J. J. UEBEL.4ND J. c. MARTIN
4618
[COSTRIBUTIOX FROM THE N O Y E S CHEMICAL
LABORATORY, LXlVERSITY
Vol. 86 OF ILLISOIS, LTRBAXA, ILLINOIS]
Nuclear Magnetic Resonance Studies of Diazirines. An Application to Conformational Analysis in Six-Membered Carbocyclic Rings' B Y J. J. UEBEL' A N D J.
c. h I . 4 R T I N 3
RECEIVED JVXE 4 , 1964 The nuclear magnetic resonance spectra of 8-thiabicyclo[3.2.l]octane-3-spiro-3'-diazirine ( I ) and 1,Z-diaza6-methylspiro[2.5]-l-octene (11) are of interest because of the large chemical shift differences between the axial and equatorial protons of the methylene groups adjacent to the spiro carbon atoms. These differences (1.5; and 1.40 p . p . m . , respectively, in CCI4) largely reflect the shielding of the equatorial protons resulting from t h e magnetic anisotropy of the diazirine ring. This large chemical shift difference in I was exploited, through the use of double irradiation techniques, to determine t h a t the geminal and vicinal spin-spin coupling constants are opposite in sign ( J a , e= -15.2, JI,,= +2.6, and J I , , = $ 4 . 2 c.P.s.). The temperature dependence of the large chemical shift difference between the comparable protons in diazirine I1 was used to determine accurate values for 15'(0.42 f 0.14 e . u . ) and AH ( - 1.91 f 0.04 kcal./mole) for the conforinational equilibrium between the two chair conformers of this compound. ii-e suggest the generality of the method for accurate measurements of conformational equilibria in six-membered rings and the determination of A-values for various substituents.
Analysis of Nuclear Magnetic Resonance Spectra.Unusual interest is attached to the n.m.r. spectra of compounds I and I1 as a result of the large chemical shift differences between Ha and He, the axial and equatorial protons adjacent to the diazirine ring.
1.44 D's/molecule
S A
1.44D's/molecule
K
N=N
/"
N S
The spectrum of I ,2-diaza-6-methylspiro [5.21-1octene (11) is characterized by a broad, high-field doublet near r4 9.4 corresponding to two protons which are coupled to their geminal neighbors by an apparent coupling constant of about 12 C.P.S. The apparent chemical shift difference between these geminal protons (1.32 p.p.m. a t -50') was measured by spin-decoupling techniques which involved the irradiation of the low-field protons and measuring the frequency of irradiation necessary to effect the collapse of the high-field doublet. The assignment of the high-field multiplet to protons He, made on the basis of a consideration of expected magnetic anisotropy receives confirmation from the spectra of partially deuterated compounds. The high-field double multiplet in I1 becomes a single broad multiplet (Fig. 1) upon the incorporation of 1.14atoms of deuterium per molecule into the apositions. Peak area measurements on the n.m.r. spectrum showed the upfield multiplet to contain 0.33 + 0.06 deuterium atoms per molecule. Since the compound contained a total of 1.44 atoms of deuterium per molecule, 1.11 f 0.06 atoms of deuterium must have been incorporated into those a-protons which absorb a t lower field. The synthesis of the partially deuterated I1 proceeded from the parent ketone as shown. Since the axial
2.54 D's/mo!ecule
