Selective Acetal Synthesis

If there are substantial differences in the equilibrium constants for acetal formation of two carbonyl groups, it may be possible to form one acetal in preference to another. Selective acetal formation occurs in the competition between an aldehyde and a ketone. For example, 3-oxocyclohexanecarbalde-hyde reacts with one equivalent of ethylene glycol to give an acetal that protects the aldehyde group. 

The ability to protect an aldehyde in the presence of a ketone allows chemical reactions of the ketone group without competitive reactions that would occur in the original unprotected compound. For example, the Wolff-Kishner reduction converts the carbonyl group to a methylene group. 

The ketone cannot be reduced selectively by a Clemmensen reduction because it requires HCl. The acid hydrolyzes the acetal, so the aldehyde is no longer protected, and thus both carbonyl groups would be reduced. 

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The chemistry of vinyl acetate synthesis from the gas-phase oxidative coupling of acetic acid with ethylene has been shown to be facilitated by many co-catalysts. Since the inception of the ethylene-based homogeneous liquid-phase process by Moiseev et al. (1960), the active c ytic species in both the liquid and gas-phase process has always been seen to be some form of palladium acetate [Nakamura et al, 1971 Augustine and Blitz, 1993]. Many co-catalysts which help to enhance the productivity or selectivity of the catalyst have appeared in the literature over the years. The most notable promoters being gold (Au) [Sennewald et al., 1971 Bissot, 1977], cadmium acetate (Cd(OAc)j) [Hoechst, 1967], and potassium acetate (KOAc) [Sennewald et al., 1971 Bissot, 1977]. 

The effect of the catalyst composition upon the catalyst activity, selectivity, and reaction pathways was examined using a conventional high pressure fixed reactor and a TAP reactor. Particular emphasis was placed upon the effect of Au and KOAc on the acceleration or impedance of the pathways associated with vinyl acetate synthesis. A summary of the key findings is given below ... 

Marchand and co-workers ° synthesis of 5,5,9,9-tetranitropentacyclo[5.3.0.0 .0 °.0 ] decane (52) reqnired the dioxime of pentacyclo[5.3.0.0 .0 °.0 ]decane-5,9-dione (49) for the incorporation of the four nitro groups. Synthesis of the diketone precursor (48) was achieved in only five steps from cyclopentanone. Thus, acetal protection of cyclopentanone with ethylene glycol, followed by a-bromination, and dehydrobromination with sodium in methanol, yielded the reactive intermediate (45), which underwent a spontaneous Diels-Alder cycloaddition to give (46). Selective acetal deprotection of (46) was followed by a photo-initiated intramolecular cyclization and final acetal deprotection with aqueous mineral acid to give the diketone (48). Derivatization of the diketone (48) to the corresponding dioxime (49) was followed by conversion of the oxime groups to gem-dinitro functionality using standard literature procedures. 

It is clear that ruthenium-cobalt-iodide catalyst dispersed in low-melting tetrabutylphosphonium bromide provides a unique means of selectively converting synthesis gas in one step to acetic acid. Modest changes in catalyst formulation can, however, have profound effects upon liquid product composition. 

Nevertheless, the critical role of the iodide fraction in ensuring a selective acetic acid synthesis is illustrated by the... 

Modern catalysts for vinyl-acetate synthesis contain Au in the chemical formulation, which manifests in much higher activity and selectivity. This is reflected by fundamental changes in the kinetics, such as for example switching the reaction order of ethylene from negative to positive [8]. As a consequence, in more recent studies the formation of vinyl acetate can be described conveniently by a power-law kinetics involving only ethylene and oxygen ... 

The case study of vinyl acetate synthesis emphasises the benefits of an integrated process design and plantwide control strategy based on the analysis of the Reactor / Separation / Recycles structure. The core is the chemical reactor, whose behaviour in recycle depends on the kinetics and selectivity of the catalyst, as well as on safety and technological constraints. Moreover, the recycle policy depends on the reaction mechanism of the catalytic reaction. 

Unlike the first step, the saponification is highly selective. The synthesis of the 2,2,2-trifluoroethyl acetate 5 requires high temperature (150-180°C) and pressure (15 bare). This reaction involves polar aprotic solvents such as NMP, DMSO and sulfolane. The major drawbacks of this process are corrosion and waste water disposal. 

The former synthesis proceeds via epoxide 278 which was ring opened by azide, the resulting alcohol was protected and full reduction of the lactone and mesylation gave 279. Reductive cyclization and deprotection then provided 280 (Scheme 23). The 6-epi analogue 111 was prepared by converting 275 to pyrrolidine 276. Selective acetal removal and primary hydroxyl mesylation then allowed reductive cyclization followed by deprotection to give 277. Similar chemistry was also used to convert 281, closely related to 275, to (2R)-2-hydroxy-6-e/ /-castanospermine 282. ... 

In this section, four examples illustrating the application of the rate-based approach discussed above to the RD modeling are presented. The systems selected are methyl acetate synthesis, MTBE synthesis, ethyl acetate synthesis and transesterification of dimethyl carbonate. In the first example, dynamic process modeling is highlighted, whereas in three other examples, different aspects of steady-state modeling are discussed. 

For the methyl acetate synthesis, dynamic modeling effects are investigated, whereas for other systems, the focus is on different steady-state issues, for example the influence of liquid-liquid separation, operational conditions and different column internals (ethyl acetate) or selectivity effect (dimethyl carbonate transesterification). The comparison between the simulation and experimental data made for all RD case studies proves that the rate-based approach is capable of predicting correct process behavior, both steady state and dynamic. 

Bishomocubanes have been used to provide a synthesis of the fluxional C.oH 10 isomer hypostrophene (984) in 12% overall yield. Treatment of cyclopentadiene with ethyl nitrite and ethoxide gives (980). Deoximation and selective acetalization gives (981), which on irradiation and then hydrolysis gives (982) which was reduced, mesy-lated, and substituted with iodide to give (983). Reduction by Na-K alloy of the 1,4-di-iodide gives hypostrophene. A [2 2] cycloaddition in the hypostrophene... 

Monte Carlo simulations to examine how changes in the surface composition, ensemble size, shape and specific structural arrangements of Pd and Au for model substrates influence the simulated activity and selectivity , The simulation of vinyl acetate synthesis over Pd(lll) results in a very low production of vinyl acetate. The surface is essentially poisoned by the acetate and oxygen intermediates that form. At the steady-state, ethylene has a difficult time finding free Pd sites available on which to adsorb. Higher pressmes of ethylene are required in order to adsorb ethylene to any appreciable degree. This is consistent with experimental results. 

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

By selection of appropriate operating conditions, the proportion of coproduced methanol and dimethyl ether can be varied over a wide range. The process is attractive as a method to enhance production of Hquid fuel from CO-rich synthesis gas. Dimethyl ether potentially can be used as a starting material for oxygenated hydrocarbons such as methyl acetate and higher ethers suitable for use in reformulated gasoline. Also, dimethyl ether is an intermediate in the Mobil MTG process for production of gasoline from methanol. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

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