Thermodynamics mixtures

The diastereomeric ratio of the trimethylsilyl triflate catalyzed amidoalkylation of a number of silyl enol ethers at — 40 CC appears to be dependent on the substituents in the substrate87. At — 40 °C the diastereomeric ratio is shown to be kinetically controlled. On allowing the reaction mixture to warm to 20 "C slow epimerization, increasing the amount of the minor isomer, is observed. In the case of the naphthalene derivative, sodium methoxide catalyzed epimerization of the kinetic mixture [(antijsyn) 88 12] produces the thermodynamic mixture [(antijsyn) 9 91]. 

A portion of the product was heated to reflux with methanolic sodium methoxide to convert it into the thermodynamic mixture of trans- (ca. 65%) and cis- (ca. 35%) isomers. Small amounts of the isomers were collected by preparative gas chromatography using an 8 mm. by 1.7 m. column containing 15% Carbowax 20M on Chromosorb W, and each isomer exhibited the expected spectral and analytical properties. The same thermodynamic mixture of isomers was prepared independently by lithium-ammonia reduction5 of 2-allyl-3-methyl-cyclohex-2-enone [2-Cyclohexen-l-one, 3-methyl-2-(2-propcnyl)-],6 followed by equilibration with methanolic sodium methoxide. 

An interesting case of metal-assisted ring opening of (109) has been described by Wolczanski using the low-valent (silox)3Nb fragment that binds (109) in the //2(N,C) mode (Scheme 50). Derivative (113) undergoes C—N insertion by thermolysis in benzene at 70 °C only. The reaction gives 0.5 equiv. of (109) and 0.5 equiv. of (114) as a thermodynamic mixture of cis,cis-, trans,cis-, trans,trans- and cis,trans-isomers.255-257... 

Since we are mainly interested in combustion in the gas phase, we must be able to describe reacting gas mixtures. For a thermodynamic mixture, each species fills the complete volume (V) of the mixture. For a mixture of N species, the mixture density (p) is related to the individual species densities (pi) by... 

A series of thiazolo[2,3- ]isoquinolines 426, 3-one derivatives 427, and J-oxide derivatives 428 have been studied in detail as regard to their spectroscopic properties <2001T3499, 2002TA2329, 2003T1173>. These compounds have been prepared using previously reported chemistry. One of the 3-one derivatives 427 was prepared in enantiomeri-cally pure form and therefore gave access to optically enriched 428. Isolated diastereoisomers of this A-oxide were however found to be unstable and to epimerize to give a thermodynamic mixture of syn- and //-diastereoisomers. This epimerization was accompanied by a racemization (Scheme 110). 

Since (C6H5)3P = Se also effects cleavage of (C6H5)3P = CHR to give RCH = CHR and (C6H5)3P, selenium can be used in catalytic amounts this version provides the thermodynamic mixture of the geometric forms of the alkene. 

Thermal cracking of wax. From thermal cracking a thermodynamic mixture might have been expected, but the wax-cracker product contains a high proportion of 1-alkenes, the kinetically controlled product. Still, the mixture contains some internal alkenes as well. For several applications this mixture is not suitable. In polymerisation reactions only the 1-alkenes react and in most cases the internal alkenes are inert and remain unreacted. For the cobalt catalysed hydroformylation the nature of the alkene mixture is not relevant, but for other derivatisations the isomer composition is pivotal to the quality of the product. 

Nevertheless this kind of isomerization cannot be considered as a general method for the synthesis of all the alk-l-enylphosphoniums, because it often affords thermodynamic mixtures of a,/ - and / ,y-unsaturated phosphonium salts157 280 (equation 37). 

This C—H substitution process results in a Markovnikov orientation, with the H that is allylic to the more substituted end of the alkene preferentially abstracted. The stereochemistry of the resulting ir-allyl complex does not represent the stereochemistry of the starting alkene, as the complexes are capable of isomerization under the conditions in which they are formed. Typically, a thermodynamic mixture is obtained, with the syn form of the complex predominating over the anti form (equation 1). The syn form is more stable due to unfavorable steric interactions that the anti form encounters with the coordination sphere of the palladium. 

We had several options to deal with the expected 1 1 diastereomeric mixture of 7 and 15, but none of them was in the end satisfactory. We had previously found that diastereomeric mixtures of certain other double Michael adducts (Figure 5) could be converted to thermodynamic mixtures upon treatment with base, presumably by a retro-Michael-Michael process.3 4 In the case of 7 and 15, the hope was that the two isomers could be equilibrated via a retro-Michael reaction to 17, internal bond rotation, and reclosure by a Michael reaction. Unfortunately, 7 and 15... 

