A Novel Approach of Using NBS as an Effective and Convenient Oxidizing Agent for Various Compounds a Survey

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1 Journal of Chemistry and Chemical Sciences, Vol.8(1), 59-65, January 2018 (An International Research Journal), ISSN X (Print) ISSN (Online) A Novel Approach of Using NBS as an Effective and Convenient Oxidizing Agent for Various Compounds a Survey Shruthi P 1 and P M Ramadas Bhandarkar 2 1 Research Scholar, Department of Chemistry, The National Institute of Engineering, Mysuru , INDIA. 2 Prof. & HOD, Department of Chemistry, The National Institute of Engineering, Mysuru , INDIA. shruthip356@gmail.com (Received on: January 4, 2018) ABSTRACT N Bromosuccinimide is a oxidizing agent that is used as source for bromine in radical reactions and various electrophilic additions. It was first shown by Ziegler and co-workers that NBS reacts with Cyclohexene to give 3-bromocyclohexene and succinimide. NBS effectively gains electrons from the reactants to form a product. As it has a free bromine in it, it is a strong oxidizing agent. Keywords: NBS, oxidation, direct concentration, alkoxy amides. 1. INTRODUCTION N Bromosuccinimide or NBS is a strong brominating oxidizing reagent used in radical substitution and electrophylic addition reactions. NBS is a source of bromine radical/ positive halogen 1. NBS is an oxidant for a variety of substrates both in acidic and alkaline solutions. Allylic bromination of substrates such as alcohol, amines with NBS leads to elimination of HBr in the presence of base leads to product. It is a derivative of succinic acid 2. NBS is most needed for industrial and laboratory uses as it is used for allylic substitution of bromine. NBS produces low concentration of bromine, so substitution reaction occurs easily. Fig.1 Benzylic substitution of bromine by NBS. 59

2 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) If high concentration of bromine is produced the addition reaction may occur; hence NBS is widely used for substitution reactions in Industries and laboratory3. 2. CONVERSION OF N-ALKOXYAMIDES TO CARBOXYLIC ESTERS WITH NBS Direct conversion of N-alkoxy amides to carboxylic esters through tandem NBS mediated oxidative homo-coupling and thermal de-nitrogenation. Fig. 2. Treatment of N-alkoxy amides with NBS to form corresponding esters Treatment of N-alkoxy amides with NBS in toluene was found convenient and corresponding carboxylic esters including those bearing a bulky or long chain substituant in satisfactory to excellent yields. Convenient and economic approach to a direct transformation of an alkoxy amide into carboxylic ester functional group via oxidative homo-coupling and subsequent thermal de-nitrogenation. It also facilitates the synthesis of sterically hindered carboxylic esters. Ester is a important functional group that has found wide occurrence in polymers, pharmaceutical agents and biologically relevant natural products. Many methods were reported for the synthesis of esters but the formation of hindered esters continues to remain as a challenge. Special re-agents and procedures are required for achieving these sterically bulky carboxylic esters. In contrast formation of carboxylic esters do not hamper the synthesis of hydroxamic esters. In this regard a direct conversion of N alkoxy amides to carboxylic esters as an efficient strategy to the synthesis of hindered esters can be envisaged. In this research work a more convenient one step conversion is reported through reactions of alkoxy amides with readily available NBS in toluene. This alternate method provides access to sterically hindered esters 60

3 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) Path a Fig.3. Path a for conversion of N-alkoxy amides to hindered esters. The advantage of this method in comparison to the existing methods are 1. Its directness of one step 2. Low cost of reagents. Heavy metal oxidants such as Nickel (IV) per oxide hydrate, seric amonium nitrate, silver oxide are always used as oxidants for dimerization reactions. Path b Fig.3.1. Path b for conversion of N-alkoxy amides to hindered esters. N alkoxy amides after being converted to N chloro hydroxomates could react with sodium azide to furnish the ester products via heron rearrangements. This method is well applied to synthesis of some highly hindered esters4. Path c Fig.3.2. Path c for conversion of N-alkoxy amides to hindered esters. 3. DIRECT TRANSFORMATION OF ETHYLARENES INTO PRIMARY AROMATIC AMIDES WITH NBS AND IODINE AQ. AMMONIA. In this research work, the transformation of a variety of ethyl arenes into corresponding primary aromatic amides via treatment with NBS in the presence of catalytic 2, 21 azobis in a 61