hydrogens are expected8 to exchange more rapidly than the equatorial ones on stereoelectronic grounds, it is expected that the position which has a greater excess of deuterium is axial, trans to the predominantly equatorial methyl group in 11. Since the downfield a-hydrogen signal in I1 gives evidence for more deuterium than that of the upfield a-hydrogens, it is concluded it corresponds to Ha and the upfield signal to He. The changes in peak shape observed on deuteration.are consistent with this assignment (Fig. 1). The spectrum of diazirine I is shown in Fig. 2 . The absorption a t T 6.4 (two protons) is assigned to the bridgehead protons (HI), the multiplet near 7.8 (six protons) to a superposition of signals from the ethylene bridge protons and Ha, and the multiplet near 9.3 to He. These assignments were made on the basis of chemical shift analogies in model compounds,9, including the precursor ketone I11 and diaziridine IV, and the analogous compounds in the series leading to 11. Spin-decoupling experiments confirm these assignments. The chemical shift difference between Ha ( T 7.i.5) andH, ( r 9.32) isexceptionallylarge-1.57p.p.m. The principal assumption made in relating the spectrum of I to that of the model compound I1 is S
s
(1) Taken from t h e Ph.D. Thesis of J J . U , University nf Illinois, 1964. 12) Sun Oil C o . Fellow, 1961-1962
( 8 ) Fellow of the Alfred P. Sloan Foundation, 1962-1964. ( 4 ) G \-. I ) Tiers. J Phrs. ( ' h e m . , 62, llRl (1958). ( 5 ) S. G Cohen and I < . Zand, J . A m . Chem. Soc., 84, 586 (1962). ( 6 ) W. H. G r a h a m , i b z d . , 84, 1063 (1962). (7) H. 41.hIcConnel1, J . Chem. P h y s . . 27, 226 (1957).
( 8 ) E. J. Corey and R . A . Sneen, J . A m . Chem. Soc.. 78, 6269 (1956). (9) J C. Martin and P. I). B a r t l e t t , h i d , 79, 2533 (1957). (IO) D a t a taken f r o m " S . M . R . Spectra Catalog" compiled by N. S. Bhacca, I,. F . Johnson, and J. N. Shoolery of t h e Instrument Division of Varian Associates, Palo Alto, Calif,, 1962.
4619
N.M.R.O F DIAZIRINE
Nov. 5 . 1964
c
A
k
,li
40
214
C.PA.
DECOUPLED FROM A
n A 40
30
20
h
FROM C
Fig. 2.-Spectrum of I with chemical shifts (expressed in C.P.S. from TMS a t 60 m c . ) for Hi ( A ) , H, and the ethylene bridge (B), and He (C). t
CmPeSm Fig. l.-He n.m.r. spectrum of isotopically normal and of partially deuterated I1 (c.P.s. from TMS a t 60 Me.).
t h a t the six-membered ring of I is in the chair conformation, l1 an assumption which may be defended on the basis of reasonable chemical analogies.l 2 This assignment for Ha and He receivessome support from other considerations. From an inspection of Biichi models the H1-C-C-He dihedral angle is estimated t o be about 55' and the HI-C-C-Ha angle, 65'. The values of (2.6 c.P.s.) and 1 1 ,(4.2 ~ c.P.s.), though larger than those predicted13 b y the Karplus equations (1.2 and 2 . 5 c.P.s., respectively), are in the correct order for this assignment and the assumed geometry. The pronounced magnetic shielding observed for He reflects an anisotropic magnetic susceptibility associated with the diazirine ring which parallels t h a t observed for cyclopropyl ring^.'^,'^ The ring current in the plane of the three-membered ring which is (11) T e m p e r a t u r e studies indicate t h a t I probably h a s a strong conformational preference, presumably in t h e boat-chair equilibrium. Upon raising t h e t e m p e r a t u r e f r o m ca. 2 5 O to ca. 8 0 ° , the upfield q u a r t e t ( H e ) shifted only a b o u t 0.7 C.P.S.downfield, with a similar upfield shift of t h e downfield q u a r t e t ( H a ) . T h e shift is of a n order of magnitude predicted f o r a n energy difference between upper a n d lower s t a t e s of a b o u t 3 kcal./mole. These chemical shift changes are small, however, a n d m a y h a v e their genesis in effects o t h e r t h a n those associated with conformational changes in t h e molecule. (12) ( a ) H. S. Aaron a n d C. P . R a d e r , Abstracts, 145th Xational Meeting of t h e American Chemical Society, New York, N . Y.,S e p t . , 1963, p . 42Q; (b) M . R . Bell a n d S. Archer, J . A m . (:hem. Soc , 8 2 , 151 ( 1 9 6 0 ) ; (c) E . A. Allan, E. Premuzic, a n d I,. W. Reeves, Con. J . Chem., 41, 204 (1963); I,. W. Reeves a n d K . 0. S t r o m m e , i b i d . , 38, 1241 ( 1 9 6 0 ) ; A. J. Berlin a n d F . R . Jensen, Chem. I n d . ( L o n d o n ) , 998 ( 1 9 6 0 ) . ( d ) X. J . I.eonard, Record Chem. Progr. (Kresge-Hooker Sci. Lib.). 17, 243 (1956). (13) ( a ) M . K a r p l u s , J . Chem. P k y s . , 3 0 , 11 (195Q), (b) J . A m . Chem. Soc., 81,2870 (1963). (14) K . B. Wiberg a n d B J . N i s t , i b i d . , 83, 1226 (1961). (15) D . J . Patel. M. E. H. Howden, a n d J. I ) . Roberts, ibid., 8 6 , 3218 (1963).
