Rapid deuterium and tritium labelling of aromatic compounds using alkyl-aluminium dihalide catalysts: competing rearrangement of polysubstituted aromatics

TetrahedronLetters No. 41, pp 4075 - 4078, 1973.

RAPID DEUTERIUM ALUMINIUM

PergamonPress. Printed in Great Britain.

AND TRITIUM LABELLING OF AROMATIC

DIBALIDE

CATALYSTS:

COMPOUNDS USING ALKYL-

COMPETING REARRANGEMENT

OF POLYSUBSTITUTED

AROMATICS J.L. Garnett. M.A. Long, R.F.W. Vining University

of New South Wales, Kensington,

NSW, 2033, Australia

T. Mole CSIRO Division

of Applied

Chemistry,

P.O. Box 4331, Melbourne,

VIC.

3001, Australia (Receivedin UK 14 August 1973; acceptedfor publication6 September1973) A wide range of metal halide catalysts have recently been found to 1,2,3 catalyze deuterium and tritium labelling of aromatic compounds. The most thoroughly

investigated

dihalides which,

of these catalysts are the organoaluminium

in the presence

of traces ot water as co-catalyst,

rapid exchange of isotopic hydrogen between perdeuterobenzene

induce

and other

aro,natic compounds: equilibrium is often attained within minutes at room 1 temperature. This deuterium-labelling technique is of considerable value, not only because deuteration,

it is the fastest known one-step procedure

for aromatic

but also because the labelled compound in most cases is recovered

quantitatively. A modification organoaluminium

of the above method allows tritium labelling.

dihalide

(or alternatively

is dissolved

The

in the aromatic compound to be labelled

both the compound and the catalyst are dissolved

in an

alkane solvent), and this solution is exposed to a small amount of tritiated water of high specific activity. along with the simultaneous An important advantage

Rapid hydrolysis

incorporation

of the catalyst occurs

of tritium into the organic compound.

of this method of tritium labelling is that the

labelled products may be obtained with high radiochemical purity.

The trace amounts of high specific activity

produced by other tritium

as well as chemical

impurities commonly 4

labelling techniques are not encountered.

We now report that during the labelling of some disubstituted accompanying

rearrangement

caution is necessary classes of compounds.

of aromatic

in the application

benzenes

substituents has been observed, of the labelling technique

Thus in the deuteration 4075

and

to such

of the xylenes using

0075

No. 41

benzene-d

as source of isotope, two concurrent

6

labelling or the xylene, are possrble. intermolecular

migration

or intermolecular

migration

deuterated

almost to equilibrium

Similarly m-diethylbenzene

Substantral

with both xylenes and m-diethylbenzene

substituent migration

at elevated

is observed

temperatures.

Thus the

to dialkylbenzenes,

but care

in the choice of reaction conditions. the dibromobenzenes

In contrast, extensive

all three xylenes have

at 25O with only slight migration

labelling technrque does appear to be applicable is necessary

(to give toluene).

after 15 minutes at this temperature.

can be deuterated

of an ethyl group to benzene.

is much faster than

of a methyl group

is observed at 25O whereas

or

to yield toluene may occur.

of the xylenes

migration

Negligible

in addition to

The xylenes may rsomerise,

of CH3 to the benzene-d6

The table shows that deuteration isomerisation

reactions,

intermolecular

accomplished.

and bromotoluene

transfer of the bromo group whenever

The exact extent to which this rearrangement

However short reaction periods and low temperatures minrmum of rearrangement.

is

occurs appears to

Chloro substituents

favour exchange with a

appear to be relatively

iodo substituents may be even more labile.

of bromo groups was also observed

deuteration

This effect is under further study

depend on the precise reaction conditions.

labile, while

are likely to undergo

non

Extensive migration

in the more highly substrtuted

tetrabromo-

benzene. The nature of the co-catalyst in these reactions is also important. 1 hydrogen chloride is useful as a co-catalyst. As an alternative to water, If the addition of the hydrogen controlled,

chloride

((1

HCl per EtA1C12)

it is sometimes possible to achieve deuteration

rearrangement

of labile substituents.

