83800-58-2

Upstream product

• 104892-38-8 (1-Benzyl-3-phenyl-ureido)-acetic acid ethyl ester 
• 5680-79-5 glycine ethyl ester hydrochloride 
• 100-52-7 benzaldehyde 
• 103-71-9 phenyl isocyanate 
• 53386-64-4 methyl 2-(benzylamino)acetate 
• 591-50-4 iodobenzene 
• 6777-05-5 1-benzylhydantoin 
• 6436-90-4 ethyl 2-(benzylamino)acetate 
• 582-61-6 benzoyl azide 

Relevant academic research and scientific papers

Solution-phase synthesis of a combinatorial thiohydantoin library

An efficient one-pot three-component synthesis of thiohydantoins was developed. In the first step, amino acid esters were alkylated by imine formation with aldehydes and reduction by sodium triacetoxyborohydride. In the second step, an isothiocyanate was added together with a molar equivalent of triethylamine, leading to the thiohydantoin product in high yield and purity after an extractive aqueous workup. This procedure was used to generate a combinatorial library of over 600 discrete thiohydantoins on a 0.1 mmol scale. Sampling of 10% of this library showed the thiohydantoin to be the major product in all cases, with purities of 52-98% by HPLC analysis. The cyclization conditions can also be adapted to the synthesis of hydantoins.

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)

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.

1,3-dipolar cycloaddition of nitrones with 5-methylenehydantoins: Synthesis and transformation of new spirohydantoin derivatives

1,3-Dipolar cycloaddition of various acyclic nitrones with 5-methylenehydantoin derivatives afforded new chiral spiroadducts in good yields. All the spirohydantoins were obtained through a regio-and stereospecific pathway, and the spirocarbon atom was linked to the isoxazolidine oxygen atom. A representative example of the reduction of the spirohydantoin 8 with Zn/AcOH led to the substituted 1,3-aminoalcohol hydantoin 20.

Combinatorial chemistry of hydantoins

Access to combinatorial chemistry of hydantoins is provided by convenient and versatile methods for the solid phase synthesis of libraries of 3,5-, 1,3- and 1,3,5-substituted hydantoins. The preparation of trisubstituted hydantoins features a Mitsunobu reaction for introduction of the substituent on N-1.

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.