Preparation of 2-Bromopentane B. A. Howell and R. E. Kohrman Central Michigan University, Mt. Pleasant, MI 48859
The recent publication of an article on the use of a Grignard reagent in the synthesis of insect pheromones ( 1 J and the subsequent appearance of this experiment in various undergraduate organic laboratory manuals ( 2 4 ) stimulated our interest in the preparation of 2-bromopentane, which is the starting material for the above sequence of reactions. Although the cost (5)of 2-bromopentane in the above experiment is not excessive ($1.48/student based upon $24.351500 g), the educational value of an extension of this synthesis appeared worthwhile. Replacement of a hydroxyl group witb a halide is one of the most fundamental reactions in undergraduate organic chemistry yet the efficacy and scope of the reaction is not extensively discussed in most textbooks. Many texts hint at the potential for rearrangement in reactions of secondary halides but only a few detail the significance of the problem (6). In all but primary alcohols substitution is often accompanied by rearrangement, yet textbook examples are typically of the neopentyl type. What needs to be made apparent in these discussions is that secondary alcohols will afford substantial mixtures of secondary halides in a variety of halide substitution reactions. It is perhaps because of the above problems that undergraduate organic laboratory manuals do not include many alcobol substitution reactions; the reaction of hydrohromic acid with l-butanol, 2-butanol, and cvclobexanol heing among the principal exceptions. We would like to suggest that the preparationof 2-bromopentane from ~ - ~ e n t a & might l repiesent an instructive addition to the previously described pheromone synthesis in that it is economical, it extends the synthetic nature of the problem, and most importantly, it amplifies the mechanistic vagaries of the substitution reaction. However, it should be clearly understood that due to the difficulty of separating 2-bromo~entanefrom 3-bromo~entane.unless the reaeents are carefully chosen and good laboratory techniques em~loved. . . the resultant oroducts will be contaminated with structural isomers. Theory
Historicallv, reaction of 2-~entanolwith hvdroeen bromide gas (7-lo), aqueous mixtures'of sulfuric acid and hydrobromic acid (7,8), and . phosphorous tribromide (7.10). vields mix. tures of the 2-bromo- and 3-bromopentane r&gigfrom 70130 to 9416 depending upon reagents and conditions.
The extent of rearrangement apparently depends upon conditions utilized for the reaction andlor workup (lo),and, indeed, 2-bromopentane and 3-bromopentane may be equilibrated by shaking with concentrated aqueous sulfuric acid solution which yields a 66/34 mixture (11). Essentially this same mixture of products may also be obtained by treating 3-pentanol witb a mixture of aqueous sulfuric and hydro932
Journal of Chemical Education
bromic acids (lo).' The foregoing observation^ can be most simply accounted for bv the initial formation of a carbocation intermediate which may readily rearrange to an isomeric secondary ion of comparahle energy. H,Ot
CH$HCH,CH,CH,
-
F
CH, HCH2KH,CH,
Protonatiou of the alcohol, followed by loss of water, would generate the 2-pentyl cation (111). A 1.2-hydride shift would generate the isomeric secondary 3-pentyl cation (IV). It is known tbat the barrier to 1,2-bydride migration in simple alkyl cations of this kind is small; M kcallmole (12-15). The formation of primary carhocations is not expected. These highly energetic species are simply inaccessible in solution (14-18). Reversion of N to IlIcan occur by hydride migration from either of two carbon atoms adjacent to the cationic center. Therefore, on a statistical basis alone, the equilibrium concentration of ions should contain a 2:l preponderance of the 2-pentyl carbocation. Capture of the equilibrium distribution of carhocation intermediates by bromide ion should afford a product mixture containing 67% 2-bromopentaneand 33% 3-bromopentane. This is precisely the distribution of products obtained when the reaction is conducted under conditions which permit full equilibration to occur. This observation lends strong support to the suggestion that the two possible secondary ions are of comparable energy. Since the rate of reaction of the cations with bromide ion is comparahle to tbat of 12-hydride migration (6). short reaction times should favor the predominant formation of product corresponding to the structure of the particular starting material, either 21 or 3-pentanol. Again this is supported by experimental observation (7-11). A simple two-dimensional reaction coordinate diagram which corresponds to the scheme formulated above may be The exact composition of the product mixture is again dependent upon the specific reaction conditions. The statistical distribution of p.rod~~ is tobtained ~ only when the mixture is in contact with the aqueous acidic medium sufficientlylong for full equilibration to occur. The rate of reaction of the carbocation with bromide ion is comparable to the rate of 1,Bhydridetransfer to generate the isomeric secondary carbocation (for pertinent discussion see ref. (6)).
