Ortho acid esters, formation

The authors suggest that the most probable scheme is an initial intramolecular cyclisation of the ortho-acid ester centres generating the corresponding anhydrides which then react as usual to produce polyamic acids, finally subjected to thermal imidization. The intermediate compound 35 in Fig. 16 would be the first step of polyamic acid formation when one anhydride group has been produced and immediately opened by one amine function. The reaction is thermally controlled to produce oligomers which are marketed in the form of either adhesive films, pastes, or solid powders. Polycondensation and imidization are completed on processing at high temperature, followed by a postcure at 316°C. 

This point is well-illustrated by the data of Table 19, which show the effect of methyl substituents on the rate coefficients for methyl ester formation from benzoic acid. The compounds fall naturally into three classes. Those with no ortho substituent react 3-4 times as fast as those which have one orthomethyl group, while 2,6-dimethylbenzoic acid, the only compound with two orf/io-substituents, did not give the ester at a measurable rate. 

Orf/io-substituents in general reduce the rates of acid-catalyzed ester formation and hydrolysis. Some typical data are collected in Table 20. In each series the rate coefficient decreases as the size of the ortho substituent increases. Only the smallest substituent of all, the fluorine atom, does not have a marked effect. 

The data for acid-catalyzed ester formation in cyclohexanol are doubly interesting. The activation parameters are closely similar to those for the acid-catalyzed hydrolysis of the corresponding ethyl esters. The enthalpy of activation is considerably higher than for esterification in methanol this is probably a result of steric inhibition of solvation, as well as non-bonded compression in the transition state, as suggested by the entropies of activation, which are also significantly higher than with methanol, especially for compounds without ortho substituents which presumably have more transition state solvation to lose. 

One can also acetalize carbonyl compounds completely without using the alcohol in excess. This is the case when one prepares dimethyl or diethyl acetals from carbonyl compounds with the help of the ortho formic acid esters trimethyl ortho formate HC(OCH3)3 or triethyl ortho formate HC(OC2H5)3, respectively. In order to understand these reactions, one must first clearly understand the mechanism for the hydrolysis of an orthoester to a normal ester (Figure 9.13). ft corresponds nearly step by step to the mechanism of hydrolysis of 0,0-acetals, which was detailed in Figure 9.12. The fact that the individual steps are analogous becomes very clear (see Figure 9.13) when one takes successive looks at... 

For a review of the formation of ortho esters by this method, see DeWolfe, R.H. Carboxylic Ortho Acid Derivatives, Academic Press, NY, 1970, pp. 12-18. 

As a further test, we attempted to convert the 14-OH group to hydrogen in 10, to confirm that the 14-OH group participated in the abstraction of the 2 -hydrogen of dithiane 10. Compound 16 was synthesized from naltrexone methyl ether [22] and then subjected to the same acetal exchange reaction as above. Under the same conditions, acetal 18 was obtained instead of the objective ortho ester (Scheme 4), consistent with our hypothesis that the 14-OH group participated in the ortho ester formation. Subsequently, the obtained ortho ester 12 was readily hydrolyzed with acid to give ester 19 (Scheme 5). 

Bismuth(lll) salts such as BiCls, BiBrj, Bi(OCOR)3, and Bi (OTf), [166] have been widely used as Lewis acid catalysts to mediate C-C bond formation. Bi (OTf) 3, Bi2O3, and BiCl, catalyze Friedel-Crafts acylation with acyl chlorides or acid anhydrides [167]. Both electron-rich and electron-deficient arenes are acylated in high yields under catalysis by Bi(OTf)3 (Scheme 14.82). Under microwave irradiation the catalytic activity of BiX3 (X = C1, OTf) in the acylation of aromatic ethers is enhanced [168]. The N-acyl group of p-substituted anilides migrates to the ortho position of the aromatic nucleus under BiCls catalysis [169]. Treatment of 2,3-dichloroanisole with the ethyl glyoxylate polymer in the presence of a catalytic amount of Bi(OTf)3 affords an a,a-diarylacetic acid ester quantitatively (Scheme 14.83) [170]. 

The addition of methyl groups to the oxetane precursor increases the rate of ortho ester formation by a factor of 22,000 over the OBO derivative and decreases its rate of acid catalyzed hydrolysis by a factor of 2. ... 

Oxidation of aldehydes with peroxy-acids is not so synthetically useful as oxidation of ketones and generally gives either carboxylic acids or formate esters. However, reaction of ortho- and para-hydroxy-benzaldehydes or -acetophenones with alkaline hydrogen peroxide (the Dakin reaction) is a useful method for making catechols and quinols. With benzaldehyde itself, only henzoic acid is formed, but orr/jo-hydroxy-benzaldehyde (salicylaldehyde) gives catechol almost quantitatively (6.65) and 3,4-dimethylcatechol was obtained by oxidation of 2-hydroxy-3,4-dimethylacetophenone. 

Phosphoms modified phenolics are synthesized by condensation of phosphoric acid esters and phosphorus oxychloride with phenolic resins or phenol in the presence of 1,4-dioxane [175-178], The formation of eight-membered cyclic ring structures by intramolecular esterification (Scheme 28) occurs if ortho-linked novolacs are used in the reaction with difimctional phosphorus oxychlorides [177],... 

Ester formation is evidently involved, since silica did not dissolve in acetone under the same conditions. Also it was shown that the surface of the silica gel used as a source of silica was fully esterified. However, it is not certain that the dissolved species was the ortho ester or esters of polysilicic acids. The polymerization of the dissolved silica on cooling suggests that the dissolved species may have contained some silanol groups either from traces of water in the system or from residual silanol groups on the gel that was used, even though the latter had been dehydrated at high temperature. 

Chimerical decomposition with the cleavage of one bond and formation of another bon is close to concerted decomposition. ortho-Substituted esters of perbenzoic acid decompose very rapidly if the substituent X is the iodine atom, RS radical or a substituent with the double bond. The accelerating eifect of these ortho-substituents is explained by the fact that the cleavage of the O—O bonds in the transition state is compensated in part by O—X bond formation, for example. 

Acylated Corticoids. The corticoid side-chain of (30) was converted iato the cycHc ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR )2 iu benzene solution ia the presence of i ra-toluenesulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) ia nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively iato prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The iatermediate ortho esters also are active. Thus, 17a,21-(l -methoxy)-pentyhdenedioxy-l,4-pregnadiene-liP-ol-3,20-dione [(96), R = CH3, R = C Hg] is at least 70 times more potent than prednisolone (89). The above conversions... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

A reaction which has proved to be of much use in synthetic organic chemistry is the formation of the ortho and/or the para isomers of a hydroxyketone (CVI and CVTI) by treatment of a phenolic ester (CV) with an acid catalyst, viz. 

The Popik group has recently begun to explore the potential of phenols to photorelease ethers and alcohols attached to an ortho-hem,y c group. For example, they have shown that esters and ethers of (3-hydroxymethyl)naphthalene-2-ol (i.e., 70) efficiently release the corresponding alcohols and acids upon exposure to UV irradiation ( 0.3),50 with formation of naphthoquinone methide 71 occurring in the process (Eq. 1.17). 

Fries rearrangement.1 Rearrangement of phenyl esters with Lewis acids results in a mixture of ortho- and para-phenolic ketones. In contrast, reaction of an o-bromophenyl ester with sec-butyllithium results in exclusive formation of the orf/jo-phenolic ketone by an intramolecular acyl rearrangement.2... 

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