Bridgehead reactivity in protoadamantane

Tetrahedron Letters No. 43, pp.3987 - 3990, 1971.

Printed in Great Britain.

Pergamon Preen.

BRIDGEHEAD REACTIVITY IN PROTOADAMANTANE By Amna Karim and M.A. McKervey Department of Chemistry, The Queen's University, Belfast BT9 SAG Edward M. Engler and Paul v. R. Schleyer Department of Chemistry, Princeton University, Princeton, N.J. 08540 (Beceived in IH 1 September 1971;

accepted lor publication 22 September 1971)

The solvolytic reactivities of bridgehead substrates have recently been placed on a 1 quantitative basis through the application of computer conformational analysis calculations. It is desirable to test the predictive power of this treatment for other reactions involving carbocations, e.g., ionic bromination.

Protoadamantane

(I), with four different bridgehead

positions, appeared to afford a suitable complex substrate for this purpose, especially since direct substitution of I has not been reported. Exposure of protoadamantane

(I)' to bromine at 80' for three hours gave predominately

(%95X) a single tertiary monobromide, m.p. 80-H', structure could readily be dismissed.

for which the 8-protoadamantyl bromide

The alcohol, m.p. 235-236', obtained on hydrolysis of

the bromination product with hydrochloric acid-dimethylformamide 8-hydroxyprotoadamantane

was distinctly different from

(II), m.p. 258-259', prenared by Wolff-Kishner

8-hydroxyprotoadamantan-4-one

reduction of

(III).3

The formation of essentially a single monobromide is in agreement with the conformational analysis calculations, Table I, which indicate that the 6-position should be most reactive, appreciably more reactive than the 3-position and much more reactive than either the l- or the 8-positions.

These calculations evaluate the change in strain energy (A strain) in going from

ground state (approximated by the parent hydrocarbon)

3987

to the transition state (approximated

No. 43

39as

by

the

appropriate

carbonium Table

Position

ion).

I.

Calculated

A Strain,

Bridgehead

kcal/mole

Reactivities

80% Ethanol,

-1. b

kBr(calc)sec

kBrrel

(calc)b

6-Protoadamantjl

10.8

4.7

x lO-5

1.00

3-Protoadamantyl

12.9

6.6

x lo+

0.14

8-Protoadamantyl

17.7

7.4

x 10-s

1.6

x lO-3

1-Protoadamantyl

18.3

4.2

x lo-*

9.5

x lo+

1-Adamantyla

12.3

1.2

x lo-5

0.26

a For -log

details

of

the

approach

used,

see

80% EtO.H, JO0 = 0.41

k+romide,

ref.

1.

a Based

A Strain(calcd)

-

on equation

0.12.

JO0 a -1

kBr(Obs)c,sec

(3)

from

1.50

x 10 -4

7.24

x lO-5

ref.

1:

experimental

from

5 Calculated

data. That

the

confirmed

bromination

through

the

reaction

conditions

towards

bromination.

was 6-bromoprotoadamantane

product

following

chemical

6-methylprotoadamantane This

argument

hydrogen

atom by

a methyl

reactivity

towards

bromination

of

was

convenient at

have

the

8-position,

Reaction

of

benzene

afforded

pyridine

into

m.p.

to

preparative

already

a 9:l

g.1.p.c.

The methyl

exposed

to

hot

25% sulphuric

occurred

6,7

group

giving

followed

with

acid

a new alcohol

by

fixes

cobalt the

in

from

the

observation

reasonable

whereupon

with

less

groups,

bromination

(VI) (ca.

with

m.p. the

the

upon

catalysed

that

air

methyl

group.

treatment

of

Table

the

of

one

of

I) a

relative

these

it

was

methyls

and iodine

was

converted

in

with

(VII )(dinitrophenylhydrazone 445

isomer alcohol

oxidation by oxidation

with

which VII

were

were

mixture

with

of

located

as

by follows. was

rearrangement

chromic

comparison

separated

IX so produced

+ adamantane

The position VII

(see

In practice

but

which

171-172’)

the

on

was

similar

replacement

tetraacetate

30% yield)

a protoadamantane

X which

C-8

that

V),

site.

lead

preponderant hydride,

under

reactive

assumption

methyl

product,

then

positions.

