Chemical shifts in the nmr spectra of substituted cyclohexanols

TetrahedronLetters No. 17, pp. 741-747, 1962. in Great Britain.

Pergamon Press Ltd. Printed

CHEMICAL SHIFTS IN THE NMR SPECTRA OF SUBSTITUTEDCYCLOHEXANOLS E.L. Eliel, M.H. Gianni and Th.H. Williams Department of Chemistry,University of Notre Dame, Notre Dame, Indiana and J.B. Stothers Department of Chemistry,The University of Western Ontario, London, Ontario (Received19 May 1962; in revised form 15 June 1962)

FOR some years it has been known1 that the NMR signal for axial protons in 2 substitutedcyclohexanes is found at higher field than the signal for correspondingequatorialprotons. This result has been rationalized in terms of diamagnetic

anisotropy of carbon-carbon

4 ment proposed by McConnell .

bonds3 following a treat-

More recently it has been claimed5 that the

chemical shifts for 21 different substituted cyclohexanols may be consistently interpreted

in terms of carbon-carbon

bond anisotropy

Cyclo-

regard to magnetic

susceptibility)

hexane derivatives

are inherently suitable for studies of this type, since

their conformations

using appropriate parameters.

(with

are well understood'

and, in many cases, rigid so that

the distances between atoms and bonds within the molecule can be computed readily.

1

2 3

R.U. Lemieux, R.K. Kullnig, H.J. Bernstein and W.G. Schneider, Chem. Sot. a, 6098 (1958).

J. Amer.

For nomenclature and general background, see E.L. Eliel, Stereochemistrv of Carbon Comoounds Chap. 8. McGraw-Hill, New York (1962). See L.M. Jackman, Aoplications of NMR Spectroscopy Chap. 7. Pergamon Press, London (1959).

4 H.M. McConnell, J. Chem. Phvs. g, 226 (1957). 5 J.I. Musher, J. Chem. Phvs. 3!j, 1159 (1961). 7Ll

in Orsanic Chemistry

74.2

Chemical

shifts

in the NMR spectra

We have now examined available

in

examined compounds are

by Musher.

proton

group

therefore

dominantly carbinol

protons.

case,

chemical

shifts

there

(145-225 trying noted effect vs.

8,

solely

to

is

fit

our data

with

an axial

6

methyl

6) for

is

observed.

whereas The other

2-methyl

of 7 cps

(entries

group

1,

a range

of over

of

11 vs.

7).

of

to take in the

100 cps

the axial

and

protons

cps).

In

of Musher5 we

concerned (entries

with 8 vs.

the 20,

12

any treatment 394 based

anisotropy)

about

that

(198.5-249.5

proton

predicts

a deshieldinq

discrepancy

of 3 cps

interest

in fact,

pre-

are the data

of

One is

experimentally major

is

calculations

on an axial

exercises

16 vs.

It

with

equatorial

shift

the range

discrepancies.

bond diamagnetic

10 cps),

carbinols

(hexamethyldisiloxane

protons

which Musher (and,

on carbon-carbon to

between

the theoretical

group

compounds in which

and therefore

cover

the equatorial

serious

6

in these

(and the carbinol

for

signals

protons

overlap of

an equatorial effect

appreciable

for

by a downfield

in ours).

the carbinol

protons

in the two tables

reference

tetramethylsilane

and that

(amounting 10 cps

of

data

equatorial

groups

previously

from tetramethylsilane

2 has data

hydroxyl

No.17

cyclohexanols

from those

downfield

in parentheses

cps)

13 vs.

Table

cyclohexanols

the carbinol

1 contains

to cps and corrected

two especially of

axial

Listed

of

for

or entirely

whereas

the difference

Musher’s

different

shifts

Table

largely

or entirely

account

that

is

axial)

Musher converted into

1 and 2.

substituted

of 36 substituted

these

in cps at 60 Mc/sec

in Tables

the hydroxyl

26 of

The chemical

expressed

listed

the NMR spectra

laboratory,

OJ~

of

is

4 times There

a shielding_ effect

quantitative

of

in nature:

the predicted are also

about

other,

shielding less

In some cases, the experimental agreement between our data and Musher’s Our chemical shifts are averaged from repeated up- and downis poor. field scans using at least two different sidebands from a calibrated audio-oscillator for each compound and with the possible exception of entries 10, Tables 1 and 2 (where only a few scans were made) are reproducible to + 1 cps. There is, however, in some cases, an uncertainty cf. ref. 12. of l-2 cps as to the exact location of the band center.

