96 HAPPAND JANZEN
The Journal of Organic Chemistry
Electron Spin Resonance Studies of Radical Formation in Nucleophilic Addition Reactions. 11. Cyanide Ion Addition to Electrophilic Compounds. The N-Methyl-9-cyanoacridanyl Radical' JOHNW. HAPPAND EDWARD G. JANZEN Department of Chemistry, The University of Georgia, Athens, Georgia 50601 Received April 14, 1969 The electron spin resonance spectrum of N-methyl-9-cyanoacridanyl radical has been obtained by the cyanide ion addition to N,Nf-dimethyl-9,9'-biacridinium dinitrate (lucigenin) in dimethyl sulfoxide or -formamide. The same radical is produced upon the addition of cyanide ion to air-saturated solutions of N-methylacridinium salts or N-methyl-9-cyanoacridan. N-methyl-9-cyanoacridanyl radical is found to be unusually stable to oxygen. A carbanion air-oxidation mechanism is suggested for radical production. Radicals are also produced in the addition of cyanide to acridine, acridine N-oxide, g-cyanoanthracene, N-methylpyridinium iodide, NJ3,5-trimethylpyridinium iodide, and N-methyl-3-carbamoylpyridiniumiodide. Structural assignments have been made from all the radicals produced except for the last-named compound by the aid of coupling constants derived from molecular orbital calculations.
I n a previous report we have described the results of an electron spin resonance (esr) study of the addition of hydroxide ion to N1N'-dimethyl-9,9'-biacridinium dinitrate (lucigenin, abbreviated DBA2+) in the absence of air or oxidizing agent.2 The initial addition of hydroxide to DBA2+ is followed by ionization of the carbinol to the pinacolate. Dissociation of the pinacolate to N-methylacridone ketyl is postulated, although this radical has not been detected. Three types of esr spectra are obtained, depending on the concentration of base and time after mixing. Structures have been assigned to two of these spectra. The radicals are believed to be produced by N-methylacridone ketyl reduction of DBA2+ and the hydroxide addition product of DBA2+. These reactions are accompanied by weak chemiluminescence, probably due to the one-electron oxidation of IY-methylacridone ketyl. I n previous studies of chemiluminescence of DBA2+ in biological systems, it has been shown that cyanide ion enhances the light emission under normal conditions of chemiluminescence.a Our results on the hydroxide ion addition to DBA2+suggested that similar addition and radical-formation reactions might be taking place with cyanide ion and DBA2+. An esr study of this reaction and of other cyanide additions to electrophilic aromatic compounds is reported here. Included are DBA2+, N-methylacridinium chloride, N-pyridinium iodide, N-methyl-3,5-dimethylpyridinium iodide, N-methyl-3-carbamoylpyridinium iodide (N-methylnicotinamide), acridine, acridine N-oxide, and 9-cyanoanthracene. I n all cases, readily detectable esr signals can be obtained in the presence of air. From analyses of the esr spectra, assignments for the structures of the radicals are made. Details of the stoichometry and kinetics of radical formation will be reported in future publications. Experimental Section Equipment.-The described.
equipment used for this study has been
(1) This work was supported by the Atomic Energy Commission, Contract AT-(40-L)-2851. (2) E. G . Janzen, J. B. Pickett, J. W. Happ, and W. DeAngelis, J . Ore. Chem., 86, 88 (1970). (3) J. R . Totter, Photochem. Photobiol., 8, 231 (1964).
Chemicals.-Acridine and 3,bdimethylpyridine were obtained from Aldrich Chemical Co. Lucigenin was obtained from K & K Laboratories, Inc. ;9-cyanoanthronitrile and nicotinamide were obtained from Eastman Organic Chemicals. Other chemicals were commercially available and were of reagent grade. 1-Methylpyridinium iodide was prepared from pyridine and methyl iodide, mp 116-117' (lit, mp 117°).4 The reaction of 3,5-dimethylpyridine with methyl iodide gave 1,3,5-trimethylpyridinium iodide, mp 270-271' (lit. mp 270').6 l-Methyl-3carbamoylpyridinium iodide was prepared from nicotinamide and methyl iodide, mp 205-206' (lit. mp 206.5-207.0°).6 10-Methylacridinium chloride was synthesized by treating acridine with dimethyl sulfate followed by ion exchange with NaCl to form the chloride salt according to the method of Albert,' mp 182-183' dec (lit. mp 183' dec). Q-Cyano-lO-methylacridinium chloride was prepared from g-cyanoacridine and dimethyl sulfate followed by ion exchange with NaC1. Recrystallization from absolute ethanol gave orange crystals, mp 195-196' * dec. 9-Cyanoacridine was synthesized from acridine and KCN by the method of Lehmstedt and Dostal, mp 179-180' (lit. mp was prepared 181°).9 9,lO-Dihydro-9-cyano-10-methylacridan from the reaction of 10-methylacridinium chloride wth KCN according to the procedure of Kaufmann and Albertini, mp 142-143' (lit. mp 143').1° Acridine N-oxide was prepared from acridine and p-nitroperbenzoic acid in chloroform, mp 168-169' (lit. mp 169').11
Results and Discussion 9-Cyanoacridanyl Radical.-The addition of potassium cyanide to DBA2+ in nitrogen-purged solutions of DBAZ+ in dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) results in a change in color from amber to cherry red. A weak esr signal is detected, which can be resolved into the same spectrum as shown in Figure 1. The coupling constants extracted from the spectrum are listed in Table I. The radical is thought to be N-methyl-9-cyanoacridanyl radical (11), produced by the following reaction (eq 1). The structural assignment has been confirmed by electrolytic reduction of N-methyl-9-cyanoacridinium chloride. The same spectrum as shown in Figure 1 is obtained. (4) E. M. Kosower, J . Amer. Chem. Soc., 77, 3883 (1955). (5) J. A. Elvidge and L. M. Jackman, J . Chem. Soc., 859 (1961). (6) R . N. Lindquist and E. H . Cordes, J . Amer. Chem. Soc., 90, 1269 (1968). (7) A. Albert, "The Acridines," St.Martin's Press, New York, N. Y., 1966, pp 343, 344. (8) F. Kehrmannand M. Sandoz, Ber., 61, 388 (1918); F. McCapra, D. G. Richardson, and Y. C. Chang, Photochem. Pholobiol., 4, 1111 (1965). (9) K. Lehmstedt and F. Dostal, Chem. Ber., 72, 804 (1939). (10) C. Kaufmann and A. Albertini, Ber., 42, 1999 (1909). (11) M . Ionesou, I. Goia, and H. Mantsch, Rev. Roum. Chim., 11, 243 (1966); G . Anthoine, J. Nasielski, E . Vander Donckt, and N. Vanlautern. Bull. Soe. Chim. Belg., 76, 230 (1967).
