RESEARCH
CIDNP theory evolves at symposium Scientists seek basic understanding of changes in NMR spectra during free radical reactions ORGANIC Organic chemists can now add another technique to their bag of analytical tools: chemically induced dynamic nuclear polarization (CIDNP). Most of the scientists who have explored this new phenomenon since its discovery in 1967 were represented at a two-day symposium on CIDNP to compare applications of the technique and—perhaps more important at this time—to try to reach some agreement on its theory. There is one major enticement to try the new technique: No new instruments are needed. CIDNP effects are observed with ordinary nuclear magnetic resonance spectrometers. The only requirement is that free radical intermediates must be involved in the chemical reaction. Unpaired electron spins interact with the spins of nuclei such as protons in organic molecules to change the intensities of NMR absorption peaks and to produce NMR emission peaks—the most distinctive indication that CIDNP is being observed. Papers presented at the Houston symposium showed that CIDNP effects can be used to provide several types of information about organic reaction mechanisms: • The altered NMR spectra of reaction products result from interactions between pairs of "caged" radicals, even though these intermediates maybe present too briefly or in too small a concentration to be detected with an ESR (electron spin resonance) spectrometer. • Products formed from singlet or triplet precursors can be distinguished by their characteristic CIDNP spectral patterns. • In exchange reactions where products are chemically identical with reactants, CIDNP effects indicate that a reaction is occurring and provide information about its mechanism. • CIDNP effects show that chemical reactions can be influenced by nuclear spins. Concern. The mechanistic information derived from CIDNP observations depends on the theory used to explain CIDNP. A fundamental un36 C&EN MARCH 9f 1970
derstanding of nuclear polarization was thus a major concern of symposium participants. By the time the symposium ended, what might be called the Kaptein-Closs theory seemed to have won general acceptance. An NMR absorption peak is produced when radio-frequency ( R F ) energy from the spectrometer causes a nucleus to change from a low-energy "spin state" (nuclear spin parallel to the spectrometer's external magnetic field) to a spin state of higher energy (nuclear spin antiparallel). The intensity of the absorption peak depends on the population of nuclei in the lower spin state as well as in the higher spin state. Equal populations would give no net absorption. If there were a greater number of nuclei in the higher spin state, RF energy from the NMR spectrometer would stimulate emission of energy when "tuned" to match the energy difference between the upper spin state and a lower less-populated spin state. This stimulated emission effect observed with CIDNP is analogous to the stimulated emission of light by a laser. When CIDNP is observed, the magnetic field of an unpaired electron seems to "couple" with the magnetic field of a nucleus resulting in a nonequilibrium population of nuclear spin states. The free radicals of interest are produced during chemical reactions. The nuclear polarization resulting from dynamic processes is thus referred to as being chemically induced; hence the term CIDNP. CIDNP was first observed in 1967 by two groups of investigators. Dr. Hanns Fischer and Dr. Joachim Bargon, then at Technische Hochschule, Darmstadt, West Germany, saw NMR emission and enhanced absorption lines during rapid thermal decompositions of organic peroxides and azo compounds. Dr. Harold R. Ward and Dr. Ronald G. Lawler at Brown University, Providence, R.I., reported similar effects during reactions of alkyl halides with alkyl lithium compounds. Dr. Ward and Dr. Lawler point out that two different types of CIDNP phenomena have been observed. One type exhibits "net polarization," in which
the amount of RF power emitted or absorbed by a set of magnetically equivalent protons is much greater than that absorbed during an NMR experiment with nuclei in the normal equilibrium spin states. In the earlier and now revised view of Dr. Ward and Dr. Lawler, net polarization was explained by theories of dynamic nuclear polarization that preceded the discovery of CIDNP, and by analogy with the Overhauser effect of nuclear spin state changes induced by microwave radiation. Donors. Net polarization was observed in reactions of peroxides with atom donors originally reported by Dr. Fischer. Thermal decomposition of dibenzoyl peroxide dissolved in cyclohexanone, for instance, gives an NMR emission line from the product benzene. The emission is thought to result from the intermediacy of phenyl radicals that acquire hydrogen atoms from the solvent to form benzene with protons in nonequilibrium spin state populations. Net polarization for equivalent protons has also been observed in other thermal decompositions and rearrangements, in photochemical reactions, and in