Bromoacetanilide

Bromoacetanilide [103-88-8] M 214.1, m 167 . Crystd from aq MeOH or EtOH. Purified by zone refining. 

Unprotected 3-tetrazolephenylboronic acid 325 was coupled with 4-bromoacetanilide in the presence of PdCl2(DPPF) to afford product 326 in 74% unoptimized yield (Equation 57) <2004OL3265>. 

Bromination in acetic acid now results in monobromination, but it gives a mixture of isomers. Fortunately, steric hindrance by the bulky acetamido group shields the ortho positions from attack to a large extent only about 10% of the 2-bromo derivative is formed. This isomer remains in solution when the mixed product is recrystallized and pure 4-bromoacetanilide is readily isolated. Finally, hydrolysis of the amide function liberates the amino group and 4-bromoaniline results (Scheme 9.4). 

Synonyms. N-(4-Bromophenyl) acetamide 4 -Bromoacetanilide Bromoanilide Antisepsin Bromoantifebrin. 

N - Acetyl JV-chloro - 4 bromoacetanilide Bhombohedra from pet. ether. M.p. 108-9 AcOH. —> 2-chloro-4-bromoacetanilide. 

A soln. of acetanilide in 5 2 methylene chloride/methanol treated with benzyltrimethylammonium chlorobromate(l-) at room temp., and stirred for 20 min - 4-bromoacetanilide. Y 97%. Tetrabutylammonium and benzyltrimethylammonium tribromide were also effective in the presence of methanol, but reaction times were longer (cf. Synth. Meth. 42,471). F.e. incl. dibromination of amino- or hydroxy-subst. acetanilides s. S. Kajigaeshi et al.. Bull. Chem. Soc. Japan 61, 2681-3 (1988). 

Bromoacetanilide is slightly less reactive toward further electrophilic substitution than acetanilide, but it is still sufficiently reactive to be chlorinated under mild conditions without a strong Lewis acid catalyst. Thus, molecular chlorine dissolved in acetic acid chlorinates 4-bromoacetanilide to produce 4-bromo-2-chloroacetanilide (20) as shown in Equation 21.12. The formation of the 2- rather than the 3-chloro isomer demonstrates the more powerful directing effect of the acetamido group as compared to the bromo substituent. 

Setting Up Suspend 500 mg of 4-bromoacetanilide in a stirred solution of 1 ml of concentrated hydrochloric acid and 1.3 ml of glacial acetic acid contained in the conical vial. If necessary, heat the mixture gently with stirring until it becomes homogeneous and then cool the solution to 0 C. Prepare a solution of 150 mg of sodium chlorate in about 0.5 ml of water. 

Discuss the differences observed in the IR and NMR spectra of acetanilide and 4-bromoacetanilide that are consistent with the formation of the latter in this procedure. 

Would 4-bromoacetanilide or 4-bromo-2-chloroacetanilide be more reactive toward electrophilic substitution Explain. 

Bromo-3-chloroacetanilide is a possible product from chlorination of 4-bromoacetanilide. Why is this isomer not produced to any significant extent ... 

Halogenation Electrophilic Aromatic Substitution to Yield 4-Bromoacetanilide... 

Purification and Characterization. Purify all but 10 mg of the crude 4-bromoacetanilide by recrystaUization from 95% ethanol using the Craig tube. Weigh the dried product and calculate the percent yield. Determine the melting point, compare both the aude and recrystallized materials by TLC analysis (plates with fluorescent indicator. Revalue for 4-bromoacetanilide is 0.32 using as solvent system ethyl acetate hexane (2 3), and a UV lamp for visualization purposes), and compare your observed melting point to the value given in the literature. 

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