4 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) mixture of ethyl acetate and water followed by reaction with molecular iodine and aqueous amonia in 1 pot. Primary aromatic amides are used in pharmaceuticals and intermediates for the synthesis of aromatic nitriles, carboxylic acids and hetero cyclic compounds such as oxazoles. The 1 pot transformation of methyl arenes into aromatic nitriles involves the treatment with NBS. Ethyl arenes were also converted to primary aromatic amides by the treatment with NBS. These reactions looked highly useful and attractive. Its applicability to the 1-pot preparation of primary aromatic amides from ethyl benzene and P-Bromo ethyl benzene with molecular iodine, TBHP and aqueous amonia under the same reaction conditions. This treatment of ethyl benzene followed by many reactions gave benzamide as yield. To improve the yield, optimization of the reaction condition was done by changing the solvents. Fig.4.Transformation of ethylarenes into primary aromatic amides Condition A (solvent:acoet,x:3.5,y:2.5,temp:rt) Condition B (solvent:ch3cn,x:3.5,y:3,temp:60^0c) Condition C (solvent:ch3cl,x:5,y:3.5,temp:60^0c) The reaction mechanism is as follows Fig.5. Possible reaction mechanism Alpha bromo ethylarene is formed in the reaction of ethylarene with bromine atom formed from NBS [wohl-ziegler reaction] 62

5 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) The 2 nd wohl-ziegler reaction of alpha bromo ethylarene occurs to give alpha, alpha dibromo ethylarene. The hydrolysis of alpha, alpha dibromo ethyl arene in a mixture of ethyl acetate / aceto nitryl / chloroform and water under warming condition proceeds to give aryl-methyl ketone SYNTHESIZE ALPHA AMINO KETONES FROM BENZYALIC SECONDARY ALCOHOLS In this research paper it is informed the synthesize of pharmaceutically important alpha amino ketones which exists widely in many natural products and pharmaceuticals, eg. bupropion, pyrovalerone etc. These are potential pharma cotherapies for anti depressant and cocaine addiction. Alpha amino ketones were synthesized from readily available benzylic secondary alcohols and amines using N-bromosuccinimide. The traditional methods to synthesize alpha amino ketones from ketones, which incorporate handling of toxic reagents such as bromine or metal catalyst. But in this novel onepot greener reaction avoids direct usage of toxic and corrosive bromine, as it is generated in situ in the reaction and be utilized. This method is elegant, greener and one-pot protocol for the synthesis of alpha amino ketones via sequential alcohol oxidation, alpha bromination of ketone/c-n bond formation using readily available NBS. 1-phenylpropan-1-ol was used as a model substrate and it was treated with NBS in CH 3CN at ambient temperature for 24 hours. Fig.6. Alpha amino ketones synthesis from benzylic secondary alcohols The optimized reaction conditions revealed that alpha ketones can be synthesized in excellent yield using NBS in 1.4-dioxane from benzylic additional oxidants or peroxides. By using similar method they have synthesized psychoactive drug Amfepramone and pyrovalerone. Fig One step synthesis of Amfepramone 63

6 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) Fig One step synthesis of Pyrovalerone To understand the reaction mechanism. The reaction of alcohol was carried out with NBS in the dibromo ketones. The result clearly shows that reaction proceeds through sequential alcohol oxidation and alpha bromination of ketones. The reaction was monitored by H NMR spectroscopy. The results clearly reveal that the oxidation of alcohol is fast and within few minutes alcohol is oxidized to ketone. Ketone is further converted to alpha bromo ketone by in situ generated Br CONCLUSION Fig. 7. Possible reaction mechanism Through this survey, it can be concluded that NBS is used as an oxidizing agent in all of the research work. Since the research work have used NBS, the experiments are all reduced to 1-step. NBS is found out to be a very convenient oxidizing agent and acts as a low cost reagent. 64

7 Shruthi P, et al., J. Chem. & Cheml. Sci. Vol.8(1), (2018) Finally NBS can be used as an oxidizing agent for many of the industrial processes based compounds. It is time consuming, requires many steps and cost exhaustive for industries to perform oxidation. Hence through our work and also by using NBS it helps to solve all these problems efficiently and in a better manner. REFERENCES 1. J. Dauben et al., N Bromosuccinimide, I, Allylic bromination, a general survey of reaction variables. 2. P M Ramadas Bhandarkar, K N Mohana., Oxidation of Phenylpropanolamine with NBS in acid and alkaline solutions a kinetic and mechanistic study, Oxidation Communications, 33, Issue 2 (2010). 3. K N Mohana, P M Ramadas Bhandarkar., photochemical decomposition of NBS and NCS in aquaeous solutions, Bulgarian Chemical Communications, Vol 36, Issue 4 (2004). 4. Shimokawa et al., Direct transformation of ethylarenes into primary aromatic amides with NBS and I 2 aquaeous NH 3, ACS publications (2016). 5. Zhang et al., Direct conversion of N-alkoxy amides to carboxylic esters through tandem NBS mediated oxidative homo coupling and thermal denitrogenation, The Journal of Organic Chemistry (2013). 6. Somraj Guha et al., a versatile and 1-pot strategy to synthesize alpha amino ketones from benyalic secondary alcohols using NBS, ACS publications (2014). 65