Aromatic nucleophilic substitution reactions of 1-dialkylamino-substituted activated benzenes with various amines in dimethyl sulfoxide

Tehhedron Vol. 46. No. 16. pp. 5567.5578. 1990 Printed in Great Britain

AROMATIC

NUCLEOPHILIC

ACTIVATED

Shizen

oo4o4020/90 $3.00+.00 0 1990 Pagamon Press plc

*

Sekiguchi

Department

SUBSTITUTION

BENZENES

Hiromi

,

of Applied

REACTIONS

OF l-DIALKYLAMINO-SUBSTITUTED

WITH VARIOUS AMINES

Ishikura,

Chemistry,

IN DIMETHYL

SULFOXIDE'

Hirosawa.

and Nobuyuki

Yukitoshi

Gunma

University

Kiryu,

Gunma

376,

Ono Japan

(Received in Japan 9 March 1990)

AbstractIn the reactions of 1-dialkylamino-2,4,6-trinitroand l-dialkylamino-2,4_dinitrobenzenes with various amines in dimethyl sulfoxide, l-dialkylamino group is easily replaced with primary n-alkylamines at room temperature, and in a low yield with pyrrolidine only among secondary amines.

INTRODUCTION The The

aromatic

nucleophilic

with

alkyl-

SR,

> NR2,

conditions.8-13 the

present

with

groups, groups,

are

and

recently

primary

such

other

On the

easily

We have

This

hardly

more

paper

amines

by primary

takes

these

reports

place.

expanded two

the

> SOPh

> Cl,

2,3

aromatics

> I- > Br- > Cl- > Hz0 and

has

been

reactions

missed of

in dimethyl

diethyl-,

that

> OAr,

OR,

> PhNH-

although and

> these

reaction

investigation

for a long

such

as

time.

1-dialkylamino-2,4-dinitronaphtha-

sulfoxide

n-alkylamines

> ROH,

nucleophiles,

it is natural

results,

> Ph3C-

(DMSO),

1-dialkylamino

pyrrolidino,

and pyrrolidine,

diisopropyl-,

but

and piperidino substitution

by

and N-methylbutylamines

1,14,15 these

reactions amino-amine

and on

I > N3 > NR3+

is NH2-

reactions

to benzene

in the detailed exchange

their

reaction

5567

derivatives

and

found

respects.

reactions

(SNAr)

(1) or l-dialkylamino-2,4-dinitrobenzenes

in OMSO

Br,

and N-methylbutylamino,

as dimethyl-,

recently

between

2.4,6-trinitrobenzenes secondary

field.

investigated

of substrates

in the

amines

diethyl-,

such

> NH3

reactions

that,

replaced

dialkylamines,

difference

found

been

of nucleophilicity

kinds

of these

or secondary

as dimethyl-,

piperidine,

> ArNH8

exchange

> OTs

order

on the

basis

scarcely

is F > NO2

> OH-

dependent

amino-amine

We have lenes

(SNAr) are a well-studied .. of dialkylamino-substituted activated

have

an approximate

> ArO-

are greatly

however,

ability

and

> RO- > R2NH

orders

reactions

leaving-group

S02R

ArS-

substitution

reactions

except for the 4-7 addition reactions with amines giving anionic o complexes, because 8 groups have been regarded as poor leaving ones. Generally an approximate

dialkylamino of

substitution

or arylamines,

nucleophilic

order

nucleophilic

mechanism.

of l-dialkylamino(2) with

primary

and

the

5568

s. %KlGUCHI

et d.

RESULTS The

present

reactions

are

expressed

as shown

"2

1(X = NO*) or 2(X = H 1 (1) a; R'=

(1).

