus, when aniline-& (99% isotopically enriched) was reacted with azobenzene, only 4-(phenylazo)diphenylamine-d5 (2a)was produced, as is evident by electron impact mass spectral analysis showing a molecular ion with mlz = 278. When the identical reaction was carried out using azobenzenedlo and undeuterated aniline, the corresponding 4-(phenylazo)diphenylamine-& (2b)was observed (mlz = 282). This ion showed the loss of C&,Nz+ to give a n intense (10)It has been observed that the reaction of aniline and superoxide can produce (4-nitrosophenyl)phenylamine,which can further condense with another molecule of aniline to generate 2. See: (a) Frimer, A. A.; Aljadeff, G.;Ziv, J. J.Org. Chem. 1983,48,1700-1705. (b) Stuehr, D. J.; Marletta, M. A. J. Org. Chem. 1985,50,694-696.
Figure 2. Visible electronic absorption spectra in DMSO of (- - -1 authentic sample of 2 before addition of TMA(OH).SH20, A,, = 424 nm, and (-1 after addition of final [21= 2.2 x TMA(OHjSH20 t o the DMSO solution of 2, ,A = 574 nm.
fragment ion a t m h = 172 corresponding to (2,435NHC&+, which is consistent with our structural assignment. A small amount of 2 (
