Two Multistep Reactions

A few well-known and widely used reactions use a cocktail of several different reagents and proceed by multistep mechanisms that are not easily discerned by the beginning student. Two of these reactions, the Swem oxidation and the Mitsunobu reaction, are discussed here. You will find that faculty members enjoy asking graduate students to draw mechanisms for these particular reactions, so you should learn them well  

When an alcohol is treated with a reaction mixture derived from oxalyl chloride, DMSO, and Et3N, it is oxidized to the aldehyde or ketone. The order of addition is important. First, oxalyl chloride is added to DMSO then, Et3N and the alcohol are added, and the reaction mixture is allowed to warm to room temperature. The by-products are Me2S (very smelly ), CO2, CO, and Et3NH+ cr. 

DMSO is nucleophilic on O. It reacts with the electrophilic oxalyl chloride by addition-elimination. 

S now has a good leaving group attached. Cl- can come back and attack S, displacing the oxalate, which decomposes to give C02, CO, and CD. The S-O bond is thereby cleaved. 

At this point S is a good electrophile. Now, the alcohol and Et3N are added. The alcohol is deprotonated and attacks S, displacing CD. 

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Another aspect of qualitative application of MO theory is the analysis of interactions of the orbitals in reacting molecules. As molecules approach one another and reaction proceeds, there is a mutual perturbation of the orbitals. This process continues until the reaction is complete and the new product (or intermediate in a multistep reaction) is formed. PMO theory incorporates the concept of frontier orbital control. This concept proposes that the most important interactions will be between a particular pair of orbitals. These orbitals are the highest filled oihital of one reactant (the HOMO, highest occupied molecular oihital) and the lowest unfilled (LUMO, lowest unoccupied molecular oihital) orbital of the other reactant. The basis for concentrating attention on these two orbitals is that they will be the closest in energy of the interacting orbitals. A basic postulate of PMO... 

Identification of the intermediates in a multistep reaction is a major objective of studies of reaction mechanisms. When the nature of each intermediate is fairly well understood, a great deal is known about the reaction mechanism. The amount of an intermediate present in a reacting system at any instant of time will depend on the rates of the steps by which it is formed and the rate of its subsequent reaction. A qualitative indication of the relationship between intermediate concentration and the kinetics of the reaction can be gained by considering a simple two-step reaction mechanism ... 

This chapter takes up three aspects of kinetics relating to reaction schemes with intermediates. In the first, several schemes for reactions that proceed by two or more steps are presented, with the initial emphasis being on those whose differential rate equations can be solved exactly. This solution gives mathematically rigorous expressions for the concentration-time dependences. The second situation consists of the group referred to before, in which an approximate solution—the steady-state or some other—is valid within acceptable limits. The third and most general situation is the one in which the family of simultaneous differential rate equations for a complex, multistep reaction... 

In Chapter 6 we considered the basic mles obeyed by simple electrode reactions occurring without the formation of intermediates. However, electrochemical reactions in which two or more electrons are transferred more often than not follow a path involving a number of consecutive, simpler steps producing stable or unstable intermediates (i.e., they are multistep reactions). 

Thus, in the case of two-step reactions, different methods of determining the exchange CD generally yield different results (in contrast to the case of simple reactions discussed earlier) Extrapolation of the limiting anodic and cathodic sections of the semilogarithmic plots yields values and if, respectively, while the slope of the linear section in an ordinary plot of the polarization curve yields the value of ig. It is typical for multistep reactions that the exchange CD determined by these methods differ. 

Gaiser and Heusler53 have shown that the electrode reaction Zn2+ + 2e Zn proceeds in two steps Zn2+ 4- e Zn+ and Zn+ + e Zn(s). Van Der Pol et a/.,54 using ac coupled with the faradaic rectification polarography method, also concluded that this reaction is a multistep reaction. Hurlen and Fischer55 have studied this reaction in an acid solution of potassium chloride and... 

Nonetheless, a wide variety of potential methods are available to achieve the goal of nanoencapsulation for the purpose of facilitating the use of two or more incompatible catalysts in cascade reactions. The many multistep reactions that are of importance in the fine chemicals industry are prime targets for the application of the principles of nanoencapsulation and, therefore, of green chemistry. 

Methylenetriphenylphosphorane reacted with Zn N(SiMe3)2 2 in a multistep reaction (Scheme 78) to furnish initially the 1,3-dizincatacyclobutane 119, featuring two three-coordinate zinc atoms, and finally the cr-zincated phosphorus ylide 120.176... 

The reaction consists formally of a 1,2 hydrogen shift. Ab initio calculations have been carried out for free HCCH. The transition state resembles the vinylidene and lies 45 kcal.mol 1 above HCCH. A transition metal fragment could favor this path by stabilizing the vinylidene species and all structures relatively close to this structure on the potential energy surface. Alternatively, the transition metal fragment can give entry to a multistep reaction pathway which is no more a 1,2 hydrogen shift. Two paths have been considered. 

