Thermodynamic control product

Chloro 1 3 butadiene (chloroprene) is the monomer from which the elastomer neoprene IS prepared 2 Chloro 1 3 butadiene is the thermodynamically controlled product formed by addi tion of hydrogen chloride to vinylacetylene (H2C=CHC=CH) The principal product under conditions of kinetic control is the allenic chlonde 4 chloro 1 2 butadiene Suggest a mechanism to account for the formation of each product... 

As in the nitration of naphthalene, sulfonation gives the 1-substituted naphthalene. However, because the reverse reaction (desulfonation) is appreciably fast at higher temperatures, the thermodynamically controlled product, naphthalene-2-sulfonic acid, can also be obtained. Thus it is possible to obtain either of the two possible isomers of naphthalene sulfonic acid. Under kineticaHy controlled conditions naphthalene-l-sulfonic acid [85-47-2] (82) is obtained thermodynamic control gives naphthalene-2-sulfonic acid [120-18-3] (83). 

The Pummerer reaction346 of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position347. The overall mechanism is illustrated in equation 129. 

The use of the enolsilyl ether of 1-menthone [16, 19, 21-23] and of some free triflic acid favors the formation of the thermodynamically controlled products as with free 2,2 -dihydroxydiphenyl [22] and only subsequently added HMDS 2 [22]. On reacting silylated alcohols and carbonyl compounds with pure trimethylsilyl triflate 20 under strictly anhydrous conditions no conversion to acetals is observed [24]. Apparently, only addition of minor amounts of humidity to hydrolyze TMSOTf 20 to the much stronger free triflic acid and hexamethyldisiloxane 7 or addition of traces of free triflic acid [18-21, 24, 26] or HCIO4 [25] leads to formation of acetals. 

The majority of biocatalytic reactions are thermodynamically controlled. Product yield is thus dependent on the equilibrium position of a reaction. Optimization of the product yield requires knowledge of the equilibrium position in different organic solvents. Several works described and compared models for the prediction of the equilibrium position in two-phase media [6, 28, 29, 33]. 

The Hofmann degradation is the most well-known C—N bond cleavage reaction, and its value to structural elucidation of alkaloids has been demonstrated (76). Hofmann degradation of tetrahydroberberine methohy-droxide (1) led to two products base A (2), the C-14—N bond cleavage product, and base B (3), the C-6—N bond cleavage product (Scheme 2) (17,18). The former was the major product when 1 was heated under reduced pressure, but the latter, the thermodynamically controlled product, predominated when the reaction was carried out at atmospheric pressure or in an alkaline medium because base A recyclized back to the starting quaternary base through the transannular reaction. In fact, 2 was heated in aqueous alcohol to afford 1. The mechanism of this recyclization reaction was discussed by Kirby et al. (19). 

Although C is the first isolable product to be formed it can pass to the more stable form D. C is called kinetically controlled product of the reaction of A. D is the product isolated after the system reaches equilibrium, it is called thermodynamically controlled product. 

Generally thermodynamically controlled product is more stable than the kinetically controlled one although the latter is formed faster then the former from a reactant. 

It has therefore been established170 from the product distributions that, while the oxymercuration is reversible, unless a base (e.g. sodium acetate) is added to the reaction medium, and gives almost exclusively the more stable compound 199, the aminomercu-ration takes place to give the kinetically controlled adduct 200, or under thermodynamic control the aminomercurial 201. Reactions are kinetically controlled when the mercurating species is a mercury(II) salt deriving from a weak acid such as mercury(II) acetate. Conversely, they are thermodynamically controlled with the covalent mercury(II) chloride. In the latter case, the presence of a strong acid in the medium allows the thermodynamically controlled product to be obtained. 

Br 20% + Br 80% thermodynamic control product ratio determined by stability of product... 

The cyclizations of cis- and lrans-2-hydroxymethyl-l-cyclohexylamine and cis- and lram-2-aminomethyl-l-cyclohexanol with 4-nitrobenzaldehyde have been studied by means of H NMR spectroscopy in CDCI3 solution (90ACSA364 91T2229). The time-dependent spectra confirmed that the reactions of all these amino alcohols proceeded via Schiff bases. With the exception of cis-2-hydroxymethyl-l-cyclohexylamine, the thermodynamically more stable perhydrobenzoxazine epimer is also the kinetically favored product. In the former case, from amino alcohol 21 (R = H), the Schiff base 37 with N-outside predominant conformation is formed first due to kinetic control, the less stable epimeric ring form 38 is obtained with N-outside predominant conformation. The thermodynamically controlled product 33 is formed subsequently, via the less stable open-chain form 37, in a slow equilibration process (90ACSA364). 