c-dibromobenzene

and E-chlorobromobenzene

1s carefully

without

extensive

In this way we have deuterated mainly to the d4 state, with less

than 25% cleavage to monobromobenzene. We thus wish to emphasise of polysubstituted

are amenable to deuteration

and tritration,

be selected such that competrng isotope incorporation. bromopolysubstituted

that care should be exercised

aromatics by the present method.

in the labelling

Most aromatic compounds

since a reaction temperature

rearrangement

However, with a few compounds, particularly

aromatics,

reactions may predominate.

can

reactions are much slower than

current evidence

the

indicates that rearrangement

4wl

No. 41

Reactions of Polysubstituted Benzenes on AEempted Deuteration with Benzene-d 6' -_Disubstltuted Products benzene Conditions TABLE.

0.2

or p-xylene

25O.30 min.

Aromatic Extent of deuteration&

unchanged o,m, or p-xylene

d

4

p-xylene

llo" ,15 h.

o-xylene, m-xylene, p-xylene and toluene (8:20:9:14)

d

m-xylene

110°,15 h.

p-xylene, m-xylene, p-xylene and toluene (8:20:9:8)

d

p-xylene

110°,15 h.

g-xylene, m-xylene, p-xylene and toluene (4:20:12:3)

d4 d4-d5

m-diethylbenzene

25O ,30 min.

m-diethylbenzene, (15:l)

ethylbenzene

m-diethylbenzene

25O ,15 h.

m-dlethylbenzene, (5:2)

ethylbenzene

m-diethylbenzene

105O,15 h.

o-dibromobenzene q-dibromobenzene

p-dibromobenzene p-dibromobenzene

25O, 3 min. 25O. 15 h.

25', 15 h. 1'15O.15 h.

o,m,p-diethylbenzene benzene (1:4)

ethyl-

d3-d4

10% p-dibromobenzene 90% bromobenzene

d -d 3 4

100% p-dichlorobenzene 100% p-dichlorobenzene

p-dichlorobenzene

105O ,15 h.

100% p-dichlorobenzene

25O.15 h.

ca. 80% toluene ca. 80% bromobenzene ca. 20% o-bromotoluene

8OO.2 h.

d4-d5

d4-d5

d4-d5 d _d

90-95% toluene 90-95% bromobenzene 5-10% recovered bromotoltiene 100% bromobenzene

.Typical reactlon procedure:

d -d 4 5

100% bromobenzene

25O,15h.

tetrabromobenzene

d4-d5

30% o-dlbromobenzene 70% bromobenzene

25O,30 min.

105O.15 h.

d4-d5

d3-d4

p-dlchlorobenzene

o,m, or p-bromotoluene

4

70% o-dibromobenzene 30% bromobenzene

p-dichlorobenzene

o-bromotoluene

4

lpl

were added to 0.1 ml disubstituted

d-d 4 5 3 4 d -d 4 5 d4-d5 d3-d4 d -d 4 5

--

water then 0.2 ml of 0.6M EtAlC1,/C6D6 benzene.

At the end of reaction the

sealed ampoule was opened, the EtAlC12 was destroyed

by dil. aq. HCl, and

the aromatic compounds were analyzed by glc and mass spectrometry. These data represent

the largest peak in the low voltage mass spectrum.

all cases the deuterium

distribution

In

is close to that expected at equilibrium

Acknowledqements We thank the Australian

Research Grants Committee and the Australian

Institute of Nuclear Science & Engineering at the University

for their support of the research

of New South Wales.

References w.

s..

23,

m.

m.,

21

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J.L. Garnett, M.A. Long, R.F.W. Vining, T. Mole, 2. Amer --

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J.L. Garnett, M.A. Long, R.F.W. Vining, T. Mole, J.

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