Science
^-Bromosuccinimide chemistry gets a new look Research reveals that the compound not only acts as a source of bromine but generates a free radical via chain reaction in excited state For many chemists, N-bromosuccinimide (NBS) is best known from organic chem istry exam questions where it can be called forth, along with bromine, to brominate a wide range of organic com pounds. The usual explanation is that the molecule acts as a source of bromine, which participates in a free radical chain reaction that uses up bromine and organic molecules and produces brominated products. But NBS not only produces bromine, it generates a succinimidyl free radical; and the chemistry of that radical is be ginning to be re-examined. New ideas on succinimidyl radical chemistry are emerging from the laboratory of Dr. Philip S. Skell of Pennsylvania State University. Recent work by Skell, Dr. James C. Day, now with Rohm & Haas, and others at Penn State show this radical system to be unusual in two ways: It is unexpectedly reactive; and two succini midyl radicals are involved in its chem istry, a ground state and an excited state, each with its own distinctive behavior. In fact, succinimidyl may be the first exam ple, but probably not the only one, of a free radical that can be generated by a chain reaction in the excited state. Undergraduate examinations excepted, the principal use of NBS is in allylic bromination reactions. And the classic reaction conditions, worked out by Dr.
Karl Ziegler in the 1940's, specify carbon tetrachloride as the solvent for NBS. This was an unusual choice, since NBS is only slightly soluble in this solvent. An expla nation, worked out by Skell and Day in 1974, is that there are two different free radical pathways that can lead to the bromination of alkenes. One involving a bromine free radical uses bromine mole cules as the source of bromine for the re action. The other uses a succinimidyl free radical and has NBS as the source of bromine for the reaction. It is to minimize the influence of this second reaction that Ziegler kept the NBS concentration low, Skell and Day concluded. From here, the chemists decided to deliberately maximize the reaction that uses succinimidyl radical. By switching to another solvent, methylene chloride, which allows more NBS into solution, and scavenging bromine with an alkene, they found they could make the succinimidyl radical chain the dominant pathway for the reaction. "No one so far has been able to get any physical evidence for the existence of succinimidyl," Skell points out. "Electron spin resonance, any kind of spectros copy—all these fail. It's entirely on the basis of chemical evidence that we have recognized it." And what is this chemical evidence? "We're getting bromination using NBS with rates of reaction that are completely inconsistent with a bromine radical chain. That leaves only succini midyl," Skell explains. This conclusion was reached simultaneously in 1974 by different routes—by the Penn State chemists and by Dr. James G. Traynham of Louisiana State University. For example, bromine free radicals preferentially react with tertiary hydro gens, followed by secondary ones, and will not react at a significant rate with primary
Succinimidyl radical can add to the aromatic ring of styrene or to the ethylene bond
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C&ENMay 15, 1978
Bromination can occur via two free radical pathways
hydrogens. Following this rule, reaction of η -butane with bromine and NBS gives bromine substitution only at the 2-position. The same reaction using NBS and a bromine scavenger, however, gives 25% bromination of a terminal carbon and 75% bromination of an internal carbon, the Penn State group finds. Similar product ratios occur with N-chlorosuccinimide and N-iodosuccinimide, providing further evidence that it is the succinimidyl part of the molecule that is determining the reaction rate and, hence, the product distribution. These relative reaction rates suggest that the succinimidyl radical is reacting at every collision, Skell says. Succinimidyl radical undergoes some very unusual chemistry, the Penn State group finds. Quite unexpected are the reactions with benzene and other aromatics, which lead to the succinimidation of these arènes. In competition with unactivated alkenes, the addition to benzene is twice as fast, they find. Even with an activated alkene such as styrene, the double bond is only twice as reactive as the phenyl part of the molecule, a most unusual behavior for the reaction of styrene with free radicals. The chemists conclude that the transition states for these reactions resemble the starting materials, not the products—a conclusion that is consistent with a very fast free radical reaction. Some of Skell's experiments point to two different succinimidyl free radicals. These radicals can be formed by two different reactions and react differently in at least two situations. One form is generated by reaction of alkyl free radicals with NBS. The product of this reaction will react preferentially with neopentane in a reaction mixture of neopentane and methylene chloride. It also undergoes a ring opening reaction to become β-bromopropionyl isocyanate. This form Skell calls S;. The other form of succinimidyl free radical is formed by reaction of bro mine free radicals with NBS. This form reacts equally rapidly with neopentane and methylene chloride and does not un dergo ring opening. Skell calls this the Si
form. It is the S2 form of the free radical that reacts so unusually with styrene, he points out. Much of the chemistry of succinimidyl radicals can be accounted for by postu lating that an excited state of the free radical is being generated in the exo thermic reactions being studied, Skell says. He suggests that S2 is an excited state of the free radical with the unpaired electron in a sigma orbital of the nitrogen atom. Si is a ground state configuration with the free electron in the pi orbital. "In principle, this is exactly what you would expect," Skell says. "Anything that is going to exist in the ground state would have a whole variety of excited states as well. But in practice, very little chemistry of excited states of radicals has been studied. And I'm not aware of any radical that has been generated in the excited state in a chain reaction, which is a ther mal reaction. The usual way to make ex cited states is to irradiate the ground state and have it absorb large amounts of en ergy so that radicals jump into their ex cited states. But here, in thermal chain reactions, we can get the excited state species as well as the ground state species." If this model is correct, the S2 radical is of higher energy than the Si form. It reacts more rapidly with substrates than Si does, perhaps reacting with every col lision. A model for its behavior might be the hydroxyl free radical, which is known to react at every collision. For this radical, the ratio of reaction rates at aromatic carbons and olefinic ones is about 4.3, not greatly different from the ratio of 2.0 found for S9. If succinimidyl radical is being gener ated in both a ground state and an excited state in thermal reactions, as Skell suggests, there are likely to be other free radicals that can be generated in their excited states by a similar method. The Penn State group is beginning to look at
Ring opening occurs only with excited succinimidyl
/?~Bromopropiony I isocyantlf
the reactions of phenyl radicals to see if they, too, can be generated in a ground and excited state in chain reactions. The group intends to look at carboxylate rad icals in the same way. If this search is fruitful, then a whole area of chemistry may open up. "Excited state radical chemistry is virtually un known," Skell says. "Chemists just didn't recognize that it was possible to even get at these excited states except by photoactivation. And photoactivation of things that are present at 10~7 or 10~ 8 M, as these free radicals generally are, is al most impossible to do." He sees succini midyl as only the first in a whole family of free radicals whose excited state chemis try may soon begin to unfold. Rebecca L. Rawls, C&EN Washington
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Penn State's Skell explains new thinking on succinimidyl radical chemistry May 15, 1978 C&EN
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