Molecular-orbital calculations acidity

The relative acidities in the gas phase can be detennined from ab initio or molecular orbital calculations while differences in the free energies of hydration of the acids and the cations are obtained from FEP sunulations in which FIA and A are mutated into FIB and B A respectively. 

Molecular orbital calculations predict that oxirane forms the cyclic conjugate acid (39), which is 30 kJ moF stabler than the open carbocation (40) and must surmount a barrier of 105kJmoF to isomerize to (40) (78MI50500). The proton affinity of oxirane was calculated (78JA1398) to be 807 kJ mol (cf. the experimental values of 773 kJ moF for oxirane and 777-823 kJ moF for dimethyl ether (80MI50503)). The basicity of cyclic ethers is discussed in (B-67MI50504). 

Protonation of the anion [SN2] by acetic acid in diethyl ether produces the thermally unstable sulfur diimide S(NH)2. Like all sulfur diimides, the parent compound S(NH)2 can exist as three isomers (Scheme 5.5). Ab initio molecular orbital calculations indicate that the (cis,cis) configuration is somewhat more stable than the (cis,trans) isomer, while the (trans,trans) isomer is expected to possess considerably higher energy. The alternative syn,anti or E,Z nomenclatures may also be used to describe these isomers. The structures of organic derivatives S(NR)2 (R = alkyl, aryl) are discussed in Section 10.4.2. 

Radicaloid substitution has not been extensively studied in the thiophene series. Molecular orbital calculations indicate that substitution should occur in the a-position. This has been found to be the case in the Gomberg-Bachmann coupling of diazohydroxides with thiophenes which has been used for the preparation of 2-(o-nitro-phenyl) thiophene, 2-(p-toluyl) thiophene, " " and 2-(p-chloro-phenyl)thiophene. " Coupling in the /8-position has been used for the preparation of 1,3-dimethyl-4,5-benzisothionaphthene (148) from 2-amino-tt-(2,5-dimethyl-3-thienyl)cinnamic acid (149). A recent investigation describes the homolytic phenylation of 2- and 3-phenyl-... 

Simple resonance theory predicts that pentalene (48), azulene (49), and heptalene (50) should be aromatic, although no nonionic canonical form can have a double bond at the ring junction. Molecular orbital calculations show that azulene should be stable but not the other two, and this is borne out by experiment. Heptalene has been prepared but reacts readily with oxygen, acids, and bromine, is easily hydrogenated, and polymerizes on standing. Analysis of its NMR spectrum shows that it is... 

Fig. 8.—Favored Conformation of Some o-Amino Acid Zwitterions as Indicated by Molecular-orbital Calculations. ...

Pullman, B., and A. Pullman. 1974. Molecular Orbital Calculations on the Conformation of Amino Acid Residues of Proteins. Adv. Protein Chem. 28, 347-526. 

There is considerable literature precedent for this reaction. In particular, Fotsch and Chamberlin (10) have reported that open chain y,8, 8,e and 6, -epoxy ketones and esters undergo cyclization in the presence of acids to form the corresponding dioxacarbenium ions. In addition, molecular orbital calculations were conducted to determine the heats of formation of the intermediates IX and X. Data from these calculations are given in Table 2. These calculations suggest that 1,6-attack (X) is... 

Information about the possible structures of molybdate and its pro-tonated forms in solution has been obtained from molecular orbital calculations (62). By considering bond orders obtained from a Mulli-ken population analysis and the agreement between experimental and theoretical UV spectra it was concluded that [Mo04]2 and [HMoOt I are tetrahedral and that the neutral acid is octahedral. For the latter a somewhat distorted octahedral structure based on the formula Mo02(OH)2(H20)2 was proposed (62). The alternative structure Mo03(H20)3 was not taken into account in the calculations. 

The new treatment had its origins partly in ab initio molecular orbital calculations of substituent effects and partly in extensive studies of gas-phase proton transfer reactions from about 1980 (Section V.A). Various aspects of this work essentially drew attention to the importance of substituent polarizability. In 1986 Taft, Topsom and their colleagues252 developed a scale of directional substituent polarizability parameters , oa, by ab initio calculations of directional electrostatic polarization potentials at the 3-21G//3-31G level for a large set of CH3X molecules. The oa values were shown to be useful in the correlation analysis of gas-phase acidities of several series of substrates252, and such work has subsequently been extended by Taft and Topsom151. 

Molecular Orbital Calculations on the Conformation of Amino Acid Residues of Proteins... 

It has been suggested that, regardless of the transition state structure during solvolysis, the norbomyl ion might have yet another structure under the stabilizing influence of strong acid media. Before considering those systems it is appropriate to discuss the current theoretical status as provided by molecular orbital calculations. 

The phosphorus analogue of pyrrole, phosphole, has a degree of aromatic character, according to molecular orbital calculations and nmr spectra (Brown, 1962 Chuchman et al., 1971). 1-Methyl-phosphole has a p/fg-value of 0-5 (Quin et al., 1969), much higher than that of pyrrole. It polymerizes rapidly in aqueous acid. The site of protonation of 1,2,5-triphenylphosphole is phosphorus according to the infrared spectra of some of its stable salts (Chuchman et al., 1971). 

Ultraviolet spectra of benzoic acid in sulphuric acid solutions, published by Hosoya and Nagakura (1961), show a considerable medium effect on the spectrum of the unprotonated acid, but a much smaller one in concentrated acid. The former is probably connected with a hydrogen-bonding interaction of benzoic acid with sulphuric acid which is believed to be responsible for a peculiarity in the activity coefficient behaviour of unprotonated benzoic acid in these solutions (see Liler, 1971, pp. 62 and 129). The absence of a pronounced medium effect on the spectra in >85% acid is consistent with dominant carbonyl oxygen protonation. In accordance with this, Raman spectra show the disappearance in concentrated sulphuric acid of the carbonyl stretching vibration at 1650 cm (Hosoya and Nagakura, 1961). Molecular orbital calculations on the structure of the carbonyl protonated benzoic acid have also been carried out (Hosoya and Nagakura, 1964). 

A solubility study coupled with IR and titrameric measurements and ab initio molecular orbital calculations was performed on 2,3-pyrazinedicarboxylic acid <2000JST(526)191>, demonstrating that the dicarboxylic acid exists in the solid as such and not in a zwitterionic form. In addition, one internal and one external 0---0=C hydrogen bond per molecule were proposed. 

In the case of mercuration (soft electrophile), attack at the 2-position is favoured. These observations accord with predictions based on molecular orbital calculations, that hard electrophiles (nitronium ions) should attack at C-4 and soft electrophiles (e.g. HgS04) at C-2 (68JA223). Furthermore, very hard electrophiles (e.g. S03) are predicted to attack at C-3. This is hard to verify because pyridine 1-oxide reacts at C-3 as its conjugate acid (or... 

Since ketones are stronger acids than carboxylic esters (Table 8.1), we are not surprised that 8 is a stronger acid than 10. But cyclization of 8 to 9 increases the acidity by only 2.1 p/C units while cyclization of 10 to 11 increases it by 8.6 units. Indeed, it has long been known that 11 (called Meldrum s acid) is an unusually strong acid for a 1,3-diester. In order to account for this very large cyclization effect, molecular orbital calculations were carried out two conformations of methyl acetate and of its enolate ion by two groups.136 Both found... 

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