postulated to explain chemical shift observations in cyclopropane derivatives seems t o have its counterpart in the diazirines.6,16 The increased shielding of He observed on oxidation of IV to I is also in keeping with the expected effect of a nitrogen-nitrogen double bond, assuming an anisotropy similar to t h a t in a carbon-carbon double The region of space in which shielding fields are induced is perpendicular to the plane of the double bond. Protons He and Ha of I approximate the AM portion of an AMX three-spin system. Values which we derived for the parameters describing this portion of the spectrum are listed in Table I. Signs of Coupling Constants in Diazirine 1.-For a system which may be approximated b y a n AMX representation, Evansz0 has demonstrated how relative signs of coupling constants can be obtained using double irradiation techniques. The protons Ha, He, and HI in the bicyclic diazirine I meet this requirement. The further coupling of the HI protons to the protons of the ethylene bridge does not interfere with the application of the method. All other coupling constants to the AMX system are relatively very small. 'The schematic representation of Fig. 3 may be used to describe the experiments which were performed. It is possible, for example, to cause the collapse of lines 1 and 2 without collapsing the 3,4-doublet by irradiating with a second frequency different from that of the 1,2-doublet by 183.8 c.P.s., a value which is seen, from the first entry in Table 11, to suggest that (16) J. P . F r e e m a n , J . Org. Chem., 28, 2508 (1963). (17) I,. M J a c k m a n , "Applications of S u c l e a r Magnetic Resonance Spectroscopy in Organic Chemistry," Pergamon Press, New Y o r k , N . Y . , lY59. (18) ( a ) W. A. Ayer, C . E. McDonald, a n d J. R. Stothers, C o n J . Che:., 41, 1113 (1963), ( b ) R . K . Fraser, ibid., 40, 78 (19621, (c) G. S l o m p , F. A MacKellar, a n d I.. A. P a q u e t t e , J. A m . Chem S O L . ,8 3 , 4472 (1961) (19) For increased shielding by C=O see: ( a ) 0. I,. C h a p m a n , H G S m i t h , a n d R . W. King, ibid., 86,806 ( 1 9 6 3 ) , 1,. Crombie a n d J . W. Town. P r o c . Chem. SOC.,299 (1961). (20) 13. F . E v a n s , Mol. P h y s . , 5 , 183 (1962):
J. J. CEBELS A N D J. C. MARTIN
4620
Vol. h(i
The Use of Diazirines in Conformational Analysis. The free-energy difference between an axially arid 311 equatorially substituted cyclohexane ring is a quantity of fundamental importance in conformational analysis. This quantity is usually designated by the symbol . I r 5 and considered to be a characteristic property of the substituent. I t is defined by eq. 1 as it applies to the equilibrium between V and lr1, where Sa and 9, represent the mole fractions of the species. The most widely used methods for the determination of conformation by n.m.r. spectroscopy take advantage of the fact that axial and equatorial protons on cyclohexane rings have different chemical shifts. For a monosubstituted cyclohexane the tertiary proton may occupy two distinct positions --axial, VI, or equatorial, V,-each of which has its own particular associated chemical shift, 6, or 6,, respectively. At normal temperatures an average line position is ~~
Fig. 3.-Schematic
for H I , Ha,and H e portion of spectrum of diazirine I.