Convemlon 01 2-Pentanol to 2-Bromopentane
Reaaent HBr (anhydrous)
Overall 2-Bromo- 3-BromoYield pentane pemane (%la
1%)
1%)
13 30
60 59
87 70
PBr3. O0
41°
96
63p& TOSY~ chloridel~vridina:DMSOINaBr
83
99+*
24
99+d
Aqueous (48%)hydrobromic acid NaBrlH,SO, (aq)
. . .a
. . .b
...b
4
. . .e .:
The yields repatad here are not optimum yields but mfiectmoseachieved in an undergraduate bboratay. T r e a m t of Walmhol rhsodim bromide in cmcemated (98%)squaurmHMc acid ~ l Y t i o n a m a mc-imqenwur mixture. When me reaction wasattempred wm viww stlnlng to emve intimate mixing of me raagem, dl(2qewl)emer was omaingl in mm vialo
I Rosress of Reaction
+
Reanion coordinate diagam for Itw conversion of 2-pentanol to a minure of 2- and 3-br~mpentane in aqueous hydrobromic acid. found in the figure. In this formulation the rate-determining activated complex (VII) would have the structure shown below while the activated complex for hydride transfer could be represented as VIII.
mmpleted within one 34- laboratmy session. d S ~ ~ p ~a n lh yod r~~ u~ mnditlons s l ~ must be maintained. NO 3-bromopentane m i d be detected by glpc.
of mixtures of the bromopentane isomers is instructive, we have found that analysis by glpc is the most convenient and satisfactory (26). We have examined the conversion of 2-pentanol to 2-bromooentane bv a varietv of methods (26). Product mixtures were analyze2 hy glpc ;sing a 10 m X 4.65 mm id aluminum rhrncolumn oacked with 10%Aoiezon N on 80-100 mesh ---~ ~-~-. mosorb W,AW operated at b'with a helium flow rate of 60 mllmin. Under these conditions the retention times of the 3-bromo and 2-bromo isomers are 45.1 and 48.9 minutes, res~ectively.~ The results are shown in the table. Based upon these results, we have adopted the treatment of 2-pentanol with phosphorus tribromide as the preferred method for the preparation of 2-hromopentane in our sophomore-level organic chemistrv laboratorv. In terms of cost. ease of operation and quality of product generated, this rep: resents the most suitable choice. The reaction is one that can be safely accomplished in a beginning laboratory and affords a product comparable in quality to that of commercial 2bromopentane. ~
I t must be emphasized that while this simple mechanistic scheme accounts for the exoerimental ohservations in these cases, it neglects any consideration of hydrogen assistance in ionization. ion-oairine.. . ohenomena. or solvation. While hvdrogen pa&ip&on in ionization in &nplesecondary syste&s is often thounht to be unimoortant (15. 19) it olavs a more prominent rile in many, cases (20-23).~~ i r t h k rkhile , hydrogen-bridged species such as VIII have been found, most generally, to represent activated complex structures (191, in certain instances these species have been shown to represent energy minimia, i.e., intermediates (13). Reactions which avoid the formation of cationic intermediates afford only unrearranged '2-bromopentane. Among these is the treatment of the alcohol with triphenylphmphine dihromide (24), a relatively expensive reagent. Pure i-hromopentane may be prepared from the appropriate silver carhoxylate via the Hunsdiecker reaction (9) or from the corresponding carboxylic acid utilizing the Cristol modification (25) of that reaction (26). Bromide ion displacement of tosylate from the 2-pentyl ester under rigorously anhydrous conditions affords only 2-bromopentane (10) and probahly represents the method of choice for preparation of the pure isomer 126). Indeed. under Droner conditions the treatment of 2-pe~takolwith'phosphor& tribromide provides good aualitv .2-bromooentane (26). A related reaction which converw 2-pentanoitoa halohkane via a non-ionic pathway involves the treatment of the dmhol with thionvl chloride. This reaction affords only 2-chloropentane albLit in low yield 110). Methods of analysis of hromopentane mixtures produced bv a varietv of methods include measurement of refractive indices (7,8,26,27), determination of the melting points of anilide derivatives ( 9 ) .infrared spectrosropy (lo), and gasliquid partition chromatography (glpc) (I1,26). Although an analysis which utilizes a measurement of the refractive indices
.
