Thermodynamically favorable Section

The last chapter in this introductory part covers the basic physical chemistry that is required for using the rest of the book. The main ideas of this chapter relate to basic thermodynamics and kinetics. The thermodynamic conditions determine whether a reaction will occur spontaneously, and if so whether the reaction releases energy and how much of the products are produced compared to the amount of reactants once the system reaches thermodynamic equilibrium. Kinetics, on the other hand, determine how fast a reaction occurs if it is thermodynamically favorable. In the natural environment, we have systems for which reactions would be thermodynamically favorable, but the kinetics are so slow that the system remains in a state of perpetual disequilibrium. A good example of one such system is our atmosphere, as is also covered later in Chapter 7. As part of the presentation of thermodynamics, a section on oxidation-reduction (redox) is included in this chapter. This is meant primarily as preparation for Chapter 16, but it is important to keep this material in mind for the rest of the book as well, since redox reactions are responsible for many of the elemental transitions in biogeochemical cycles. 

Methanol still proceeds through an initial C H bond scission, but reacts with water before the OH bond breaks. Alternatively, formaldehyde formation likely occurs along the same pathway as CO formation. This is true if HCO is an intermediate in the decomposition pathway. Furthermore, the lack of a kinetic isotope effect for CH3OD indicates that formaldehyde is not the product of an initial O-H scission.94 Because formaldehyde and formic acid are not the thermodynamically favored products of methanol oxidation, they must be the result of kinetic limitations preventing the full oxidation to C02, analogous to the production of H202 for the reduction of oxygen (see next section). 

The first phase of our efforts was the unambiguous synthesis of each model substrate. PN and PX were already well characterized materials (1) While direct synthesis of the phenyl and carbomethoxy compounds from PN and/or PX was attempted, this approach was unsuccessful due to the sluggish reactivity of the norbornenyl double bonds in these molecules (2). A successful approach to CBN and (fiBN based on N-phenyl maleimide (NPMI) trapping of the respective thermodynamically favored 1-substituted cyclopentadienes is shown in Equation 1. Similarly, kinetic trapping of 2-phenyl cyclopentadiene, from the in situ dehydration of 3-hydroxy, 3-phenyl cyclopentene, gives a clean yield of (f)VN (Equation 2). The remaining phenyl isomer (VX) and the three other carbomethoxy isomers (CBX, CVN, CVX) were all obtained by the thermal isomerization chemistry described in the next section of this paper. They were each isolated in pure form by liquid chromatography We were unable to obtain any (f)BX or any of the 7-substituted isomers by any means. 

Carbene fluorescence in solution is usually red shifted by 25-30 nm with respect to the band position observed in matrix at 77 K. This shift is attributed to emission from nonequilibrated conformations at low temperature. In matrices, the carbene is produced in a locked conformation similar to that for the precursor diazo compound but, in solution, it approaches the thermodynamically favored configuration. This difference has been demonstrated by variable temperature EPR studies of sterically congested carbenes (see Section 3.1.1.3). So, in solution, the equilibrium conformation is reached rapidly and only fluorescence from the relaxed state is observed. In support of this suggestion, the shift for dimesitylcarbene is smaller than for other carbenes, indicating that shifts are smaller when the carbene structure is such that it restricts conformational change. 

Reaction 9.1 might seem to be thermodynamically favored, but in fact no kinetically easy route from triply bonded N2 to N03 exists, since the endothermic intermediate NO (Section 8.4.2) is likely to be involved. As written, reaction 9.2 has prohibitive energetics, but in practice the process is more complex than this. For example, the fact that free 02 is not formed, but is in effect consumed in other biochemical reactions, makes for a favorable energy balance. The limiting factor is again kinetics, as plausible intermediates such as hydrazine (H2N—NH2) are endergonic compounds. 

Other very important applications of C-terminal thioester-functionalized peptides include their usage in the condensation of large unprotected peptide fragments (ligation see Vol. E22a, Section 4.1.5). 4,5,74 In this process the thioester-modified unprotected peptide reacts with the N-terminal cysteine of a second unprotected peptide giving a thioester intermediate. This step is followed by a rapid intramolecular S—>N shift with formation of the thermodynamically favored amide bond at the ligation site. 

Cyclization of 1,3,5-hexatriene occurs only when the central double bond has the cis configuration. The reaction is reversible at elevated temperatures because of the gain in entropy on ring opening (see Section 4-4B). The cyclobutene-1,3-butadiene interconversion proceeds much less readily, even in the thermodynamically favorable direction of ring opening. However, substituted dienes and cyclobutenes often react more rapidly. 

Many pericyclic reactions take place photochemically, that is, by irradiation with ultraviolet light. One example is the conversion of norbornadiene to quadricyclene, described in Section 13-3D. This reaction would have an unfavorable suprafacial [2 + 2] mechanism if it were attempted by simple heating. Furthermore, the thermodynamics favor ring opening rather than ring closure. However, quadricyclene can be isolated, even if it is highly strained, because to reopen the ring thermally involves the reverse of some unfavorable [2 + 2] cycloaddition mechanism. 

Another characteristic of electrophilic reactions of pseudoazulenes is the application of numerous cations as the electrophile, for example, diazonium salts and Vilsmeier- Haack s reagent (see Table VI), tropylium ion,135 triphenylmethyl cation,"4 pyrylium ion,119 and dithiolium ion.166 Very stable cations are formed (e.g., 120) addition of base releases the substituted pseudoazulene (see example in Eq. 10). Generally reactions of this type are thermodynamically favored (see also Section IV,B). The site of substitution... 

The second approach forms the triple bond by a double dehydrohalogenation of a dihalide. This reaction does not enlarge the carbon skeleton. Isomerization of the triple bond may occur (see Section 9-8), so dehydrohalogenation is useful only when the desired product has the triple bond in a thermodynamically favored position. 

Nitric acid is produced by the selective oxidation of NH3 over a gauze catalyst composed of 90%Pt, 10%Rh (some gauze is 90% Pt, 5% Rh and 5% Pd).30 This reaction was used in the Selectivity section to demonstrate the high efficiency with which PtRh leads to NO production as opposed to more thermodynamically favored N2. 

Many unstable substances are simply reactive, i.e., kinetically unstable. In recent years a realization of this has led to the design of ligands or substituents that diminish reactivity. Most commonly, this is done simply by placing so much steric hindrance in the potential reaction path that an otherwise thermodynamically favored reaction cannot get underway. In other cases, it is a question of choosing ligands or substituents that are themselves unable to engage in a type of reaction that could result in decomposition. In this section examples of both of these approaches will be presented. 

Hydrido alkyl species L M(H)(R) are particularly prone to elimination of R—H this thermodynamically favored reaction is the reverse of C—H activation (see Section 21-4) and explains why for a long time intermolecular C—H activation remained elusive. For example, the protolysis of (TMEDA)PtMe2 by HC1 does not lead to the direct electrophilic attack of H+ on the Pt—Me bond but gives thermally unstable hydrido alkyl (TMEDA)Pt(H)ClMe2 which undergoes reductive elimination via a coordinatively unsaturated 5-coordinate intermediate 97... 

This reaction is used for the synthesis of nitric acid in the Ostwald process (see Section 7.8.1). Without catalysts, and at higher temperatures, ammonia bums in an oxygen atmosphere with a pale yellow flame forming the thermodynamically favorable products dinitrogen and water (AH = -1267kJmol ). At high pressures, mixtures of ammonia and oxygen are explosive. 

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