Methylation ortho

Perfluorohexamethylbenzene is converted to perfluoropentamethylbenzoic acid by sequential treatment with sodium methoxide, then concentrated sulfuric acid, and finally fuming sulfuric acid [37] (equation 38). The intermediate methyl ortho ester and methyl ester of the acid can be isolated... 

The condensation of dichloride 57 with the dianion of N-methyl ortho-tolylamide 56 affords pyrrolo[2,3-d]-[2]benzazepin-6(lH)-one 58 (R = p-tolyl). The product 58 contains four rather than just two imino groups. This can be explained... 

N-METHYL-ORTHO-TOLUIDINE N-METHYl-PARA-TOLUIDINE N, N-DIME PHYL-ORTHO-a OLUIDINE 2.4-XYLIDINE N, N-... 

An intEiesting variant on the Wilgerodt reaction offers a simple three-step procedure that avoids the wastage involved in the schemes above, which require the incorporation of an extra carbon atom that must later be eliminated. The sequence starts with the acylation of isobutylbenzene (49-1) with propionyl chloride to give propiophenone (49-2). Reaction of that with thallium 111 nitrate and methyl ortho-formate in methanol leads in high yield to the methyl ester (49-3) of ibuprofen [50]. This would be the method of choice for preparing the dmg but for two unfortunate facts the extreme toxicity of thallium and the very high sensitivity of analytical methods for the detection of metals. It proved to be virtually impossible, in practice, to produce samples that showed zero residues of thallium. 

M. Polito, E. D Oria, L. Maini, P.G. Karamertzanis, F. Grepioni, D. Braga, S.L. Price, The crystal structures of chloro and methyl ortho-benzoic acids and their co-crystal rationalizing similarities and differences, CrystEngComm 10 (2008) 1848-1854. 

The widely employed Leimgruber-Batcho protocol for indole synthesis comprises two consecutive steps—the formation of enamines followed by a reductive cyclization. The formation of enamines (such as 14, Scheme 7) presumably required an initial deprotonation of the methyl ortho to the aromatic nitro-group by methoxide generated from DMF-DMA under elevated temperatures (overnight heating in DMF) [27]. The use of microwave irradiation at 180 °C allowed the reduction of the time of formation of enamines such as 14 from 22 h (at 110°C) to 4.5 h (and even to 40 min in several... 

Fig.3. Maleamic acid cyclization by methyl ortho-acetate...

In 1964, Hauser and coworkers used aryl amides for electrophilic reactions on the aromatic ring75. TV-Methylbenzamide underwent dilithiation to give, after reacting with electrophiles, the ortho alkylamide compound 39. In those conditions, TV-methyl ortho toluimide reacts with electrophiles on the ortho methyl group via the dilithium derivative 40 to give product 41 (equation 12). 

Methyl ortho-p-methylbenzoate Ki2S07Na+ Dunlap and Cordes,... 

METHYL NITRITE METHYL ORTHO SILICATE see METHYL SILICATE 2606 624-91-9 ... 

On the other hand, the small Hammett p value and the dependence on a rather than on a+ observed in the hydrolyses of methyl ortho benzoates in 70% methanol—water are somewhat unusual for an A1 mechanism. These facts are in better agreement with an A-SE2 mechanism [169]. It must be expected that the pK of the electrically neutral substrate (as a base) is further decreased by the non-aqueous solvent. A change of mechanism from A1 to A-SE2 then may be possible. 

The directed metalation of aromatic systems that was discussed in Section 2.1.3.3 has one ramification that was not mentioned there the directed lithiation of an o-methyl group. Although the resultant species is formally a resonance-stabilized anion, and therefore covered in Volume 2 of this series, we mention it here for consistency with the other topics covered. In particular, the examples that have appeared in recent years involve substrates having a methyl ortho to a tertiary amide. Intentional use of such a directed lithiation has been used in the synthesis of the isocoumarin natural products hydrangenol and pyllodul-cin.137,138 Interestingly, the directed metalation of 5-methyl-oxazoles and -thiazoles occurs in preference to deprotonation at a 2-methyl group (azaenolate) (Scheme 33). ... 

Micelles concentrate reactants from the surrounding medium and provide microenvironments favorable to reaction. Rate enhancement arises from electrostatic and hydrophobic interactions between reactants and micelles. Rates may be strongly dependent on the struture of the reactant. For example, the hydrolysis of methyl ort/iobenzoate is catalyzed by micellar sodium dodecylsulfate, whereas the hydrolysis of methyl ortho-formate (which has less hydrophobic character and less affinity for the micelle core) is not ". The more pronounced the hydrophobic nature of the reactant, the more rapid is the micellar catalysis. ... 

The most general route involves coupling an alkyne with ort/to-iodobenzoic acid or with methyl ortho-iodobenzoate." Both mono- (giving 3-substituted isocoumarins" ) and disubstituted alkynes will serve, allowing considerable flexibility for the construction of substituted isocoumarins. 

In a similar way, prodrug 59 was obtained from methyl ortho-tolyl uronate 66 (67) by (i)-bromination with A-bromosuccinimide to 67, (ii)-hydrolysis to 68, (iii)-activation using disuccinimidocarbonate to 69, and (iv)-condensation with doxorubicin to 70, which was finally deprotected in situ into 59 during in vitro test of enzymatic behaviour (Fig. 5) (66). 

CH3Si(OCH3)3 methyltrimethoxy-silane CH3C(0CH3)3 methyl ortho- acetate... 

Look for positions that are doubly or triply activated. In each structure count up the ntimlKT of methyls ortho or para to each open position. 

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