Maeda, Ingold / EPR of Diazirinyl Radicals
837
an asymmetric conformer can optimize one hydrogen bond in References and Notes a fl turn a t the expense of the other and still maintain undis(1) (a) Harvard University; (b) Oak Ridge National Laboratory. torted backbone angles. This is the case for c y c l ~ - ( G l y - ~ - (2) (a) I. Karle and J. Karle, Acta Crystallogr., 16, 969 (1963); (b) I. Karle, J. Gibson, and J. Karie, J. Am. Chem. SOC.,92, 3755 (1970). Pro-D-Ala)z. The intermolecular hydrogen bonds seem to (3) J. Brown and R. Teller, J. Am. Chem. Soc., 98, 7565 (1976). support the effect. The stronger one reinforces the peptide twist (4) M. 6.Houssain and D. van der Helm, J. Am. Chem. SOC., 100, 5191 (1978). away from a possibly favorable I N - H 4 0 interaction and (5) E. Blout, C. Deber, and L. Pease, in "Peptides, Polypeptides and Proteins", the weaker one reinforces the twist toward the existing favorProceedings of the Rehovot Symposium, 1974, Wiley-lnterscience,New able 4N-H . * 10 hydrogen bond. York, N.Y., 1974. (6) K. Kopple, T. Schamper, and A. Go, J. Am. Chem. SOC., 96, 2597 We take this opportunity to correct 41from 109' to -109' (1974). in the studyt6 of the naturally occurring cyclic peptide, p(7) The density was determined experimentally by flotation of several crys!als in n-heptane-carbon tetrachloride mixtures. amanitin. (6) G. Germain, P. Main, and M. M. Woolfson, Acta Crystallogr,, Sect. A, 27, -B 6-R- ,(1971) .- . Acknowledgment. W e wish to thank Drs. Lila Pease of (9) E. Hughes,"J. Am. Chem. Soc., 63,1737 (1941). (IO) C. Johnson, "ORTEP, a Fortran Thermal-Ellipsoid Plot Program", USAEC Amherst College, C.-H. Niu of the National Institutes of Renort ORNL-3794. 1965. - Health, and Elkan Blout of the Harvard Medical School for (11) Y. Leungand R. Marsh, Acta Crystallogr., 11, 17 (1956). providing the title compound and making the NMR data Jpn., 47, 1129 (1974). (12) T. Ashida and M. Kakudo, Bull. Chem. SOC. (13) C. M. Venkatachalam, Biopolymers, 6, 1425 (1966). available to us. W e acknowledge support of this research by (14) (a)L. Pease, Ph.D. Thesis, Harvard University, 1975; (b) C . 4 Niu, unpubthe National Institutes of Health (GM 06920) and the Nalished results. (15) In one case, that for cyclo-(a-Phe-L-Pro-GIy)p, the molecule appeared to tional Science Foundation (CHE-7719899). This research was be CZsymmetric from NMR spectra, but displayed four amide I stretches sponsored in part by the Energy Research and Development in an infrared spectrum (in CHCIS).'~ This result suggests that some conAdministration under contract with Union Carbide Corp. formational asymmetty may occur in this type of peptide, yet go unobserved
-.
-
. - r -
-
I
by NMR. Unfortunately,the solubility of cyclo-(Gly-L-Pro-o-Aia)2in CHCI:, was too low to examine it in the same manner. (16) E. C. Kostansek, W. N. Lipscomb, R. R . Yocum, and W. E. Thiessen, Bo-
Supplementary Material Available: Temperature factors ( i page). Ordering informaCion is given on any current masthead page.
chemistry, 17, 3790 (1978).