~
~
~
~
~~~
Experimental
The conversion of 2-oentanol to 2-bromooentane offers a good illustration of theproblems which areassociated with substitution in secondarv systems and orovides a focal ooint for the discussion of these riartions in amore meaningfu.1 way than can be achieved in the lecture hall. In addition, it i~ermits the synthesis of insert pheromones ( I ) to be based ubon the inexpensive 2-pentanol as the ultimate starting macerial (5). We have utilized this reaction in the sophom~re-levellab;r a w course for the past six semesters with excellent results. A reasonable yield of product, uncontaminated by excessive amounts of the isomeric 3-bromopentane, can he obtained within the time ronstraints imposed hy a 3-h laboratory period. A detailed description of the procedure utilized is provided below. 2-Bromopentane
In a 250-ml round-bottomed flask is placed 37.0 ml (30.0 g, 0.34 mole) a Epentanol. The flask is fitted with a Liebig condenser bearing Hydrogen participation in the ionization of primary substrates may be very important. For example, it has tong been known that, upon protonation, l-butanol undergoes ionization to afford the 2-bulyl cation
,-~.
123.
Though the separation is not as great, a satisfactoryanalysls can be obtained with a total retention time of less than 10 min using this column operated at 150' with a helium flow rate of 60 mllmtn. Volume 61 Number 10 October 1984
933
a Claisen adapter. One arm of the adapter is dosed with a calcium chloride drying tube while the other is fitted with a dropping funnel hearing a calcium chloride drying tube. The reaction flask is placed in an ice-water bath and its contents allowed to cool to near OO. Phosphorus trihromide (12.0 ml, 34.22 g, 0.126 mole) is transferred to the dropping funnel (caution: phosphorus tribromide reacts with water in the atmosnhere to liberate hvdroaen bromide) and sloaly added tdropwse,s&h that thetempra~ureofthemixturedws not rise ehove lo0) ru the cold 2-pentnnul. The contents of the flask should he swirled rntermittrntly throughout the p e r i d allowed for reartion. When the addition of phosphorus tribrumide is complete, i~ allowed to warm to room temperature o\,er a period of t h mixture ~ approrimstrly 0.5 h. The mixture la then poured onto 100 ml of crushed ire contained in a 600-ml beaker and stirred until hvdrolvsis . . is complete. (caution: the reaction of water with phosphorus trihromide is strongly exothermic and produces hydrogen bromide which must be properly vented o r trapped.) The mixture is extracted with three 30-ml portions of pentane. The pentane layers are combined and washed, successively,with 20ml of cold (O°C) 98% aqueous sulfuric acid solution (caution: concentrated sulfuric acid solution is strongly dehydrating-skin contact should he avoided), 20 ml of water, two 20-ml portions of saturated aqueous sodium bicarbonate solution and 20 ml of saturated aqueous sodium chloride solution. The pentane solution is slowly filtered (dropwise) through a cone of anhydrous sodium sulfate supported by a gh-wool plug in a powder funnel (a small powder funnel filled to