The NBS Reaction A Simple Explanation for the Predominance of Allylic Substitution over Olefin Addition by Bromine at Low Concentrations Carl C. Wamser Portland State University, Portland, OR 97207 Lawrence T. Scott University of Nevada, Reno, Reno, NV 89557 N-hromosuccinimide (NBS) has long been known as an effective reagent for hromination at an d y l i c position (I ). The mechanism most consistent with the evidence is a free radical chain process hased on hromine atoms and Brz (2,3) illustrated in Scheme I with propene as a typical alkene. Scheme I Overall Reaction:
Propagation Steps: 1) 2)
3)
--
+ CH3CH=CH2 HBR + .CHpCH=CH2 HBr + NBS BIZ + SI BIZ + .CH&H=CHz Br. + BrCH2CH=CHZ Br.
An earlier, somewhat simpler mechanism (4) based upon succinimidoyl radicals as the abstracting species (Scheme 11) has been shown to he inconsistent with many experimental observations ( 5 )under the normal (Ziegler) conditions of the NBS reaction, i.e., CCld solvent at reflux. Scheme N Overall Reaction: (same as Scheme I) Propagation Steps:
trations of Brp do in fact give increased yields of allylic suhstitution products a t the expense of addition products (7,s); however, one would still like to understand why. Other textbooks provide brief rationales hased upon reversihility arguments (9),and one textbook offers a qualitative argument hased on kinetic order that implies a competition between electrophilic hromine addition and radical hromine substitution (Ion). We present here the derived rate laws for three possible reactions of molecular hromine with an alkene: (1) free radical allvlic suhstitution. (2) free radical addition. and (3) electroph~l~c additwn. Under the normal (Ziegler) conditions of an NBS reaction 1C'C'la . . solvent at retlux), . . ambient hromine concentrations are very low, and the expected rate laws show the following kinetic orders: (1)free radical suhstitution, 112-order in Brz; (2) free radical addition, 3/2-order in BIZ; (3) electrophilic addition, first-order in BIZ. All three processes necessarily decrease in overall rate as Brz concentration decreases; however, free radical suhstitution follows the lowest kinetic order (i.e., decreases the least rapidly) and therefore becomes the predominant pathway for reaction of an alkene with Brz a t very low concehtratioris. Klnetlcs of Radlcal Substitution Free radical halogen suhstitution follows a classic chain mechanism involvine the stem shown in Scheme 111(1I ). Note that the two propa&ion stkps for substitution arethe same as two of the stens included in the Scheme I mechanism for NBS suhstitutio~ Scheme 111 Initiation:
Br2
Termination:
2Br
Propagation-substitution: 1)
Teachers who present the currently accepted mechanism (Scheme I), however, are haunted by the persistent question; "If Brz is involved, why doesn't it add to the double bond?" After all, decolorization of Brz in CCld is the classic test for unsaturation. Underlying this problem is the more general question: What factors govern the reaction of Brz with an alkene, to give either allylic suhstitution or double hond addition? This question has heen treated very unevenly in organic shrmistry tbxtl~,oks,at both l,eginningand advanced levels. Many texthooks simplv aswrt (without explnnntion) rhnt low concentrations of Biz favor substitution-over addition (6). There have been experimental reports that very low concen650
Journal of Chemical Education
Br.
