Methanol solvolysis

The results of the methanolic solvolysis study shown in Fig. 7.15 reveals that nucleophilic attack on the cyclopropyl quinone methide by methanol affords the pyrido[1,2-a]indole (73 ppm) and azepino[l,2-a]indole (29ppm) trapping products. Initially, nucleophilic attack on the cyclopropane ring affords the hydroquinone derivatives (see Scheme 7.17) that oxidizes to the quinones upon aerobic workup. 

FIGURE 7.15 Enriched 13C-NMR of the methanolic solvolysis pyrido [l,2-a]indole-based cyclopropyl quinone methide. 

Moreover, mass law retardation was evident on the conversion of cis-[PtMe(MeOH)(PEt3)2] in methanol/ether mixtures. In a general comparison of previously performed isomerizations of cis-[PtRCl(PEt3)2], the authors concluded that methanol solvolysis followed by dissociation of the methanol competed with direct dissociation of the chloride, and that a geometry change of the 3-coordinate intermediate applied in each case. The exception was when R was mesityl, the bulk of this ligand presumably being responsible for the anomaly. Scheme 4 combines these conclusions. 

Analogous reactions take place in other solvents which like water contain an —OH group Solvolysis in methanol (methanolysis) gives a methyl ether... 

Suggest a structure for the product of nucleophilic substitution obtained on solvolysis of tert-butyl bromide in methanol and outline a reason able mechanism for its formation... 

Thiirenium ions formed as intermediates in the solvolysis of tran5-/3-thiovinyl sulfonates react with methanol to give product with retention of configuration (Scheme 75) (79MI50600). 

There is some evidence for the formation of unstable benzazetidines from [2 + 2] cycloaddition of benzyne to imines (75BCJ1063). A novel formation of a benzazetidine is reported in the solvolysis of the exo iV-chloro compound (297). Neighbouring group participation by the benzene ring leads to the cation (298), which is intercepted by methanol to give the benzazetidine (299) (81CC1028). 

The dlenophlle, 3-acetyl-2(3H)-oxazolane, Is an attractive Intermediate for the synthesis of vicinal aminoalcohols with cIs configurations. It reacts with 1,3-dienes, even under quite mild conditions, to form (4+2) cycloadducts. Its high reactivity with deactivated 1,3-dienes Is noteworthy. This property is present also in 2(3H)-oxa201one which can be obtained easily through solvolysis of 3-acetyl-2(3H)-oxa2olone In methanol. 3-Acetyl-2(3H)-oxazolone, on UV irradiation In the presence of a sensitizer, combines easily with olefins to form (2+2) cycloadducts, the hydrolysis of which leads to the class of cis-2-aminocyclobutanols. 

Deoxygenation is sensitive lo solvent and structure. Alcohols lend lo favor loss of oxygen, as illustrated in selected data of Accrombessi et al. (/). Additionally, methanol and ethanol may give substantial amounts of solvolysis products, in this case methoxy- and ethoxycyclohexanols. 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

There seem to have been only two investigations on dediazoniations in a protic solvent, where the observed products indicate that, in addition to DN + AN solvolysis, an aryne is likely to be present as a metastable intermediate. Broxton and Bunnett (1979) have found that 3-nitroanisole is formed in the dediazoniation of 2-nitroben-zenediazonium ions in methanol in the presence of methoxide ions. This has to be interpreted as a product arising from 3-nitro-l,2-benzyne as an intermediate. The occurrence of the aryne mechanism in poly (hydrogen fluoride)-pyridine mixtures, as discovered by Olah and Welch (1975), is mentioned in Section 8.2. 

The second method is termed ad eosdem competition— to the same (products, plural) . Consider the solvolysis of 4-chlorobenzyne by methoxide ions and methanol. The nucleophile adds to one end or the other of the triple bond. Because of the 4-chloro substituent, both meta and para isomers are formed. Thus, there are four parallel reactions ... 

Negative evidence for a common intermediate is just as important, for it can thereby eliminate a contending mechanism. The solvolysis of 2-halo-2,3,3-trimethylbutanes in methanol provides such an example.17 If it occurs by the elimination of a carbocation, the intermediate should undergo elimination and substitution reactions independent of the identity of the halide. These are shown as follows ... 

The principal solvolysis reactions for PET are methanolysis with dimethyl terephthalate and ethylene glycol as products, glycolysis with a mixture of polyols and BHET as products, and hydrolysis to form terephthalic acid and ethylene glycol. The preferred route is methanolysis because the DMT is easily purified by distillation for subsequent repolymerization. However, because PET bottles are copolyesters, the products of the methanolysis of postconsumer PET are often a mixture of glycols, alcohols, and phthalate derivatives. The separation and purification of the various products make methanolysis a cosdy process. In addition to the major product DMT, methanol, ethylene glycol, diethylene glycol, and 1,4-cyclohexane dimethanol have to be recovered to make the process economical.1... 

The hydrochloride may be isolated in a 35% yield as a stable and easy to handle white solid. The free amine T8[(CH2)3NH2]8 can be prepared in a quantitative yield by the reaction of T8[(CH2)3NH3C1]8 in methanol with a basic Amberlite IRA-400 exchange resin (Table 24, entry 3). Alternatively, if the initial solvolysis of H2N(CH2)2Si(OEt)3 is carried out in a basic medium the free amine is reported to be formed directly in excellent yield (Table 24, entry 4). In this case, decomposition of the resulting amine was not reported (see below). 

Essentially similar results and conclusions were obtained by Peterson and Indelicato (158) in the solvolysis of the corresponding tosylates and brosylates, 171 b (R = p-CHj Cfi H4 or p-BrCg H4 ) and 171 c (R = p-CHj 5 H4, p-BrCg H4 ), in 50% aqueous methanol at 130°. In this case, the trans isomer was found to react at a rate 10 times that of the cis isomer. Furthermore, the trans isomer gave 95% 2-butyne and 5% 2-butanone, whereas the cis isomer gave 72% 2-butyne and 28% 2-butanone as products. Also, as expected (vide supra) for a unimolecular solvolysis reaction, the cis brosylate reacts at a rate four times that of the corresponding tosylate. 

Further evidence for neighboring sulfur involvement and ion 208b in the solvolysis of 207 comes from the investigation of the stereochemistry of the products and the observed rearrangements (181). Solvolysis of ester 211 in 4 1 acetone methanol at 25° gave only one geometric isomer, 212, as product. 

Anchimeric assistance in the solvolysis of /3-arylthiovinyl sulfonates was demonstrated by means of kinetic studies on model compounds (182). In a variety of solvents ranging from nitromethane and methanol to acetic acid, the /3-arylthiovinyl sulfonate 216 was shown to react 20 to 33 times faster than the triphenylvinyl sulfonate 217. Different accelerating factors were... 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

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