CONFIGURATION OF N-NITROSAMINES
Oct. 20, 1964 [CONTRIBUTIONFROM
4373
KEDZIECHEMICAL LABORATORY, MICHIGAN S T A T E UNIVERSITY, EASTLANSING, MICH.]
THE
Structural Studies by Nuclear Magnetic Resonance. IX. Conformations of N-Nitrosamines
Configurations and
BY GERASIMOS J. KARABATSOS' A N D ROBERT A. TALLER RECEIVED APRIL30, 1964 Configurations, and in some cases conformations, were assigned t o thirteen nitrosamines from analysis of their 60-Mc. n.m.r. spectra. In contrast to a-methyl, a-methylene, and 6-methyl protons, which resonate a t higher magnetic fields by about 0.3-0.8 p.p.m. when cis than when trans to the nitroso oxygen, a-methine protons resonate at lower fields by about 0.2-0.6 p.p.m. d s a result of stereospecific association between nitrosamine and benzene, whereby the ring is closer to the lrans than to the cis protons, trans protons experience a greater upfield shift than cis protons when the solvent is changed from aliphatic to aromatic. This shift inequality can be used as a reliable criterion of assigning configurations. For the trans isomers the data are in accord with conformations in which the nitrogen-nitrogen bond is eclipsed with a substituent on the tetrahedral carbon. The detection of only one set of resonances for methyl phenyl nitrosamine is due to the presence of only the cis-methyl isomer, not to rapid isomer interconversion. Both isomers of ethyl phenyl nitrosamine and isopropyl phenyl nitrosamine were detected
Nuclear magnetic resonance has been used extensively and successfully in the study of problems arising from restricted rotation about single bonds, double bonds, and partial double bonds. Amides (I), nitrosamines (11), and nitrites (111) fall in the category of compounds involving restricted rotation about partial
I
IIa
I11
IIb
double bonds. In contrast to amides which have been studied extensively,z nitrites3 and nitrosamines4 have attracted little attention. Configurations5 I I a and I I b were determined* for several nitrosamines by assuming that protons will resonate a t lower magnetic fields when cis than when trans to the nitroso oxygen. This assumption led to the conclusion that the ratio [IV],/ [VI is about three. CH3
CsHsCHz
\+
\+
N=N
/
CsHsCHz
IV
\
0-
N=iY
/
CHI
1:
RlRzC=IiZ
\
0-
vI
The n.m.r. spectra of nitrosamines should show similarities to those of amides and to those of VI. From our experience6 with the n.ni.r. of VI, we doubted the correctness of configurational assignments to nitros(1) Fellow of t h e Alfred P. Sloan Foundation. (2) (a) W . D . Phillips, J. Chem. P h y s . , 2 3 , 1363 (1955); (b) H . S. Gutowsky, Discussions Faraday Soc., 19, 247 (1955); (c) H . S. Gutowsky and C. H. H o l m , J. Chem. Phys., 2 6 , 1228 (1956). (d) R . A. Ogg, J r , , J. D. Kay a n d L . Piette, J. Mol. S p e c f r y . , , l 66 , (1958); (e) C. Franconi, Z . Eleklrochem., 6 6 , 645 (1961). Sciema e Technics, n . s . , 4 , 183 (1960); ( f ) D G . d e Kowalewski, Arkiv K e m i , 16, 373 (1960), (9) V. J . Kowalewski and D. G. d e Kowalewski, J. Chem. P h y s . , 32, 1272 (1960); (h) E . W. Randall and J. D. Baldeschwieler, J . M o l . Spectry., 8 , 365 (1962); (i) J. V. Hatton a n d R. E. Richards, MOL.Phys., 3, 253 (1960), 6, 139 (1962); (j) M. T . Rogers and J. C. Woodbrey, J. Phys. Chem., 6 6 , 540 (1962); (k) L. A.. LaPlanche and M . T . Rogers, J . A m . Chem. Soc., 8 6 , 3728 (1963); 86, 337 (1964); (I) R . M . Moriarty, J . Oug. Chem., 2 8 , 1296 (1963). (3) (a) L. H . Piette, J. D. R a y , and R. A. Ogg, J r . , J. Chem. Phys., 2 6 , 1341 (1957); (b) W. D. Phillips, C. E . Looney, and C. P. Spaeth, .I. M o l . Speclry., 1, 35 (1957); (c) W . D. Phillips, A n n . N. Y. Acad. Sci., 70, 817 (1958). (4) C. E. Looney, W. D. Phillips, and E. L. Reilly, J . A n . Chem. Soc., '79, 6136 (1957). (5) We shall use the term configuration for structures I I a and I I b in order to avoid confusion with subsequent discussion of the conformations of Ri and R2. (6) Previous paper in the series: G. J . Karabatsos, F . M. Vane, R . A. Taller, and N . Hsi, J A m . Chem. SOL.,8 6 , 3351 (1964).