At

first,

+

F$RzNH

(1)

3(X = NO2 or H)

R2= Me

(2) a; R'= _

(3) a; Ry= Me,

R4= H

b; R'= RL= Et

b; R;=

R;= -[CH2]4-

b; R3=

Et,

R4= H

c: R'=

c; R = R = -[CH2]5-

c; R3=

Pri,

‘1

_

7

Bu,

R2= Me

^

we measur

NR3R4

xx

‘R4NH

in equation

R2= Me

_

?

d; R'= Rc= -[CH2]4-

d:

R"=

Bu,

12 e: R = R =-[CH2]5-

e; R3=

BU t,

R4= H R4= H R4= H

f; R3= benzyl,

R4= H

R3= p-methoxyphenyl,

g:

R4= H

h: R3= p-methylphenyl, i; R3= phenyl. j;

R3=

the

time-dependent

Time-dependent (la)

absorption

"C to elucidate

Just la (2.54 change

Spectra

in

corresponds

curve

b to 5a16 d via

of

to the change

(Figure

curve

R4 = H) according

the

Reaction

the

expected

to be the

considered,

reaction

of

of

la with

excess

k4, and

k

5 the reactions

for pyrrolidine.

butylamine

in DF

I-Dimethylamino-2,4,6-trinitrobenze

As

generally

the

proposed

to proceed

ones.

butylamine

of butylamine

seem

). a DMSO

solution This

complexes.

curve

of 8 and

to

10 (R3 = Bu.

nucleophilic In our

in detail.

to la and

b changed

in Table

substitutio present

formation

in Scheme 1 later,

to terminate

1, where in the

at the

the

case

formation

key

steps

are

of nucleophilic of

7 at best

c

cola

of 3d (R3 = Bu. R4 = H) can be 16-18 The reaction can be by Hasegawa.

as shown

shown

in DMSO

-1

a 1s attributed

formation of a mixture 17 who studied the of Hasegawa,

after

as those

addition

curve

the

excess

sequences

a + b. where

h after

Indicates

with

same

therefore,

in curve

In 4.5

1).

c, which

to the results

reaction

amines

reaction

H

DMSO

of 2.4.6-tt-initroanisole

k3,

of the

R4=

R4 = H

path.

upon addition of butylamine (3.0 X lo-* M; M means mol.1 -5 the presence of some x 10 M) turned out red. indicating

curve

the

spectra

reaction

Absorption Rutylamine

with

the

R4= H

p-nitrophenyl,

k; R' = Me,

at.25

R4= H

clearly seconda except

I-Dialkylamino-substituted

5569

activated benzenes

OZN

i’_ (Rb=H)

!.i

NR3R4 NO2

-NF+

02N NO2

N R3R’1 02N

2

9_ (R~=H)

(f+‘=H) Scheme

1

5570

S.SEKIGUCHIer al.

Wavelength,

nm

Figure 1. Time-dependent absorption spectra relevant the reaction of 1-dimethylamino-2,4,6-trinitrobenzene -5 2.54 x 10 M) with butylamine (3.0 x lo-' M) in DMSO a la: b just after addition of the amine: c 1 25 "C: d. 4.5 h.

Determination

of

Substitution

Substitution of which

the

The

reaction

1) Among reactive

ii) The 56-58).

As

3) steps

are

of

an amine iii)

bulkiness

were

summarized

1, 5. 7-13, occurs

yield

primary

19-37).

decreases

with

in order

In the case

which and

reduction

38-40, iv) For

other, see

which

Discussion).

21, see

27,

31,

32,

k5 steps

and

not

in Table

1, in the

methylamine

substitution

(Runs

in yield

34)

except

of added

(6 +

with

footna,

is the most primary

to the and

is larger. for

(Runs

general

reaction

sufficiently

11-13

amine

7) and

the yield

be attributed

abstraction),

the

the exchange

would

alkylamines,

can

Moreover,

the

for

steps

of primary

studied,

amount

important

k4 (proton

(Runs

decreasing

very

of R3 group,

13. 20.

generally

1, the deprotonation

both

listed

easily.

in Scheme

is decreased,

are

following. alkylamines

shown

42-44)." 12,

and

comparatively

reactions

described.

in the

the nucleophilic

(runs

n-alkylamines

conditions

are

at h:

Products in the present

products

results

to (la,

14-18,

If the

to proceed.

and (7 +

amount

proceed.

decreases

with

sluggishness 20-22,

it does

increasing

at the

24-29,

as R3 and

Id, where

1-6.

acid-catalyzed

31-36,

R4 are

k3 (addition). 38-40,

bulkier

not decrease

and

(Runs

5.

so much

Discussion).

