B r o m i n a t i o n w i t h N -B r o m o s u c c i n i m i d e i n T e t r a b u t y l a m m o n i u m B r o m i d eAbstract: Highly regioselective nuclear bromination of activated aromatic and heteroaromatic compounds has been accomplished using N-bromosuccinimide in tetrabutylammonium bromide. Predominant para-selective monobromination of activated aromatics such as phenols and anilines, rate acceleration of bromination for moderately activated and less reactive substrates on addition of acidic montmorillonite K-10 clay, with or without microwave assistance, are the notable features of this protocol.Bromination of aromatics and heteroaromatics is an electrophilic substitution reaction of immense synthetic and industrial importance. Brominated arenes and heteroarenes are useful as pharmaceuticals, flame retardants, agrochemicals, specialty chemicals 1 and synthetic intermediates capable of undergoing carbon-carbon bond formation via transmetalation reactions such as Heck, Stille, Suzuki, Sonogashira and Tamao-Kumada reactions. 2 In general, ring brominated aromatics and heteroaromatics exhibit interesting biological activities. 3 Halogen substituted pyrimidines and purines are particularly important for their chemotherapeutic, biochemical and biophysical properties. 4 Apart from their usefulness as fluorophores and potential intermediates for photophysical probes, 5a bromocoumarins are also important as synthetic precursors of furocoumarins and dihydrofurocoumarins that are widely used as photosensitizers and chemotherapeutic agents to combat skin diseases, 5b-d and naturally abundant linear coumarins. 5e Despite their usefulness, scanty work is documented for regiospecific monobromination of coumarins. 5f,g Bromination of activated arenes and heteroarenes is often an unselective reaction resulting in a mixture of mono-and polybrominated derivatives with consequent tedious separation problems and poor atom economy. Therefore, the search for new regioselective methods of bromination has evoked great contemporary interest. Use of NBS for nuclear bromination in polar media such as DMF, 6a MeCN, 6b,c aqueous NaOH, 6d in the presence of acids, 6e,f,g silica gel, 6h zeolite, 6i HZSM-5 6j and isopropylamine 7a is well-documented. These protocols offer different levels of selectivity depending primarily on the extent of activation of N-Br bond in NBS, 6e,f,7a actual brominating species involved 6d and control exhibited by the heterocyclic ring and oxygenated function, if present. 7b,c The increasing use of room temperature ionic liquids as alternative green solvents and catalysts 8 for organic transformations prompted us to evaluate the efficacy of NBS for nuclear brominations of arenes and heteroarenes in tetrabutylammonium bromide (TBAB). 8a,9 Herein we reveal our results in Table 1. Activated aromatic substrates represented by phenols and anilines undergo monobromination at 100°C with paraselectivity in a clean fast process. Gratifyingly, this method gives monobrominated products uncontaminated with di-or tribromo ...
A simple clean expeditious protocol for the deprotection of 1,3-dithianes and 1,3-dithiolanes has been developed using 30% aqueous hydrogen peroxide activated by iodine catalyst (5 mol%) in water in the presence of sodium dodecyl sulfate (SDS) under essentially neutral conditions. The method showed tolerance for a number of phenol protecting groups such as allyl, benzyl, TBDMS, TBDPS ethers, phenolic acetates, and benzoates as well as aminoprotecting BOC, Cbz carbamates without any detectable overoxidation.Protection of carbonyls and their deprotection at some appropriate stage are important transformations often encountered in synthesis of multifunctional natural and unnatural organic compounds because of their ubiquity and remarkable synthetic flexibility. Carbonyls are wellprotected as S,S-thioacetals and -ketals that are easy to prepare and stable enough under basic as well as acidic conditions. 1 1,3-Dithianes are of special synthetic importance as they are versatile acyl anion equivalents and utilized for carbon-carbon bond formation by way of metallation. 2 However, damasking of these procarbonyl derivatives is not always straightforward and often requires oxidative conditions that are marred with side reactions. Traditional cleavage of these protecting groups with mercury(II) chloride 3 or hazardous and polluting heavy metal salts such as AgNO 3 -NCS, 3a AgNO 2 /AgClO 4 -I 2, 4a Tl(NO 3 ) 3 , 4b,c Tl(OCOCF 3 ) 3 , 4d Cu(NO 3 ) 2 , 4e SeO 2 , 4f (PhSeO) 2 O 4g or toxic volatile methyl iodide 5 adds to waste disposal problems. Of the numerous cleavage procedures currently available for these robust two-stage protecting groups, 6 a good many rely on affinity of sulfur towards soft electrophiles generating labile sulfonium ion intermediates which are competent nucleofuges and, therefore, susceptible to hydrolytic ring opening. An alternative tactic is to oxidize 1,3-dithianes and 1,3-dithiolanes to the corresponding sulfoxides or sulfones as a prelude to hydrolytic cleavage. Utilization of hypervalent iodine reagents such as bis(trifluroacetoxy) iodobenzene (BTI), 7 Dess-Martin periodinane (DMP), 8 and o-iodoxybenzoic acid (IBX) 9 for dethioacetalization marked a significant development in view of their low toxicity, mildness, and efficiency. Notably, oxidation reactions with IBX and DMP tolerate the presence of water to a certain level but a large amount of it is reported to be detrimental to their efficiencies. 9d,e In fact, deprotection of 2-methyl-2-phenyl-1,3-dithiane with DMP was very sluggish (48 h) in water. 8 BTI-mediated deprotection releases stoichiometric amount of trifluoroacetic acid that causes removal of TBDPS and olefin isomerization. Cleavage protocols based on elemental iodine [I 2 (1.2 equiv)-AgNO 2 / AgClO 4 , THF; 4a I 2 (3 equiv), DMSO 10 ] have limitations of high cost and explosion-prone nature of the assisting silver salts or loss of products during workup. A recent attempt of catalytic deprotection of 2-phenyl-1,3-dithiane with iodine (20 mol%) in DMSO under neutral conditions 11 wa...
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