Large concentration effects on the magnitude of secondary alpha-deuterium kinetic isotope effects

Tetrahedron Letters,Vol.26,No.l,pp Printed in Great Britain

LARGE

CONCENTRATION

EFFECTS

DEUTERIUM

0040-4039/85 $3.00 + .oo 01985 Pergamon Press Ltd.

25 - 28,1985

ON THE MAGNITUDE

KINETIC

ISOTOPE

OF SECONDARY

ALPHA-

EFFECTS

Chemistry

Kenneth Charles Westaway* and Zbigniew Waszczylo, Department, Laurentian University, Sudbury, Ont.,

Chemistry

Peter James Department,

P3E 2C6

and Smith and Kanchugarakoppal S. Rangappa, University of Saskatchewan, Saskatoon, Sask.

S7N OWO

Because the secondary alpha-deuterium kinetic isotope effects in some S 2 and E2 reactions are strongly concentration dependent, isotope effects measu p'ed at a single concentration could lead to erroneous conclusions about the mechanisms and transition state structures.

Physical

organic

hydrogen-deuterium

chemists

kinetic

of SN reactions

mechanism

Measuring

determining

the rate constants

normal

either

reaction

concentrations

the kinetic

would

isotope

effect

conditions.

effect. these

be equal

centration Large isotope

or approximately

found,

effects

of their

the

transition

involves

property

however,

can occur

small

equal

that

effects

it is assumed

for both

of the reaction

or the method

that very when

very

large small

small

changes

on the rate

that these

substrates that

used

changes

and that

is independent

to measure

changes

in the

constants

the isotope

in the magnitude are made

the of

of

in the con-

of the reactants. changes

effects

in the magnitude

have been observed

CH3CH2CH2CH2-Cl

+ C6H5-S-

and the E2 elimination f-butoxide

C6H5-CH2CH2 -Cl(F)

of secondary with

in the SN2 reaction

ion in N,N-dimethylformamide

potassium

have

substrates,

of the reactants

ons of the reactants noxide

to determine

for a reaction

it is accepted

might

substituted

is a specific

We have

isotope

effect

of secondary

years

the structure

isotope

Although

of the reactants

the concentrations

the magnitude

for severa1

for the reaction of the two isotopically labelseparately 4,5 or in a competitive experiment 3,6 under the

for the two isotopically changes

been using effects

and to elucidate

stateslB4.

led compounds

have

isotope

in $-butyl

+ &-BuO-

alpha-deuterium

small

between

at 20°C,

p>

reactions

very

changes

n-butyl

equation

chloride

alcohol

at 4O“C,

c6H5-CH- -CH2+

____;)

25

and thiophe-

1,

chloride equation

[ll

+ cl-

CH3CH2CH2CH2-S-C6H5

of 2-phenylethyl

kinetic

in the concentrati-

and fluoride 2, Table

t-BuOH _

with

1.

+ Cl-(F-)

121

26

Table

1.

between

Secondary E-butyl

reactions

e-deuterium

chloride

of 2-phenylethyl

in L-butyl

alcohol

kinetic

isotope

and thiophenoxide chloride

effects

for the SN2 reaction

ion in DMF at 20°C and for the E2

and fluoride

with

potassium

L-butoxide

at 40°C.

Substrate

* g--C3H7CH2-Cl

* C6H5-CH2CH2-Cl

* C6H5-CH2CH2-F

[Substrate]

4.45-4.17

X lOs3 M

4.044 X 10m3 M

7.859 X lOs3 M

[NaSC6H51

a-57-8.63

x iow3 M 0.0896

0.1618

[KOt-Bu] k

H'

M-'s--~

(4.35 5

(5.54 f

0.025a) k

D'

M-'s-l

X lO-2

1.085

[Substrate]

7.52-7.94

X 10m3 M

[NaSC6H5 1

4.20-4.95

X lO-3 M

+ 0.011~

[KOt-Bu]

k

(5.02 i-

*

1.190

indicates

a. Standard

the point

squares

to within b. The error Error

standard

7.891 x 1o-3 M

1.149

of isotopic

? 0.02'C

0.3264

x lo-4

deviation

x 10

of both

x 10

-5

* O.O1gb

rate constants

value

coefficient

throughout

is calculated

using

Il/2 where

constants

were

obtained

for the least

The temperature

> 0.999.

was constant

each kinetic

run.

the formula:AkH and AkD are the

for the undeuterated

the SN2 and the E2 reactions

in the absorbance

of diluted

at 260 nm and 248 nm, respectively, acid-95%

(quench the reaction ion or t-butoxide

O.lOoaj 1.036

order

(AkD/kDj2

for the rate

-4

+ O.O1ob

run was

2 +

X lO-5

and deute-

respectively.