Id dnd could

le,

interestingly

be ascribed

the

reduction

to the conformations

in yield of

Id and

is very

different

le' (Runs

38-40

from and

each

42-44,

I-Dialkylamino-substituted

5571

activated benzenes

Table 1. Exchange reactions of 1-dialkylamino-2,4,6trinitro(1) or l-gialkylamino-2,4_dinitrobenzenes with various amines

(2)

---_-___----____--_--__~---_-__~----_-_------__----_-__Run

Substrate la la la

:b ;: la 5 6e : 9 10 11 12 13 14 15b 16' 17d lae :; ;: 23 24 22: 27 28 % :: z 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

50

la la la la la la la la la la la la la la la la la la lb lb lb lb lb lb lb lb lc IC

lc lc IC IC

lc Id Id :: le

le le le le la la la la

R1

R2

Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me

Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Me Et Et Et Et Et Et Et Et Me Me Me Me Me Me Me

:: Et Et Et Et Et Et n-Bu n-Bu n-Bu n-Bu n-Bu n-Bu n-Bu

-W214-

-(CH2)4$${4I -(

CH;);-

-(CH2)5-(CH2)5-(CH2>5-

-p2 Me Me Me

$9, Me Me Me

R3

Me Me Me Me Me Me Me Me Me Me Me Et i-Pr n-Bu n-Bu n-Bu n-Bu n-Bu n-Bu t-Bu t-Bu t-Bu

R4

H H H H H H H H H H : H H H H H H H H H H H H H H H H H H H H H H H H H H

Reaction temp./'C

Reaction time/h 10

min

00.: 0:5 0.5 0.5 2 10 10 min 0.5 2 5 5 ::: :*: 0:5 2 2 5 10 2 2 2

:: Et Et i-Pr i-Pr i-Pr n-Bu Me Et Et I-Pr i-Pr i-Pr n-Bu Me Et i-Pr n-Bu Me Et l-Pr i-Pr n-Bu

H" H H H H H H

:: n-Bu n-Bu

EE:

::

Me Me

10 24

: 65.5 2 2 2 5 2 5 5 22 ; 2 ; 2 6.5 2

Yield/ x

5572

s. SEKIGUCHI et d.

Table

(continued)

1.

Run

Sub-

R1

R2

R3

R4

Reaction

Reaction

Yield/

____~4~~"~_____________________l"p-14E__--_

::

Et Et n-au n-Bu Me Me Me Me Me Me Me Et Et n-Bu n-Bu

lc IC

60

la

::

lb la

68

Me Me Me Me

Et Et Me Me Me Me Me Me Me Me Me Et Et Me Me

Me Me Me Me

50 50 50

:: :: 50 50

80: Sl! 82: ::

la la la la

85 86

5: 2c

Me Me Me Me Me Me Me Me Me Me Me Me Me Me

Me Me Me Me Me Me Me Me Me Me Me Me Me Me

MeOPh MePh MePh MePh Ph Ph NO Ph NO'Ph M$ Me Me

LI H H H H H H H H

2: 17

::

:

::

10

:

3 10

G 30 50 30 30 50

H

15 5 12 19

10 10 ::

:: 30

-gHz)&

i

48 10 10 10 10 24 48

::

-W214-W2)4-W2)5-

le

::

::

::

:

24 10 min min 2 10 2 2 5 5 10 24 5

: 56 40 : 0 87 90 8 16 34 7 11

10

:: 50 50

10

24

:

2

:: 50

:49 14

________________.______--_---------__-~-_______~~~-------or

a[llo ratio), for

methyl-

solutions (molar

0.5

[210 unless and were

ratio).

d[amine]o/[llo ratio). h MePh = phenyl.

fPhCH2

mmol;

otherwise

[aminelO/[llo noted:

ethylamines. used,

the

40%

E(molar

l(molar

p-methylphenyl.

ratio).

iPh

=

70%

=

phenyl.

ml;

as

aqueous 0.5

ratio).

e[amine]o/[l]o

gMeOPh

benzyl.

10

b[amine]o/[l]o

respectively.

C[amine]o/[llo

=

and

3(molar

[210

or

solvent(DMS0)

lO(molar

p-methoxyphenyl. jN02Ph

=

p-nitro-

I-Dialkylamino-substituted

The

exchange

occur

(Runs

v) do not also

found

in the

very

low,

VI)

yield,

(Runs which

VII)

71,

could

Of

reactive,

viii) which

and

aromatlc

replacement

to have

an

only

amines.