amines; e . g . , protons usually resonate a t higher fields when cis than when trans to 2 . Furthermore, when R1 is methyl and Rzis benzyl, the thermodynamically more stable isomer has 2 cis to the methyl rather than to the benzyl group. This paper summarizes our studies on nitrosamines. Results Figure 1 shows the 60-Mc. n.m.r. spectra of dimethyl, methyl ethyl, methyl isopropyl, and methyl t-butyl nitrosamines. The configurational assignments are made on the reasonable assumption that the ratio VII/VIII increases as R changes from ethyl to isopropyl to t-butyl. The assignments therefore by preR
CHI
CH3
\&=x / \
\&=K
/
R
0-
\'I I
\
0-
VI11
vious investigators? should be reversed. Table I summarizes the chemical shifts and syn/ anti ratios of thirteen nitrosamines. The chemical shifts are accurate to hO.03 p.p.m. with relative values between cis and trans protons being accurate t o =kO.Ol p.p.m. The notation used to distinguish the various protons on the R groups is shown in A, each proton being referred to as cis or trans with respect to the
\
SSO
/' CHg-CHia
d
nitroso oxygen. The synlanti ratios were determined by integration of peak areas and are accurate to *50/o. Two observations are pertinent to subsequent discussion of conformations: (a) In R ( C H 3 ) N N 0 the resonance of the trans-P-methyl of the R group shifts to lower fields as R changes from ethyl ( T = 8.62) to isopropyl (7 = 8.58) to t-butyl (7 = 8.46). (b) In R [ C H ( C H 3 ) 2 ] N N 0the resonance of the trans-a-methine shifts to higher fields by 0.3-0.4 p.p.m. as R changes from methyl ( T = 5.15) to benzyl ( T = 5.43) to isopropyl ( T = 5.74). Table I1 summarizes the differences in the chemical shifts of cis and trans protons. A positive A6 means that cis protons resonate a t higher fields than trans, a negative reverse. The pertinent points are: (a) While
GERASIMOS J. KARABATSOS A N D ROBERT A. TALLER
4374
TABLEI CHEMICAL SHIFTS( T-T~ALUES)
--
- __ Ha(CH)---
-RIRINKO----. Solvent
cc1,
Syn is the isomer having Iil
R!R*NKO--Ri R2 CH3 CH3 CHI CHzCHa CHs (CH2)CHs CHI CH(CHz)? CH3 CHKsHa CH~CHJ CsHa CH?CHa CHzC6Hs
CLS
4 87 5 4 88 4 4 92 5 5 11 ,5 5 19 6 to the oxygen
CH(CHa)? CHICHI)? CH(CHa)? a
( a - CHa)--CClr CsH8
----A6 Seat
+0.75 72 74 + 71 74
+
+ +
-0.80 - + O 78 t 78 f T 75 + 81 +
+
Methylene of benzyl group.