J,,, and J I , ~are opposite in sign. All of the experiments described in Table I1 support the relative signs ascribed to the 1-values in Table I. The absolute sign of the geminal coupling constant Ja,e was taken as negative in keeping with the results of experirnents21s22 comparing directly the signs of C13-H and TABLE I SPECTRAL PARAMETERS' FOR DIAZIRISE I Proton
He H.3 H,
Protons
Chem. shift: C.P.S.
Coupling constants, c p.s.
40.2 f 0 . 2 134.4 I . 2 .2 214.2
JI., 2.6 i0.2 JI,, 4 2 i .2 Ja,e -15 2 i . 2
Chem. shift difference Chem. shift diffeience calcd. f r o m spectrum, obsd. by spin decoupling, C.P.S. c.p 5.
94.2 i0 . 4 93.7 i 0 5 Ha-% 1i4 4 f 0 5 H1-K 174 0 i . 4 i 8 3 f l 0 H1-K 79.8 .4 Calculated by fitting the observed spectrum using an iterative procedure and the program for the IBM 7090 computer described by J . D . Swalen and C . A . Reilly, J . Chem. P h y s . , 37, 21 (1962). Chemical shifts are downfield from TMS in c.P.s., a t 60 Mc.
+
TABLE I1 DETERMISATION OF RELATIVE SIGSSOF COUPLING COSSTASTS" Coupling constants
Relative sign
Js,p:Jl,aSame, calcd. Opposite, calcd. (Found)
-Collapsed lines, frequenciesbI and 2 3 and 4
85.3 89.5 89 5 I and 3
X
v, Ne A
-AF
=
=
11 a n d 12
74 3 85 3 74 3 7 0 . 1 70 1 8 9 . 5 67 0 70 0 82 5 d and 7
6 and 8
Jl,a: J1.,
Same, calcd. 9 k . 0 9 3 . 4 95 8 9 3 . 4 90 8 90 8 9 7 . 6 Opposite, calcd. 97 6 (Found) 94 0 92 5 9 5 . 0 92 0 0 Chemical shift differences and coupling constants from Table I were used to calculate t h e frequencies a t which the doublets are expected to collapse. Frequency values, in c . P . s . , represent differences, a t 60 Mc., between the center of gravity of the doublet undergoing collapse and the frequency of irradiation in the decoupling experiment. Lines are designated with reference to t h e numbering in Fig. 3 .
geminal H-H coupling constants. Since the sign of the CI3-H coupling constant is known with some certainty,?3 the assignment of a negative value to the geminal H~-H coupling constant is relatively secure. The difference in signs of the geminal and vicinal coupling constants has now been established for a number of different molecular geometries.2 4 ( 2 1 ) P. C. 1,auterhur and K. J Kurland, .I. A m C ' k e m . SOL..8 4 , X405 (19 6 2 ) .
( 2 2 ) F. A . I.. Anet, i b i d , 84. 3767 ( 1 8 6 2 ) . a n d references therein ( 2 8 ) SI Karplus. ibtd.,8 4 , 2458 ( I Y 6 2 ) . see also .4. I3 Buckingham a n d K . XIcI,auchlan, Proc C h e m SOL.,1 4 1 ( 1 0 6 3 ) . ( 2 1 ) fa) I
