Thermodynamic synthesis

Koehler JP, Aguirre P, Blass E. Evolutionary thermodynamic synthesis of zeotropic distillation sequences. Gas Sep Purif 1992 6 153. 

Rowan SJ, Stoddart JF (1999) Thermodynamic synthesis of rotaxanes by imine exchange. OrgLett 1 1913-1916... 

Koehler, J., Aguirre, P., and Blass, E. Evolutionary Thermodynamic Synthesis of Zeotropic Distillation Sequences, Gas Separ. Purif. 6, 4153 (1992). 

Kozlov, G. V Shustov, G. B. Zaikov, G. E. The reaction cessation in polycondensation process fractal analysis. In book Progress in Chemistry and Biochemistry. Linetics, Thermodynamics, Synthesis, Properties and Applications. Ed. Pearce, E. Zaikov, G. New York, Nova Science Publishers, Inc., 2009,61-72. 

Boroxine formation, through the cyclotrimerization of three boronic acid units, is another reversible reaction recently applied in dynamic covalent synthesis (Figure 1.3u). The forward reaction is entropicaUy driven by the release of water molecules upon condensation and is favored where electron-donating groups in the para position are used [42]. To date, this reaction has only been used in the designed thermodynamic synthesis of a Cj-symmetric [4]rotaxane 26, apparently under thermodynamic control (Scheme 1.12) [43]. However, it could be envisaged that... 

Figure 17 Kinetic and thermodynamic synthesis of disulfide-linked hemicarceplexes 46 guest and 47 guest2 from cavitands 48 and 49, respectively.

It is remarkable that fatty acid synthesis for a long stretch runs in common with the reverse of /S-oxidation, but deviates in one significant step. A very similar situation will be found with the carbohydrates. The detour is more favorable thermodynamically (synthesis is favored by the equilibrium) but does require one extra ATP per C unit. Note also that the detour permits separate regulation of synthesis and degradation. 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

Olefin synthesis starts usually from carbonyl compounds and carbanions with relatively electropositive, redox-active substituents mostly containing phosphorus, sulfur, or silicon. The carbanions add to the carbonyl group and the oxy anion attacks the oxidizable atom Y in-tramolecularly. The oxide Y—O" is then eliminated and a new C—C bond is formed. Such reactions take place because the formation of a Y—0 bond is thermodynamically favored and because Y is able to expand its coordination sphere and to raise its oxidation number. 

In polycyclic systems the Birch reduction of C—C double bonds is also highly stereoselective, e.g. in the synthesis of the thermodynamically favored trans-fused steroidal skeletons (see p. 104 and p. 278). 

R. A. Greenkorn, L. B. Koppel, and S. Raghavan, "Heat Exchanger Network Synthesis—A Thermodynamic Approach," 71 stAlChE Meeting, Miami, Fla., 1978. 

T. Umeda, T. Harada, and K. Shiroko, "A Thermodynamic Approach to the Synthesis of Heat Integration Systems in Chemical Processes," Proceedings of the 12th Symposium on Computer Applications in Chemical Engineering, Montreaux, Swit2edand, 1979, p. 487. 

Hexa.cya.no Complexes. Ferrocyanide [13408-63 ] (hexakiscyanoferrate-(4—)), (Fe(CN) ) , is formed by reaction of iron(II) salts with excess aqueous cyanide. The reaction results in the release of 360 kJ/mol (86 kcal/mol) of heat. The thermodynamic stabiUty of the anion accounts for the success of the original method of synthesis, fusing nitrogenous animal residues (blood, horn, hides, etc) with iron and potassium carbonate. Chemical or electrolytic oxidation of the complex ion affords ferricyanide [13408-62-3] (hexakiscyanoferrate(3—)), [Fe(CN)g] , which has a formation constant that is larger by a factor of 10. However, hexakiscyanoferrate(3—) caimot be prepared by direct reaction of iron(III) and cyanide because significant amounts of iron(III) hydroxide also form. Hexacyanoferrate(4—) is quite inert and is nontoxic. In contrast, hexacyanoferrate(3—) is toxic because it is more labile and cyanide dissociates readily. Both complexes Hberate HCN upon addition of acids. 

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

Synthesis. Iminoboranes, thermodynamically unstable with respect to oligomerization can be isolated under laboratory conditions by making the oligomerization kineticaHy unfavorable. This is faciUtated by bulky substituents, high dilution, and low temperatures. The vacuum gas-phase pyrolysis of (trimethylsilylarnino)(aLkyl)haloboranes has been utilized as an effective method of generating iminoboranes RB=NR as shown in equation 19 for X = F,... 

In the attempt at diamond synthesis (4), much unsuccesshil effort was devoted to processes that deposited carbon at low, graphite-stable pressures. Many chemical reactions Hberating free carbon were studied at pressures then available. New high pressure apparatus was painstakingly buHt, tested, analy2ed, rebuilt, and sometimes discarded. It was generally beheved that diamond would be more likely to form at thermodynamically stable pressures. 

For the equiUbrium-controUed enzyme-catalyzed peptide synthesis the equiUbrium position Hes far over in the direction of the hydrolysis, and under physiological conditions, the product yield is negligible. The equiUbrium position is deterrnined exclusively by thermodynamic factors and like any other catalysts the enzymes only accelerate the attainment of the equiUbrium. 

---