Journal of the Faculty of Environmental Science and Technology,

Okayama University
Vol.lO, No.1, pp.l05-109, February 2005

1,3-Dibromo-5,5-dimethylhydantoin, a useful reagent for

ortho-monobromination of phenols and polyphenols
Ashraful Alam,a,b Yutaka Takaguchia and Sadao Tsuboia, *
(Received November 29, 2004)

Ortho-monobromination of phenols and polyphenols by 1,3-dibromo-5,5dimethylhydantoin (DBDMH) is described. A simple addition of commercially
available DBDMH to phenols and polyphenols in chloroform at room
temperature resulted in a good to excellent yield of corresponding
ortho-monobromo derivatives.

Keywords: ortho-monobromination, phenol, polyphenol, DBDMH

Introduction

less hazardous reagents like dioxane dibromide,6

Aromatic bromination with bromine is one of the

phenols and other active aromatics, milder and

most widely used and extensively studied

DBD hydrobromide perbromide,7 tetrabromo-

cyclohexadienone,2 tetraalkylammoniumtribrom-

Owing to low reactivity, highly toxicity, and

ides8 have developed. These reagents yield

handling

liquid

selectively para-brominated phenols unless the

behavior of bromine, some other alternative

para-position is substituted. Several methods for

brominating agents such as NBS, I tetrabromo-

ortho-bromination

electrophilic aromatic substitution reactions.

inconvenience

due

to

the

of

phenols

have

been

cyclohexadienone have been developed. For the

appeared, but some of them required low tem-

bromination of phenols, bromine in halogenated

perature or other uses very unstable brominating

hydrocarbons or AcOIt is often the reagent of

agents and most of them suffers from the

choice. However, for many substances, mixtures

formation of dibromo derivatives. 1o

of mono- and poly-brominated compounds are

s
obtained. For selective monobromination of

Scheme 1.

*Corresponding author, Phone/Fax: 81-86-251-8898;

E-mail: stsuboi6@cc.okayama-u.ac.jp
aDepartment of Environmental Chemistry and
Materials, Faculty of Environmental Sciences and
Technology, Okayama University, Okayama, Japan.
bOn study leave from Dept. of Chem., Shahjalal Uni.
of Sci. and Tee., Sylhet-3114, Bangladesh.

There are several reports of bromination of

aromatics using N-bromosuccinamide (NBS)1O or

105

J. Fac. Environ. Sci. and Tech., Okayama Univ.10 0) 2005

106

by DBDMH in the presence of HBF4'Et2011 or

derivative in 92.5% yield and high purity

other strong acids such as methyltrifluoroacetic

Monobromination of carboxylic acid by

compared to the reported Br2liso-Pr2NHJtoluene

method (68% isolated yield, lit. 14 74%). But

DBDMH in aqueous NaOH has been reported, 13

unfortunately, similar treatment of 2a with

but it is not applicable for other aromatics except

DBDMH yielded the mixture of mono-, dibromo

carboxylic acids. Herein, we report a very simple

derivative and the unreacted starting material,

ortho-

which was difficult to separate by column

acid. 12

and

convenient

method

for

the

chromatography.

using

method was examined for 2a and resulted in a

1,3-dibromo-5,5-dimethylhydantoin

Then,

the

Br2/iso-Pr2NH

monobromination of phenols and polyphenols

mixture of mono- and dibromo components in

(DBDMH) (Scheme I).

1.5: 1 ratio with only 61 % yield. In the presence

of

different

organic

acids12

such

as

Results and discussion

methylsulfonic acid, DBDMH also yielded a

All the reactions were carried out in ordinary

mixture of bromides and some other unknown

chloroform at room temperature. The yield in

compound. Changing the solvent to DMF,

DMF was worst and the starting material was

treatment with excess DBDMH for short reaction

remained unreacted after long period of time.

time was also failed. Then, suddenly it was found

Results of the bromination of variety of phenols

that if DBDMH is added at once instead of in

and polyphenols by DBDMH are summarized in

portion, the reaction goes smoothly and yielded

Table 1. Most of the phenols and polyphenols

pure monobromo derivative in surprisingly high

gave the single bromo- derivative, whereas some

yield (98%). Whereas, for all other reactions the

of them yielded small amount of dibromo

DBDMH was added in several portions and it

derivatives (entry 8 and 9). Treatment of la with

was not so much sensitive to the mode of

DBDMH

addition (at once or in portion).

yielded

the

corresponding

2-Br

Table 1. Bromination of phenols and polyphenols by DBDMH.