+ CHa-CH=CH2
-
-
2Br
(hi)
Brz
(kt)
HBr + CHrCH=CH2
(kl)
The kinetics for this chain mechanism depend on the termination step which is operative (11). Termination steps are radical-radical combination reactions, and the predominant termination step will he determined by the relative concentrations of the different free mdicali iresent in the system. E'or simple nlknnv bruminations hg Hr, in the gas phase, terminatioi by recombination of two hromine atoms has heen established (12,13). This is consistent with the relative energetics of the two propagation steps, which may he calculated from hond dissociation energy data (lob). Step 1is typically endothermic while step 2 is exothermic. Thus hromine atoms react more slowly than alkyl radicals, the predominant free radicals present are hromine atoms, and the most likely termination is by combination of two hromine atoms. With this termination step, the rate law derived from Scheme 111 is as follows ( l l , l 2 ) :
The applicability of this rate law to NBS hromination of alkenes requires several assumptions and clarifications. Inclusion of step 2 from Scheme I, reaction of HBr with NBS to form Brz and succinimide, is not expected to affect the kinetics since that reaction is extremely rapid (14). This rapid scavenging of HBr by NBs also precludes reversibility of the first propagation step (Scheme I, step 1). The last propagation step (Scheme I, step 3) is substantially exothermic and has not been found to he significantly reversihle under any circumstances (13). For the kinetics of NBS suhstitution, therefore, we will consider all of the propagation steps to he effectively irreversible. This is a critical point and will become the basis for differentiating the kinetics of the radical suhstitution and addition mechanisms. Assignment of the appropriate termination step for NBS hrominations of alkenes is more problematic than for simple alkane hrominations by BIZ. For substitutions a t allylic or other reactive positions, propagation step 1 is no longer endothermic hut is thermoneutral or slightly exothermic. Step 2 (Scheme 111) remains exothermic, hut the clear difference in energetics between the two propagation steps is obscured. For BIZ bromination of a comparably reactive hydrocarbon, toluene, termination has been demonstrated t o occur predominantly via henzyl radicals, rather than via bromine atoms (13). Furthermore. NBS conditions involve verv low Bro concentrations which sht,uld slow propagation step 2 and increase the lifetime of thr alkvl radicals. Actual ex~erimental determinations of the kinetics of NBS hrominations in CC14 have never heen reported. The onlv reported rate law is for NBS hromination-of cyclohexene inehenzene solution a t 20-40°, initiated by added azohisisohutyronitrile (AIBN) (15). The rate law shows a first-order dependence on alkene and half-order dependence on initiator, which is consistent with termination via bromine atoms rather than allylic radicals. We will use Scheme 111and eqn. (1)to describe the suhstitution kinetics for bromination in the presence of NBS. To the extent that there are additional termination steps involved, the kinetic order in Bm may he higher. Termination solely via allyl radical combination would lead to a 312-order dependence on Bra (zero-order in alkene), and termination solely by cross-combination would lead to a first-order dependence on BIZ (%-order in alkene) (11,12). Klnetlcs of Radical Addition Free radical addition t o double bonds also follows a wellestablished chain mechanism involving the two propagation steps shown in Scheme IV (12,16,17). The same initiation and termination steps as for radical substitution are operative. Kach of the two steps is typically exot her& and overall addition of Hrd toa double bond generally is thermodynamically more favomblr than allylic substitution. Thus any favoring of suhst~tutionover addit~onmust involve kinetic rather than-thermodynamic control of the reaction. Scheme IV
Propagation-addition: 3) BP
+ CHrCH=CH2
Considering the limiting case of very low Brz concentration, where k-3 >> k4[Brz], the effective kinetic order for radical addition will he 3 / ~in BIZ (eqn. (3)). Rate (addn) = (ki/kt)1/2(k3/k-3)k~[CH3CH=CHz][B~2]3J2 (3) Under these conditions of decreasing. Br2 .concentration, radical addition will decrease in rate more rapidly than sub: stitution hecause addition follows a hiaher kinetic order. Alternatively, we may consider the ratio of substitution to addition (eqn. (4) = eqn. (1) + eqn. (Z)),which shows an explicit dependence on the concentration of BIZ;that is, greater suhstitution a t lower Brz concentrations. An analogous equation has heen derived (2a, 22) and demonstrated to correlate the experimental ohservations (23.24) for the case of allylic chlorination of propene, an important industrial process.
Identical termination steps (via Br.) have heen agswned for both the radical addition and the radical substitution reactions. If other steps are involved, there will he parallel effecta on the two rate laws. Klnetics of Electrophllic Addition The rapid decolorization of Br2 in CC4 solution is a familiar test for unsaturation (25). The mechanism for addition in oolar solvents is well estahlished as a two-step ionic process i26'); however, recent investigations have dem.onstraied that bromine addition in CCb follows a two-part rate law, including terms iirst-order in alkene and hoth first- and serond-order in Br2 (27). Scheme V illustrates the mechanistic steps which lead to the observed combination rate law. The first (overall second-order) term is analogous to that observed for most electrophilic additions (28). In the case of bromination in CC4, the evidence points to initial reversible formation of a charge-transfer complex between Brz and alkene (equilibrium constant Ks), followed by dissociation as the rate-determining step (ks). The unusual third-order term indicates that there is a mechanistic pathway in which a second molecule of Br2 is kinetically significant. This effect reflects the possibility for assistance in the dissociation of the initial BIZ-alkene complex in a nonpolar solvent; a second m o l e d e of Br2 allows formation of the bromocation plus Bre(k7). Scheme V
CH3CH=CH2
+ Brz F. [CH&H=CH%...Brz]
Rate (addn) = Ks(CH3CH=CHz][Brz](ks + k7[Br2])
-
4) Brz + C H ~ - ~ H - C H ~ B ~ CHa-CHBr-CHzBr
+ Br . (ha)
Abundant evidence can he found for the reversibility of bromine atom addition toalkenes (7.18-21 J. Acrurdinalv. the reversal of step 3 in Scheme IV (rate constant k-3) &it be taken into account when analyzing the kinetics of radical addition. Doing so leads to the rate law given in eqn. (2).