-
+
CH(CHB)Z CHiCsHs C'sHa
c.
6 44 6 53
5 5 6 4 4 5
56 53 5,s 53 57
86 21 28 64
CiS
t i avs
6.98 7.04
6 23 6 24 7 04 6 28 6 29 7 01 6 34 6 38 6 99
7.60 7 00 7 07 7.54 7.05 7 13 7 52 7.03 7.11 7 41 7.02 7 08 7 51 7 15 7.14 7 56 6 68 6.62 T 19
87 91
45 72 70 26
6 6 6 6 6 6
c1s
ti
a?is
rqn /antr'
78/22 73/27 79/21 89/11 89/11 90/10 100/0 100/ 0 100/o 79/21 78/22 77/23 74/26 79/21 78/22 100/0 100/0
8 8 9 8 8 9
98 95 42 88 91 41
8 67 8 62 9 26 8 59 8 58 9 15 8 46 8 16 8 91
9 9 9 9 9 9 8 8 9
18 08 50 10 02 36
8 8 9 8 8 9 8
28 30 96 41 33 99
4 . 7 7 (5.98)' 4 . 7 6 ( 5 93)' 5.22 (6.42)b 4 78 4.75 5.16 5 54 5.47
06 9T 28 74 25
9; 85
1oa/o 50/50
81 67 20 70 58 01 78
53/47 55-15 84/16 82/18 88/ 12 -%/4
-97/3
26 -100/0 -100/0 57/43 64/36 58/32
8 68 8 55
8 94 8 82 9 17 8 85 9 20
8 95 8 48 8 82
Methylene of the ethyl group
at,,",)
T A B L EI1 PP
VALUES, I N
hl
, OF
SITROSAMINES
-S(B-CH3)---\ Neat CClr
7---
Seat +O +O
88
57
+O +O
63 62
1 0 42 +0 d l
58 52 65 52)a
1 0 38
fO
-0 20 + O 50 +0.45 +O 60 ( + O 45)" 1-0.44
6
5 83 5 85 6 49
5 22 ( 6 58)h 5 28 (6 58)b 5 57 ( 6 85)b 5 22 5 30 5 54 5 99 5 99 6 39 4 84 5 15
5 45 5 -13 5 82
5 10 5 13 5 23
A8 (6,,, -
--
6 41 6 48 6 91
6 5 5 5
cc14
a
-
5 17 5 15 5 60
4 97 4 97 5 12
CsH6 Seat CCI, CsHs Seat CCl, CsHs CCI, CsH6 Seat CCl, CsHs CCI, C6H6
trans
CiS
R-eat CCl, CsHs Seat CeHs Neat CCI, CsH6 Seat CCl, C6H6 Seat CCI, CSIIE Seat CCI, CsHs Seat CCI, CsHs Seat
SITROSAMISES
H a (CH?)----
7 -
tvans
cis
OF
Vol. 86
+O f O +0 (+O
+o 55
-0
18
-0 48
(+O
+O
+o
43 35)Q 38
-0 35 -0 21
-063 30 - 09
-
- 1 06 -0 59 -0 36
+o +O
+O
33
+O
16
1 0 33
+O
26
19 37
+O
41
4-0 30
+ + +
37
40 26
+ +
T O 2Y
+O
-0
31
CaHs
44
27
-
38 3.5 22
Compound is a solid.
