In the Laboratory Electrophilic Anti Addition of Bromine to 2 Methylbut 2 ene with the N Methylpyrrolidin 2 one Hydrotribromide Complex W Jean Fran ois Berrien Olivier Provot Delphine Joseph and Alain Bekaert Laboratoire BIOCIS UMR 8076 U F R de Pharmacie Universit Paris Sud 5 rue J B Cl ment 92296 Ch tenayMalabry cedex France olivier provot chimorg u psud fr Despite the fact that bromine is very toxic by inhalation highly corrosive and may cause serious burns its electrophilic addition reaction continued to be featured in the second year laboratory course at Paris XI University It had customarily been performed by the addition of a solution of bromine in chloroform to olefinic compounds such as 2methylbut 2 ene 1 The laboratory exercise also required two liquid purification techniques liquid liquid extraction followed by two kinds of distillation Furthermore preparation of the chloroform solution of bromine 8 required manipulation of large quantities of bromine and even the use of the resulting solution could not prevent bromine fumes Moreover the addition reaction of bromine to 2methylbut 2 ene is an exothermic process inducing evaporation of olefinic compound and therefore decreasing the overall reaction yield For safety considerations we proposed that bromine no longer be used and be replaced in the student laboratory by another brominating agent CH3 N CH3 O 2 MeOH Br2 HBr N O HBr3 HBr3 2 Scheme I Reaction to prepare MPHT H3C H H3C CH3 2 methylbut 2 ene N CH3 N O HBr3 2 O HBr Br2 2 MPHT H 3C H3C Br H CH3 Br 2 3 dibromo2 methylbutane Journal of Chemical Education Synthesis of the MPHT Complex To a 2 L round bottomed flask cooled in an ice bath and equipped with a dropping funnel and a condenser were added successively 200 mL of MeOH and 250 mL one drop per second of a commercial solution of HBr 30 in acetic acid while maintaining the internal temperature between 10 C and 15 C Molecular bromine 60 mL was then added by the dropping funnel 2 drops per second The solution was stirred for 10 minutes and the crude brown mixture became orange Commercial N methylpyrrolid 2 one 250 mL was then added by the dropping funnel 2 drops per second After 10 minutes the MPHT complex started to precipitate in the media The mixture was stirred for 1 hour at 10 C and orange crystals were collected dried washed with Et2O 4 50 mL and dried under vacuum to give 440 g of MPHT as orange crystals yield 87 mp 122 124 C lit 2 mp 124 C IR cm 1 3339 2935 1640 1420 1228 1011 962 850 Scheme II Reaction of MPHT with an olefin 1348 Experimental Procedure We simplified the Daniels Chiddix and Glickman procedure 2 to develop a reaction that could be easily performed in typical laboratory settings MPHT CH3 In our university molecular bromine has been substituted by the N methylpyrrolidin 2 one hydrotribromide complex MPHT ref 2 whose crystalline data have been recently published 3 This orange crystalline complex has been prepared by an experienced chemist in large quantities following a slightly modified version of Daniels procedure ref 2 Scheme I The MPHT complex is a stable solid that can be stored several months at room temperature after a six month storage test at room temperature no decrease in the free bromine titer could be detected MPHT is not corrosive not necrosing less toxic and easier to handle for students than molecular bromine This complex smoothly liberates bromine in organic solvents according to Scheme II The addition reaction was performed at room temperature in dichloromethane using 2 methylbut 2 ene Discoloration of the resulting orange solution could be observed by students as long as MPHT is consumed N Methylpyrrolidin 2 one hydrobromide and N methylpyrrolidin 2 one are byproducts of the reaction and are removed by washing the organic layer with water Over a one year period the majority of the 230 students successfully completed this experiment with overall yields ranging from 35 to 80 Vol 81 No 9 September 2004 www JCE DivCHED org In the Laboratory 1H NMR 200 MHz CDCl3 2 25 m 4H 2 90 t 4H J 8 0 Hz 3 00 s 6H 3 75 t 4H J 7 2 Hz 14 6 s 1H 13C NMR 50 MHz CDCl3 18 3 31 4 33 3 52 8 178 3 Anal Calcd for C5H9NO 2 HBr3 C 27 33 H 4 33 N 6 38 Found C 27 62 H 4 32 N 6 61 Synthesis of 2 3 Dibromo 2 methylbutane In a conical flask were mixed 4 95 g 7 5 mL of 2methylbut 2 ene 70 mmol and 50 mL of CH2Cl2 To this solution 30 7 g of MPHT 70 mmol was then added with a spatula A discoloration of MPHT was observed after each addition When the addition of the complex was complete the crude organic layer was washed with water 3 150 mL After each extraction it was possible to observe reduction of the volume of the organic layer indicating that Nmethylpyrrolidin 2 one was transferred from the organic to the aqueous layer After drying the organic layer with CaCl2 5 g the crude mixture was distilled at room temperature to collect CH2Cl2 Then the 2 3 dibromo 2 methylbutane was distilled under reduced pressure bp 50 C 18 mm Hg lit 4 bp 49 51 C 18 mm Hg IR cm 1 2979 2934 1450 1377 1098 1051 1H NMR 200 MHz CDCl3 1 90 s 3H 2 05 2 20 d 3H J 6 7 Hz 2 25 s 3H 4 50 4 65 q 1H J 6 7 Hz 13C NMR 50 MHz CDCl3 23 5 28 0 34 9 59 4 68 2 Hazards Bromine is toxic by inhalation very toxic for aqueous organisms and may cause serious burns Bromine must be used with gloves by an experienced chemist in a fume hood and in the presence of a saturated solution of sodium thiosulfate Hydrobromic acid N methylpyrrolidone methylene chloride and MeOH are toxic and contact with the skin or eyes ingestion and inhalation should be avoided Methylene chloride is a suspected carcinogen The use of gloves should be encouraged and when possible all transformations should be carried out in a fume hood For each manipulation of any chemical in the laboratory eye protection is re www JCE DivCHED org quired The toxicity level of MPHT is not actually known as it is a new synthetic complex We suppose the MPHT toxicity is comparable to that of pyrrolidone hydrotri bromide PHT 5 which is supposed to be very toxic by inhalation and in contact with skin and irritating to eyes respiratory system and skin So MPHT must be handled with the same care as PHT that is in case of contact with eyes wash plentifully with water and call a doctor and take off immediately any soiled or splashed clothes Conclusion The ease of MPHT use in bromination reactions together with its crystalline state make it less dangerous than the use of molecular bromine This complex also proved to be