2221-12-7

Usage

Uses

Used in Pharmaceutical Industry:
2,4-Imidazolidinedione, 1-methyl-3-phenylis used as an anticonvulsant for the treatment of epilepsy, as it helps stabilize the electrical activity in the brain and prevent seizures.
2,4-Imidazolidinedione, 1-methyl-3-phenylis used as a treatment for certain types of irregular heartbeats, providing a means to regulate heart rhythm.
2,4-Imidazolidinedione, 1-methyl-3-phenylis used as a treatment for neuropathic pain, offering relief from nerve-related pain conditions.

Upstream product

• 107-97-1 sarcosine 
• 64-10-8 phenyl carbamate 
• 67513-17-1 N-methyl-N-hydroxycarbonylmethyl-N'-phenylurea 
• 90840-21-4 N-methyl-N-phenylcarbamoyl-glycine nitrile 
• 13200-60-7 Sarcosine ethyl ester 
• 201230-82-2 carbon monoxide 
• 615-43-0 2-iodophenylamine 
• 104892-37-7 N-methyl-N-(carbethoxymethyl)-N'-phenylurea 
• 111184-57-7 N-Methyl-2-(1-methyl-3-phenyl-ureido)-acetamide 
• 103-71-9 phenyl isocyanate 
• 615-36-1 2-bromoaniline 
• 111184-56-6 3-methyl-5-phenylhydantoinamide 
• 616-04-6 1-methyldiazolidine-2,4-dione 
• 591-50-4 iodobenzene 

Downstream Products

• 67513-17-1 N-methyl-N-hydroxycarbonylmethyl-N'-phenylurea 

Relevant academic research and scientific papers

Method for synthesizing N - substituted hydantoin compounds (by machine translation)

The invention discloses a synthetic method of N - substituted hydantoin compounds, which comprises the following steps: taking an acyl azide compound shown as a formula I and a glycine ethyl ester compound as shown in a formula II as a raw material, carrying out heating reaction under the presence of an additive to obtain N - substituted hydantoin compounds as shown in formula III. In the formula, R1 And R2 Independently selected from hydrocarbyl, substituted hydrocarbyl, aryl, substituted aryl or aralkyl; R2 Selected from hydrocarbyl or aryl; R3 Selected from a hydrogen atom and a hydrocarbyl group. To the synthesis method, the functionalized N - substituted hydantoin compounds can be efficiently synthesized, the synthesis steps are few, the conditions are mild, the operation is safe, the raw materials are nontoxic, cheap and easily available, and the synthesis method has the N - substituted hydantoin compounds with the nitrogen heterocyclic skeleton with novel structure, the yield can reach 92%, the purity is 99%, and industrial synthesis is easy. (by machine translation)

Cu-catalyzed N-3-Arylation of Hydantoins Using Diaryliodonium Salts

A general Cu-catalyzed, regioselective method for the N-3-arylation of hydantoins is described. The protocol utilizes aryl(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence of triethylamine and a catalytic amount of a simple Cu-salt. The method is compatible with structurally diverse hydantoins and operates well with neutral aryl groups or aryl groups bearing weakly donating/withdrawing elements. It is also applicable for the rapid diversification of pharmaceutically relevant hydantoins.

Copper-Mediated N-Arylations of Hydantoins

A set of two broadly applicable procedures for the N-arylation of hydantoins is reported. The first one relies on the use of stoichiometric copper(I) oxide under ligand- A nd base-free conditions and enables a clean regioselective arylation at the N3 nitrogen atom, while the second one is based on the use of catalytic copper(I) iodide and trans-N,N′-dimethylcyclohexane-1,2-diamine and promotes arylation at the N1 nitrogen atom. Importantly, the combination of these two procedures affords a straightforward entry to diarylated hydantoins.

A large gem-dimethyl effect in the cyclization of ω-phenylhydantoic acids: Computational modeling of the gem-dimethyl effect on the acid- or base-catalyzed cyclization of hydantoic acids and esters

