Simple and Regioselective Bromination of 5,6-Disubstituted-indan-1-ones with Br2 Under Acidic and Basic Conditions

Taeyoung Choi,Eunsook Ma

doi:10.3390/12010074

Abstract

Bromination of 5,6-dimethoxyindan-1-one with Br(2) in acetic acid at room temperature produced exclusively the corresponding 2,4-dibromo compound in 95% yield. Reaction of 5,6-dimethoxyindan-1-one with Br(2) in the presence of KOH, K(2)CO(3) or Cs(2)CO(3 )at ~0 degrees C( )gave the monobrominated product 4-bromo-5,6-dimethoxyindan-3-one in 79%, 81% and 67% yield, respectively. 5,6-Dihydroxyindan-1-one was dibrominated on the aromatic ring affording 4,7-dibromo-5,6-dihydroxyindan-1-one both in acetic acid at room temperature and in the presence of KOH at ~0 degrees C. 5,6-Difluoroindan-1-one and 1-indanone were alpha-monobrominated in acetic acid and alpha,alpha-dibrominated under KOH conditions at room temperature.

Highlights

Bromoaromatics are widely used as intermediates in the manufacture of pharmaceuticals, agrochemicals and specialty chemical products [1]
When compound 1 was reacted with Br2 in CCl4 or in CHCl3 for 2 hrs at room temperature, 2,2-dibromo-5,6-dimethoxyindan-1-one (2) was obtained in 44% or 22% yield as the major product and 2,2,4-tribromo-5,6-dimethoxyindan-1-one (3) was obtained in 5% or 2% yield, respectively, along with recovered starting material
If the C4 hydrogen were not substituted with bromine, a correlation should be observed between the C4 and C3 hydrogens in the NOESY spectrum, but we did not observe such a cross peak, we conclude that the 4-bromo derivative was synthesized

Summary

Introduction

Bromoaromatics are widely used as intermediates in the manufacture of pharmaceuticals, agrochemicals and specialty chemical products [1]. Selective α-bromination of carbonyl compounds is another important transformation, as the resulting α-brominated products are versatile synthetic intermediates. Some of the reported methods involve the use of NBS/NH4OAc [16], hypervalent iodine sulfonate/magnesium halides under microwaves [17], N-halosuccinimide/TsOH/CH3CN [18], Br2/C2symmetric diphenylpyrrolidine catalyst [19], nonselective dibromination/selective debromination [20], N-methylpyrrolidin-2-one hydrotribromide complex (MPHT) [21]. The reaction conditions studied involved the use of Br2 under neutral, acidic and basic conditions and a variety of well known brominating reagents such as KBr, NH4Br and pyridinium bromochromate

Results and Discussion

VIII IX X

Conclusions