a-methyl and a-methylene protons resonate a t higher fields when cas than when trans to the nitroso oxygen, a methine protons resonate a t lower fields (negative A s ) . (b) Mrhile positive A6 values are smaller in benzene than in carbon tetrachloride- with diisopropyl nitrosamine the notable exception-negative A6 values are larger in benzene. (c) While A6 values for a-methyl, a-methylene, and @-methyl vary over small ranges, those for the a-methine vary over large ranges. Table 111 summarizes 1 v ( V I , benzene - v n C d i bon retrachlonde) values compiled from the data of Table I. The pertinent points are. (a) Av values are higher for the trans than for the corresponding cis-pro-
tons, with the @-methyls of diisopropyl nitrosamine again the notable exception. In this respect nitrosamines behave similarly to amides and in direct opposition to compounds having the structure R1R2C= N N H X (b) As the sizes of R1 and Rs of dialkyl nitrosamines increase Au values for &-a-methine protons are very small and decrease as the R of R[CH(CH8)2]NXO increases in size. Table I V summarizes the effect of several solvents on the chemical shifts of methyl ethyl nitrosamine. Figure 2 shows the effect of dilution (benzene solvent) on the chemical shifts of methyl ethyl nitrosamine Figure 3 compares the effect of dilution on the chemical
Oct. 20, 1964
CONFIGURATION O F
N-NITROSAMINES
4375
TABLE I11 COMPARISOK OF CHEMICAL SHIFTSOF KITROSAMIKES IS BESZENEASD CARBOSTETRACHLORIDE -----R~R+ili--Ri
CHI CH, CH3 CH3 CHJ CH3 CH3 CH2CH3 CHzCH3 CHzCsHj CH2CsHj CH(CH3)z CH(CHah Q
=
CH3 CHzCHa (CHz)aCHs CH(CHah C(CH3)3 CHzCsH5 CsH5 CHzCsHj CsH5 CH(CH3h C6H5 CH(CHa)z C6H:
y,n benzene
-
va(a-CH%)---
y----A
7AuU(a-CH3)-lvans
cis
trans
32 4 28.2 25 8 23.4 19.8 25.2 34 2
48.0 43.2 39.6 36.6
25.8 19.8
38.4 32.4
39.6
21.6
33.6
17.4 (16.2)h 24.0 14.4 18.6
2 7 . 6 (29.4)*
u,,carbontetrach,oride;
y~(a-CHg)-
cis
Carbon tetrachloride Cyclohexane Acetone Dimethyl sulfoxide Methanol Benzene Toluene o-Xylene m-Xylene p-Xylene Isodurene Chlorobenzene Bromobenzene Iodobenzene m-Dichlorobenzene Anisole S,N- Dimethylaniline Sitrobenzene Pyridine Phenol
trans
6 . 4 8 5 85 6.53 5.92 6.42 5.82 6.44 5.86 5.82 6.91 6.48 6 90 6 . 4 3 6 92 6 . 4 4 6 88 6 . 4 1 6.88 6 . 4 1 6 91 6 . 4 2 6.67 6.18 6 . 7 2 6 22 6.73 6.21 6 60 6 . 0 6 6.32 6.44 6.36 5.81 6 . 5 0 5 99 6 85 6 55
rr(o-CH3)cis tvans
-T(P-CH~)cis lvans
7 07
8.95 8.62
6.29 6.39 7 . 0 1 6 28 7 02 6 . 3 1 6.94 7.54 7.01 7.53 6.95 7.54 6.94 7.51 6.92 7.51 6.90 7 . 5 1 6 91 7 28 6 . 6 7 i 32 6 . 7 1 7 32 6 69 7.19 6.53 7 40 6 82 6 94 6.93 6.27 7.07 6.46 7 . 4 3 7 01
8.97 9 01 8.92 9.42 9.37 9.37 9.35 9.34 9.34 9.20 9.24 9.24 9.13 9.29 9.37 8 94 9 12 9 36
8.67 8.71 8.63 9 26 9.19 9.16 9.15 9.14 9.12 8.97 9.02 9.01 8.86 9.09 9.17 8.66 8 88 9.21
TABLEY PARTIAL ULTRAVIOLET SPECTRA OF NITROSAMINES IN CYCLOHEXASE" A,,.
mp
L
X 103
K?