about onethird of capacity is sufficient) into a 125-ml Erlenmeyer flask. The bulk of the pentane is removed from the solution by evaporation. The residue is transferred to a 50-ml round-bottomed flask for distillation. A small amount of pentane may he used to rinse the last traces of residue into the distillation flask. Distillation of the residue orovides. after a lrmall forerun of low-boiling material rlargely penmneflammable) has heen collected, a main fraction of the product, 2brumopenmn~,hp llX°C (715torr). If the product i~ tu be used for the preparation of the corresponding organomagnesium reagent, it should be collected under anhydrous conditions; the receiver may be e ahoroteeted with a calcium chloride drvina tube or a small ~ l u of sorbant cotton. ~~~~~~~~
~~~~
~~
~
~
~~
~
~
~
Safety Considerations As noted in the description of experimental procedure presented above, proper attention to safety should be maintained in conducting thisemriment. In addition to the standard precautions (28)required when &ng out any procedure in the organic chemistry laho&ry, particular care should be exercised in handling phosphorous trihromide. In our case, the phosphorous trihromide is maintained in a dispensingpipet in the hood. When the student has the reaction setup in place, he or she brings the dropping funnel to the hood and the appropriate volume of phosphorous tribromide is placed directly into the funnel, which is closed before it is removed from the hood. Each student should he provided a pair of protective gl~ves.~Quenching of the reaction bv oourine the mixture onto ice must he done in the hood. If a hood is unavailable, addition of water can he made directly into the reaction flask via the dropping funnel. In this case, the hydrogen bromide evolved may be trapped using a trap of standard design (29,30).Removal of solvent from the product mixture has been done by evaporation on a steam bath in the hood. In laboratories suitably equipped, solvent removal by rotary evaporation is an excellent alternative. Distillation of the product is best accomplished using a heating mantle as a heat s o u r ~ e . ~
934
Journal of Chemical Education
Acknowledgment T h e interest, enthusiasm, and assistance of members of t h e CHM 547 class of Winter term 1978 (Rebecca A. Haaksma, Rohann Mateja Black, Dong Ok, Erik Walles, Thomas Lillie, Gregory Y e u t t e r a n d Richard Chapman) is gratefully acknowledged. Lnerature Clted (1) Einten, R M., Pander, J. W.,and k o x , R. s., J. C m . EDEDUC.,~~, 382 11977).
(2) Ault.A.,"Tshruquee and EipeM1entsfm OlgmicChemiatry,"AUpand Bacon, Inc. New York, NY, 1979,p. 403. (3) I m o i . R. S.. and Criasman, J. K.. "Laboraton, M s n d for O w i c Chemistri," WadavorthPublishing Company.Belmont. CA, 1979,PP. 7W1.87-88 (4) Durst, H. D..and Gokel. G. W.."Erpnmatal Organic Chemistry." McCm-HillBook Company, New York, NY. 1980. pp. 296301. (5) "Catalog-Haadbook of Pine Chemicals," Aldrich Chemical C o m p y . Milwaukee, WI. 1980.p. 156. (Commercialmaterialisdesrribedaabing97%2-bromopentans. The cast per student may inaesse aubafantially in the near future. At present, 2-bro. mooenlane is not available from Aldrich. We have been m u r e d that Aldrieh will