(5)
Considering the limiting ease of very low BIZ concentration, where kg >> kv[Brz] in eqn. ( 5 ) ,the kinetics for electrophilic addition will be first order in Brg (eqn. (6)). Rate (addn) = k&[CH3CH=CH2][Brz]
~ c H ~ - & H - c H ~ B ~(k3,k-3)
(K5)
(6)
Under these conditions of decreasing BIZ concentration, electrophilic addition will decrease in rate more rapidly than substitution because addition follows a higher kinetic order. An Estlmate of the "Low" Concentration of Bromine Although it is generally accepted that NBS allylic suhstitution reactions owe their success to the maintenance of a low steady-state concentration of Brz, estimates of that steadvstate concentration are not found in the literature. ~ e a s u r a b i e Brz concentrations are observed when NBS is used for hromination of relatively unreactive compounds (without allylic hydrogens). For example, the rapid development of a yellow Volume 62 Number 8 Augwt 1985
851
M Br2Jwas r e p u r t ~ dduring irradiation of NHS color 15 X in CHICILor C H K N solvent (2.91. During the bromination of l-hromohutane bv irradiation uf a 0.1 A l N H S solution in M Br2 was CH2CI2,steady-state concentration of 7.5 X observed; in fact this system holds a remarkably steady concentration of Brz through 85%of the reaction period, called "hromostasis" hv the authors (14). . . In the Dresence of alkenes, however, the reaction mixtures are free of discernible Brz (29). The lack of discernible bromine can be estimated to correM; given the exspond to a concentration of less than tinction coefficient of 206 M-'cm-' at ,A, = 415 nm, a lov4 M solution of BIZwould show a discernible absorbance of 0.02 for a l-cm path length. This very low steady-state concentration of Brz in the presence of alkenes has at least two interesting implications. The first deals with the Brz decolorization test for unsaturation. Electrophilic addition of Brz to alkenes is indeed rapid and effective at normal (discernible) Brz concentration. The reported kinetics for reaction of typical alkenes with Brz in CC14 indicate that the kinetics shift from second-order to first-order in Brz in the range M to 10-4 M (30). Only after the Brz concentration has been reduced below discernible levels (i.e., decolorized)does the electrophilic addition become increasingly slow and eventually less competitive with allylic substitution. A second important implication of the low steady-state Brz concentration is that the steady-state NBS concentration must also be kent verv low in order to avoid the succinimidovl mechanism (Scheme 111. Alkyl radicals have been estmated t o react lod times faster w i t h Hr, than with NBS (361; however, if Brz is extremely scarce, abstraction from NBS rather than Brz becomes feasible. The specific use of CC4 as solvent is important here; in CC4 the solubility of NBS is only 6 X M at room temperature (29); furthermore, it has been suggested that the rate of dissolution may be too slow to maintain a saturated solution (14). Thus, in order to favor the Br2 chain (Scheme I) over the NBS chain (Scheme II), a steady-state concentration of Brz of only about 6 X M is required. As a final note, it should be mentioned that the Scheme I1 (NBS chain) mechanism has been forced under certain conditions, specifically the use of a solvent such as CHzClp - which provides high NBS concentrations and the addition of specific s~!avt~nyers which reduce the concentration oi iree Br2 and HBr (3.29.321. Summary Under the normal conditions of an NBS bromination, that is, C C 4 solution with very low concentrations of Brz as the active brominating agent, addition to a double bond cannot compete kinetically with free radical allylic substitution. Substitution follows a half-order de~endenceon Brl concentration. Radical addition alsocannot compete effectively with subsrirutivn because t h e initial bromine atom addition to a double bond is reversible, and that reversibility becomes increasingly important at lower Brz concentrations; the effective kinetic order in Br2is 3/2 under these conditions. These
652
Journal of Chemical Education
kinetic effecu explain the high selectivity of NBS for allylic hromination, even though frec Rr2 is the active brominating agent, and even though-the addition products are typicall; more favorable thermodynamically.
Acknowledgment Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for partial support of this work (CCW). LTS gratefully acknowledges financial support from the National Science Foundation.
Literature Cited (I,
18
.
Z~rxlcr.K Spdth. A . S
