R: reactions

Elber, 1996] Elber, R. Reaction path studies of biological molecules. In Recent developments in theoretical studies of proteins (Advanced series in physical chemistry, Vol. 7). R. Elber, editor. World Scientific, Singapore, 1996. 

In a system containing N chemical species, any or all of which can participate in r chemical reactions, the r reactions can be represented schematically by the foUowing algebraic equation, where j = 1, 11, r ... 

The general criterion of chemical reaction equiUbria is the same as that for phase equiUbria, namely that the total Gibbs energy of a closed system be a minimum at constant, uniform T and P (eq. 212). If the T and P of a siagle-phase, chemically reactive system are constant, then the quantities capable of change are the mole numbers, n. The iadependentiy variable quantities are just the r reaction coordinates, and thus the equiUbrium state is characterized by the rnecessary derivative conditions (and subject to the material balance constraints of equation 235) where j = 1,11,.. ., r ... 

B A R B f E R Reaction In situ Grignard generation in the presence of an electrophile... 

The conversion of c>-hydroxyaryl ketones la to chromones 2a and/or coumarins 3a with aliphatic acid anhydrides in the presence of the sodium or potassium salt of the corresponding acid and the reaction between lb and aromatic acid anhydrides and the salt of the corresponding acid to form flavones 2b (Allan-Robinson) is called the Kostanecki-Robinson (K-R) reaction. ... 

The mechanism of the K-R reaction has been studied by several groups. " However, the mechanism proposed by Baker and Szell appears to be the most likely pathway. Szell and coworkers agreed with the original mechanism postulated by Baker based on product isolation, spectroscopy and kinetic studies. The o-hydroxyacetophenone 4 is first acylated... 

A modification of the K-R reaction was introduced by Mozingo. This method involved reacting an o-hydroxyacetophenone with an ester in the presence of metallic sodium to form a 1,3-diketone. Treatment of the diketone with an acid then delivered the chromone via an intramolecular cyclization reaction. This method was applied to the preparation of 2-ethylchromone (21). 0-hydroxyarylketone 22 was allowed to react with ethyl propionate (23) in the presence of sodium metal.The resulting sodium enolate was then quenched with acetic acid to deliver the 1,3-diketone 24. Upon heating 24 in glacial acetic acid and hydrochloric acid, 2-ethylchromone (21) was delivered in 70-75% overall yield. 

Typically, the K-R reaction is run at temperatures that often exceed 160 "C. However, a mild variation has been developed using acetic formic anhydride where the transformation occurs at ambient temperature. Okumara and coworkers smoothly converted hydroxyl ester 25 to chromone 26 in 76% yield with acetic formic anhydride and sodium formate at room temperature.Beckett and Ellis also used these conditions to synthesize two chromones in high yield when 27 and 28 were converted to 29 and 30, respectively. ... 

Seshradi and coworkers showed that potassium carbonate was an effective base in the K-R reaction for the conversion of resacetophenone (37) to 7-hydroxyflavone 39a and 7-hydroxy-4 -methoxyflavone 39b in 57% and 46% yield, respectively. In addition, the reaction proceeded at a significantly lower temperature than the traditional K-R reaction by conducting the reaction in refluxing acetone. 

In the course of synthesizing DNA-gyrase inhibitors Hogberg, Mitscher, and coworkers determined that an effective means of constructing the core of their inhibitors was via a K-R reaction. Under mild conditions, keto ethylester 52 was acylated using acetic formic anhydride in the presence of sodium formate to deliver chromone 53 in 75% yield. 

In the realm of natural product synthesis, Kepler and Rehder utilized the K-R reaction to synthesize ( )-calanolide A (56), a potent non-nucleosidal human irmnunodeficiency virus (HIV-1) specific reverse transcriptase inhibitor. Propiophenone 57 was allowed to react with acetic anhydride in the presence of sodium acetate to afford benzopyranone 58 in 56% yield subsequent deacetylation of 58 gave 59. Flavone 59 was then transformed to ( ) calanolide A (56) over several steps. 

Over the years the venerable K-R reaction has been instrumental in constructing flavones for SAR programs and natural product synthesis. ... 

The K-R reaction has also been useful for structural confirmation of natural products such as tambulin (71), a flavonoid isolated from the seeds of Xanthoxylum acanthopodium In the critical reaction (O-ethoxyphloroacetophenone (72) was allowed to react with anisic anhydride (38b) in the presence of sodium anisate (73) at 170 C to deliver flavone 74 in 65% yield. Flavone 74 was then converted after multiple steps to diethyl ether 75 which corresponded to the diethyl ether of tambulin (71). 

Over the years there have many reports of isoflavone syntheses utilizing the K-R reaction. 

Enti y SubsQ ate r R" Reaction Conditions Product Yield (%) of ... 

Starting Material RCOCH, R Reaction Conditions Product Product of Hydrolysis ... 

Sulfoxide R Reaction Temp (°C) Ratio (E/Z) Ratio of Dia-stereomers at Sa Overall Yield (%)... 

Takahashi, R and Katta, V.R., Reaction kernel structure and stabilizing mechanisms of jet diffusion flames in microgravity, Proc. Combust. Inst., 29,2509, 2002. 

R reaction rate s catalyst particle shape factor t time (min)... 

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