Regiospecific synthesis of bromojuglone derivatives

REGIOSPECIFIC Stephen Department

SYNTHESIS

OF BROMOJUGLONE

W. Heinzman

of Chemistry,

DERIVATIVES

and John R. Grunwell*

Miami

University,

Oxford,

OH 45056

A large yield highly regiospecific one step procedure for the synthesis of 2- and Abstract: 3-bromo-5-acetoxy-1,4_naphthoquinone has been achieved from the reaction between N-bromosuccinimide and 1,5- and l,&diacetoxynaphthalene, respectively.

The utility Alder

reactions

inexpensive

of halogen with

starting

chlorojuglone materials

methoxy-1,4_naphthoquinone thoquinone novel

N-bromosuccinimide In connection naphthalene

Mare4

hydrogen

from 1-naphthol,

showed

Also,

tions

suggested

in the presence juglone

Bhatt has prepared

and hydrochloric

acetic

We were

acid mixture

unable

and isolated

to make this reaction

produced

Thus,

and 1,5_diacetoxynapthalene

which

proceed

in glacial

can intercept

the reaction

N-bromosuccimide

4105

methylene

de la

chloride deriva-

acetic acid with two equiva5a These observaacetate.

2 (Scheme dissolved

gave 2-hromo-5-acetoxy-1,4-naphthoquinone

I).

bromo-

P.B.D.

trichlorotetralone

in the absence

the intermediate

between

1,5-dihydroxy

of an acetylated

in anhydrous

dibromohydroxynaphthalene

of 1,5_diacetoxynaphthalene

with

in high yield.

via the intermediate

a

between

respectively.

of bromine

small amounts

of 1,5_diacetoxynaphthalene

the corresponding

that halogenation of water,

equivalents

of 1,5_diacetoxynaphthalene

to report

from the reaction

we reacted

several

Z-chloro-1,4-naph-

We wish

acid-L“1

of 2- and 3-bromojugl_one

with other

the bromination

derivative.

while

of 1,5- and 1,8-dihydroxynaphthalene,

studies

of the Diels-

makes the synthesis of halojuglone compounds from 1 Rapoport has synthesized 2- and 3-bromo-5-

procedures

peroxide

of the acetates

that the chlorination

lents of bromine

the regiochemistry

desirable.

gave 2,4-dichloro-l-hydroxy-5-acetoxynaphthalene tive 1.

directing

and the diacetates

in a water,

derivative.

elements

derivatives

highly

by multi-step

one step synthesis

juglone

atoms as control

of halide

I), should

form a halo-

in water,

in excellent

ion and

acetic

yield

acid

(Table

SCHEME

I

co GoAc

l4

0

I

+ += 0 -

AC6

m *0

0

Et-

4

c-2

Er

0+

0 -HBr

>

AH

AC A

4

\1

OH

0+

4307

The regiospecific ant is demonstrated reaction

between

substitution

further

of the halogen

by the formation

N-bromosuccimide

group

in the react-

of 3-bromo-5-acetoxy-1,4_naphthoquinone

atom ortho

to an acetoxy

7 from the

The 2- and 3-bromojuglone

and 1,Sdiacetoxynaphthalene.

ace-

probut distinct melting points, spectral data, and liquid chromatographic 5b The hydrolysis of the 2- and 3-bromojuglone acetates have the corresponding known

tates have similar perties.

2- and 3-bromojuglones

8 and 9 whose products

distinguished

phase liquid

by reverse

one recrystallization

of water

with

formed

proved

The stoichiometry

no naphthoquinone Thus,

reactant

with

was produced,

formed

a third

the product

bromide

equivalent

A solution

intermediate

is 3 equivalents

with

of each crude product

which

group probably

corresponding

after

is also the product arises

from addition

to 4 in Scheme

The several

a tribromoacetoxy

the bromoketone

in the formation

3 after trapped

deacetylation by water

by tautomerization

of bromonium

naphthalenone

relative

by N-bromosuccinimide

ion 2 which was

ion with

yields.

of N-bromosuccinimide

in the para position

to be intermediates

followed

of N-bromosuccinimide

of NBS gave better

2 equivalents

although

brominated

of 0.005 moles

of 5 min.

of substrate

to a solution

acid and 100 ml of water,

(generally

30-45 min.)

to the solution,

followed

were washed

with water

over MgS04,

and evaporated

lized from ethanol quinones

can be

I.

products

The

which

is shown

subsequent

group

I.

Bromonium

the dibromide

the bromide

acid,

in low in the

bromonaphthoquinone.

in Scheme

by water.

elimination

acetic

was isolated

of the product

of

2,4-dibromo-

in water,

to an acetoxy

to provide

to afford

per equivalent When

5.

Bromination ion and 3

4 which

in turn

The reaction

of hydrogen

bromide

of 5 gave

,6.

over a period

time

Analysis

1,5_dihydroxynaphthalene.