232 5.87 233 5 . 79 235 6.23 2 74 7 02 275 6.77 250 5 53 224 7.69 In 957, ethanol a hypsochromic shift occurs of about 3-5 mp. CH3 CHa (CHshCH CHs CH3CH2 ( CHa hCH
a
-
R IRz S S O--.-
R,
6.0
C.P.S.
cis
lvans
28 2
38.4
27.0
30 0
34.2 33.0
31.8
23.4
25.2 24.6 20.4
25.8
2.4 30.6 21.0 20.4 2.4 18.6 21 .o 24 0 * Methylene of the ethyl group.
tetrachloride to benzene suggests stereospecific association between the benzene ring and nitrosamine, whereby the ring is attracted by the positive charge on the nitrogen and repelled by the negative charge on the oxygen (IX).' The data amply justify such an association.
i.14
tetrachloride are used as solvents dilution has practically no effect on the chemical shifts. Table V summarizes some pertinent ultraviolet spec-
----
24.6
for convenience the differences are expressed in
TABLEIY SOLVESTEFFECTSo s THE CHEMICAL SHIFTSOF METHYL ETHYLSITROSAMINE Solvent
tYans
cis
9.0
shifts of methyl ethyl nitrosamine and methyl t-butyl nitrosamine. IVhen dimethyl sulfoxide or carbon
-ba(O-CH3)-
--Av'(a-CH)--
cis
R1
CH3 CH2CHa (CHahCH CsH5 CsHi C6H:
tral values of nitrosamines in cyclohexane. Discussion Solvent Effects.-The larger upfield shift of the resonances of the trans protons over those of the cis protons when the solvent is changed from carbon
IX
For example: (a) Figure 2 shows t h a t on dilution with benzene the resonances of the trans protons shift to higher fields more rapidly than those of the corresponding cis. (b) Av-values (Table 111) of alkyl methyl nitrosamines decrease as the alkyl group is changed from methyl to t-butyl. Such a change is consistent with I X , since increase in the size of R1 and/or R2 should decrease the equilibrium constant for (1) by destabilizing I X . The more rapid upfield shift of the RlRzNXO
+ CbH6
R1&SNO.C6H6
(1)
resonances of methyl ethyl nitrosamine over those of methyl t-butyl nitrosamine (Fig. 3) illustrates the same point. The behavior of the chemical shifts of methyl ethyl nitrosamine as a function of solvent (Table 11') is also consistent with I X . Alkyl substitution on the benzene ring shifts the resonances-with respect to those in benzene-of the trans protons to slightly lower fields, probably as a consequence of destabilization of I X by increased nonbonded interactions.8 Conformations.-In the absence of coupling between protons of R1and those of Rn( I I ) , elucidation of the conformations of R1and R? must rely solely on chemical shifts. Accurate knowledge of the anisotropy of the KNO group would simplify the problem and permit the assignment of reliable conformations. In the absence of such information, however, the simplest avenue open is intelligent guessing of the anisotropic effects of NNO by comparing i t with other groups. From the practically identical behavior of the chemical shifts of nitrosamines and RIRnC=SZ compounds it is reasonable to assume that the anisotropic effects of NNO and C=NZ are qualitatively similar. From ( 7 ) Similar interactions have been suggested for amides: ref P i , k , l . (E) Similar effects were observed with phenylhydrazones: G . J . Knrabatsos and K . A . Taller, J . A m . Chem. Soc.,86, 3624 (1963).