reactions of organolithium reagents with alkyl dihalides. The second type of CIDNP phenomenon described by Dr. Ward and Dr. Lawler is characterized by the "multiplet effect." Multiplet patterns in normal NMR spectra occur when the energy levels of absorbing protons are altered by interactions with the spins of nearby protons (spin-spin coupling). In the CIDNP multiplet effect, unpaired electron spins interact with nuclear spins; some absorption lines are enhanced and others are changed to emission lines. As a rule, the scientists say, "for each strong absorption line, there is a strong emission line in the multiplet/' Dr. Ward and Dr. Lawler explain the multiplet effect by a process they refer to as "nuclear spin selection," in which nuclear spins influence the products of a chemical reaction involving free radicals. They envision the reaction of an alkyl iodide and an alkyl lithium, for example, to proceed through formation of a radical pair in a "primary cage." The singlet (electron spins paired) and triplet (electron
spins unpaired) electronic states of the pair of radicals in the solvent cage are believed to have nearly the same energies. With energy differences small enough, a small magnetic field arising from the coupled interaction of an unpaired electron with nuclear spins might be enough to induce transitions between triplet and singlet electronic states. In particular, it is the rate of these transitions that might be influ enced. If only singlet states lead to reaction products—which is likely—the result is that nuclear spin states influ ence the length of time two radicals stay in the singlet state and thus in fluence the probability of getting product molecules from that state. Control rate. In the example of alkyl iodides and alkyl lithiums, Dr. Ward and Dr. Lawler propose control by nuclear selection of the rate at which disproportionation products (olefins and saturated hydrocarbDns) are produced from the singlet sta:e of the caged radical pair, and the rate at which chain transfer products (iodides of both alkyl groups) are produced from the triplet state. It is these product alkyl iodides that exhibit the CIDNP multiplet effect. Dr. Fischer's quantum mechaiical approach, however, led him—before
the symposium—to reject the term CIDNP in favor of chemically induced spin selection (ciss). However, his treatment still doesn't rely on the Overhauser effect, but instead postu lates the sudden formation of a pri mary caged radical pair with spin states determined by the spin states of the reactants. In a second step, the spin states of the caged radical pair develop adiabatically (energy levels changing slowly enough to al low mixing of states) to give products or free uncaged radicals. Bonding spin states invoking specific nuclear spin configurations lead to products, and antibonding states with other nu clear spin configurations lead to free radicals. The free radicals then go on to form transfer products by sud den reaction with other chemical spe cies in solution. Dr. Fisher has now returned to the term "chemically induced dynamic nuclear polarization," reflecting the conclusion that the symposium par ticipates were really using only dif ferent terms to describe the same phe nomenon. Dr. R. Kaptein at University of Lei den, the Netherlands, and Dr. Ger hard L. Closs at University of Chicago have developed similar theories for nuclear polarization that explain both
types of phenomena described by Dr. Ward and Dr. Lawler. The KapteinCloss theory also goes beyond any re quirement of primary cage formation. CIDNP effects are still thought to re quire radical cage formation, but "sec ondary" cages formed in later steps of chemical reactions may also permit changes in nuclear spin state popula tions. The theory thus accounts for CIDNP effects in coupling products from radicals generated separately, as well as in products from radicals gen erated in pairs from either singlet or triplet precursors. Mixing states. The Kaptein-Closs theory relies on mixing singlet and triplet electronic states through hyperfine interactions between nuclear and electron spins. Interactions be tween an electron's spin and its orbital energy are also important as they af fect electron spin and thus nuclear spin polarization. Dr. Closs feels that these spin-spin and spin-orbital in teractions can account for both net enhancement (or absorption) and the multiplet effect. He rejects the Overhauser effect as an explanation for "net polarization" for several reasons: • The Overhauser effect requires an external magnetic field, whereas Dr. Closs' theory bases the development
"Multiplet effect" shown by promts of alkyl iodide-alkyl Hthium reaction
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MARCH 9, 1970 C&EN 37
