Ortho carbonate

The major influence of the methyl group is electronic The most important factor IS relative carbocation stability To a small extent the methyl group sterically hinders the ortho positions making attack slightly more likely at the para carbon than at a single ortho carbon However para substitution is at a statistical disadvantage because there are two equivalent ortho positions but only one para position... 

In some instances the attack of the arene on the nitrilium salt occurs at the ipso carbon rather than the ortho carbon. For example, the Bischler-Napieralski cyclization of phenethyl amide 10 affords a 2 1 mixture of regioisomeric products 11 and 12. The formation of 12 presumably results from attack of the ipso aromatic carbon on the nitrilium salt 13 followed by rearrangement of the spirocyclic carbocation 14 to afford 15, which upon loss of a proton vields product 12. ... 

Condensation of prednisone, 40 with tetraethyl orthocarbonate leads to the cyelie ortho-carbonate 41 liydrolysis proceeds by protonation on the most accessible ether oxygen (that on carbon 21) to give the 17 mixed carbonate ester 42. Acylation with propionyl chloride proceeds on the remaining hydroxyl group to afford prednicarbate (43) [10],... 

Choi, N. S., and Heller, J., Erodible agent releasing device comprising poly(ortho esters) and poly(ortho carbonates), U.S. Patent 4,138,344, February 6, 1979. 

The scheme proposed by the authors81 includes the formation of a hydrogen bond between the proton at the ortho-carbon atom of the phenyl ring and one of the nitrogen atoms of cyclostannylene followed by the Sn-N bond cleavage and C-Sn bond formation. The second Sn-N bond is cleaved... 

The one-step mechanism, depicted in path a, consists simply of a 1,2-shift of an ortho carbon. While this process is an all-carbon version of the Wolff rearrangement, the bond order of the migrating bond is substantially greater than 1.0. Hence this would represent an unprecedented reaction of carbenes. 

For 2-fluorophenylnitrene (lOf), the barrier for cyclization at the fluorinated ortho carbon is computed to be ca. 3 kcal/mol higher than that for cyclization at the unfluorinated ortho carbon (Table 6).87 These results are in agreement with experimental observations that nitrene lOf rearranges rapidly to a ketenimine in solution810 and that 2,4-difluorophenylnitrene (lOd) undergoes ring expansion some 15 times faster than 2,6-difluorophenylnitrene (10b).81 c,d Both lOf and 2,4-difluorophenylnitrene (lOd) can cyclize at an unfluorinated ortho carbon but this is not possible for 2,6-difluorophenylnitrene (10b). 

The results in Table 7 for methyl-substituted phenylnitrenes show that 2-methyl (11a) and 4-methyl (lid), which can both cyclize toward an unsubstituted ortho carbon, have barriers that are ca. 1.5-2 kcal/mol smaller than 2,6-dimethyl (lib) and 2,4,6-trimethyl (11c), both of which can only cyclize toward a substituted carbon.92 This agrees well with the predicted 2.0 kcal/mol difference in barrier heights for the two cyclization modes of 2-methylphenylnitrene (11a).87... 

Because no unpaired spin appears at the meta carbons of lb, a cyano substituent at one of these carbons should have only a small effect on the barrier to cyclization at either of the two, non-equivalent ortho carbons. However, if a para cyano substituent tends to localize spin at the carbon to which it is attached, the concomitant decrease in unpaired spin density at the ortho carbons might raise the barrier to cyclization. 

Incorporation of additional donor functionality into the periphery of phosphinomethanide ligands also has dramatic consequences for the structures of their alkali metal complexes. The complex [Li C(SiMe2Ph)(PMe2)2 ]3 (49) crystallizes as solvent-free cyclic tri-mers (Fig. 18), in which each lithium is primarily coordinated by two P atoms from one ligand and the carbanion center of an adjacent ligand (138, 139). This is supplemented by an essentially -interaction with the ipso and an ortho-carbon of the phenyl ring associated with the carbanion bonded to lithium. Each Li is thus bound by two P atoms, two aryl carbons, and a central carbon of the phosphinomethanide ligands. 

