Alkoxy acceleration

New ring-opening methods for phenylthio-substituted cyclopropylcarbinols generate intermediates with various possibilities for further transformation an example is shown in equation lOS " An overall [3 -I- 3]-annulation process is offered by combination of the Trost route to 2-vinylcyclobutanones and an alkoxy-accelerated rearrangement (equation 109). ... 

This transformation was presumed to occur via an intermediate vinyl sulfoxide, which underwent a [3,3]-sigmatropic rearrangement via a chairlike transition state with the methyl group quasi-equatorial to afford 52. Since the rearrangement occurred under very mild thermal conditions, it was proposed that this may be a type of alkoxy accelerated pericyclic reaction.57... 

Chloromethylation of the aromatic nucleus occurs readily with alkyl and alkoxy substituents accelerating the reaction and halo, chloromethyl, carboxyl, and nitro groups retarding it. 

Other miscellaneous compounds that have been used as inhibitors are sulfur and certain sulfur compounds (qv), picryUiydrazyl derivatives, carbon black, and a number of soluble transition-metal salts (151). Both inhibition and acceleration have been reported for styrene polymerized in the presence of oxygen. The complexity of this system has been clearly demonstrated (152). The key reaction is the alternating copolymerization of styrene with oxygen to produce a polyperoxide, which at above 100°C decomposes to initiating alkoxy radicals. Therefore, depending on the temperature, oxygen can inhibit or accelerate the rate of polymerization. 

Metal-Catalyzed Oxidation. Trace quantities of transition metal ions catalyze the decomposition of hydroperoxides to radical species and greatiy accelerate the rate of oxidation. Most effective are those metal ions that undergo one-electron transfer reactions, eg, copper, iron, cobalt, and manganese ions (9). The metal catalyst is an active hydroperoxide decomposer in both its higher and its lower oxidation states. In the overall reaction, two molecules of hydroperoxide decompose to peroxy and alkoxy radicals (eq. 5). 

Ester interchange (transesterification) is a reaction between an ester and another compound, characterized by an exchange of alkoxy groups or of acyl groups, and resulting in the formation of a different ester. The process of transesterification is accelerated in the presence of a small amount of an acid or a base. 

The application of in situ-generated (alkoxy)palladium(II) species (Scheme 14.23) can be extended to reactions of a-carbonates with organoboron compounds. Crosscouplings of allenes 108 with aryl (or alkenyl) boron acids or their esters catalyzed by a palladium(O) complex afforded the 2-aryl(alkenyl)-l,3-butadienes 109 in excellent yields (Scheme 14.24) [53], The coupling reactions of 9-BBN-derived intermediates such as ester 111 can be accelerated by applying K3P04 as additive (Eq. 14.15). 

The existence of a protonated oxazolone has been demonstrated indirectly by a simple experiment. When p-nitrophenol was added to an excess of 2-alkoxy-5(4//)-oxazolone in dichloromethane, a yellow color appeared. The color persisted until all the p-nitrophenol had been consumed by the oxazolone. The anion of p-nitro-phenol is yellow. The explanation for the color of the mixture is the presence of the p-nitrophenoxide anion that was generated by abstraction of the proton by the oxazolone. In summary, protonation of the O-acylisourea suppresses the side reaction of oxazolone formation as well as the side reaction of A-acylurea formation and accelerates its consumption by enhancing its reactivity and generating an additional good nucleophile that consumes it. Protonation of the oxazolone suppresses epimerization by preventing its enolization and also increases the rate at which it is consumed.4 68 78 79... 

Furthermore, the preparation and reactions of 2-methoxythiophene were studied by Sice (70). This compound was obtained by a copper catalysed Williamson synthesis. It was also found that iodothiophene reacted readily with sodium alkoxides, whereas bromothiophene reacted slowly and chlorothiophene did not react at all. Sodium iodide accelerated the reaction of bromothiophene. The ortho, para orienting alkoxy group on carbon atom 2 increased the directive influence of the sulphur atom to the 5 position but competed with it to induce some attack on the 3 position by electrophilic reagents (nitration, acylation). The acylation of 2-methoxythiophene with stannic chloride at low temperatures furnished a mixture of two isomers. The 5-methoxy-2-acetothienone was obtained in higher yield and was identified by its ultraviolet absorption spectrum. 

Being less basic than the saturated analogs, vinyllithium as all other acyclic or cyclic 1-alkenyllithiums can be prepared from iodo or bromo and sometimes even chloro precursors using butyllithium or fert-butyUithium (Tables 12 and 13). Hetero-substituents such as dialkylamino, alkoxy and silyloxy groups or halogen atoms again accelerate the exchange process considerably (Table 14). This holds for 0-lithiated hydroxy or carboxy functions as well (Table 15). 

This oxidative dimerization can be minimized by increasing the dilution and adjusting the use of accelerants.185 Alcohols producing aldehydes, which equilibrate with a substantial proportion of hydrate, tend to be very prone to this side reaction. In fact, the reported examples186 of this side reaction involve intermediate aldehydes possessing an alkoxy group at the a position, which greatly activates aldehydes to hydration or to hemiacetal... 

Chlorohydrins are compounds characterized by alpha halo-alpha alkoxy groups bound to a common carbon atom. These compounds undergo rapid hydrolysis at this shared carbon atom. Bis(2-chloroisopropyl)ether, a chlorohydrin, has two such carbon atoms, and both react very rapidly with water. In fact, the reactions are so fast that acid and alkaline contributions have not been determined. It is likely, however, that base accelerates the reaction kinetics. The proposed reaction pathway for this compound is based on the reported pathway for bis(chloroethyl)ether (Figure 13.4). The reported rate constant for bis(chlorome-thyl)ether, of 0.23 sec-1 was based on an observed half-life of a few minutes. Similarly, for bis(2-chloroisopropyl)ether, both of the chloro substituents are reactive, and a half-life of a few minutes can be assigned to this compound, as well. 

Treatment of 9-oxabicyclo[3.3.1]nonan-l-ols 1014 with a combination of lead tetraacetate and copper diacetate affords 3-allenyl tetrahydropyran-2-ones 1015 via an alkoxy radical accelerated ((-fragmentation pathway (Equation 396) <2001TL2047>. 

The accelerated rate for alcoholysis with le, which was observed for the 10 % Pd/C catalytic system, was also seen with the Mn(CO)sBr catalyst. Reactions of le with primary, secondary or tertiary alcohols resulted in moderate yields of the corresponding silyl ketals after 2 h (Table 8 and 9). When mono-alkoxy silane from 3-hydroxy butyrate (lg) was treated with homoallyl alcohol in the presence of Mn(CO)sBr as the catalyst under the standard conditions, 76 % of the silyl ketal was obtained. These silyl ethers possess neighboring carbonyl groups that can participate in the reaction by forming a more reactive pentacoordinated silicon center upon addition of the silane to the metal center.. 

The occurrence of base-catalyzed substitutions of one alkoxy group by another in stable oxyphosphoranes was discussed in Section VIII.129 The rate of these substitutions is enormously accelerated by pyridine or by 2,4,6-trimethylpyridine, and depends on the base concentration. A reasonable interpretation is that the coordination number of the phosphorus increases in the transition state or in the intermediate of this reaotion (113) or (H4). 

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