Decreasing the number of reaction steps via a one-pot reaction associating two or more catalytic steps. This can be achieved by multistep reactions carried out by cascade catalysis without intermediate product recovery, thus decreasing the operating time and reducing considerably the amount of waste produced. 

Divisek et al. presented a similar two-phase, two-dimensional model of DMFC. Two-phase flow and capillary effects in backing layers were considered using a quantitatively different but qualitatively similar function of capillary pressure vs liquid saturation. In practice, this capillary pressure function must be experimentally obtained for realistic DMFC backing materials in a methanol solution. Note that methanol in the anode solution significantly alters the interfacial tension characteristics. In addition, Divisek et al. developed detailed, multistep reaction models for both ORR and methanol oxidation as well as used the Stefan—Maxwell formulation for gas diffusion. Murgia et al. described a one-dimensional, two-phase, multicomponent steady-state model based on phenomenological transport equations for the catalyst layer, diffusion layer, and polymer membrane for a liquid-feed DMFC. 

Adding the substituents in the correct order is crucial in mastering ciromatic synthesis problems. Examine the two reaction sequences given in Figure 8-4. Both sequences involve the same reagents however, the order is reversed. This shows that the reaction sequence is important. You need to plan ahead in any multistep reaction sequence. 

We should be able to generalize these findings to other more complex reaction systems, such as for two component multistep reactions to polymerizations and to non-Newtonian power law fluids. 

As-described compounds have also been proposed to be formed as intermediates in the gas phase in the traditional two-component MOCVD process (pre-reactions). For instance, the deposition of AlN from AlMe3 and NH3 [11] most likely proceeds through a multistep-reaction mechanism including both the adduct Me3Al-NH3 and the heterocycle [Me2AlNH2]3, that is formed after elimination of one equivalent of methane, as more or less stable reaction intermediates. This is supported by the fact that both compounds have been successfully used for the deposition of AIN in the absence of any additional NH3 [12]. The same was found for the deposition of InP from InMe3 and PH3 [13]. 

One of the important applications of mono- and multimetallic clusters is to be used as catalysts [186]. Their catalytic properties depend on the nature of metal atoms accessible to the reactants at the surface. The possible control through the radiolytic synthesis of the alloying of various metals, all present at the surface, is therefore particularly important for the catalysis of multistep reactions. The role of the size is twofold. It governs the kinetics by the number of active sites, which increase with the specific area. However, the most crucial role is played by the cluster potential, which depends on the nuclearity and controls the thermodynamics, possibly with a threshold. For example, in the catalysis of electron transfer (Fig. 14), the cluster is able to efficiently relay electrons from a donor to an acceptor, provided the potential value is intermediate between those of the reactants [49]. Below or above these two thresholds, the transfer to or from the cluster, respectively, is thermodynamically inhibited and the cluster is unable to act as a relay. The optimum range is adjustable by the size [63]. 

The synthesis of cyclic carbonates, starting from olefins, can be also carried out via a multistep method based on two separate reactions. To this end, C02 and the carboxylation catalyst have been added to the same reactor in which a preliminary epoxidation process had been carried out. 

A recent example is the hydrolysis of chloranil with aqueous sodium hydroxide, which is a multistep process leading to the chloranilate dianion, Fig. 5.21 [26]. In a two-phase reaction system consisting of solid chloranil and aqueous sodium hydroxide, the rate-limiting step is the initial attack of hydroxide ion on chloranil. Hydrolysis rates at the 010, 100 and 001 cleavage planes of chloranil were separately measured [27], and different reactivities were found this was rationalised by considering the exposure of the initially reactive functionality (assumed to be the carbonyl group) at the surface, as shown in Fig. 5.22. Hydrolysis at the 010 and 100 planes was shown to be a surface reaction driven by the hydroxide concentration adjacent to the interface the 001 plane was shown to react more slowly by prior dissolution of chloranil before reaction. 

Multi-electron (multistep) electrode processes will be studied in Sect. 3.3, underlining the key role of the difference of the formal potentials between each two consecutive electrochemical steps on the current-potential curves and also the comproportionation/disproportionation reactions that take place in the vicinity of the electrode surface. In the case of two-step reactions, interesting aspects of the current-potential curves will be discussed and related to the surface concentrations of the participating species. 

In Sect. 6.2, multi-electron (multistep) electrochemical reactions are surveyed, especially two-electron reactions. It is shown that, when all the electron transfer reactions behave as reversible and the diffusion coefficients of all species are equal, the CSCV and CV curves of these processes are expressed by explicit analytical equations applicable to any electrode geometry and size. The influence of the difference between the formal potentials of the different electrochemical reactions on these... 

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