Among

the

previous

side

is a key step

with

is far much

important

for

of 2 with

of

1,15

we

the

replacement

among

have

longer

on

for

substitution

the

reactive

of 2b

n-alkylamines time

reduces

and the

reported

the

1-dialkylamino amines

the magnitudes

group

is comparatively

75-83).

The

k3 step

the yield (R

nucleophllic primary group

and

comparatively

kg.

k_g,

klO.

and

for 2b.

Discussion).

substitution

fast.

k_,0.

see

secondary

by primary

was

of

is the highest

uns 84-86.

reactions

amines

n-alkylamines Although k,,,

the

in DMSO or

the overall k,, step

to occur.

R’R2N

~;IHR~R~

kjo, R3R4NH

>

%O !.L

RlR2N

NR3R4

NR3R4

N02+R3R4f&2

kll

; a-

1’ / 14

Scheme are

NO;! +R1R2NH+R3R’1NH

No2

NO2 ‘3

latter

between

(Runs

T,T5,16

NO2

naphthalene

the yields

anilines.

n

in the

It

1-benzylamino-2,4,6_trinitrobenzene

NO2

of

was

1,7,15

although

reaction

p-electron-donating less

(11) with

of

secondary

depends

results

generally

of pyrrolidine

55-61).

reactivity

methylamine.

R’ R2 \ / N

These

for pyrrolidine

pyrrolidlne,

the

reactions

to the conformation

study,

by pyrrolidine rate

except

specificity

(Runs

intermediate

an aniline

reactions

be attributed

2). where

reactlon

with

benzylamine

1-dialkylamino-2,4_dinitronaphthalenes

(Scheme

the

piperidine

For

the

p-nltroanillne to be very

In the

the

amines

involving

1-dialkylamino-2,4-dinitronaphthalenes.

not with

from

seems

could

of

75-81).

result

secondary

product.

whereas

(addition)

that but

is found

70,

substltutlon

(3f)*

of

place,

Benzylamlne

anillnes

1 with tendency

reactions

interesting

takes

of

This

similar

is conspicuously are

reactions 47-69).

5573

activated benzenes

roughly

the nucleophlllclty derivatives.

similar

2

to those

obtained

of pyrrolidlne

IS not

in the present so higher

than

reactions, in the

but

reactions

5574

s. SEKICUCHI et d.

DISCUSSION

Reactivity

and pKa

In 1974

Gravltz

of addition and

and

compounds

indicated

that

20

Jencks

formed

reported

from

an amino

the

kinetics

of the proton-catalyzed

N.O-trimethylenephthalimidium

group

with

higher

pKa

ion and

is a better

0

leaving

breakdo\

amines

one

in water,

[equation

(2)

0 -)-HX

(2)

1

X= R2N From together

Table with

their

MeNH2

amines

does

affect

Jencks.

the

present

Of primary

The much to the

be attributed

lower

reactivity

reactivity

of

to their

Structure

of

the

the

dine, the

in the

Z),

state

by X-ray'

bond,

the unshared

which

pyrrolldine).

Such

the

analyses

structural

nitrogen)

bond

at

the

methylamine

except

k3 and

would

helps

the proposal factor

k5 step

on the

k4 steps

IS the most

(T.S.)

from 2A).

can

and

later.

could be attributab 19 The less

from

the slower

at the

on pyrrolidino bond

with

1-dialkylamlno

secondary

amlnes.

of pyrrolidine,

absorption

For T.S.

pair

replace with

nucleophilicity

NMR

nitrogen]

spectral kll step

nitrogen

respect

evidence (R3R4NH

we propose 14,15 and

= pyrroli-

IS antiperiplanar

to the

length

IS

1.313

i,

Which

28),l 1s

It was almost

found

equal

that

to the

to

C(l)-N(pyrrolidin

the dialkylamino group to leave, giving 14' (R3R4N = f would play an important part. in 14 , therefore, (part

rate

group 1.14,15

a conJugation by X-ray

too

reactive,

be discussed

mainly

of

should

is a key step

k3 and

k4 steps.

result

pyrrolidine

higher

electron

4.60

k3 step.

