Stereoelectronic effects in ring closure reactions: the 2′-hydroxychalcone – flavanone equilibrium, and related systems

1990 ◽  
Vol 68 (10) ◽  
pp. 1780-1785 ◽  
Author(s):  
Colin M. Brennan ◽  
Ian Hunt ◽  
Terence C. Jarvis ◽  
C. David Johnson ◽  
Peter D. McDonnell
Keyword(s):  
Double Bond ◽  
Michael Addition ◽  
Protonated Form ◽  
Ring Closure ◽  
Rate Limiting Step ◽  
Michael Adducts ◽  
Main Pathway ◽  
Rate Limiting ◽  
Bond Character ◽  
Influence Of Substituents

The 2′-hydroxychalcone (2-HOC6H4COCH=CHC6H4X)–flavanone equilibrium in trifluoroacetic acid (TFA) has been examined. The influence of substituents X on the rate of attainment of equilibrium shows that the 6-endo-trig mode of ring closure by Michael addition is disallowed, by demonstrating a negative ρ value for the reaction rate when X is varied. Reaction therefore proceeds either on the carbonyl-protonated form, which allows twisting about the 2,3 bond, its double bond character being reduced by resonance, or through direct rate-limiting protonation on the 2,3 double bond. Either pathway permits the allowed 6-exo-trig mode of ring closure to be followed. Alternative mechanisms involving intermolecular Michael addition of trifluoroacetate, followed by intramolecular 6-exo-tet displacement are considered. Such Michael adducts can be detected in the ring closures of 2-crotonyl-4-methylphenol and 4,4-dimethyl-1-(2-hydroxyphenyl)-2-penten-1-one in TFA, but they do not appear to lie on the main pathway, because the reactions proceed with equal facility in methanesulphonic acid/chloroform medium, which does not contain a suitable nucleophile for such a mechanism. Further important mechanistic information is given by studying the reactions in TFA-d, together with measurements on the (E)-2-methyl-3-oxo-5-arylpent-4-en-2-ol and 3′-methoxychalcone systems. These isotope effect studies, which yield kH/kD values of about 3, indicate that the proton is in flight during the rate-limiting step, and provide evidence against the mechanism involving a preequilibrium carbonyl protonation, such as in the Nazarov rearrangement of 3′-methoxychalcones, where kH/kD is ca. 0.7. Some results are also reported for ring closure of the 2-aminochalcones in TFA. Keywords: 2′-hydroxychalcones, flavanones, 3′methoxychalcones, 3-aryl-6-methoxyindanones, 2′-aminochalcones, 2-aryl-1, 2, 3, 4-tetrahydroquinolines, Baldwin's rules.

Hydrolysis of a monocyclic oxyphosphorane containing a five-membered ring

1991 ◽  
Vol 69 (12) ◽  
pp. 2075-2083 ◽  
Author(s):  
Glenn H. McGall ◽  
Robert A. McClelland
Keyword(s):  
Rate Constant ◽  
Methoxy Group ◽  
Ring Closure ◽  
Rate Limiting Step ◽  
Acid Base Equilibrium ◽  
Reaction With Water ◽  
Effective Molarity ◽  
Rate Limiting ◽  
Hydrolysis Of ◽  
Good Agreement

A kinetic study is reported for the hydrolysis of 2,2-diphenyl-2-methoxy-1,3,2-dioxaphospholane 1. This phosphorane exists in aqueous solution in a pseudo acid–base equilibrium with an observable phosphonium ion, the ring-opened (2′-hydroxyethoxy)diphenylmethoxyphosphonium ion 5. The equilibrium constant Ka ([1][H+]/[5]) is 9 × 10−9, values determined by kinetic and spectroscopic methods being in good agreement. This phosphonium ion is, however, not involved in the overall hydrolysis reaction, which proceeds via the thermodynamically less stable cyclic five-membered phosphonium ion derived by loss of the exocyclic methoxy group from the phosphorane, the 2,2-diphenyl-1,3,2-dioxaphospholan-2-ylium ion 6. This route for the overall hydrolysis is established by analysis of the products, and by the observation that the rate constant for the disappearance of 5 in acid solutions is 40 000 times greater than that for an analog that differs only in not being able to cyclize, the (2′-methoxyethoxy)diphenylmethoxyphosphonium ion 7. At all pH, the phosphorane 1 and the ring-opened phosphonium ion 5 exist in equilibrium, and the rate-limiting step in the overall hydrolysis is the cleavage of the exocyclic methoxy group to give the cyclic phosphonium ion 6, which is rapidly converted to products by reaction with water. The actual equilibration reaction involving 1 and 5 cannot be observed at any pH, even with stopped-flow spectroscopy. The non-catalyzed ring closure of the phosphonium ion 5 reforming the phosphorane 1 occurs with a rate constant of 200–500 s−1, corresponding to an effective molarity of (2–5) × 107 M for the intramolecular hydroxy group in this reaction. The rate-limiting exocyclic cleavage is assisted by H+, with a very large rate constant 2 × 109 M−1 s−1. Catalysis by general acids is also observed. The Brønsted plot has a slope α of 1.0 for the weaker acids, with a break for acids with pKa < 3. This "Eigen"-type behavior is proposed to arise from a transition state with little phosphonium ion character, in which the proton is almost completely transferred for the weaker acids. Key words: phosphorane, phosphate, phosphonium, hydrolysis.

