Aromatic Electrophilic Substitution by Hydrogen. IV. The Mechanism of the Acid-catalyzed Decarboxylation of Aromatic Acids1

1954 ◽  
Vol 76 (1) ◽  
pp. 9-14 ◽  
Author(s):  
W. M. Schubert ◽  
Jere Donohue ◽  
J. D. Gardner
Keyword(s):  
Electrophilic Substitution ◽  
Acid Catalyzed

Nucleophilic Cyclization/Electrophilic Substitution of (2,2-Dialkoxyethyl)ureas: Highly Regioselective Access to Novel 4-(Het)arylimidazolidinones and Benzo[d][1,3]diazepinones

Synthesis ◽  
2020 ◽  
Vol 52 (21) ◽  
pp. 3263-3271
Author(s):  
Andrey V. Smolobochkin ◽  
Almir S. Gazizov ◽  
Nazerke K. Otegen ◽  
Julia K. Voronina ◽  
Anna G. Strelnik ◽  
...  
Keyword(s):  
Substitution Reaction ◽  
Electrophilic Substitution ◽  
Biologically Active ◽  
Electrophilic Substitution Reaction ◽  
Reaction Sequence ◽  
Active Compounds ◽  
Acid Catalyzed ◽  
High Yields ◽  
Nucleophilic Cyclization ◽  
Mechanism Of The Reaction

Imidazolidin-2-one and 1,3-benzodiazepin-2-one scaffolds are structural motifs of many biologically active compounds. Herein, we report a highly regioselective acid-catalyzed intramolecular nucleophilic cyclization/intermolecular electrophilic substitution reaction sequence of (2,2-dialkoxyethyl)ureas. The reaction benefits from readily available starting materials, a simple workup procedure, moderate to high yields of target compounds, and provides a convenient entry to previously unknown 4-(het)arylimidazolidinones and 5-(het)arylbenzodiazepinones. The proposed mechanism of the reaction is also discussed.

What’s in a name? The MacDonald condensation

2016 ◽  
Vol 20 (08n11) ◽  
pp. 855-888 ◽  
Author(s):  
Timothy D. Lash
Keyword(s):  
Total Synthesis ◽  
Electrophilic Substitution ◽  
Historical Review ◽  
Dicarboxylic Acids ◽  
Type Systems ◽  
Air Oxidation ◽  
Bond Forming ◽  
Expanded Porphyrins ◽  
Acid Catalyzed ◽  
Porphyrin Synthesis

In 1960, MacDonald and coworkers introduced a new method for porphyrin synthesis that involved the acid-catalyzed condensation of dipyrrylmethane dialdehydes with [Formula: see text],[Formula: see text]-diunsubstituted dipyrrylmethanes or the related dicarboxylic acids, followed by an air oxidation. The key bond forming steps entail electrophilic substitution at two pyrrole units with the aldehyde moieties to generate, following elimination of water, a 5,15-dihydroporphyrin or porphodimethene intermediate. Following addition of sodium acetate, or in later procedures zinc acetate, the dihydroporphyrins readily air oxidize to the fully aromatic porphyrin system. This strategy, which parallels chemistry contemporaneously developed by R. B. Woodward at Harvard for the total synthesis of chlorophyll [Formula: see text], demonstrated that dipyrrylmethanes were sufficiently stable to be utilized as intermediates in porphyrin syntheses and that porphodimethene formation circumvented acidolytic scrambling reactions that might lead to isomeric porphyrin products. This type of chemistry was later adapted by Johnson, Woodward and others to prepare porphyrin-type systems by a “3 + 1” strategy, or expanded porphyrins by “3 + 2” or other combinations of oligopyrrolic precursors. In recent years, the term “MacDonald condensation” has been increasingly used to describe other types of chemistry involving oligopyrrolic intermediates. Following on from a historical review of this area, guidelines for the identification of MacDonald-type reactions are proposed.

scholarly journals The Highly Regioselective Synthesis of Novel Imidazolidin-2-Ones via the Intramolecular Cyclization/Electrophilic Substitution of Urea Derivatives and the Evaluation of Their Anticancer Activity

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4432
Author(s):  
Almir S. Gazizov ◽  
Andrey V. Smolobochkin ◽  
Elizaveta A. Kuznetsova ◽  
Dinara S. Abdullaeva ◽  
Alexander R. Burilov ◽  
...  
Keyword(s):  
Quantum Chemistry ◽  
Electrophilic Substitution ◽  
Simple Procedure ◽  
Urea Derivatives ◽  
Quantum Chemistry Calculations ◽  
Anti Cancer ◽  
Acid Catalyzed ◽  
And Control ◽  
Cancer Activity

A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was rationalized by quantum chemistry calculations and control experiments. The anti-cancer activity of the obtained compounds was tested in vitro.

THE DECARBOXYLATION OF ANTHRANILIC ACID

1952 ◽  
Vol 30 (7) ◽  
pp. 529-540 ◽  
Author(s):  
W. H. Stevens ◽  
J. M. Pepper ◽  
M. Lounsbury
Keyword(s):  
Carbon Dioxide ◽  
Melting Point ◽  
Isotope Effect ◽  
Anthranilic Acid ◽  
Electrophilic Substitution ◽  
Reaction Rate ◽  
Mineral Acid ◽  
Detailed Mechanism ◽  
Rate Determining Step ◽  
Acid Catalyzed

Anthranilic acid is known to decarboxylate on being heated above its melting point, or on being boiled in water. We have found that the aqueous decomposition can be acid catalyzed, but that, after the concentration of added mineral acid approximates that of the anthranilic acid, the reaction rate decreases with increasing mineral acid concentration. A mass spectrometer study of the carbon dioxide produced in the decomposition has shown that C12-carboxyl anthranilic acid decomposes at the same rate as C13-carboxyl anthranilic acid. Thus, unlike all other organic acid decarboxylations in which an "isotope effect" has been searched for thus far, the decarboxylation of anthranilic acid does not show an "isotope effect". From the experimental facts available, it appears that the mechanism of the decarboxylation is best explained as bimolecular electrophilic substitution, with the attack of a proton being the rate determining step. While other possibilities are not entirely excluded, a proton attack on the α carbon of the zwitterion is the detailed mechanism suggested as being most probable.

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