only

the

from

for pyrrolidine

as at the

z

1.00

steric

as will

of

kg Step

(Figure

C(l)-N[dlalkylamlno(nucleofuge)

nitrogen)

values,

alkylamines

introduction,

to elucidate

transition

analyses

Scheme

depends

amlnes

at the

some

1, the

k5 step,

reactivity

% p-N02PhNH2

different

that

following

> PhNH2

11.00

in Scheme

at the

the

5.08

reactivity a

as well

primary

State

shown

rate

that

x Bu(Me)NH

of 1-dlalkylamlno-2.4-dlnitronaphthalenes

in order

following

than

Transition

reactions

structural

fast

pK

is very

in the

> p-MePhNH2

10.94

therefore,

the

similar

low nucleophlllcity.

As described

Accordingly,

although

k5 step

which

As

of secondary

at the

anilines

values,

reactions.

to the

2. Et2NH

10.73

pKa

indicate

5.31

z Me2NH

be expected,

is shown

> p-MeOPhNH2

9.35

It could

having

amines

results

> PhCH2NH2

10.63

11.12

to occur,

sluggishness

These

on their

n-alkylamlnes

could

oC).21

% piperidine

exchange

replacement

of nucleophilic

> PriNH2

10.60

not depend 20

and

the

In the

(25

11.27

Gravltz

owing

> BuNH2

> pyrrolldine

"a

which

order

values

10.64

8utNH2

for

reactivity

pKa

> EtNH2

10.62

PKa

the

1

By

the C(l)-N(pyrrolidino ;C=N-

bond

one.

and

the

I-Dialkylaminu-substituted

T. S.

3Fld

Figure 2. NO2 groups

plane

of 2-nitro

C(2')

and C(5')

to the the

repulsion

validity

of T.S.,

more

can

peri-hydrogen extent,

to case

(Figure

of a nucleofuge

of

In

13.

this from

as shown

in Id at the expense

would the

be due

conslderatlon

that

the

kinds

antiperiplanar The yield when

the

(runs

did

with

ZB).

effect

primary

faster

should

of T.S.

could

groups

seems

and

groups

would,

the considerable be some

extent

of

groups.

except

(Figure

(11)

group

6-nitro

G-nltrc

alkylarnines,

reactions,

6-nitro

although

there

stabilization

the similar

of Z-nitro

of 2- and

support

These

derivatives

of Z- and

that

of 2- and

than

the

In the present

Consequently,

in 3 (2 Id),

cause

according

would

amlnes. l5

1, for which

the planes

react

would

secondary

than

the conformation

would

of evidence

for t-butylamine, 28).

p-methoxyaniline

In spite from

of

a

values, parallel to nucleophiliclty, the greater reactivity for a 75 and 76) than for pyrrolidlne (run 55) depends on the difference

of amines

not

greatly

ring.

exist

lines

N(pyrrolidino). by 28".

pK

conformation

bulkiness

of

the coplanarity

of assuming

pyrrolldine

of their

p-methoxyanlline

not of

of substitution

to the ease

expectation

between

in 14' does

involving downward

C(8a)

for the naphthalenc

the sterlc

more

the plane

conjugation

group

(all

and

for other

to lhat

k5 steps

These

1 (Figure

transformation

coplanarity

facility

for

the benzene

conjugation Greater

than

ZB),

release

deviate

groups.

1-dlalkylamlno (k5 step)

3

k,, and

C(2).

This

2A.

to the cases

replace

In the present

to some

in Figure

)

by 26" and C(l),

and a-CH2

14 for pyrrolldlne

of T.S.

the

upward ring,

Z-nitro

be applied

pyrrolidinc

transformation hold.

is deviated

the pyrrolidino

of the process

could

to affect

Transition state at the omitted for simplicity).

between

giving

reasoning only

group of

5575

activated benzenes

(primary

or

secondary),

that

IS, the

faclllty

to assume

the

in T.S..

so much

decrease

of nucieophllic

amine

in the

reactions

increased

(Runs

of

Id with

38-40),

primary

whereas

amines,

It sharply

even did

S. SEKIGUCHI et al.

in the less

reactions

steric

Id (Figure coplanar the

of le (Runs

hindrance 28).