General -I__

acetic

for the ace-

isomer.

Z-bromo-1,4_naphthoquinone,

4-equivalents

for the oxidation

the carbonium

The cmr data6

by 36".

The 2- and 3-bromoacetates

to separate.

was reacted

mechanism

loses hydrogen

II. 7

of a dibromo

led to reacting

In practice

compounds

of the diacetate produced

differ

The loss of the acetyl

of the reaction

do not appear

A possible

carbonyl

impossible

diacetoxynaphthalene.

yield.

gave

and 1-naphthol

l-naphthol

5-acetoxy-1-naphthol

points in Table

chromatography.

of Z-aceto-l-naphthol.

to the acetyl

success

are shown

showed no trace of the other

1-Naphthylacetate upon reaction

melting

-.

tates and the hydrolysis

badly

discolored.

The resulting

solution

NaHC03

the product

if the ethanolic

in 50 ml of

for lengths

100 ml of water were

(6x50 ml).

(5x100 ml), saturated

The combined NaCl

The bromoquinones

was allowed

acid was added

dissolved

at 55-60°

Subsequently,

quinones.

solution

acetic

(0.02 moles)

was stirred

with dichloromethane

saturated

to afford

in 50 ml of warm

on the substrate.

by extraction

although

dissolved

of N-bromosuccinimide

dependent

(4x100 ml),

Method

of added

extracts

(1x100 ml),

dried

may be recrystal-

to rise above

50" the bromo-

Table

I.

Oxidation

of Naphthalene

Substrates

Derivatives

Time

with N-Bromosuccinimide

Productsa

Yields

M.P.

1,5-Diacetoxynaphthalene

45 min.

Z-bromo-5-acetoxy-l-4-naphthoquinone

>90%

154.5-156'

1,8-Diacetoxynaphthalene

45 min.

33bromo-5-acetoxy-1,4-naphthoquinone

>90%

149-150"

l-Naphthylacetateb

30 min.

50%

131-132"

1-NaphtholC

30 min.

2-bromo-1,4-naphthoquinone II

Z-Aceto-1-naphthol

30 min.

a)

Identity of products other derivatives.

b)

Yields

c)

l-Naphtha1

Table

II.

II

was established

13

C-NMR

isolation

over 30 min.

(22.63 MHz)

Spectral

84%

on the basis

are low due to an inefficient added dropwise

85%

of ir, nmr, ms, m.p.

and conversion

procedure.

at 45'C.

Data'

8

Atom

6

C-l

177.5(s)

176.3(s)

176.0(s)

181.7(s)

c-2

138.5(s)

139.5(d)

140.9(s)

141.5(d)

C-3

141.5(d)

141.2(s)

140.3(d)

142.4(s)

c-4

180.9(s)

181.6(s)

187.5(s)

183.1(s)

c-5

149.9(s)

150.9(s)

161.8(s)

162.2(s)

C-6

130.4(d)

130.3(d)

125.2(d)

124.6(d)

C-7

134.9(d)

135.7(d)

136.5(d)

137.3(d)

C-8

126.4(d)

125.4(d)

120.9(d)

119.8(d)

C-9

132.7(s)

133.9(s)

130.8(s)

131.9(s)

c-10

123.3(s)

122.9(s)

114.7(s)

114.2(s)

c-11

169.2(s)

169.3(s)

_--

---

C-12

20.99(q)

to

9

20.99(q) References

1.

.J. Savard

2.

R. L. Hannan,

and I?. Brassard, R. B. Barber

3.

P. T. Perumal

and M. V, Bhatt,

4.

P.B.D.

de la Mare,

5a. A. H. Carter, 5b.

R. H. Thomson,

Tetrahedron

Letters,

and H. Rapoport, Tetrahedron

4911

(1979).

J. Org. Chem., c, Letters,

3099

2153

(1979).

(1979).

Act. Chem. Res., 1. 361 (1974).

E. Race

and F. M. Rowe, 3. Chem.

SOC.,

236 (1942).

J. Org. Chem., 13, 377 (1948).

6.

Our cmr assignments are based on those made for juglone acetate: M. Kobayashi, Y. Terui, K. Tori, and N. Tsuji, Tetrahedron Letters, 619 (1976).

7.

We wish to acknowledge Denis Foerst of the Environmental Research Center, Environmental Monitoring and Support Laboratory, Cincinnati, OH for performing the liquid chromatographic analysis which was conducted on a Waters Model 440 liquid chromatograph using 5 pm Li Chrosorb RP-2, 4.6 mm x 25 cm column at 1300 psi and a flow rate of 1.00 mL/min with 37% The retention acetonitrile and 63% 0.65 Mm Milli-Q filtered distilled water as eluent. time for 6 was 17.7 min and for ,7 was 16.6 min. (Received

in USA

6 February

1980)