On the regioselectivity of the nucleophilic aromatic photosubstitution. The photoreaction of 4-nitroveratrole with n-hexylamine.

Tetrahedron Letters,Vol.28,No.36,pp Printed in Great Britain

ON THE REGIOSELECTIVITY

4191-4194,1987

OF THE NUCLEOPHILIC

THE PHOTOREACTION

Departamento

AROMATIC

OF 4-NITROVERATROLE

Albert Cantos, Jorge Marquet,* de Quimica. Bellaterra

oo40-4039/87 $3.00 + .OO Pergamon Journals Ltd.

PHOTOSUBSTITUTION.

WITH n-HEXYLAMINE.

and Marcia1 Moreno-Ma%s

Universidad

Authnoma

08193. Barcelona.

de Barcelona.

Spain

4-Nitroveratrole is photosubstituted with n-hexylamine giving rise to two isomeric Summary: Mechanistic and N-hexyl-2-methoxy-4-nitroaniline. N-hexyl-2-methoxy-5%nitroaniline anilines, evidence indicates that the first is produced in an S 2Ar" reaction through singlet and triplet whereas the second arises from a ra 2.lcal ion pair via electron transfer from excited states, the amine to a triplet excited state.

The Nucleophilic

Aromatic

tool in the photoaffinity room temperature

labelling

Recently,

Varma5

hydrolysis

of several

fast reaction

from the preparative

has applied

the Laser Flash

nitrophenyl

between

ethers

the nucleophile

Photohydrolysis with

of nitroanisoles

respect

fact only clearly tivity depends

holds

are used

Photolysis

a

meta

potential,

scheme

The meta

report6

(inverse

are used,

?J(C H3)2

4191

involves states

to

the

thermal

that this

the regioselecis preferred

for

amines of lower ionization

Iho2

Scheme 1

that

excited

we demonstrated

regioselectivity

into para when

hv

viewpoint.

state.

hv

(CH312NH

in the dark at has been exten-

ethers triplet

(Scheme 1).

+ CH3NH2

useful

to the study of the photo-

mechanistic

since when amines

but it changes

are inert

from the mechanistic

regioselectivity

In a previous

of the nucleophile.

as a potentially

This reaction

technique

a general

in their ground

show

for OH- as a nucleophile

on the features

and partially

proposing

to the nitro group'.

amines of high ionization potential

ethers

(OH-) and the nitrophenyl

which give rise to a series of -complexes

reaction)

Nitrophenyl

technique4.

but under UV light they react with nucleophiles.

sively studied by Havingal,

2,3

has been suggested

Photosubstitutionl

4192

We wish original pathway

to describe 6

explanation

,

here a series introducing

to the para substitution

In the Table

the relative

produced

(in

the

yields

that have electron

of production

led us to modify transfer

our

step in the

of the -meta vs.

with n-hexylamine

are reported.

due to the fact that both photoproducts

conditions)

measured

by G.C..

Table.-

Effect of triplet quenchers, 4-nitroveratrole

( a(meta/ #para)

of 4-nitroveratrole

for our studies standard

studies

not considered

products.

isomer in several photoreactions this nucleophile

of mechanistic

a previously

in

appropriate

radical

scavengers

relative

amounts

the para We chased

(meta and para) were for

the

ratio

to be

and solvents on the photoreactions

of

with n-hexylaminea.

+ C6H13NH2 NO2

NO2

NO2

Solution Reaction

saturated with -

Solvent

Additive

tZ meta@paraf

Air

MeOH/H20(20:80)

-----_--__-

Air

MeOH/H20(20:80)

Potassium

Air

MeOH/H20(20:80)

1,3-Cyclohexadienec

Argon

MeOH/H20(20:80)

------_----

Air

MeOH/H20(20:80)

m-Dinitrobenzene _

Argon

MeOH/H20(20:80)

MV2+ 2Cl- f

Air

Isopropanol

-_---------

Hexane

---_-----_-

Air

5.9

SorbateC

16.3 >30 4.2

d 730 >30 22 L%

a) 4-Nitroveratrole (2.5x10m3M), n-hexylamine (2.5~10~'M), 125W Hg high pressure lamp, Pyrex filter, lh of irradiation. b) Ratio by G.C. analysis. The value results from five measurements, eliminating the higher and lower ones and averaging the remaining three values. The product9 vere identifi-9 by comparison with authentical samples. c) 5.1x10 M. d) 3.7x10 M. e) A filter prepared with 0.005 g of p-nitroanisole in 1 ml of MeOH and 100 ml of water was used in ad$Stion 70 the Pyrex filter to EJiminate light under 320 nm and ensure MV was not absorbing. f) 1.8x10 M. g) Very complex mixture of products.

The selected (125W,

standard

Hg high pressure

with respect

to substrate.

