Indian Journal of Chemistry Vol. 44B, January 2005, pp. 184-187

Note

Synthesis of α-bromoalkanones using urea-hydrogen peroxide complex and sodium

bromide over silica gel-acetic acid

Satya Paul, Puja Nanda & Rajive Gupta* Department of Chemistry, University of Jammu

Jammu 180 006, India

E-mail: rajgupta@sancharnet.in

Received 4 February 2004; accepted (revised) 16 June 2004

α-Bromoalkanones 2 have been synthesized by the reaction of alkanones 1 with UHP-NaBr over SiO2-acetic acid in solvent-free conditions under microwave irradiation.

IPC: Int.Cl.7 C 07 C 45/00 Bromination with molecular bromine is one of the most widely and extensively studied reactions. The use of molecular bromine in preparative chemistry is a serious cause of concern due to its toxicity and corroding properties as only one out of two bromine atoms becomes part of the product, the other atom becomes the corroding hydrogen bromide, which must be neutralized before it is discarded1. Thus, bromination with molecular bromine may be qualified as environmentally unfriendly reaction2.

The other reagents which are used as alternative to molecular bromine are pyridinium dichlorobromate3, copper (II) bromide4, 1,4-dioxane bromooxonium bromide5, tribromoacetophenone6, zeolites/bromine7, N-bromosuccinimide/trifluoroacetic acid8, ammonium tribromides9, like pyridinium, phenyltrimethyl-ammonium, tetramethylammonium and tetrabutyl-ammonium tribromides. Among these reported reagents, many are quiet expensive or suffer from harsh reaction conditions or when used make use of solvents. In these environmentally conscious days, researchers have been directed towards development of procedures that are both environmentally desirable and economically acceptable.

The most acceptable method is one, which involves in situ generation of bromine, so that it can be handled easily. It can be done by oxidation of hydrogen bromide or an alkali-metal bromide by potassium permanganate, sodium bromate and hydrogen peroxide10. Alkali bromide in combination with

hydrogen peroxide has also been used for addition to unsaturated double or triple bonds11a,b, aromatic electrophilic substitution11c, 12, synthesis of amine tribromides13 and for oxidation of alcohols, alde-hydes11b or sulfides14. Some researchers11a,12,15 have utilized a combination of hydrohalic acid and suitable oxidant such as tert-butyl hydrogen peroxide or hydrogen peroxide, which in situ generates positive halogen species for the halogenation of organic substrates. Recently, benzylic bromination has been reported with sodium bromide and hydrogen peroxide15b. The method is eco-friendly but suffers from drawback as chlorinated solvent was used. α-Bromoalkanones are the important synthons used

for the synthesis of variety of biologically active heterocyclic compounds16. These have been used to protect hydroxy groups17 and are also used for the synthesis of p-bromomandelic acid, which is a valuable reagent used in the analysis of zirconium and hafnium18. These also find use as reagents for the identification of organic acids by conversion to crystalline phenacyl esters19.

Microwave (MW) irradiation has been used for the rapid synthesis of a variety of compounds20. Hetero-geneous reactions facilitated by supported reagents on various mineral oxides under MW irradiation have received special attention in recent years21, 22.

Keeping in view the importance of α-bromo-alkanones in organic synthesis and our continued interest in developing environmentally benign methodology22, we have successfully developed a new method for the synthesis of α-bromoalkanones using urea-hydrogen peroxide and sodium bromide (UHP-NaBr) over SiO2-AcOH (Scheme I).

To our knowledge, this reagent has not been used for α-bromination of alkanones under microwave irradiation. The salient features of our method are: (i) no need of liquid hydrogen peroxide, and (ii) discards chlorinated solvents and gives high yield of

UHP-NaBr / SiO2 -AcOH

MW, 300W

O

R

OBr

R

Scheme I

NOTES

185

brominated alkanones. In our previous communica-tions, we have reported the selective synthesis of α-bromo and α, α-dibromo alkanones using dioxane dibromide/SiO2 (ref. 22a) and hexamethylene tetramine-bromine complex/basic alumina22d. This new method can be used as alternative to other existing methods as it is safe, economic and environmentally friendly.

Results and Discussion Urea-hydrogen peroxide23 (UHP, Figure 1) is an

alternative to 90% hydrogen peroxide and acts as a source of anhydrous hydrogen peroxide. Use of UHP-NaBr seems to be very convenient in view of the above precedents. In this reaction system, full utilization of bromine is achieved with little environmental problems, as the waste is only water. Acetic acid was used to obtain acidic conditions. The mechanism of α-bromination of alkanones with UHP-NaBr over SiO2-AcOH is shown in Scheme II.

Number of α-bromoalkanones have been synthe-sized from alkanones using (UHP-NaBr) over SiO2-AcOH (Table I). Experimental conditions have been carefully monitored to get maximum yield. UHP was prepared by recrystallizing urea in 30% hydrogen peroxide. The conditions, which gave maximum yield, are 1.1 mmole of sodium bromide, 1g of UHP and 0.1 mL of acetic acid impregnated on 1g of silica.