Kinetic Applications of Electron Baramagnetic Resonance Spectroscopy. 33. Diazirinyl Radicals' Y. Maeda2 and K. U. Ingold* Contributionfrom the Dicision of C'hernistry, National Research Council of Canada, Ottawa K1 A OR6, Ontario, Canada. Receiced J u l y 28, I978
___I
Abstract: Some 3-substituted diazirinyl radicals, KC=NN-, have been generated by photolysis of the parent bromides in the presence of hexa-n-butylditin. The principal EPR parameters for 3-alkyldiazirinyl and 3-phenyldiazirinyl are similar: a N ( 2 N ) = 7.8 Ci, g = 2.0042. I N D O calculations give I4N and I3C hyperfine splittings in good agreement with experiment. Diazirinyls are IT radicals, the two nitrogens' 2p, atomic orbitals making the major contribution to the semioccupied orbital. Diazirinyls decay with second-order kinetics to yield the corresponding nitrile. Like other N-centered three-membered ring radicals, they do not form nitroxides. Studies on the products of reaction of aziridinyl, CH2CH2N., with tert-butylperoxy have revealed that a nitroxide is probably formed, but it decomposes (to ethylene and NO) too rapidly for i t to be detected. It is suggested that analogous processes occur with diazirinyls and other N-centered three-membered ring radicals.
'The t h e r m ~ i l ~and - ~ photolytic8--l3decomposition of 3alkyl-3-halodiazirines and 3-aryl-3-halodiazirines,I,l4 have been studied as sources of "free" halocarbenes, 2. The possiR
A
hV
I
'
'C:
x
/
+
N,
2
bility that free radicals are involved in some of the systems investigated does not appear to have been explored, nor even suggested. W e have discovered that 3-organodiazirinyl radicals, 3, can be derived from a variety of 1. These species rep-
resent a hitherto unidentified class of nitrogen-containing radicals. In this paper we report on their generation, identifi0002-78631791 I50l-O837$Ol.OO/O
cation by EPR spectroscopy, decay kinetics, and decay products.
Experimental Section Materials. Bromodiazirines. The 3-alkyl-3-bromodiazirines and 3-phenyl-3-bromodiazirine were prepared from the corresponding amidine hydrochloride5 by oxidation with freshly prepared aqueous sodium hypobromite in MezSO according to the general method described by Graham.IJ The volatile alkylbromodiazirines ( R = CH, and CH3CH2) were collected continuously by means of a vacuum
pump which pulled them through a train of four U-tubes held at -35, -80, and -80 OC with the gases bubbling through n-pentane, and - 196 OC. These diazirines were retained in the pentane-filled U-tube. The less volatile organobromodiazirines ( R = (CH3)3C, ChHj, and C ~ H S C Hwere ~ ) extracted continuously into n-pentane and were then purified by column chromatography through silica gel. The infrared @ I979 American Chemical Socicty
Journal of the American Chemical Society / 101:4 / February 14,1979
838
spectra of the bromodiazirines were in good agreement with the literature.l4.15 3-Benzyl-3-brom0-[3-~~C]diazirinewas prepared from C6H&H2I3CN (90 atom% I3C, Merck Sharp and Dohme) by Graham's method.I4 Tetrazines, 4. These compounds were synthesized because they were pc,tential products from the bimolecular self-reaction of diazirinyl radicals (vide infra). 3,6-Dimethyltetrazine and 3,6-diphenyltetrazine were prepared by the method of Curtius et a1.I6 from the corresponding dihydrotetrazines, 5, themselves preparedI6 from hydrazine
RN-" /C-R
\
N=N
R- C \ 'N-N'
,
I
Table I. EPR Parameters for 3-Substituted Diazirinyl Radicals0 (Hyperfine Splittings in Gauss) g
uN(2N)
uH (n)b
2.004 21 2.004 20 2.004 16 2.004 18 2.004 20
7.77 7.78 7.75 7.84 7.82
2.78 (3) 2.98 (2)
c
C
C
radical C H3CN 2CH~CH~CNT (CH3)3CCN2ed C6!qsCN2*e c6H5CH2CN2ee
u'~C*
c
C
C
2.95 (2)
12.4f
In pentane a t -80 OC unless otherwise specified. n = number of equivalent H. Not resolved. A persistent radical with 3 1 3 lines was also produced on prolonged photolysis. e In toluene. f u s i n g I3C-enriched material.