It.would

to the

cases

benzene

In the

an approaching

be anticipated ring,

former

the

amine,

owing

that

exerting

pyrrolidino

in le the

larger

steric

to the

group

would

specific

piperidino

group

hindrance.

This

exert

structure should

of

be not

tendency

is seen

substituted

it was

anionic

amino

group

found

o complexes,

plays

an

that

in the

such

as 13 and

important

part

release

of the

7, the

rather

than

amino

group

steroelectronic 22 value.

from

l,l-diamino.

configuration

of

its pKa

EXPERIMENTAL 1 as an

H NMR

spectra

internal All

the

described

of

containing ratio,

with

methanol 2.93

were

operated

reference.

All

were

compounds

the

melting

prepared

points

in the

TCB

[ca.

with

5 g] used)

dilute

s, N-CH3).

of the

8.97

benzene

was

aqueous

and

"C;

(2H.

s, H3 and

H5

ring;

see

[the

1 in equation

161.5-162

B-CH3).

3.13

(4H,

q, a-CH2).

110-111

6-CH3).

1.24

(2H.

s, y-CH2),

N-CH3).

8.85

(2H,

s, H3 and

"C;

X max

8.90

"C;

396

(2H.

m,

B-CH2).

m.p.

3.28

1.55

61%;

m, i3,Y-CH2),

m.p.

3.05

(2H.

8.83

nm

nm

qui,

92%;

m.p.

75.5-76.5

s, N-CH3),

7.27

(lH,

d. H6),

370

(2H.

"C: hmax

m. a-CH2),

Yield

8.85

figures

3 and

"C, poured,

crystallized

NMR

from

(DMSO-d6)

5 indicate

the

6 =

positional

and

NMR

(DMSO-d6)

6 = 1.10

(6H.

H5).

(E 12700); 8-CH2).

NMR

2.86

(DMSO-d6)

(2H.

6 = 0.83

t, a-CH2).

3.03

(3H. (2H,

t. s,

nm (E 20000): 7 c s, HJ and H').

394

(2H,

NMR

(DMSO-d6)

nm (E 11200) ; NMR

s, H3 and

(DMSO-d6)

6 = 1.93

(4H,

6 - 1.50

(6H,

H5).

(28) "C; hmax 8.23

I-Pyrrolidino-2,4-dinitrobenzene m, B-CH2),

was

nm (E 14800):

(E 11000):

s, H3,

(le)

104.5-105.5

I-Dimethylamino-2,4-dinitrobenzene

Yield

384

50 for 2)

residue

- 10 mole

(Id)

m. a-CH2),

(4H,

389

"C; Xmax

1-Piperidino-2.4.6-trinitrobenzene Yield

(TCB)([amine]/[TCB]

The

was

solution

H5).

189.5-191

(4H.

procedure

50 ml

(lc) Xmax

I-Pyrrolidino-2,4,&trinitrobenzene 48%:

typical OMSO

(l)]).

l-(N-Methyl)butylamino-2,4,6-trinitrobenzene m.p.

tetramethylsilane

(lb)

m.p.

77%;

The the

3 h at 30 (or

Xmax

with

uncorrected.

way. (ia):

for

137-137.5

48%;

Yield

were

filtered.

m.p.

Yield

Yield

spectrometer

similar

stirred

H2S04,

I-Diethylamino-2,4,&trinitrobenzene

t,

A-600

and 2,4,6-trinitrochlorobenzene

in a 76% yield:

(6H,

on a Varian

1-dimethylamino-2,4,6_trinitrobenzene

dimethylamine

neutralized

number

il

of 2.

In conclusion,

each

42-44).

against

89%:

m.p.

101.5-102.5

3.30

(4H,

m, a-CH2).

(lH,

386

nm

d, H5).

(E 22200); 8.60

(lH,

NMR

(DMSO-d6)

6 = 3.00

(6H.

s. H3).

(2b) "C: hmax 7.23

(lH,

387

nm

d. H6),

(E 21500); 8.33

(lH,

NMR

(DMSO-d6)

d, H5),

8.70

6 = 1.93 (lH,

(4H,

s. H3).

5577

I-Dialkylamino-substituted activated benzenes

I-Piperidino-2,4-dinitrobenene Yield 87%; m.p. 91.5-92.5 m. B,Y-CH2).