In the course of their synthesis of salicylihalamide A, De Brabander et al. thoroughly studied the influence of the catalyst on the outcome of the RCM for 73, which forms the C9-C10 bond [49]. They showed that the first-generation catalyst G1 gives better E selectivity than the more active G2 complex (Scheme 2.28). The ratio of E/Z isomers of 74 does not evolve in time with G2, proving that the thermodynamic mixture of products is obtained in this case. On the other hand, kinetic product ratios are probably observed with Gl, as the E selectivity decreases with longer reaction times. 

There are two kinds of TDP processes normal TDP which leads to thermodynamic mixture of xylenes, and selective TDP (STDP) which leads selectively to pX (>80%). Typical operating conditions of these processes are given in Table 9.5. With STDP, toluene conversion is low (<30%) whereas with normal TDP, this conversion (45-50%) is close to the maximum thermodynamic equilibrium (60%). Mordenite associated with a hydrogenating metal in order to limit coking is used for normal TDP and a selectivated MFI zeolite for STDP. 

The diastereomers of EBTHI zirconaaziridines are formed in comparable amounts via C-H activation, but equilibrate quickly (within an hour) to yield a thermodynamic mixture of diastereomers. Grossman observed little difference in the loss of MeH vs MeD from deuterium-labeled (EBTHI)zirconium methyl amide complexes 161 (Scheme 2). Loss of MeH and of MeD lead to different diastereomers, although their relative rate will also reflect the primary kinetic isotope effect for C-H activation. Neither kxlk2 nor k3lk4 is large, and both are largely the result of isotope effects rather than diastereoselectivity [42]. 

Reaction of butane-1,2,4-triol 28 1 with acetone and p-toluenesulfonic acid as catalyst for 62 h gives a thermodynamic mixture of isopropylidene derivatives consisting of the dioxolane 28.2 (90%) and the dioxane 283 (10%) in a com-... 

Diastereoselective complexations affording chiral heterodiene complexes are also known (Scheme 74) 374-376 complexation of the enantiomerically pure iV-benzyl vinylim-ines was shown to proceed under kinetic control equilibration to thermodynamic mixtures possessing poorer diastereomer ratios occurred upon standing. On the other hand, the diastereoselective complexation of an enantiomerically pure enone with a side chain possessing chirality and a chelating phosphite group was shown to proceed under thermodynamic control (Scheme 75). The product (a single diastereomer was formed) could be transformed by nucleophihc addition at the -position. 

Since the ring closure was effected in equilibrating conditions, the observed ratio of the diastcrco-mers reflected their relative stability. PaS aShlO (exo-lO) was kinetically favored and was converted to endo-10 by increasing the reaction time and temperature (1H NMR). exo-10 could not be isolated due to facile reversion to 9 during workup, but the acetyl derivative exo-11 was obtained in a maximum yield of 30%2O . The trifluoroacetic acid promoted cyclization of a-substituted tryptophan derivatives 12 in chloroform- / f1 - NMR) gave thermodynamic mixtures of endo- and toco-isomers 135J. 

For example, treatment of / -thiolactone 110 with Et3N in CDCI3 gives a thermodynamic mixture of two diastereoisomeric S-thiolactones (110 100 = 60 40, equation 23). In comparison, treatment of / -lactam 111 with NaOD in D2O gives the deu-teriated /S-lactam 111 as a single diastereoisomer in quantitative yield with retention of... 

As discussed in Section 3.1.11.1, which covers the reductive cleavage of the 3-hydroxy sulfone derivatives to alkenes, the Julia reaction proceeds by the formation of an anion that is able to equilibrate to the thermodynamic mixture prior to elimination. Therefore, there is no inherent advantage in producing the erthyro- or threo-fi-hydroxy sulfone selectively fix>m the keto sulfone. The ( )/(Z)-mixture of alkenes should be the same. This method is used to produce alkenes in cases where the acid derivative is more readily available or more reactive. The reaction of the sulfone anion with esters to form the keto sulfone, followed by reduction with metal hydrides has been studied. The steric effects in the reduction do become important for the reaction to produce vinyl sulfones, which are formed from the anti elimination of the 3-hydroxy sulfone adduct, as mentioned in Section 3.1.11.6.2. Some examples of the use of esters are presented below. 

Generating the enolates of substituted cyclic ketones by using potassium hydride leads to the thermodynamic mixture of enolates, and therefore nitration of potassium enolates often does not allow for a re-... 

Acylation reactions are also very fast, being complete in 5 min at room temperature for reactive substrates. For l-phenyl-l,2-ethanediol, an unhindered terminal 1,2-diol, the initially formed products rearrange to a thermodynamic mixture over one hour at 0 and evidence of rearrangements of initial product has also been obtained for reactions from more hindered carbohydrate-derived terminal... 

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