omone cxpsriment is $4.75/atudent) (6) Streit%eser. A,. Jr.. and Hcathemk,C. H.."lntmductiontoOrganiiChhmihtry.(.bd d.. Maemillan Publishing Company, h.New . Ymk.NY. 1961,~. 250. (7) Shemill, M. L., Bsldwin, C., and Haas,D.,J Am,. C k m . Soc., 51,3034 (1929). (8) Lever, W. M., and Stdola, F.H., J. Amor. C k m . Sm., 66,1215 (1934). (9) Caaon. J.. and Mills, R. H., J.Amor. Chem. Sor.,73,1354 (1951). (10) Pinea, H., Rudin, A., and Ipatieff.V. N., J. Amer. Chem. Soe.74.1063 (19521. (11)Cason, J..snd Coneia, J. S., J. 0rg Chem, 26,3645(1961). (12) Ssundcrs. M., Hagan, E L., aad Rmnfeld, J., J.A m r . Chem. Soe..HI,6882 11968). (13) (a) Ausloos. P.. Rebbert,R E..Siezk. L. W., and'heman.T. 0.. J. A m r Chem Sw.. 94,8939 (1972): (b)Dannenberg. J. J . , G o l d b - , B J.,Barton, J. K.,DiU,K., Weinluunel, D. H., and Longaa, M. O., J Amer. Chem Soc.,l03.7764 (1981). (14) Lowy, T. H., and Richardson, K. S., "Mechanism and Thmw in OrgmicChcmistri." 2nd d.,Harper and Row Publishera.Ine.. New York, NY. 1981,Chap. 5. (15) Carey, F. A,. and Sundberg. R. J.. '"Advanad Organic Chemistri, Part A: S m e t u r s and Mechanism: Plenum P v b l i i n g Corporation, New York. NY. 1917,~~. 236
241. (161 Ref. (6),p. 176. (17) Amet1.E M..andPetm.C., J. Am?. Chem Sa.,lW.&W8(ls?S),andrsf~neeaeited therein.
(IS) Brown. H.C.,%
N o n d m i d lonPmblrm,"Plaum Pvbhhing Caporation, New
York. NY. t977.p. 67. (191 Olah, G. A,, and White, A. M., J. Amsr Chom. Soe..91,5801~1969).
(20) Reber.D. J..Neal, W. C., J~,Duliee,M. D..Hanis,J. M..and Mount,D.L., J. Amsr. Chem Sor.. IW. 8147 (1978).and referenrmeitd the&. (21) Shiner, V. J., Jr., and Jewett, J. G., J. Amer. Chem. Sw..87,1382 (19651. (22) Collins. C. J., and Bowman, N. S., (Editors), "laotop Effstain ChwidRcactiona." Littan Educational Publi~hiag,he., New York. NY. 19'70,Chsp.. 2,3. (23) Whitmore, F. C., J Amer Chem. Soc., 54,3274 11932). (24) Wiley, G.A., H e m h k m i h , R L..Rein.B. M..end Chung,B. C.,J Amor Chom. Sw., 86.964 (ISM). (25) Cristol, S. J., and Pirth, W. C., J Org. Chem..26,280 (1961). 126) Howell, R. A,, HsaLws,R. A,, and Kohrman. R B., Abatmm, 34th Fall Seisntiflc Meeting of the Midland Seetion of the American C h e m i d Society, Midland. MI. November, Is?& No. 30. 1271 .~. Lucas. H. J... Simoaon. . . T. P... and Carter. L M.,J. Amar Chom. Soc, 47, 1492
c~sis).
128) . . "Safetv in Academic Chrmiatrv Laborbotodea," hericm Chemical Society, Waah-
ington.DC, lW6. (29) Roberts, R.M..Gilberf J.C..Rodadd,L.B.,and Wingrove,A. S.,"Madmhperimental Organic Chemis~y."3rd 4. Halt, . Rinehm, and Winlton, New York, 1979. p. 130. (30) Pavia. D...I Lampman.O. M,and Kriz, G. S.. Jr., "Intmductictito Olganic Labortaw Techniques: A Contsmpmary Approsch.(. W.B.Seundem Company, Philadelphia. 1976,p. 189.
Inexpensive,disposable PVC glavailable from Fisher Scientific Company are suitable. undergaduate lnexpenslve Thwmowell mb suitable fa use in ucanic chemistry laboratory are available from Laboratoly Craftsmen, EIarteiIs Drive, &loit, WI ~ n i .2925 ,