3.30 (4H. m. a-CH2),

l-Methylamino-2.4,6-trinitrobenzene Yield 57%: m.p. 110-110.5 S. N-CH3).

393 nm (E 17100); NMR (OMSO-d6)

6=

1.60 (6H,

7.40 (lH, d, H6), 8.27 (lH, d, H5), 8.62 (lH, s, H3). (3a)

"C; A,,, 352 nm (E 15100); NMR (OMSO-d6)

6 - 2.83 (3H,

8.98 (2H, s, H3 and H5), 9.30 (lH, br s, N-H).

I-Ethylamino-2,4,6_trinitrobenzene Yield 34%: m.p. 83.5-84 t. 8-CH3),

(PC) "C; Xmax

(3b) "C; Xmax 353 nm (E 14900); NMR (OMSO-d6)

3.11 (2H, q, a-CH2),

6 - 1.23 (3H,

8.83 (lH, br s, N-H), 8.99 (2H, s. H3 and H5).

I-Isopropylamino-2,4,6-trinitrobenzene Yield 60%; m.p. 107.5-108

(3~) "C: Xmax 352 nm (E 14900); NMR (OMSO-d6)

d, B-CH3),

8.63 (1H. br s, N-H), 9.07 (2H, s. H3 and H5).

3.51 (lH, m, a-CH),

l-Butylamino-214,6-trinitrobenzene Yield 60%; m.p. 80.5-81.5 t. 6-CH3),

(3d) "C; Xmax 352 nm (E 15400); NMR (DMSO-d6)

1.54 (4H, m. B,Y-CH2),

3.11 (2H. m. a-CH2),

6 = 1.25 (6H,

6 = 0.87 (3H,

8.91 (1H. m. N-H), 9.13 (2H, s,

H3 and H5). l-t-Butylamino-2,4,6_trinitrobenzene (3e) Yield 40%: m-p. 94-95 "C; X 362 nm (E 11600); NMR (DMSO-d6) max CH3), 7.62 (lH, s, N-H), 8.91 (2H, s. H3 and H5). I-Benzylamino-2,4,6-trinitrobenzene Yield 63%; m.p. 142-142.5 dl N-CH2)'

6 = 1.28 (9H, s.

(3f) "C; Xmax 351 nm (E 15800); NMR (DMSO-d6)

7.46 (5H, 5. benzyl phenyl

proton),

6 = 4.48 (2H,

9.19 (2H, s, H3 and H5). 9.47 (lH, br s,

N-H). l-(p-Methoxy)phenylamino-2,4,6-trinitrobenzene Yield 59% (recrystallized from ethanol);

(3g) m.p. 171.5-172

"C: A,,, 401 nm (E 13000);

H3' and H5'). 7.26 NMR (DMSO-d6) 6 = 3.81 (3H,, s, OCH ), 6.96 (2H. d, p-methoxyphenyl al (2H, d, p-methoxyphenyl H2 and H ), 9.05 (2H, s, H3 and H5), 10.13 (1H. s. N-H). I-(p-Methyl)phenylamino-2.4,6-trinitrobenzene (3h) Yield 25% (recrystallized from propanol); m.p. 165-166.5 NMR (DMSO-d6)

6 = 2.29 (3H. s, p-CH3),

(2H, d. p-methylphenyl

H2' and H6'). 9.02 (2H, s, H3 and H5), 10.26 (1H. m, N-H).

l-Phenylamino-2t4.6-trinitrobenzene Yield 54%: m.p. 179-180 phenyl

protons),

394 nm (E 14000); "C; X max , H3 and H5'), 7.00 6.49 (2H, d, p-methylphenyl

"C; h

(3i) 389 nm (E 13800); NMR (DMSO-d6)

1-(p-Nitro)phenylamino-2,4,6-trinitrobenzene (3j) Yield 43% (recrystallized from propanol); m.p. 226-227 NMR (DMSO-f6)

6 = 7.32 (5H, m,

9.07 (2H, s, H3 a:d""H5). 10.19 (1H. s. N-H).