Bis(l-methylboratabenzene)lead 42 is synthesized in 63% yield by the reaction of LifCsHsBMe) with lead(n) chloride. The X-ray structure analysis of 42 reveals some remarkably short intermolecular contacts from the lead atoms to the ortho-carbon atoms of neighboring molecules which create a tetrameric packing unit. Compound 42 forms weak adducts such as 43 with nitrogen Lewis bases like TMEDA or 4,4 -dimethyl-2,2 -bipyridine.71... 

In nitrobenzene, for example, the intramolecular electric field of the nitro group increases the a electron densities at the ortho carbon nuclei, so reducing the electron density at the attached protons. This effect, in fact, overcompensates the effect of electron withdrawal by the nitro group, and a net shielding is observed (Table 5). 

Primary aliphatic or aromatic amines RNH2 are converted into carbamates RNHCC Et on treatment with carbon monoxide and di-t-butyl peroxide in the presence of palladium(II) chloride and copper(II) chloride357. Carbamic esters 304 and 305 are also obtained from aliphatic amines and ortho carbonates (R30)4C358. Vinyl carbamates R12NC02CH=CHR2 are produced from secondary aliphatic amines, acetylenes R2C=CH (R2 = Bu or Ph) and carbon dioxide in the presence of ruthenium(III) chloride359. 

Finally, the unsaturated spiro ortho carbonates were been shown to undergo double ring opening in a free radical polymerization to introduce a carbonate group in the backbone of an addition polymer (19). 

A-Chloro-Af-methoxy-Af -arylureas (84) have been reported to cyclize in good yield to 2-benzimidazolinones (85) upon treatment with NaH. Af -Alkylation prevented the reaction and the process involves anilide formation by hydrogen abstraction and an intramolecular Sat2 displacement of chlorine by the electron-rich ortho carbon (equation 11) . ... 

For the formation of the 4-ethynylquinoline complexes a mechanism was proposed involving nucleophilic attack of the terminal carbon of the butatrienylidene ligand at the imine carbon, followed by C—C bond formation between the ortho carbon of the N-aryl group and C3 of the butatrienylidene ligand. Deprotonation finally affords 4-ethynylquinoline complexes (Scheme 3.27). Some preference was observed for quinoline formation with the more electron-rich metal centers, whereas... 

Moreover, each of the four ortho carbons is also protected from the approach of external reagents by these bromine groups. This stabilization enabled us to introduce connecting groups at the para position of the monomer diazo compound (e.g., 119) to give the functionalized monomer 120, and then to connect it to an appropriate linker satisfying the topological requirement for intramolecular... 

Placement of fluorine substituents at both ortho positions raises the barrier to cyclization by 3 kcal/mol, relative to the unsubstituted system. The work of Leyva and Sagredo" demonstrated, in fact, that cyclization of the singlet nitrene 39s proceeds away from the fluorine substituent. The steric argument predicts that a single o-fiuorine substituent will have little influence on the rate of conversion of 39s to 40, since cyclization occurs at the unsubstituted ortho-carbon."" ... 

From the understanding, provided by the calculations, of the mechanism by which lb cyclizes, what can be predicted about how the rate of this reaction might be affected by substituents on the benzene ring The substiment effects would, in fact, be expected to be small, except for possible steric effects due to substituents in the ortho positions. If both ortho positions are substimted, one would expect to see a decrease in rate, relative to unsubstituted lb. On the other hand, if only one ortho position is substituted, cyclization should be about as fast as in unsubstituted lb but cyclization should preferentially occur at the unsubstituted ortho carbon. Additional (8/8)CASPT2/6-31G calculations by Bill Kamey in our group and subsequent experiments by the Platz group confirmed these qualitative predictions about the effects of ortho substituents. 

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