the change

sulfuric

0.060a) (5.95 +

The correlation

runs.

effect

M

(6.16 +

second

of the reported

in the isotope

The rates

M

i- 0.012b

substitution

The average

in each kinetic

reactants,

following

dilute

X lOs3 M

O.O1ga)

= * (kH/kD).í(AkH/kH)

rated

mixture

4.044

0.020aj

to five kinetic

line

x lo-5

0.862

x lo-2

deviation.

from three

0.070aj

(6.23 f

? 0.022b

x 10~~

f 0.004~

x 1o-2

0.031a) (kH/kDIa

x lo-4

(7.16 +

0.102a) M-'s-~

0.02aa)

0.808

0.3060 (6.03 i

-4

(5.36 *

0.02gaj

(kH/KDIcl

kH.M-s-l

x 10

(6.86 f x lO-2

M

(4.63 *

O.OOga)

(4.01 i 0.032a)

D'

M

ethanol

and eliminate

solution

for at least was used

the strong

ion in the aliquots

were

determined

aliquots

two half

to dilute

absorptions

by

of the reaction lives.

A

the aliquots

due to thiophenoxide

from the SN2 and E2 reactions,

respecti-

21

vely)

.

The deuterated

substrates

a-carbon

and in accord

evidente

of competing

for the least

and thiophenoxide are changed

instance,

isotope

a very

effect

effect

was

an SN2 mechanism

with

loose

the conclusion

state

structure

The effect

or that

chloride

of 0.808

and 0.862

and

bending

vibrations)

concerning

is used

the transition

isotope

with state.

concentration

lower

transition

at different we believe

is looser

chloride

state

fluoride

a high

structures

base

indicates

of 1.036

found

reaction

also

are suggested

from

isotope

effects

however, different.

concentration

bending

concentration

-t-butoxide, of the

is quite

a higher

reaction,

effect

chloride

t-butoxide,

out-of-plane

effects

in going

If these

state

of

isotope

(the energy

markedly

effect

different

of potassium

reactions.

of

t-butoxide

concentration

carbon

found when

isotope

reaction

are very

inverse

of potassium

C-eH(D)

when

kinetic

of the 2-phenylethyl

is increased

isotope

of the reactants

of the isotope

states

of the transition

in the 2-phenylethyl

very

While

energy

and transition

potassium

a different

the alpha

of 1.149

The larger

state

measured

effect

with

concentrations

concentrations

with 9,lO .

effect.

the large,

in both

the nature

in the 2-phenylethyl

the transition different

state

(an ~$1) mechanism

in the magnitude

around

7.73

for a carbonium

in the E2 elimination

when

was

via an SN2 mechanism

the mechanism

the E2 transition

crowding

at the higher

base

that

expected

ion

fluoride

the changes

at the lower

the conclusion

state3'11

the substrate

alpha-deuterium

for the E2 reactions

are determined

sition

the isotope

2-phenylethyl

to the transition

normal

For

conclusions.

on the concentrations

changes

found

out-of-plane

about

depends

For example,

the steric

of base

have draw

is used.

indicate

The large,

of the reactants

concentration

proceeds

or a carbonium

mechanism

respectively,

the initial

in the range

in the secondary

to indicate

t-butoxide

that

chloride

in the magnitude

found when

the substrate

has been observed

and fluoride,

CeH

state

Indeed,

the detailed

potassium

is almost

change

concentration

enough

mechanistic

that the reaction

one would

alcohol.

are large

n-butyl

the variation

(l.O42/a-D)

found when

to use in measuring

2-phenylethyl in t-butyl

between

the concentrations

In fact,

runs.

the secondary

that the reaction proceeds by way of The much larger isotope transition state 7,8 .

of this reaction

same marked

with

when

of 1.085

transition

Thus,

one happened

in the SN2 reaction

range.

a normal

and suggests

an extremely

1 show that

4.50 X lOs3 M implies

effect of 1.190 (l.O91/e-D) -3 x 10 M on the other hand, ion mechanism

coefficient

for each of the SN2 and E2 kinetic

lead to different

effect

at the 12-14 investigators , no

The correlation

found.

of Table

markedly

narrow

could

the isotope

concentration

column

99% deuterated

of other

was

> 0.999

line was

ion changes

over

of the isotope

the conclusions

in the first

kinetic

at least

(side) reactions

squares

The results a-deuterium

with

were

a loose

vibrations

tranin

at the higher suggests

is used.

that Thus,

by the isotope

effects

base concentrations. that the concentration

effects

on these

isotope

effects