Entry
1

Phenol/ Polyphenol

~OMe

1a

MeO

"'=::

.0

OH

Condition

Product
OMe

1b

5 h, rt.

MeO

~
I

.0

OH

16h, rt.

2b
BnO

3a

~OH

~
(Continued)

Br

.0

OH

92.5%;
lit. 15 74%

"'=::

Br

Single product,

.0

OH

98%

OMe

OMe

"'=::

OMe

DBDMH (0.50 eq)"

"'=::

BnO

Single product,

OMe

OMe

2a

~
~

DBDMH (0.52 eq),

OMe

Isolated yield

DBDMH (0.53 eq),

15min, rt.

3b

Br

~OH

IN

Single product,
91%

Alam et al. / 1,3- Dibromo- 5. 5- dimethylhydalltoill. a IIsef,,1 reagellt for ortho- mOllobromillatioll of phenols alld polyphenols

Table 1 (Continued)
Entry

Phenol/ Polyphenol

4a~0
OMe

'-0

5
Sa

DBDMH (0.51 eq),

OH

6a

7
7a

RO

~
h

DBDMH (0.51 eq),

1.5 h, rt

24 h, rt,
RO

I "::

Br

OH

DBDMH (0.52 eq),

HoQMe

30 min, rt.

9a

?:Me

R=Me,98%
R=Bn,95%

di-Br (15%)

DBDMH (0.52 eq),

Mono-Br,75%

12 h, rt.

di-Br,
o

DBDMH (1.20 eq),

HOOH
10a OMe

Single product

8b

Br

Ho-o-OMe

77%

Mono-Br, 85%

8a

10

7b

Single product,

OMe

OH
R=Me, Bn

Ho-o-Me

OH

Me--\--O
Me

OH
R=Me, Bn

Single product,

Br

I"::

DBDMH (0.51 eq),

OH

95%

97%

I"::

OH

OOH
Ph--\--O
Ph

OMe

Single product,

5b 0;C::
6b

OyOH
Me--\--o
Me

Br

2 h, rt.

Ph--\--O
Ph

'-0

"::

OMe

OMe

Isolated yield

4b I "::

1011, rt.

q
o

DBDMH (0.51 eq),

OH

Product
o

["::

Condition

2 h, rt,

Br

HO

10b

trace

OMe

"::

Br

OH

Di-bromo, 98%

OMe

Phenols that have two identical positions for

instance, treatment of lOa with 1.20 equiv. of

bromination (8a, 9a and lOa), getting the pure

DBDMH yielded the corresponding dibromo

monobromo derivative is somewhat difficult.

ester lOb in excellent yield (entry 10). So,

For example, a mixture of mono- and dibromo

DBDMD is also an excellent reagent for the

ester of lOa was obtained (85:15)

preparation of dibromo derivative of compounds

upon

treatment of lOa with 0.58 mole equivalent of

DBDMH. Thus the suitability of the reagent for
the dibromination

was

also

checked.

For

like lOa,

107

1. Fac. Environ. Sci. and Tech., Okayama Univ.lO (1) 2005

108

In conclusion, we can say that DBDMH is an

added after the disappearance of color and so on.

excellent reagent for the monobromination of

The progress of the reaction was monitored by

phenols and polyphenols at the ortho-position to

GC-MS,

the hydroxy group because of its stable solid

understood by observing the persistence of the

state, commercial availability, simplicity of the

color of the reaction mixture (in case of slight

reaction, clean reaction product, easy workup,

excess DBDMH was used). After completion of

and of course the high yield and purity of

the reaction, removal of the solvent followed by

product.

the separation of the solid byproduct (derived

and

sometimes

can

easily

be

from DBDMH) by simple filtration provided the

almost pure bromide. For the compounds with

Experimental

low solubility, 10% aq. sodium hydrosulfite

1,3-Dibromo-5,5-dimethylhydantoin

(Na2S204) solution was added into the reaction

(DBDMH) was purchased from TCI, Japan and

mixture, stirred for 5 min. Organic layer was

was used as it was. All the reactions were

separated, dried over MeS04 and concentrated in

carried out in the ordinary chloroform and inert

evaporator yielded the almost pure product.

atmosphere was not maintained. Reaction was

Passing

monitored by GC-MS and flash chromatography

column, it gave the pure products.

General:

through

small

chromatographic

was performed on silica gel (Merck, 60N,

spherical, neutral, 40-50 mash). IR was recorded

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