Methoxyl groups Ortho

Boron trichloride (b.p. 13°) is by comparison more selective in its action and Dean and his co-workers [60] have shown this reagent to have a clear specificity towards methoxyl groups ortho to a carbonyl function. This selectivity is illustrated in the synthesis of the microbial metabolite mycophenolic acid [61] in which demethylation of the intermediate (48) to give (49) is achieved in 95% yield using boron trichloride. 

In a recent publication, D. A. Burnham [Tetrahedron, 25, 897 (1969)] presents other calculations which indicate that protonation of the radical-anion of anisole is more likely to occur meta to the methoxyl group rather than ortho as Zimmerman proposes. 

The apparent necessity of a second signal for haustorial initiation provides another possibility for chemical control. Riopel and coworkers (2,12-14) observed a few years ago that gum tragacanth, a foliar extract, was a very potent haustorial initiator. Two active compounds were isolated (Xenognosin A shown below, and a flavonoid with similar structure). The structural features required for haustorial formation include a meta relationship of hydroxyl and methoxyl groups and an alkyl branching ortho to the methoxy substituent. 

Figure 1 and Tables I and II indicate the importance of carbon-carbon and ether bonds. The former bonds can only be disrupted using strong reaction conditions, whereas the latter bonds are broken by much milder treatment. The methoxyl groups in the ortho position in softwoods, and in the ortho and para positions with relation to the phenolic hydroxyl group in hardwoods, have a marked influence on the reactivity and solubility behavior. They can be chemically blocked or removed. 

Estimating the reactivity of various aromatic nuclei in lignin involves studies to determine the protodedeuteration rates of certain selectively deuterated model compounds. The combined effects of hydroxyl, methoxyl, and side-chain substituents are approximately additive in guaiacyl models while syringyl models show significant deviation from the predicted behavior. The reactivity of the position meta to methoxyl groups is higher while those of the ortho and para positions are lower than anticipated on the basis of combined substituent effects. 

Partial Rate Factors for Protodedeuteration in Perchloric Acid Solution. All lignin model compounds studied contained hydroxyl, methoxyl, and methyl groups as the only substituent groups. Table II summarizes what the authors believe are the most reliable partial rate factors for these substituents in perchloric acid solution. All partial rate factors are based on determinations in 57% perchloric acid solutions. The partial rate factors for ortho and para positions of methyl and methoxyl groups are based on later work by Suzuki (21). The partial rate factors for phenol were calculated from data on 2, 4, 6-trideuterophenol (6) using the value 9.1 X 10-5 hr.-1 for monodeuterobenzene by Suzuki (21) and assuming 1 3.2 ortho to para ratio. 

With 4-methoxyphenols, the phenoxyl formed is further stabilized by delocalization of the unpaired electron to the p-type orbital of the methoxyl oxygen (105 -106). This interaction is allowed in vitamin E and in compound 103 but prohibited in compound 104 because the former two compounds exist in conformation 107 and the latter in conformation 108. In conformation 108, due to the methyl groups in ortho position, the methoxyl group is twisted out of the plane of the aromatic ring and the delocalization of the methoxyl oxygen electron pair is consequently prohibited. 

An extensive study of the methoxypolynitroanilines has shown that, in this series, a nitro or methoxyl group becomes sufficiently mobile to be eliminated during the course of diazotization only when ortho or para to the diazo group and, in addition, adjacent to a nitro group.60... 

The methoxylation pattern of lactonic alkaloids was established by a combination of spectral and chemical studies. Methoxyl groups at positions ortho to the biphenyl link (at C-17 or C-21) resonate at relatively high field (<5 3.8 — 3.7 ppm) because of shielding by the adjacent aromatic ring. Methoxyl groups at the other positions absorb at <5 3.95 — 3.85 ppm. Formation of an internal ether demonstrates the presence of 17-OH (24). 

Roberts et al. have observed the unusual fragmentation of loss of formaldehyde in methyl esters of ortho-substituted ferrocenyl-benzenes 172). This novel fragmentation of loss of aldehyde has also been observed by Lupin et al. for methyl, ethyl, and n-propyl esters of ortho-substituted ferrocenyl benzenes as well as for methyl esters of alkenyl ferrocenes 134). The ortho effect, in a rearrangement depicting a six-membered transition state, has been proposed by Bursey et al. to explain this fragmentation, but it is more likely that the metal atom plays an important role, possibly with the migration of the methoxyl group to the metal 134). 

In their early studies, Pinhey et al. showed that, when the reaction of a phenol with an aryllead triacetate is performed in the presence of pyridine, only the C-arylated dienones 35 and 36 are formed in a nearly quantitative yield (90% ortho para ratio of 4 1) (Equation (38)). Under their classical conditions (phenol organolead triacetate base in a ratio 1 1 3), the reaction of methylated phenols only proceeded in high yield when both ortho-positions are substituted. There is a preference for attack ipso to a methoxyl group compared to a methyl group.45 453... 

The methoxyl group directs substitution to the positions ortho and para to it. 

---