No.17 Chemical shifts in the NMB spectra of substitutedcyclohexanols 743

TABLE 1 Chemical Shifts of Carbinol Proton in EquatorialCyclohexanol&

T

Entry

Cyclohexanol

T

-”

-r

observed'

-0

A

cal latedE B

1

trans-4-t-butyl

202(210.5)

200

2

a-3-t-butyl

206

200

3

trans-2-t-butyl

204

200

4

menthol

1%(199.5)

l93-d

196.5

5

a-4-methyl

203(206)

200

203

203

6

a-3-methyl

207(213)

200

207.5

7

u-2-methyl

179(178)

180

178

8

d-3,3,5_trimethyl

219

220

219.5

9

a-2-isopropyl

195

193d

195

2-a-cholestanol

219

220

10 11

trans-2-trans-6-dimethyl

145

160

150

12

3,3,5,5_tetramethyl

229

240

230

13

3,3-dimethyl

219

220

218

14

m-2-ethyl

185

183d

15

&-2-trans-6-dimethyl

193

180(e)e 200(a)e

16

tr-2-methyl-tran-4-t-butyl

176

180

175

17

a-2-methyl-u-4-t-butyl

214

200

214.5

18

2,2-dimethyl-trans-4-t-butyl 187

180

186.5

19

2,2-dimethyl

192

180(e)e 200(a)=

189.5(e)' 201(a)e

209

200

209

209)

200

189.5(e)e 201(a)e

20

&,

21

m-4-isopropyl

22

trans-2-&-5-dimethyl

181)

180

179.5

23

trans-2-trans-5-dimethyl

208.5)

200(e)e 220(a)e

188.5(e)' 217.5(a)e

24

isomenthol

225)

;;;w$

205.5(e)'

25

&-2-2&-5-dimethyl

223.5)

200(e)e 220(a)e

&-3,5-dimethyl

a For footnotes,see Table 2.

-,-

744

Chemical

shifts

in the NMR spectra

of

substituted

cyclohexanols

No.17

TABLE 2 Chemical

Entry

Shifts

of Carbinol

Proton

in Axial

T

-”

Syclohexanol

Cyclohexanolsa cal

-0

Ilated’

A

observedb

B

1

&-4-t-butyl

236(242)

240

2

m-3-t-butyl

24.4

240

3

&-2-t-butyl

249.5

240

4

neomenthol

241(241)

23+

5

c&-4-methyl

233 (234)

240(a)e 220(e)e

6

u-3-methyl

238 (239)

240(a)” 220(e)e

%l:;

225(224)

220(a)” 200(e)e

225(a) 217.5(e) 246

7

&-2-me

thy1

237

8

m-3,3,5-trimethyl

2i+6

240

9

&-2-isopropyl

240

23+

10

2-p-cholestanol

243

240

11

a-2-&-6-dimethyl

208

200

12

&-2-etnyl

228.5

23&

13

trans-2-fnethyl-&-4-t-butyl

214

220

214

14

&-2-methyl-&-4-t-butyl

220

220

220

15

trans-3-trans-5-dimethyl

241

240

241

16

2,2-dimethyl-&-4-t-butyl

198.5

200

196

17

&-4-isopropyl

(239.5)

240

18

&-2-&a-5-dimethyl

(227)

220

19

neoisomeathol

(242.5)

239(a)dse 240( e+=

a At 60 Mc/sec Varian ~~-60

downfield from Th!S in lU$ Ccl4 instrument.

b Data in parentheses

are

from ref.

5 (see

solution,

.

208

224.5

measured

on a

text).

4 See text. d Assuming reasonable the 2-alkyl groups. e The two entries of the ring.

distribution

correspond

of

the rotational

to the two possible

chair

conformations conformations

of

No.17

Chemical

serious

shifts

in the NMFlspectra

We-feel

discrepancies.

limitation

of

the theoretical

presented

and call

for

presently

searching

for

be useful

occurring

point

our data

745

point

shift

up a

so far

One of us (J.B.S.)

is

of

the shift

of view,

parameters

and configurational

alcohols,

it

clearly

the chemical

interpretation.

in structural

connexion,

of

data

cyclohexanols

is

such an interpretation.

cyclohexanoid

In this

substituted

the present

treatment

a refined

From the practical should

that

of

interest

that

One of

have been developed.

assignments

in the steroid

e.g.

established

of naturally

and terpene

two empirical

these

here

series.

correlations

of

is

-u = 240 - 20n, where

u is

shift

TMS standard,

solution, axial”

the predicted

hydrogens

of

under

60 Mc/sec

the conditions

frequency)

the carbinol

proton

The shifts

predicted

by this

column A, and in most cases in some cases requiring probably

no empirical not

founded

A second, distinct

for

type

carbinol

hydrogen.

analysis

of

squares nearly

so,

5 cps of

each alkyl

but it

group

These

in one conformation

for

the observed

The formula is

only

theoretical

correlation

the data

are shown in Tables

greater.

on any clear-cut

more accurate,

as shown in Fig.

1.