identified -

IV

bridgehead

a possible

aluminium

mixture

of

significantly

dimethylprotoadamantanones,

naphthenate

location

be

is

remaining

mixture

groups

lithium

product

effect

1,5-dimethyladamantan-2-one(XI),

prepared result

liquid

the

a negligible

(dinitrophenylhydrasone

reduced

This

as

if

(hydrolysis

have

blocked

excluded

of

(VIII)

was

sample

will

three

iodo-ketone

mixture

and

product

the

the

3,5-dimethyl-1-hydroxyadamantane

The ketone

major

group

two bridgeheads

an unstable

162-163’)

should

involves

bridgehead

more

argument:

(IV)

with

acid

gave

as

the

an authentic

1,3_dimethyladamantane. of

PC15/PC13

the gave

second

methyl

as major

product

No. 43

chloroolefin XII.

The nmr spectrum of XII was very similar to that of 4-chloroprotoadamantene

(XIII),' but lacked the H5-H6 coupling present in the latter. both XII and XIII.

Wolff-Kishner

H5-H3 coupling was present in

reduction of VII gave 6,&dimethyl

protoadamantane

(XIV),

b.p. 67' (12 mm). When XIV was treated with bromine under conditions whereby protoadamantane

(I) undergoes

complete bromination, only 6% reaction was observed and the remainder of the starting hydro9 carbon (XIV) could be recovered.

Thus, we conclude that the 6-position of protoadamantane

(I)

is the most reactive towards ionic bromination. The solvolysis rates of 6-bromoprotoadamantane

(IV) in 80% ethanol were: 49.65',

-4 -5 -1 set-'(AH* 24.8 kcal/mole, AS* -4 e.u.). 1.&z x 10 set ; 75.1s", 2.60 x 10

The interpolated

-4 -1 value at 70°, 1.50 x 10 agreed within a factor of three with the value predicted on the set basis of the strain calculations

(Table I).

Experimentally,

6-protoadamantyl bromide

(IV)

solvolyzes two times faster than 1-adamantyl bromide (Table I). Competitive experiments showed protoadamantane bromination than adamantane.

(I) to be slightly less reactive towards

This observation is easily reconciled with the relative

No. 43

solvolysis rates when statistical factors are taken into consideration.

Adamantane has four

equivalent bridgehead positions available for bromination while protoadamantane one 6-position. bromination

(Ii has only

on a per bridgehead basis, adamantane is less reactive towards

ThUS

than protoadamantane.

These results,

10 and prior indications

show that the strain calculations, which work so

well for solvolytic reactivities , can be applied as well to the prediction of bridgehead 1 brominations, and very likely to other substitution processes as well. References and Footnotes

0)

R.C. Bingham and P. v. R. Schleyer, J. Amer. Chem. Sot., 93, 3189 (1971).

(2)

Prepared by Wolff-Kishner reduction of protoadamantan-4-one

(3)

J.R. Alford and M.A. McKervey, -Chem. Commun., 1970, 615.

(4)

-Cf. W.H.W. Lunn, J. Chem. Sot. (C), 1970, 2134; R.M. Black and G.B. Gill, Chem. Commun.,

(4).

1970, 972. (5)

The structure proof of the minor ketone VIII will be described in the full paper.

(6)

D. Lenoir, P. von R. Schleyer, C.A. Cupas, and W.E. Heyd, m.

(7)

B.D. Cuddy, D. Grant, and M.A. McKervey, -Chem. Commun., 1971, 27.

(8)

A. Schneider, U.S. Patent 3,356,741 (1967); Chem. Abstr., 68, 62536~ (1968).

(9)

Our calculations attacked.

(10)

Commun., 1971, 26.

(Table I) indicate that the 3-position of XIV should be most readily

We are investigating this experimentally.

P. v. R. Schleyer, P.R. Isele, and R.C. Bingham, J. Org. Chem., 33, 1239 (1968); R.C. Bingham and P. v. R. Schleyer, ibid., 36, 1198 (1971); B.C. Bingham and P. v. R. Schleyer, Fortschr. Chem. Forschung, 18, 1 (1971).

This work was supported at Princeton by grants from the National

Acknowledgements. Institutes of Health Nutley, N.J.

(AI-07766). the National Science Foundation, and Hoffmann-La Roche, Inc.,

We thank Dr. A. Schneider, Sun Oil Company, for a generous gift of

1,3-dimethyladamantane.