scholarly journals Influence of the position of the double bond in steroid substrates on the efficiency of the proton-transfer reaction by Pseudomonas testosteroni 3-oxo steroid Δ4–Δ5-isomerase

1980 ◽  
Vol 185 (3) ◽  
pp. 723-732 ◽  
Author(s):  
Hadassa Weintraub ◽  
Etienne-Emile Baulieu ◽  
Annette Alfsen
Keyword(s):  
Double Bond ◽  
Proton Transfer ◽  
Transfer Reaction ◽  
Proton Transfer Reaction ◽  
Process Data ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Isomerization Process ◽  
Rate Limiting ◽  
Pseudomonas Testosteroni

Studies of the proton-transfer reaction by Pseudomonas testosteroni 3-oxo steroid Δ4–Δ5-isomerase with Δ5(6)- and Δ5(10)-steroid substrates demonstrate the importance of the position of the double bond for the efficiency of the isomerization process. Thus 3-oxo-Δ5(6)-substrates have markedly high kcat. values, whereas those of 3-oxo-Δ5(10)-substrates are very low and their apparent Km values approach equilibrium dissociation constants. The first step in the isomerization process is: [Formula: see text] which is governed by the k−1/k+1 ratio and is shown to be very similar for the two classes of substrates (3-oxo-Δ5(6)- and -Δ5(10)-steroids). They therefore differ in the steps distal to the initial formation of the Michaelis–Menten complex. The use of the deuterated androst-5(6)-ene-3,17-dione substrate enabled us to calculate individual rate constants k+1 and k−1 as well as to determine the apparent rate-limiting step in the isomerization process. With the deuterated oestr-5(10)-ene-3,17-dione substrate, no significant isotope effect was observed suggesting that a different rate-limiting step may be operative in this isomerization process. Data are presented that indicate that under optimal concentrations of the efficient androst-5(6)-ene-3,17-dione substrate, the forward reaction for ES complex formation (as defined by k+1) is limited only by diffusion and the apparent Km does not approach the equilibrium constant, suggesting that the evolution of this enzyme has proceeded close to ‘catalytic perfection’.

Ornithine Decarboxylase Activity in Cultured Endothelial Cells Stimulated by Serum, Thrombin and Serotonin

1978 ◽  
Vol 39 (02) ◽  
pp. 496-503 ◽  
Author(s):  
P A D’Amore ◽  
H B Hechtman ◽  
D Shepro
Keyword(s):  
Endothelial Cells ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Aortic Endothelial Cells ◽  
Ornithine Decarboxylase Activity ◽  
Rate Limiting Step ◽  
Bovine Aortic Endothelial Cells ◽  
Limiting Step ◽  
Rate Limiting ◽  
Serum Serotonin

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.

Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 296-306 ◽  
Author(s):  
D. C. Bradley ◽  
R. A. Poulin ◽  
R. N. Bergman
Keyword(s):  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

Recent Synthetic Approaches and Biological Evaluations of Amino Hexahydroquinolines and Their Spirocyclic Structures

2019 ◽  
Vol 19 (7) ◽  
pp. 875-915 ◽  
Author(s):  
Amr M. Abdelmoniem ◽  
Magda F. Mohamed ◽  
Doaa M. Abdelmoniem ◽  
Said A.S. Ghozlan ◽  
Ismail A. Abdelhamid
Keyword(s):  
Double Bond ◽  
Calcium Channel ◽  
Michael Addition ◽  
Antitubercular Agents ◽  
Sar Studies ◽  
Two Component ◽  
Synthetic Routes ◽  
Synthetic Approaches ◽  
Three Components

In this review, the recent synthetic approaches of amino hexahydroquinolines and their spirocyclic structures were highlighted. The synthetic routes include, two-components, three-components or fourcomponents reactions. The two-component [3+3] atom combination reaction represents the simplest method. It involves Michael addition of the electron rich &#946;-carbon of &#946;-enaminones to the activated double bond of cinnamonitriles followed by cyclization to yield hexahydroquinoline compounds. The bioactivity profiles and SAR studies of these compounds were also reviewed with emphasis to the utility of these substances as antimicrobial, anticancer and antitubercular agents, as well as calcium channel modulators.

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