4376
GERASIMOS J. KARABATSOS A N D ROBERT A. TALLER
Vol. 86
0.8
0.6
0.4
0.2
0.c
0.6
:0 .4 n
d
a 0.2
0.0 0.6
I D
0.4
0.2
0.c I
I
I
I
50
60
I
70
I
eo
I
I I 0 0 lTMS1
90
Fig 1 -60-Mc. n.tn.r. spectra of dimethyl nitrosamine ( A ) , methyl ethyl nitrosamine ( B ), methyl isopropyl nitrosamine ( C ) , and trietliyl t-butyl nitrosamine ( D ) in 4$1 ( N / v . ) carbon tetrachloride
spiri-spin coupling and chemical shifts i t was conc l ~ d e d that ~ . ~ the region in the C=NZ plane is deshielded with respect to the region above and below the plane. We will base our discussion therefore on the assumption that this is also true with the N N O group. Conformations of cis Groups.-Of the cis groups the data afford reasonably accurate conformational assignments only for the isopropyl group. Of the two conformations. X and X I , only X is consistent with the results; e.g.. it explains the fact that a-methine protons. in contrast to a-methyl and a-methylene, resonate a t lower fields when cis than when frnns to the oxygen : it also explains the fact t h a t Av-values for cis$91 C'T J Rarahatsos, R . A. Taller, and 1'. SI. Vane, J 8 8 . ?,'3L'i ( I M 3
At17
C h r m Soc.,
I
IO
I
30
I
50
I
70
1
90
MOLE%ETMENNO Fig. 2.-Cpfield shift of the proton resonances of methyl ethyl nitrosamine on dilution with benzene.
a-methine are very small, since in X the methine is farthest away from the associated benzene ring and
X
XI
should experience a smaller anisotropic effect. Conformations of trans Groups.-We will discuss our results in terms of conformation XI1 (eclipsing between R and N=N) by assuming again that site A, which is in the plane of N N O , is deshielded with remect t o site
CONFIGURATION OF N-NITROSAMINES
Oct. 20, 1964
XI11
XI1
4377
XIV
B.’O Based on these assumptions we will show t h a t when R is methyl XI11 is favored over XIV, and that the ratio [ X I I I ] / [ X I V ] decreases when R is changed from methyl to isopropyl Consider the conformations of methyl t-butyl nitrosamine, (XV), of methyl isopropyl nitrosamine XVI and XVII (with XVII statistically twice as probable as X V I ) , and of methyl ethyl nitrosamine XVIII and X I X , (with XVIII statistically twice as probable as X I X ) . If XVI is energetically equivalent to XVII, N
A-
/o-
XYI
XV
XVIII
XVIX
XIX
and XVIIT to X I X , then in all three compounds the methyl group should spend one-third time a t site A and two-thirds time a t site B. Consequently the trans-pmethyls of all three compounds should resonate a t about the same field, with the t-butyl resonating a t slightly higher fields than the isopropyl and the isopropyl a t higher fields than the ethyl (inductive effect). If XVI is favored over XVII, and XVIII over X I X , then the methyl group should spend one-third time a t site A in the t-butyl compound and progressively less than onethird in the isopropyl and ethyl compounds. Consequently the t-butyl should resonate a t lower fields than the isopropyJ and the isopropyl a t lower than the ethyl. The data support the last assumption. The pertinent conformations of diisopropyl nitrosamine are X X and X X I . Because of more severe interactions (methyl groups) in X X than in X X I i t is reasonable to expect the ratio [ X X I ] / [ X X ] to be
yo-
xx
,
/)-
XXI
larger than the ratio [XVII]/ [XVI]. By comparing the chemical shifts of diisopropyl nitrosamine with those of methyl isopropyl nitrosamine it can be shown that such is the case. (a) The trans-a-methine of diisopropyl nitrosamine should be shifted upfield with respect to that of methyl isopropyl nitrosamine. The shift in carbon tetrachloride is 0.59 p.p,m. (b) The trans-p(10) We have chosen conformation XI1 mainly on evidence obtained f r o m carbonyl and olefinic compounds For a summary of several references see A . A. Bothner-By. C. Saar-Colin, and H . Gunther, J . A m . C h e m . SOC.,64, 2748 (1962).