No precautions

conditions,

lamp),

in order to perform

Pyrex filter,

comparisons

lh irradiation,

were: MeOH/H20

(20:80),

100 times excess of nucleophile

ratio in these conditions was 5.9 (Table, exp. 1). timeta /p/ para were taken to avoid oxygen, except in the reactions in which it is indicated. The

4193

The

influence

Parallel

of triplet

reactions

quenchers

in

demonstrated

quenchers

the

standard

that

the

These

results

different

pointed

mechanistic

conditions,

the

meta

reduced.

photoproduct

Assuming

was

excited

state

Parallel (radical duction

In two

and

the

ratio is shown in the Table. para and without the addition of triplet

all

cases

when

quenchers

quantitative

were

parallel

were

experiments,

of potedzium

reduced

whereas

the

comes through of triplet

of the meta photoproduct

reported

(Table, exp.4).

coming

out through

in the

standard

so,-bate as triplet

peak areas in front of an added standard,

30%

present

ethers photosubstitutions

para photoproducts

and in the presence

that the para product

production

of

the

para

the lowest triplet excited quenchers),

the obvious

has a component

through

quencher,

the production one

was

80%

( it is

state

first conclusion

the lowest singlet

(mixed origin). reactions

scavenger

carried

out

and electron

in the

transfer

of the para photoproduct

on the production argon) with

in

4

showed a small effect in the same direction

produc t on the presence

that the production

with

increased

the meta

pathways.

+,,,a/

that in other nitrophenyl

of the chromatographic

the more depending states

that

both in the absence

with measuring of

out

the

conditions

ratio

(Table, exp.2 and 3). Even oxygen, 7 cases has a negligible influence,

on

presence

quencher)

and

in the

absence

showed

clearly

that its effect on the pro-

was much more important

of m-dinitrobenzene

than the corresponding

effect

(if any)

of the meta

isomer (Table, exp.5). The same experiment carried out (under 2+ (MV , strong electron acceptor) led to a similar result (Table,

methyl viologen

exp.6),

and in addition

viologen

radical

the solution

monocation

(MV.+,

developed

x max

an intense blue colour attributed to the methyl 8 . This colour was not apparent in control

602 nm)

m-dinitroex:;erimerAb.s, when any of the reac.ion comporlenxs was missing. Considering that both _ 2+ do not interact with the 4-nitroveratrole lowest triplet excited state', the benzene and MV best

explanation

intermediate,

for the observed

formed by electron and present

the 4-nitroveratrole, The

results

described

obtained

in the Table.

the

excited excited

disrupted

by

intermediate donating

meta

was

9

state.

meta' 'para the complexity

changed

ratio

a later

reaction

increases

products

on going

reaction

mixture,

mixture

radical

anion

excited

state of

hexane

are

path.

to isopropanol

of the reaction

of photoreduction

The reported

state and a radical

the to

excited reduction

state

facts

suggest

ion pair

lifetime

products,

and

also

from MeOU/H20

to iso-

also increases

as shown

being important. non amenable

This is even more

to analysis

could be

again

the involvement

in the production

reduction

and

fact

that

is

with

the reported

by

easier

of the para

evolution in

of a path

of

solvents

isomer.

through

the radical with

a

It can be ion pair

hydrogen

atoms

ability.

A mechanistic

scheme

isomer

from singlet

arises

The para photoproduct radical

with

It is known that the triplet excited state lifetime of nitroanisoles depends strongly 10 properties , being longer in solvents with good hydrogen bond formation 11,12 Photoreductions of nitroaromatics have been shown to proceed by electron transfer 13 to the substrate presence of good electron donors) or by hydrogen atom transfer

(in the

triplet

be the interaction

solvent

ability.

triplet

solvent

in hexane where only a very complex

obtained. on

the

the proportion

by GC/MS analysis, evident

The

would

from the amine to the lowest triplet

only in the para photoproduct

when

In this last solvent

propanol.

effect

transfer

ion pair

that agrees

arises

and triplet

by electron

that on collapsing,

excited

transfer

would

facts

to the lowest

produce

is presented

states in an SN2Ar*

in Scheme

triplet excited

the substitution

2.

type photoreaction

product

The lc

state giving

.

a

or on diffusing

4194

would

give

to reduction

rise

on going

regioselectivity ionization

potential

from

amines

regioselectivity

of photo-Smiles difference

state. This is probably A

full

nucleophiles

Scheme

of high

(para) as nucleophiles

can also explain

ionization

potential

the reported6 (meta)

to amines

reactions

upon change

of the amine

the electron

transfer

type,

with

is to the

due to the fact we are dealing with an intermolecular account

mechanistic

in

of low

in photoreactions

that in our case

will be published

change

with 4-nitroveratrole (Scheme 1). 14 for the observed change in the given in the literature

It agrees as well with the explanation

and interesting

This

products.

on

the

photoreactions

of

the important

triplet

excited

photoreaction.

4-nitroveratrole

with

different

in the near future.

so Heta Substitution

Para Substitution

Reduction Products

Scheme 2

Acknowledgements.TBcnica" gratefully

Financial

("Ministerio

de

support

Education

from y

"Comisi6n

Ciencia"

of

Asesora Spain)

de

InvestigaciBn

through

project

ne

Cientifica

y

0343/84

is

acknowledged.

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(Received

in UK 13 July

1987)