of CIDNP effects on magnetic inter actions within a radical pair. • The Overhauser effect involves one unpaired electron, but two un paired electrons are involved in pro ducing nuclear polarizations. • Nuclear polarization involves only the x,y components of nuclear and electron spin, whereas the Overhauser effect also involves the ζ component (in the direction of the external mag netic field). Dr. Closs and his coworkers find that their theory successfully accounts for CIDNP effects they observe in 1,1,2-triarylethanes formed as coupling products from benzhydryl and benzyl radicals generated by the three dif ferent reaction paths. The triplet precursor route proceeds from photo chemical formation of triplet diphenylmethylenes followed by hydrogen ab straction from toluenes. Thermal de composition of the corresponding azo compounds gives singlet precursors. To generate benzyl and benzhydryl radicals separately, benzoyl peroxide is used to abstract hydrogen from mixtures of diphenylmethanes and toluenes. Random spins. Nuclear polariza tion in the product triarylethanes falls into the two categories that Dr. Ward and Dr. Lawler term "net polarization" and "multiplet effects." Triplet pre cursors give net polarization; singlets lead to multiplets with no net polariza tion. Radicals generated separately give net polarization, but of smaller magnitude than when the product comes from triplets. The smaller extent of polarization can be explained by random orienta tion of spins before the separate radi cals collide, Dr. Closs says. After collision to form a radical pair, for mation of coupling product from the singlet state gives an increase in triplet character of the remaining pairs. Most of the eventual product polariza tion thus reflects formation from the triplet state, but not to the extent ob served when all of the radical pair precursors are triplets. Dr. Kaptein and Dr. L. J. Oosterhof at Leiden have emphasized spin-spin interactions in a radical cage. The two scientists provide experimental evidence for the cage nature of the nuclear polarization mechanism by predicting CIDNP effects in thermal de composition products from biacetyl peroxide enriched in carbon-13. Ther mal decomposition of cyclohexanone diperoxide, a cyclic molecule, gives CIDNP multiplet patterns resembling those with alkyl radicals from biacetyl peroxide. The intramolecular biradicals formed with the cyclic peroxide are necessarily "caged" and thus pro vide a model verifying caged inter action of alkyl radicals. 38 C&EN MARCH 9, 1970
New method makes possible nonbleeding indicator paper ANALYTICAL
When every meeting of analytical chemists now brings news of more highly automated analyses and new forms of spectroscopy, no one expects to hear of a breakthrough in litmus pa per. But Dr. Gunter Scheuerbrandt presented something very like this. Speaking of work by Dr. Karl-Heinz Neisius and Dr. Wilhelm Baeumer in laboratories of E. Merck, Darmstadt, Germany, Dr. Scheuerbrandt described a method to attach dye molecules by covalent bonds to cellulose to make a nonbleeding indicator paper. Using techniques developed by Dr. E. Pfeil, Marburg University, Ger many, the Darmstadt chemists form 2-sulfoxyethylsulfonyl derivatives of dyes. Treatment with sodium hydrox ide gives a vinylsulfonyl dye, which re acts with hydroxyl groups of cellulose to form a sulfonylethyl ether link to the paper (see illustration). They also fix dyes to cellulose powder to give an insoluble indicator powder for titra tions. In preparative work, a solution may be adjusted to a desired pH, says Dr. Scheuerbrandt, and the indicator powder filtered away. The pH papers can be used to de termine pH's of weakly or nonbuffered solutions, according to Dr. Scheuer brandt. Ordinarily, nonbuffered solu tions need long immersions for color change, and dyes can bleed into solu tions. Also, a chromatographic effect causes dyes to creep on paper, form
ing zones of uneven color. These dif ficulties are removed by using covalently bonded dyes, he says. Dipping. The German investigators measure pH in turbid suspensions by dipping the paper, then washing off insolubles with distilled water to see the color change underneath. The wash does not cause immediate rever sion to the color which would signify pH7, says Dr. Scheuerbrandt. In fact, although color change is instantaneous in registering pH of 3 in a prepared solution, he says, it requires four minutes in a second solution at pH of 12 to change the color to that value. Performance of the pH papers is un affected by presence of proteins or other quaternary ammonium salts, says Dr. Scheuerbrandt. pH of serum can be measured in seconds, he says. These substances usually cause errors with other indicator papers, and Dr. Scheuerbrandt reminds his listeners that there is actually a clinical method for determination of protein in urine using ordinary indicator papers, based on the degree of error the protein causes. He sees applications of the covalently dyed paper to biochemical research and in industrial laboratories for routine determinations in complex solutions. For the future, the Darmstadt men see great possibilities for the technique in making materials for chromatogra phy. Substances with different prop erties can be made to pass through a permanently dyed medium that gives local color changes to reveal their presence, yet the dyes themselves would not be eluted.