Power level of microwave oven was regulated to set the desired conditions. The power level of 300 W is most suitable power level as low power level gives low

yield and prolongation of reaction time and higher power level leads to breakage of UHP complex and thus, leading to low efficiency of the reagent system.

In order to standardize our reagent system, we have carried out series of reactions (in case of entry 1) using UHP-NaBr under different conditions employing neat conditions as well as different supports, e.g. with neat UHP-NaBr, we got 55% yield; with UHP-NaBr/SiO2, 70% yield; UHP-NaBr/SiO2-AcOH, 80% yield; UHP-NaBr/monochloroacetic acid, 62% yield; UHP-NaBr/ZnO, only 22% yield (Table II). Reactions of these reagents with other substrates (entries 2, 3 and 4) have also been carried out and similar results were obtained. Thus, UHP-NaBr/SiO2-AcOH is the most efficient and adaptable reagent for α–bromination of alkanones.

This method is selective for mono α-bromination of alkanones as no dibrominated product was observed on TLC even after prolonged period of 5 min (in case of entry 1).

Experimental Section General. Melting points were determined on a

Buchi melting point apparatus and are uncorrected. 1H NMR spectra were recorded on a JNM-PMX 60 NMR spectrometer (60MHz) in CDCl3 using tetramethylsilane as an internal standard; and IR spectra in KBr disc on a Hitachi 270-30

NHH2N

O

H

OOH

H

Figure 1 ⎯ Urea-hydrogen peroxide (UHP)

UHP H2O2

NaBr Na + Br

CH3COOH CH3COO + H

2 Br + H2O2 + 2 H = Br2 + 2 H2O

ArCOCH3 + Br2 = ArCOCH2Br + Br + H Scheme II

Table I ⎯ Synthesis of α-bromoalkanones 2 using UHP-NaBr/SiO2-AcOH (Power=300W)

Entry R Reaction Timea Yield mp (lit.mp)

tempb

°C (sec) (%) °C

1 H 100-102 90 80 44-47(48-51)24 2 4-Cl 125-27 50 79 94-95(96-97)24 3 3-NO2 137-39 70 86 90-94(90-96)24 4 4-NO2 132-34 70 82 99-100(100)24 5 4-Br 120-22 30 76 106-07(108)24 6 4-NH2 100-102 40 77 102-05(105)24 7 4-CH3 99-101 120 72 42-44(45-48)24 8 4-OCH3 112-15 120 73 65-68(69-71)24 9 2-OH 118-20 30 70 37-39(39-41)25 10 2,4-di-OH 112-14 20 72 115-17(118)25 11 2,5-di-OH 120-22 22 71 111-13(113)25 12 4-C6H5 126-29 120 78 122-24(123)24

aTime at which maximum yield was obtained. bFinal temperature was measured by introducing glass thermometer in the reaction mixture during MW experiment and gives approximate temperature range.

INDIAN J. CHEM., SEC B, JANUARY 2005

186

spectrophotometer. The reactions were monitored by TLC. For the microwave irradiation experiments described below a conventional (unmodified) household microwave oven equipped with a turntable was used (BPL BMO 800, 800 W and operating at 2450 MHz).

Synthesis of α-bromoalkanones. General pro-cedure. Alkanone (1 mmole), sodium bromide (1.1 mmole, 0.112 g), UHP (1 g) and SiO2/acetic acid (0.1 mL of acetic acid was impregnated on 1g of silica gel) were stirred with glass rod in 50mL beaker. This was then irradiated in a microwave oven at a power output of 300 W for the appropriate time (Table I). After irradiation, the contents were cooled to room tempera-ture and extracted with ethyl acetate (3×15 mL). The solid inorganic material was filtered and the solvent was removed under reduced pressure to afford the product, which was purified by crystallization from pet. ether-ethyl acetate.

The structures of the products were confirmed by 1H NMR and IR spectra and comparison with authentic sample prepared according to literature methods.

Conclusion

We have found a very simple method for selective α-bromination of alkanones. This new procedure is simple, inexpensive and eco-friendly and is a useful alternative to existing methods.

Acknowledgement

One of the authors (PN) thanks the CSIR, New Delhi for awarding SRF.

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Table II ⎯ Effect of different reagents for α-bromination of alkanones in case of entry 1 under microwave irradiation

(Power = 300W)

Reagent Reaction temp

Time(sec)

Yield(%)

°C

UHP-NaBr 75-77 180 55 UHP-NaBr/SiO2 50-52 160 70 UHP-NaBr/SiO2-AcOH 100-102 160 80 UHP-NaBr/monochloroacetic acid 120-22 10 62 UHP-NaBr/ZnO 80-82 240 22

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