The rates of the cyclization of methyl-substituted 5-phenylhydantoic acids were measured in acid solutions. A particularly strong gem-dimethyl effect (GDME) was observed with the N-methyl compounds amounting to an acceleration of six powers of ten for the 2,2,3-trimethyl derivative. The variations in the free energies of activation for the cyclization of hydantoic acids and esters were modeled by the strain energies of the tetrahedral intermediates and of the reactants calculated by the MM3 force field. The neutral tetrahedral intermediate T0 was used for reaction series involving acid catalysis and the negatively charged intermediate T- for base catalysis. Very good agreement with the experimental GDME was obtained for the acid-catalyzed cyclizations of the complete series of the N-methyl-substituted substrates, showing that the accelerations result from a greater strain increase in the reactants. The results with T- are closely parallel, indicating that the loss of GDME observed under base catalysis with 2,2,3-trimethylhydantoate esters is not due to intramolecular strain in T-. A linear correlation (slope 1.22, r=0.934) is obtained for a plot of the free energy variations against strain energies for the reaction series of 5-phenylhydantoic acids when the data for the strongly deviating parent acid is excluded. Excellent LFERs are obtained between the reaction series of esters and acids. The observed large rate enhancements induced by N-substituents explain the switches to cyclization routes in synthetic reactions. Copyright

On the disappearance of the gem-dimethyl effect: The base-catalysed cyclization of ethyl hydantoates

Buffer catalysis and solvent kinetic isotope effects in the cyclization of methyl-substituted ethyl hydantoates with ω-N-methyl (MUE) and ω-N-phenyl groups (PUE) have been studied in an attempt to elucidate the changes in mechanism and eventual reversal o

Change of Rate Determining Step Induced by the gem-Dimethyl Effekt

The base-catalysed cyclisation to the hydantoin of 2,2,3-trimethyl-5-phenylhydantoate (2; R1 = R2 = Me) is slower than that of the 2,3-dimethyl compound, even though the acceleration expected from the gem-dimethyl effect is observed for the acid-catalysed

KINETICS AND MECHANISM OF BASE-CATALYZED CYCLIZATION OF SUBSTITUTED AMIDES AND NITRILES OF HYDANTOIC ACID

Rates of base-catalyzed cyclizations of 8 substituted derivatives of hydantoic acid amide type R3-NH(5)-CO(4)-NR2(3)-CH2(2)-CO(1)-NHR1 and 9 nitriles type R3-NH(5)-CO(4)-NR2(3)-CHR1(2)-CN have been measured in aqueous and methanolic media.The cyclization of the amides in aqueous medium is also accompanied by hydrolysis of the hydantoins formed.In some cases the hydrolysis rate constant is greater than the corresponding cyclization reaction rate constant.With the least reactive amides, the cyclization is also accompanied by hydrolysis of the amide group.The ra te of the cyclization reactions in water is higher than that in methanol (at the same concentration of the lyate ions) by the factor of 10 - 100.Substitution of hydrogen at 3 and 5 positions by methyl or phenyl groups causes an acceleration of the cyclization reaction, whereas a substitution in the amide group causes a considerable retardation.The greatest acceleration of the cyclization (by as much as 4 orders) is caused by introduction of phenyl group to the N(5) position, which is due to a substantial increase of concentration of the reactive anion.

BASE CATALYZED CYCLIZATION OF SUBSTITUTED ESTERS OF HYDANTOIC AND THIOHYDANTOIC ACID

Base catalyzed cyclization rates have been measured of 22 derivatives of hydantoic and thiohydantoic acid esters in water and methanol.The cyclization of methyl and ethyl esters of hydantoic and 5-methylhydantoic acids is accompanied by hydrolysis of the ester group, whereas with the other derivatives the hydrolysis does not take place.Hydrolysis of the cyclization products (hydantoin and thiohydantoin derivatives) is not significant under the kinetic conditions.The cyclization of methyl ester of 5-phenylhydantoic acid in methanol is reversible; the equilibrium mixture contains 30percent of the starting ester.In all the cases the cyclization is subject to specific base catalysis; exceptions are esters of 5-phenylthiohydantoic and 5-phenyl-2-methylthiohydantoic acids whose cyclizations are subject to general base catalysis.Substituents always accelerate the cyclization.The 3-substituents have the greatest effects, the cyclization rate being considerably increased with bulk of the substituents; similarly large effect of 5-phenyl group consists mainly in its polar effects on the pre-equilibrium.The cyclizations are slower in methanol at the same concentration of the lyate ion: the greatest difference (up to 3 orders of magnitude) is observed with the 5-phenyl derivatives.

A ONE STEP SYNTHESIS OF 1,4-BENZODIAZEPINES:SYNTHETIC STUDIES ON NEOTHRAMYCIN

A one step synthesis of 1,4-benzodiazepines from o-haloanilines and amino acids was achieved by use of palladium catalyzed carbonylation, by which application a synthesis of the model compounds (23a and 23b) of Neothramycin (A and B) was described.An efficient chemoselective reduction of the amide was provided.