MOLE% NITROSAMINE Fig. 3.-Relative upfield shifts of the proton resonances of methyl ethyl nitrosamine and methyl t-butyl nitrosamine on dilution with benzene.
methyl should be shifted downfield. The shift ih carbon tetrachloride is -0.10 p,p.m. (c) The Av-value for the trans-a-methine should be larger for diisopropyl than for methyl isopropyl nitrosamine. Table I11 shows that while the Au-value for the cis-a-methine decreased from 9.0 to 2.4 c.P.s.,as a consequence of decrease in complex stability, that of the trans increased from 27.0 to 30.6 C.P.S. (d) The Av-value of the trans-@-methylshould decrease more sharply than that of the cis-@-methylin going from methyl isopropyl to diisopropyl nitrosamine. Table 111 shows that the corresponding decreases are 18 and 7.2 C.P.S. The change of the trans-&methyl is large enough to result in Avcis (21.0 c.P.s.) > Avlrani (20.4 c.P.s.) for diisopropyl nitrosamine. syn-anti Isomers.-The synl’anfi ratios of nitrosamines are identical with those of R1R2C=NZ compounds. In effective size, the ethyl, benzyl, and nbutyl groups are identical. The phenyl group, as found in the R1R2C=NZ compounds, has a large effective size. Apparently in isomer X X I I I the loss of overlap energy is sufficient to shift the equilibrium in favor of XXII.
When K is methyl only one set of resonances, attributed to the presence of only the cis-methyl isomer, is observed. The possibility that this may arise from rapid isomer i n t e r c ~ n v e r s i o nis~ excluded by the fact that
4378
ROBERTJ . OUELLETTE
both isomers are detected when K is ethyl or isopropyl. from From the ultraviolet spectra, e.g., decrease of A,, 275 ( R = CHa, CH2CHa) to 250 m,u ( R = isopropyl), it is deduced t h a t when K is isopropyl the interactions between phenyl and isopropyl in isomer X X I I are sufficiently large to cause loss of overlap between the phenyl and the N K O groups. The 224 m,u band. when K is isopropyl, could conceivably be the absorption of isomer X X I I I . Experimental Amines used in the preparation of nitrosamines were commercially available compounds. hlethyl-t-butS-laniiiie and ethyl-
1701. 86
benzylamine were prepared by lithium aluminuni hyclridc reduction" of t. butylformamide and S-benzylacetarIiide. Nitrosamines were prepared from the reaction of the corresponding amines xitli nitrous acid." N.m.r. spectra were determined a t 60 Mc. on a Model A-(iO spectrorneter (17arian .lssociates, Palo .Alto, Calif.), a t a temperature of about X " . Undegassed solutions were used with tetraniethylsilane as internal reference. Ultraviolet spectra were taken with a Cary 14 recording spectrophotometer.
Acknowledgment.--1i7e thank the United States Xtomic Energy Commission for financial support, Grant COO-1 189-12. (11) U . I:. Heath a n d A . J . Mattocks, J . Chem. Soc., 1 2 2 6 ( l Y 6 l j .
[CONIRIRUTIOS FROM THE E \ ' A S S CHEMICAL LABORATORY, T H E OHIO STATE IJNIVERSITY, COLKMBCS, O H I O ]
Conformational Analysis. 11. Use of the Chemical Shift of the Hydroxyl Proton in Conformational Analysis BY ROBERTJ. OUELLETTE RECEIVED .IPRIL 17, 1964 Dilution studies have been carried out to determine the chemical shift of the monomeric hydroxyl proton in cis-4-t-butylcyclohexanoland trans-4-t-butylcyclohexanol in carbon tetrachloride. T h e hydroxyl proton in the axial position occurs a t higher field than the hydroxyl proton in the equatorial position. The conformational preference of the monorneric hydroxyl group in cyclohexanol is 0.75 kcal./mole. The chemical shifts of the hydroxyl proton in pyridine and dimethyl sulfoxide are examined. These solvents do not significantly affect the conformational preference of the hydroxyl group.