6 = 7.30 (2H, d. p-nitrophenyl

407 nm (E 17700): "C: X max H3' and H5', 8.23 (2H, d, p-nitrophenyl

H2' and H6 ). 9.13 (2H, s. H3 and H5). 10.38 (lH, s, N-H).

5578

s. SEKlGUCHl

et d.

I-Methylamino-2,4-dinitrobenzene (3k). Yield (DMSO-d6) H5),

70%;

8.85 The

m.p.

6 = 3.06 (lH,

173.5-174.5

(3H,

finely

results

"C; X,ax

d, N-CH3),

split

7.14

d, H3),

of elementary

363

(lH,

8.92

analyses

(E 17700). d, H6),

(lH,

420

8.30

nm (sh,

(lH,

finely

c 7200);

NMR

doubly-split

d,

br s, N-H).

of all

the

compounds

were

within

the experimer

error.

Preparation and Determinationof Substitution Products The in the

typical

and

methylamine

the

prescribed

relative After silica

procedure

of la

reaction

(3 equiv, time

gel:

was

determination

methylamine: 40%

(Table

to methylamine),

the mixture

for the

with

1).

solution) poured

extracted

filtered,

hexane-Z-propanol

a DMSO

the (2O:l

was into

with

of substitution solution

stirred water

benzene

benzene

layer

at the

(200 mL).

acidified

subjected

and

was

describe

la (5 nnnol. 1.28

prescribed

(3 X 200 mL), was

products

containing

temperature with

dried

to HPLC

HCl over

g:

for

(3 equi\ MgS04.

[Shimazu

LC-61

v/v)].

REFERENCES S.: Shimizu, S 1. Aromatic Nucleophilic Substitution. 29; for part 28 see Sekiguchi, J. Chem. Sot. Perkin Trans. 2. in submission. Sato, M. C. F. MTP In. Rev. Sci. Arom. Compounds Org. Chem. Ser. 1. 1973. 3, : 2. Bernasconi, "Aromatic Nucleophilic Substitution," Elsevier. New York, 1968, Ch. 1. 3. Miller, J. C. F.: Gehriger, G. L. J. Am. Chem. Sot. 1984, 96, 1092. 4. Bernasconi, Bernasconi, C. F.: Terrier, F. J. Am. Chem. Sot. 1975, 97, 7458. S.; Hikage, R.; Obana, K.; Matsui, K.; Ando, Y.; Tomoto. N. Bull. Chen 2: Sekiguchi, Sot. Jpn. 1980. 53, 2921. J. Am. Chem. Sot. 1981, 103, 4871. Sekiguchi, S.: Bunnett. J. F. "Advanced Organic Chemistry: Reactions, Mechanism, and Structure," March, J. McGraw-Hill, New York, 1968, p. 498. Chem. her. 1964, 97, 3268. 9. Suhr, H. R. Angew. Chem. 1960. 72, 294. 10. Saver, J.; Huisgen. Loudon. J. D.; Shulman, N. J. Chem. Sot. 1941, 722. J. F. Quart. Rev. 1958. 12, 1. ;:: Bunnett, J. F.: Zahler, R. E. Chem. Rev. 1951, 49, 273. 13. Bunnett, J. Chem. Sot. Chem. Commun. 1988, 698. S.; Horie, T.; Suzuki, T. 14. Sekiguchi, J. Chem. Sot. Perkin Trans. 2, 1989, 178: S.: Suzuki, T.; Hosokawa, M. 15. Sekiguchi. J. Chem. Sot. Perkin Trans. 2. 1984. 547. Y. 16. Hasegawa, J. Chem. Sot. Perkin Trans. 2, 1985, 87. Y. 17. Hasegawa. J. Chem. Sot. Perkin Trans. 2, 1985, 649. Y. 18. Hasegawa, C. J. Chem. Sot. Perkin Trans. 2. 1983. 1175. M. R.; Greenhalgh, 19. Crampton, J. Am. Chem. Sot. 1974. 96. 499. N.; Jencks, W. P. 20. Gravitz. of Tables for Organic Compound Identification, Compiled by Rappoport. Z.. 21. Handbook Chem. Rubber Co., Ohio, 1967. p, 436. S.; Suzuki. T.: Hirosawa. Y.; Ishikura. H. J. Org. Chem. 1990. 55. 182 22. Sekiguchl,