Inductive effect of deuterium

The measurement of individual proS and proR p-deuterium effects for a-NeuNAcOPNP, and also the inductive effect of deuterium substitution at position 4, enabled eqn (3.12) to be solved for the acid-catalysed hydrolysis of the neutral molecule, the acid-catalysed hydrolysis of the anion and the spontaneous reaction. An isotope effect kn/ko of 1.000 for the proS and position 4 hydrons for the spontaneous and acid-catalysed reactions of the anion indicated the inductive correction in eqn (3.12) was zero. TheproR effects of 1.075 and l.OSg then lead immediately to a value of the proR hydron breaking C-O bond dihedral angle (6) of 30° and values of (kH/kD)max of 1.09g and 1.115 for the spontaneous and acid-catalysed processes of the anion, respectively. The acid-catalysed hydrolysis of neutral a-NeuNAcOPNP, by contrast, has a proS effect of 1.02s and a proR effect of 1.06g, indicating a less flattened transition state in which 6 > 30°, The value of 0.97g for the effect at C4 is too high to be wholly inductive [implausible values of (kH/kD)max result if ln(kH/kD)i is set equal to 31n0.976], but even in the absence of any inductive correction a (kH/kD)max of 1.19 results, indicating a much more electron-deficient reaction centre. 

For our model reaction, we can assume with some confidence that the linear term will predominate. Taking HX now to be an isolated CH bond, the evidence presented in Sec. II indicates that there will be a higher average electron density on the carbon atom in CD than in CH. This means that the reagent will lower the average potential energy of CD more than that of CH, and the deuterated product will be stabilized more effectively. The predicted direction of the isotope effect would be Kn < Kn, resulting from the inductive effect of deuterium. 

In cyclohexane, at 18°C., methyl deuteration decreases the stability of the chloranil-toluene and chloranil-m-xylene complex to virtually the same extent Kfi/K y 1.07 (AAf°/ ) = 13 cal. The greater amplitudes of the CH motions than those of CD should lead to a steric isotope effect in the reverse direction, as should the inductive effect of deuterium, so the evidence unambiguously indicates hyper-conjugative stabilization of this and similar complexes, and a hyper-conjugative isotope effect. 

Mention was made in the Introduction of the effect of a deuterium atom on the rate of abstraction of another hydrogen or deuterium atom bonded to the same carbon atom to form a carbanion. From the relative rates of deuteron abstraction by cyclohexylamide ion from toluene ad and from toluene-ad, Streitwieser and Van Sickle (12) calculated a 15% retardation per deuterium atom. The authors have attempted to estimate how much of this is due to the inductive effect of deuterium, and to deduce the extent of hybridization change from the remainder. From much of the discussion so far it would... 

Under the same conditions, stepwise competition between benzene and benzene-de and between toluene and toluene-dg yields kn/fco = 0.87 and 0.82 respectively. Since the isotope effect was obtained from an intermolecular competition, it must reflect the relative rate of formation of the initial x-complex, which from the effect on benzene is AAF /n = —13. cal. The effect of side-chain deuteration can be estimated as follows Assuming the association of NO2+ with the ring to be non-specific, we can split up the total effect of toluene-dg AAF" " = —113 cal. into —69 cal. due to the five nuclear deuterium atoms and —Hcai., orAAF /n = —14. cal., due to methyl deuteration. Both nuclear and methyl deuteration thus accelerate nitration, by making it easier to form the initial x-complex the inductive effect of deuterium is the obvious factor responsible. 

The importance of the inductive effect in controlling the reaction rates was further shown by Streitweiser and Humphrey596, who measured the rates of dedeuteration of toluene (a, a-d2), (a, 2,4,6-g 4), and (a, 2,3,4,5,6-g 6) by lithium cyclohexylamide at 50 °C and found the rate to be reduced by 0.4 %, 0.4 %, and 1.8 % for a deuterium atom in the ortho, meta and para positions respectively. The retardation is consistent with the +1 effect of deuterium but the differential positional effect could not be rationalised in simple and general terms. 

Deuterium substitution rednces the electron affinity of organic snbstrates. The reduced electron affinity of deuterinm-snbstitnted analogs is due to the larger electron-donating effect of deuterium when compared to hydrogen. Its inductive constant is small bnt negative (-0.0011). The deuterium electron donor effect develops in organic ion-radicals also. 

The a-secondary IE of two deuteriums on the rate of base-catalyzed CD exchange of toluene, 3A ( PhC112D)/k(PhCD is 1.31, and the [3-secondary D IE on the rate of base-catalyzed a-C-D exchange of ethylbenzene, k(PhCHDCH3)//t(PhCHDCD3), is 1.11 0.03.58 Similarly, from the rates of base-catalyzed a-C-D exchange of tolucne-a,4-r/2, -a,2,4,6-c/4, and -a,2,3,4,5,6-d6 and with an assumption of linearity of IEs, the contributions of ortho, meta, and para deuteration lead to rate retardations of 2.4, 0.4, and 1.8%, respectively.59 These are all kinetic IEs, but to the extent that the transition state resembles closely the carbanion, or to the extent that the reverse reprotonation is encounter-controlled and independent of isotopic substitution, these kinetic IEs represent equilibrium IEs on acidity. The IEs were interpreted in terms of an electron-donating inductive effect of D relative to H. 