CYANIDE IONADDITION TO ELECTROPHILIC COMPOUNDS97
Vol. 56, No. 1, January 1970
Similar results are obtained from reactions with N-methyl-9-cyanoacridan, which can readily be isolated from the addition of 1 mol of cyanide to N-methyll5 This compound exhibits a acridinium chl~ride.~~’O~ readily detectable esr signal in the crystalline solid
Figure l.-(a) Esr spectrum of N-methyl-9-cyanoacridanyl radical produced from 0.008 M N-methyl-9-cyanoacridan in DMSO saturated with potassium cyanide and air; (b) computersimulated spectrum using the coupling constants listed in Table I.
&+ 2CN-
I
kH3 D B A ~+ FH3 I
state. The signal is apparently stable for long periods of time and is not sensitive to air or oxygen. In solution N-methyl-9-cyanoacridan gives a weak signal due to N-methyl-9-cyanoacridanyl radical. Upon addition of cyanide ion a cherry red solution develops and the signal increases in intensity. Introduction of air or oxygen first leads to a large increase in signal intensity and finally to a slow decay in the signal. The absorption of significant amounts of oxygen begins after ea. 1 mol of cyanide ion has been added to N-methylacridinium chloride. The rate of oxygen absorption is fairly rapid in the presence of excess cyanide. The oxygen absorption of N-methyl-9-cyanoacridan is very slow under the same conditions. These observations suggest a carbanion oxidation mechanism with the 9-cyanoacridanyl radical as a “stable” radical intermediate (eq 3 and 4). I n the presence of other bases CN
I
I
CH3
I1
I11
I CH3
I
Although radical I1 has not been reported before, a number of stable radicals of similar structure are known. Certain 9-substituted xanthyl radicals are stable at I room temperature (9-phenyl, 12& 9-isopropyl, 12b and CH3 9-set-butyl, lzb) although temperatures of above 78 and 86” are required for the detection of 9-methyl- and 9-ethylxanthyl radicals. l Z b Diphenylmeth~xyrnethyl~~ @&io2 f and diphenyl~yanomethyl’~ radicals have also been detected at 139 and 185”, respectively. The coupling constants of these radicals are shown in Table I for comparison. The assignment of coupling constants has been made on the basis of molecular orbital calculations (see following paragraph), by analogy to the xanthyl radicals, and by deuterium substitution in the methyl group. N-Methyl-9-cyanoacridanyl radical is also obtained in the addition of cyanide ion to N-methylacridinium (e.g., t-BuOK), the same red color develops. Cyanide chloride in DMF, DMSO, or DMSO-water mixtures. ion in DMSO solution also produces the characteristic The highest concentration of radical is obtained in colors of the carbanion of diphenylacetonitrile (red) and initially air-saturated solutions containing excess cya9-phenylfluorene (pale yellow). Of interest is the nide. Under these conditions the solution turns from unusual stability of the N-methyl-9-cyanoacridanyl yellow to cherry red. radical to oxygen. Clearly, the equilibrium between the radical and oxygen and the peroxy radical favors the (12) (a) M. D. Sevilla and G. Vincow, J. Phys. Chem., 7 2 , 3641 (1988); acridanyl radical. I n the triphenylmethyl radical (b) ibid., 7V2, 3647 (1968). system the same equilibrium favors triphenylmethyl at (13) G.E. Hartzell, C. J. Bredeweg, and B. Loy, J. Org. Chem., 80, 3119
FN
(1965). (14) By the thermal dissociation of tetraphenylsuccinonitrile in nitrobenzene: 0. W. Maender, unpublished results.
(15) R. M. Acheson, “Acridines,” Interscience Publishers, New York, N. Y.,1956, p p 234-262.
98 HAPPAND JANZEN
The Joumal of Organic Chemistry
TABLE I HYPERFINE COUPLINQ CONSTANTS OF FREE RADICALS PRODUCED IN CYANIDE ADDITIONS Registry no.
0
AP
AP
22027-31-2
2.790 2.69* 2.830