Introduction The conformational preference of the hydroxyl group in cyclohexanol has been determined by kinetic, la2 e q ~ i l i b r i u r n , ~ infrared,j and n . m ~ . ~ methods. - ~ The n.m.r. methods are the most direct and powerful available a t this time. Eliel' utilized the chemical shift of the a-hydrogen in cyclohexanol and established an approximate value of 0.6 kcal.;niole for the conformational preference of the hydroxyl group. However, the signal of the a-hydrogen is broad and unresolved and, in order to improve the accuracy of the method, selective deuteration has been employed.8 Recently the conformational preference of the ethynyl group was determined indirectly from the conformation of l-ethylcyclohexanol.'" I t was shown that the chemical shift of the hydroxyl proton is linearly related to concentration in the range of 0.002 to 0.02 mole fraction of alcohol in carbon tetrachloride. The conformational preference of the ethynyl group was found to be 0.60 kcal. 'mole smaller than t h a t of the hydroxyl group. \Vinstein's~ value of 0.78 kcal. mole for the conformational preference of hydroxyl group was used in evaluating the conformational preference of the ethynyl group, Winstein's value was determined in a 2OY4, solution in carbon tetrachloride. The hydroxyl group is strongly associated under these conditions and it is conceivable that the steric size of the hydroxyl group is a function of the degree of as(1) S \Vinstein and J . P; Holness. J A m C h i m . S o c . . 77, 5562 ( l K 5 ) ( 1 ) E L . Eliel arid C. A. L u k a c h , t b t , i , 79, 5986 ( 1 9 5 7 ) . ( 3 ) I< L Eliel and R . S R o , i b t , i , 79, ( 4 ) D . S . S o y c e arid L.J . r)dtrq.,J . O r g . C ' h r n i , 2 6 , 361(1 tl(l611. ( i l I< .I\. Dickering and C C. PIice. J . A m Chenl. S o c , BO, 4931 (l1),58). ( 6 ) G Chiuidoglu a n d \V, Sfasschelein, Bull SOL. ( h i m B P ~ K 69, ~ s ,151 (1960) d r o n I . d k ? s , 3 , S i (1962). C h c m . SOL..84, 2461 (1962)
(10) Ii. J . Ouellette. t b i d
,
8 6 , 3081) ( 1 S 6 L i .
sociation. Therefore it was decided to investigate the hydroxyl group under conditions where hydrogen bonding is minimal. As a result of this investigation, the effect of intermolecular hydrogen bonding and association with solvent should be directly available. Results In the previous paper of this series,'" it was shown that the chemical shift of the hydroxyl proton is linearly related to concentration a t low mole fractions. The chemical shift of the monomeric hydroxyl proton can be obtained by extrapolation to infinite dilution. The chemical shifts of the hydroxyl protons of cis-4t-butylcyclohexanol and tmns-4-t-butylcyclohexanol are derivable from the data given in Table I . Figure 1 shows the dependence of the chemical shift as a function of the mole fraction of compound in carbon tetrachloride containing 0.001 mole fraction of tetramethylsilane as the internal standard. The extrapolated chemical shifts of the axial and equatorial hydroxyl protons expressed in c.p.s. downfield from tetramethylsilane are 25.7 and 46.4, respectively. By comparison with previous work,'" the ethynyl group deshields the hydroxyl proton by approximately 46 c.p.s. The data for the chemical shifts of the hydroxyl group in cyclohexanol are given in Table I and are illustrated in Fig. l . The chemical shift at infinite dilution is 41.6 c.p.s. The equilibrium constant for the axial equatorial conversion is 3.3 f 0 . 2 a t 40'. This equilibrium constant corresponds to a free-energy change of 0.75 kcal. mole at 40'. The chemical shift of the hydroxyl proton is independent of concentration in either pyridine or dimethyl sulfoxide in the concentration range used for the studies in carbon tetrachloride. Both pyridine and dimethyl sulfoxide shift the hydroxyl proton resonance signal to low field owing to hydrogen bonding. The chemical