The inductive effect of the donating C—D bonds to the observed large inverse secondary deuterium isotope effect has not been given proper consideration but treated as a rather minor component superimposed on the important steric component caused by larger amplitudes of vibrations of C—H bonds than those of the C—D bonds. 14C KIE have not been studied in this reaction. The C2, C V. C3 , C3, endo hydrogens are separated only by 2.11 A, substantially less than van der Waals radii (2 x 1.2 A)404. 

The major reaction product formed from the solvolysis of the trans y-silyl ester was cyclohexene formed from the carbocation 138 (Scheme 18) by 1,2-hydrogen migration to give the p-silyl cation 139 followed by loss of the silicon substituent. In contrast to the behavior shown by 136, the cis y-silyl ester 134 exhibited a small inverse p-d4 isotope effect (kH/kn = 0.97) attributed to the inductive effect of the P-deuteriums and implies that there is very little hyperconjugative stabilization of... 

The positive inductive effect of a 3-methyl group is transferred to the adjacent 2-position more effectively than that of a 2-methyl to the more remote 5-position. Compared with the rate of a-deuterium exchange for selenophene, itself, the rate is about 0.1 for 5-methyl-2-deuterioselenophene and 0.05 for 3-methyl-2-deuterioselenophene in the presence of strong bases, whereas in acidic media it is about 100 and 1000, respectively.79 The same effect of a methyl group was found... 

Cartoon of a C-L potential energy curve, illustrating the bond stretch-anharmonicity explanation of the inductive and steric effects of deuterium and tritium. The anharmonicity and zero-point energies are greatly exaggerated. 

The pattern of deuterium distribution in isotope exchange products of 1,8-nap-hthyridine and its methyl-, hydroxyl-, amino- and nitro derivatives indicates that the rate and pathway of this process depend on the pH of the medium as well as the nature and position of substituent (1988ACH267). In neutral D20 and a D20-DC1 mixture, hydrogen atoms are replaced with deuterons exclusively at positions 2 and 7. In D20 solutions containing NaOD, hydrogen atoms are replaced with deuterons in all positions of the naphthyridine system. In neutral D20, the replacement of the protons in monomethyl-substituted 1,8-naphthyridines occurs predominantly in the ortho positions with respect to the nitrogen atoms (positions 7 and 2, 7). The high reactivity of these positions is determined by the inductive effect of the substituent. 

Preparation by demethylation of 3,5-dimethoxy-4 -(phenoxy-d )ben-zophenone with 48% hydrobromic acid in refluxing acetic acid for 16 h (92%) (compound 21). The acidic treatment exchanges exclusively the deuterium atoms in the 2 , 4 and 6 positions, because of the mesomeric inductive effect of the exocyclic oxygen [906]. m.p. (NA), white solid [906] H NMR [906], C NMR [906]. 

Dilsopinocampheylborane derivatives continue to be attractive as reagents for enantloselective processes. Studies on the secondary kinetic isotope effect of deuterium on enantioselective hydroborations with (+)(Ipc)2BH have provided significant experimental evidence which provides a test for any detailed explanation of the process. The reagent has been used in a systematic study with representative heterocycles bearing an endocycllc double bond in order to establish the asymmetric induction achieved. It turns out that the reaction provides a simple and efficient method of synthesising heterocyclic boronates... 

Charton has recently examined substituent effects in the ortho position in benzene derivatives and in the a-position in pyridines, quinolines, and isoquinolines. He concludes that, in benzene derivatives, the effects in the ortho position are proportional to the effects in the para position op). However, he finds that effects of a-sub-stituents on reactions involving the sp lone pair of the nitrogen atoms in pyridine, quinoline, and isoquinoline are approximately proportional to CT -values, or possibly to inductive effects (Taft s a ). He also notes that the effects of substituents on proton-deuterium exchange in the ortho position of substituted benzenes are comparable to the effects of the same substituents in the a-position of the heterocycles. 

Both sets of results may also be discussed in terms of inductive differences between hydrogen and deuterium (see Halevi, 1963). Brown et al. (1966) jDoint out that both the inductive and steric explanations qualitatively predict isotope effects in the same direction, but that an inductive effect would be expected to operate from the 3 and 4 positions nearly as effectively as from the 2 position . Furthermore, there is no observable isotope effect on the heat of reaction of 2,6-(dimethyl-de)-pyridine with the relatively small molecule diborane A AH = —20 18 cal mol ), but a significant effect is obtained with the larger molecule boron trifluoride AAH = 230 + 150 cal mol ). 

It was of course not possible to introduce the deuterium atoms closer than three bonds away from the center of reaction , but the attenuation of the inductive effect with distance was not expected to affect the validity of the conclusions, especially considering the work of Streit-wieser and Klein (1964), who found that the isotope effect per deuterium in the solvolysis of benzhydryl chloride only decreased from 1 9% for deuterium in the ortho positions to l-5% for deuterium in the meta positions. 

---