We will see in Chapter 19 that calculations show cyclohexyl radical to be about 8 kcal/mol more stable than cyclopentylmethyl radical. Were the reaction under strict thermodynamic control, products derived from cyclopentylmethyl radical should not be observed at all. However, the transition state corresponding to radical attack on the internal double bond carbon (leading to cyclopentylmethyl radical) is about 3 kcal/mol lower in energy than that corresponding to radical attract on the external double bond carbon (leading to cyclohexyl radical). This translates into roughly a 99 1 ratio of major minor products (favoring products derived from cyclopentylmethyl radical) in accord to what is actually observed. The reaction is apparently under kinetic control. 

N-alkylations and rearrangements are important for the synthesis of glycosides. N-3 and N-4 glycoside, e.g., of 5-oxo-TPs, are obtained under different conditions as the kinetically and thermodynamically controlled product, respectively [75BSF(2)2561] therefore a thermal rearrangement from an N-3 to an N-4 glycoside is possible. Table X lists these glycosides included are those derived from thioxo-TPs and mercaptomethyl-TPs. 

The different products arise from enthalpy differences in the second step, the reaction of Br and the allyl R. See Fig. 8-5. At -80°C the 1,2-adduct, the rate-controlled product, is favored because its formation has the lower A// . 1,2-Adduct formation can reverse to refurnish the intermediate allylic carbocation, R. At 40°C, R goes through the higher-energy transition state for formation of the more stable 1,4-adduct, the thermodynamic-controlled product. The 1,4-adduct accumulates because the addition, having a greater is more difficult to reverse than that for the 1,2-adduct. The 1,4-adduct has a lower enthalpy because it has more R groups on the C=C,... 

The sulfur atom of thiophenes is weakly nucleophilic and can act in some cases as the site for attack of an electrophilic reagent. In strongly acidic solutions the a-carbon atom is protonated (66RTC1072) this could be a thermodynamically controlled product, however. Reaction of thiophene with powerful alkylating agents provides the thiophenium salt (56),... 

Attempts to reduce the quaternary salts of 4-oxo-4//-pyrido[l,2-a]-pyrimidines with sodium borohydride or lithium aluminum hydride remained unsuccessful.137 At the same time the 6,7,8,9-tetrahydro quaternary salts may readily be reduced with sodium borohydride to the 1-alkyl-l,6,7,8,9,9a-hexahydro derivatives.75-77,133 1481269 270 Sodium borohydride reduction of the 1,6- and l,7-dimethyl-3-carbamoyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidinium salts proceeds stereoselectively and yields the thermodynamically controlled product.271 The l-methyl-3-carbamoyl-4-oxo-l,6,7,8,9,9a-hexahydropyrido[l,2-a]pyrimidines were also prepared by the catalytic (Pd/C) hydrogenation of the 1,6,7,8-tetrahydro derivatives,270-272 but this reaction led to a diastereoisomeric mixture.271... 

Note that the reaction of the tetrafluoroethylene pentamer with the alkoxide anion at low temperatures (—30 to —40°C) yields the kinetically controlled product, whereas the thermodynamically controlled product is obtained at 20 °C (94JFC(67)95, 88CJC446). 

An interesting aspect of the type A heteropentalenes is the fact that each molecule is associated with two 1,3-dipolar fragments (45a<->45b) and, in principle, unsymmetrical systems can form two types of cycloadduct (46 or 47). In some cases the kinetically controlled product (46) is obtained at low temperature and the thermodynamically controlled product (47) is obtained at higher temperatures (see thieno[3,4-c]pyrroles, Chapter 3.18). For a given set of reaction conditions cycloaddition is usually site specific. For example, the non-classical thiophene derivatives of general structure (48) usually add across the thiocar-bonyl ylide fragment. This site selectivity is probably determined by the relative size of the HOMO coefficients at the alternative sites of addition. 

The addition of (Bu3Sn)(PhS)CuLi to alkynones (acetylenic ketones) proceeds in high yield and with excellent stereoselectivity for the (Z)-isomer of the product (>95%).2" The reaction of alkynyl ethers gives different regioisomers. Both kinetically and thermodynamically controlled products are obtained depending on the reaction conditions (Equation (123)).300... 

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