I
H H
straction from aziridine with photogenerated terf- butoxy radicals as originally described by Danen and K e n ~ l e r .The ~ ~ lines . ~ ~ in the EPR spectrum of 6 were broadened in the presence of oxygen or tert-butyl
5
4 R
a
C H I , C6Hr
and the appropriate nitrile. The physical characteristics of both tetrazines and both dihydrotetrazines agreed with the literature data.I6 Product Studies. The Self-Reaction. Thermolysis of 3-methyl-3bromodiazirine a t 60 OC in the presence of hexa-n-butylditin (both neat and in pentane as solvent) gave vinyl bromide as the major, and only identified, product. It is clear that diazirinyl radicals are not produced and that the vinyl bromide is formed from the bromocarA
CH3CBrN2 +N2
+ CH3CBr
-
-
+ (CH3CH2)3SiH (CH3CH2)3Sim+ RCBrN2
-
2(CH3)3CO.
+ N2
+ (CH3CH2)3Si. (CH3CH2)3SiBr + RCN2.
(CH313COH CH2
+
/N\
CH2-CH2
6 hydroperoxide (a convenient source of tert-butylperoxy radicals) and the signal intensity decreased. However, there was no sign of the unknown25aziridinoxyl radical, 7. Photolysis of 200 ILL of aziridine, 100 (CH313 C O S +
/ \
CHz-CH2
CHz-CHz
7
N-0'
/\
N-0'
/ \
CH2=CH2+
~__f
NO
CHz-CHz
WLof di-tert-butyl peroxide, and 50 IL of tert-butyl hydroperoxide in 100 WLof C6D6 for 30 min gave ethylene (identified by N M R and VPC) as the only organic product from the aziridine. Ethylene was not produced if the hydroperoxide was not present, provided that the solution was degassed and the photolysis carried out in the absence of oxygen. Nor was ethylene formed ir, the absence of aziridine. It seems clear that the aziridinoxyl radical is formed but rapidly loses nitric oxide. EPR Spectroscopic Studies. The diazirinyl radicals were generated directly in the cavity of a Varian E-4 EPR spectrometer by L'V photolysis of degassed hydrocarbon solutions of the bromodiazirine and hexa-n-butylditin. The strongest spectra were obtained with ca. 0.3 M of the bromodiazirine and ca. 0.1 M ditin at low temperatures. However, the EPR parameters were independent of temperature in the range examined, viz., -90 to 0 "C. The kinetics of radical decay were followed in the usual
(CH3)3COH
For example, 100 mg (4.7 X mol) of 3-benzy1-3-bromodiazirine, 55 mg (4.7 X 10-4 mol) oftriethylsilane, and 41 mg (2.4 X mol) of tert-butyl hyponitrite in 1.7 mL of n-pentane were degassed and heated under nitrogen a t 50 O C . The onlj products from the diazirine were 8-bromostyrene and phenylacetonitrile. Their concentrations were monitored by VPC. Yields ( X 104 mol) for diazirine, @-bromostyrene, and phenylacetonitrile were 2.4, 1.3, and 0.9, respectively, after 5 h; I . 3 , 2 . l , and 1.1 after 10 h; and 1 .O, 2.3, and I.2after 15 h. The P-bromostyrene must arise from the carbene and the phenylacetonitrile from the diazirinyl radical 2C6H5CHzCNz.-
NH
/\ CH2-
CH2=CHBr
h
(CH3)3CO,
+
(CH,),COO'+
Similar experiments with 3-benzyl-3-bromodiazirine yielded P-bromostyrene as the only identifiable product. UV photolysis of a pentane solution of 3-methyl-3-bromodiazirine and the ditin at -70 OC also gave vinyl bromide as the major, and only identifiable, product. 3-Benzyl-3-bromodiazirine again yielded only P-bromostyrene under these conditions. These results imply that formation of diazirinyl radicals is not the major reaction occurring in the EPR spectrometer. I n neither the thermal reaction nor in the photoreactions was there any trace of the anticipated tetrazine, 4. Separate experiments showed that the tetrazines were reasonably stable thermally though they were unstable toward p h o t o l y s i ~ However, .~~ even under the photolytic conditions they would have survived in sufficient quantity to be identified if they had been formed to any significant extent. Successful identification of the product of the bimolecular selfreaction of 3-substituted diazirinyl radicals was achieved by generating the diazirinyl radical thermally by the following route: (CH3)3CONNOC(CH3)3
(CH3)3CO'
2C6l