1

formula

parameters,

meters, of

is

CCl4

” hydrogens.

come within

the difference

(10%

the number of “syn-

and n is

under study,

FIG. “Syn-axial

studied

employs

those

assuming

very

approximate

although of

and

principles. a set

of

empirical

para-

with

respect

to each

have been determined

compounds which exist that

value,

has the advantage

in each position

parameters

1 and 2,

the effects

of

by a least

entirely, alkyl

groups

or in

746

Chemical

shifts

the

various

two

conformations

positions

analysis the

provides

(equatorial

for

substituted

approach

treated

as

each

alkyl

in Table

alcohols)

values

for 3 and

in Table

using

these

cyclohexanols

this

The parameters shown

(axial

calculated

were

parameter

are

of

In

cyclohexanol

conformers.

hydrogens the

NMR spectra

additive.

a shift

alcohols)

carbinol

the

are of

cyclohexanol

gives

in

the

unknowns. group the

and

for

in

for

the the

each

carbinol the

In Tables

parameters

for

Thus,

axial

those

4.

shifts

No.17

of hydrogen

equatorial 1 and

cases

2,ColumnB

where

enough

TABLE 3 Shift

Parameters

for

Equatorial

2-Me (eq.) 2-Me

-28

Cyclohexanols? 2-t-Bu

(in

cps) -2

(eq.)

0

(ax.)

11.5

3-t-Bu

(eq.)

3-Me (eq.)

1.5

4-t-Bu

(eq. )

-3

3-Me (ax.)

10.5

2-Et

(eq.)

-21

-3

2-i-Pr.(eq.)

4-Me

(eq.)

-11

a These values are to be added to a base value of -u = 206 cps to obtain the predicted -o (from TMS in lC$ CC14 at 6OMc/sec) for the equatorial cyclohexanol with the appropriate alkyl substituent. TABLE 4 Shift

Parameters

for

Axial

Cyclohexanols’

(in

cps)

2-Me (eq.)

-17

2-Me

(ax.)

-24

2-t-Bu

(eq.)

7

3-Me

(eq.)

- 0.5

3-t-Bu

(es.)

2

3-Me

(ax.)

5

4-t-Bu

(eq. )

-5

a These values are to be added to a base value of -u = 242 cps to obtain the predicted -u (from TMS in 10% CC14 at ~OMC/S~C) for the axial cyclohexanol with the appropriate alkyl substituent. data

are

usually of This

available within

additivity further

to 1 cps

of

the

suggests

afford of

independent

those

shifts that

checks.

calculated, caused

any

by alkyl

deformation

The observed

suggesting

that

substituents of

the

the is

cyclohexane

shifts

are

assumption a good ring

one. from

the

No.17

Chemical

perfect

chair

carbinol

is

of

hexanol” which

9 using

in good

are not

4-t-Bu

plus

cyclohexanols

on the chemical

747

shift

of

correlations to apply

axial

of

We gratefully Foundation. We are Richer for samples Dr. J.D. Talman for

vs.

shift

of

1.07

by Anet

11

cyclokcal/mole

although

(for

six

other

compounds

3- and

2-,

seventeen

parameters

investigations

Eliel

which

and

experimentally

correlate

to establish

to a much greater

for

.4-Me

ten

the generality will

be en-

number of

compounds.

acknowledge support of this work by the National Science also indebted to Drs. J. Sicher, W. Dauben and J.-C. of some of the cyclohexanols used in this work and to helpful discussion.

7

E.L.

an

2,7,10,12

are required

approach

AOH, the

E.L. Eliel, ,I. Chem. Educ. 2, 126 (1960). 8 J.-C. Richer, L.A. Pilato and E.L. Eliel, Chem. & Ind. 2007 (1961). 9 S. Winstein and N.J. Holness, ,I. Amer. Chem. SOC. 22, 5562 (1955). 10

the

the two confor-

to the value

to correlate

and we hope that

for

the 2-isopropyl

series,

for

an equatorial

reported

parameters

more data

the present

leads

values.

omitting seven

obtained

recently

are used

and in the Clearly

that

for

a value

and the observed

This

published

the base value)

shifts.

analysis

with

series,

group

parameters

conditions.

enough checks,

observed

one can calculate

the hydroxyl

by this

than other

shifts;

couraged

substituted

any effect

that

shift

agreement

observed

these

the

similar

In the equatorial there

of

cyclohexanol

somewhat higher

if

to note

preference

under

is

has little

of

in the cyclohexanols.

of

position

mations

in the NMR spectra

interesting

energy

axial

form7j8

proton

It free

shifts

and M.H. Gianni,

‘1 F.A.L. Anet, J. 12 A. Lewin and S. Winstein,

Tetrahedron &,

Letters

97 (1962).

1053 (1962).

,I. Amer. (2hem.&,

246.4 (1962).