Tritium, substitution reactions

In Table 24.5 (Wolfgang 1965 Seewald et al. 1968 Small and Rowland 1968 Chou and Rowland 1971 Tachikawa and Yanai 1972 Saeki and Tachikawa 1973 Numakura et al. 1973 Numakura and Tachikawa 1973) several examples of the isotope effect experimentally obtained are listed. The effect ranges between 1.25 and 1.41 for recoil tritium substitution reaction, but is much larger (3.1-7.2) for photochemically produced tritium (2.8 eV) in hydrocarbon mixture gases. 

Since the terminal carbons of both the diene and dienophile change the hybridization from sp to sp, the corresponding C-H out-of-plane vibration frequency increases during the Diels-Alder reaction." Therefore, deuterium or tritium substitution at the termini positions will potentially lead to differing reaction rates. An inverse 2°-KE is expected for the forward reaction < 1) while the reverse reaction would experience a normal 2 -KIE > ) Houk and Singleton have pioneered the use of both experimental and compntational KIEs to determine the nature of pericyclic TSs, and we discuss here their studies of the Diels-Alder reaction. 

The literature on the effect of deuterium and tritium substitution on the rates of solution reactions is an extensive one17 and beyond the scope of this chapter. We shall discuss briefly several different types of studies that have been made. 

Rate constants and tunneling splittings associated with proton transfer are sensitive to deuterium (and tritium) isotope effects resulting from the large difference in mass between the isotopes. Deuterium (and tritium) substitution thus provides a tool for studying these processes experimentally. The corresponding kinetic isotope effect (KIE) for a single proton transfer reaction is defined by... 

Tritium substitution in the 3 -position of ATP and UTP also yielded isotope effects following their reduction by the B 12-dependent RTPR, suggesting that the initial step of the reactions catalyzed by RTPR is a rate-limiting abstraction of the 3 -hydrogen (47, 49). The isotope effect with RTPR was rather insensitive to the pH of the media, although the formation of small quantities of H20 was still observed. 

Results with inert moderators also support the view that some of the abstraction and all of the substitution reactions are hot . Helium is an effective non-reactive moderator for tritium since its mass is close to that of tritium (cf. Section II, E). As the concentration of helium in an organic system being subjected to tritium recoils is increased, the probability of a reactive encounter between a hot tritium atom and the substrate is decreased. Product distributions should shift in the direction of what might be expected from thermal tritium atoms. In the presence of helium the yield of HT (Eq. (8)) goes up and the yield of RT (eqs. (9) and (13)) goes down (cf. Estrup and Wolfgang, 1960b) in accordance with what one would predict. 

Estimates of the energy range in which reaction takes place (Lee et al. 1960b, Henchman et al. 1960) are consistent with the view that the abstraction and substitution reactions take place with tritium atoms whose kinetic energy is above 3 eV and below 10-15 eV. Furthermore, Henchman et al. have estimated the reaction probability for these reactions to be between 0-2 and 0-4. (These numbers were based on ... 

Attack on the C—H bond by the incoming tritium atom at larger angles results in substitution reactions. 

Abstraction and substitution reactions also take place in alkenes. No definitive answer on intramolecular distributions of tritium, i.e. CT= versus —CHT— in substitution reactions in the gas phase has been obtained as yet but the indications are that there is no great selectivity for substitution of one or the other types of hydrogen (Lee et al., 1960a). Isomerization about the double bond following substitution has been discussed. 

Alkanes.—Hydrogen Substitution. Whereas thermal hydrogen atoms react with alkanes exclusively by hydrogen abstraction, tritium atoms goierated by nuclear recoil also undergo the energetic substitution reaction (52) in high yield. ... 

The billiard ball atom-atom collisions favouring the easier replacement of D do not explain the observed experimental deuterium isotope effects in substitution reactions with hot tritium. The linear structures, T— H—R , of the transition states have also been rejected. An attempt has been made to rationalize the experimental findings by... 

There are several lines of evidence for formation of cr complexes as intermediates in electrophilic aromatic substitution. One particularly informative approach involves measurement of isotope effects on the rate of substitution. If removal of the proton at the site of substitution were concerted with introduction of the electrophile, a primary isotope effect would be observed in reactions in which electrophilic attack on the ring is rate-determining. This is not the case for nitration nor for several other types of aromatic substitution reactions. Nitration of aromatic substrates partially labeled by tritium shows no selectivity between protium- and tritium-substituted sites. Similarly, the rate of nitration of nitrobenzene is identical to that... 

It is interesting to see the pressure dependence of hot tritium reaction in cyclobutane C4H8. Recoil tritium attacks this molecule to give tritiated cyclobutane (substitution reaction) in an excited state, which either stabilizes by collision with a third body or decomposes into two molecules of ethylene. This is shown in the following scheme ... 

For the H substitution reaction of recoil tritium, binding energy also plays an important role. In the T + CH3X reaction, where X = SH, NH2, Cl, OH, and F, the yield of substituted CH2TX increases with binding energy of C-X. This is due to weakening of the C-H bond by introduction of X. 

Threshold energy for hydrogen substitution reaction is more difficult to measure. Chou and Rowland (1969) used photolysis of TBr to obtain hot tritium atoms for the substitution reaction. They compared the yield of substituted CD3T in methane to the DT abstraction yield whose threshold energy is known to be smaller. The ratio substitution/abstraction was extrapolated to zero at which the threshold value of energy for substitution was determined to be 1.5 eV. 

As shown in Scheme 34, [4,6- H2]-tryptophan and [5,7- H2]-tryptophan were synthesized and fed to cultures of Aspergillus amstelodami. The [5,7- H2]-tryptophan was incorporated into echinulin and neoechinulin B with 2% and 103% retention of tritium activity, respectively. The [4,6- H2l-tryptophan was incorporated into echinulin with 102% retention of tritium activity and into neoechinulin with 48% loss of tritium activity. These experiments are complementary and clearly demonstrate that the introduction of the isoprene units go via a direct electrophilic aromatic substitution reaction mechanism. It shoidd also be noted that Fuganti et al. isolated cryptoechinulin from Aspergillus amstelodami during the course of their biosynthetic work on echinulin [58]. 

Among numerous radical substitution reactions [23, 24] those of the Sh2 type at a saturated carbon atom have been studied in the most detailed fashion. The simplest and at the same time most important example is given by the substitution of a hydrogen atom of methane by tritium (or another hydrogen isotope) ... 

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