Substituted hydantoins formation

The described fluorous-tag strategy has also been applied to the synthesis of biaryl-substituted hydantoins (Scheme 7.81) [94]. 4-Hydroxybenzaldehyde was converted into the corresponding perfluorinated species, which was then subjected to a reductive amination. The resulting amine was treated with an isocyanate to produce the fluorous-tagged urea, which spontaneously cyclized to form the corresponding hydantoin. Finally, the fluorous tag was detached by a Suzuki-type carbon-carbon bond formation to furnish the desired target structure in good yield. 

A limiting factor in the use of these CSPs is the fact that the formation of the solute/CSP complex is dependent on the existence of complimentary interaction sites on the solute. However, this is not a problem with a wide variety of enantiomeric compounds. Type I CSPs have been used to stereochemically resolve alkyl carbinols, aryl-substituted hydantoins, lactams, succinimides, phthalides, sulfoxides, and sulfides (20). 

Bucherer, H. T., Libe, V. A. Syntheses of hydantoins. II. Formation of substituted hydantoins from aldehydes and ketones. J. Prakt. Chem. 

Urea, methylurea, and dimethylureas react with glyoxylic acid and its methyl ester to give a-substituted hydantoic acid derivatives (16) and substituted allantoic acid derivatives (17), which can be cyclized to 5-substituted hydantoins (18). Although allantoin (18) formation from urea and... 

For example, Yu et al. showed that polystyrene-bound peptides could be hydrolyzed in 7 min in a domestic MW oven, a process normally taking 24 h. Furthermore, traditional soHd-phase peptide couplings were achieved in 4 min in 99-100% conversion with no detected racemization. A broad range of solid-phase reactions was found to undergo substantial rate acceleration, including Claisen and Knoeve-nagel condensations, nucleophilic substitutions, sucdnimide and hydantoin formation, and Suzuki coupHngs. 

Several syntheses of l,3-dioxoperhydropyrrolo[l,2-c]imidazoles have been developed using different strategies. a-Substituted bicyclic proline hydantoins were prepared by alkylation of aldimines 135 of resin-bound amino acids with a,tu-dihaloalkanes and intramolecular displacement of the halide to generate cr-substituted prolines 136 and homologs (Scheme 18). After formation of resin-bound ureas 137 by reaction of these sterically hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products <2005TL3131>. 

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

A phase-transfer catalysed nucleophilic displacement reaction on chloro-acetanilides by cyanate ions, followed by ring-closure (Scheme 5.10), provides a simple and viable synthesis of hydantoins [41], The formation of the hydantoins is inhibited by substituents in the orf/to-position of the aryl ring, but the addition of potassium iodide, or tetra-n-butylammonium iodide, generally increases the overall rate of formation of the cyclic compounds, presumably by facilitating the initial nucleophilic substitution step. 

When hydantoins are treated with acetic anhydride, sodium hypochlorite, or nitiric acid, substitution takes place at the N-l position, followed by the formation of a 1,3-disubstituted hydantoin.1 Intramolecular processes yield only the amide cyclized products (102).255,256... 

Addition of 2,5-dihydro-2,2-dimethyl-5,5-bis(propylthio)-l,3,4-oxadiazole in refluxing benzene and an aryl isocyanate releases the bis(propylthio)carbene in situ which then adds easily to the aryl isocyanate to yield a substituted isatin with the ketone functionality protected as a thioacetal (eq 4)7 Ring closure also occurred when the 2,5-dihydro-2,2-dimethyl-5,5-bis(propylthio)-1,3,4-oxadiazole carbene precursor was added to 1-naphthyl isocyanate in refluxing acetonitrile (eq 5)7 Formation of thioacetal protected isatin products are unique to the bis(propylthio)carbene as other nucleophilic carbenes added to aryl isocyanates afforded only modest yields of hydantoin products. ... 

Reactions.— The nucleophilic reactivity of the thiocarbonyl sulphur atom in thioureas has been further exemplified in a series of papers reporting on S-alkylation reactions of open-chain " as well as cyclic thioureas using alkyl halides. Ried and his co-workers have reported that (4-quinazolyl)thioureas (315) react smoothly with methylene iodide in the presence of triethylamine to yield the 1,3-thiazetidines (316). The ready formation of (316) was attributed to the special effect of the intramolecular hydrogen bonding in (315), as common thioureas usually did not enter into this reaction in a well-defined and profitable way. 5,5-Diphenyl-2-thio-hydantoin reacted with symmetrical ao>-dibromo-alkanes to yield the cyclization products (317). The action of excess of methyl iodide on N -substituted N-(o-aminophenyl)thioureas afforded the benzimidazoles (318), alternatively obtainable by treatment of the same thioureas with mercuric chloride." " In a similar manner, l-amino-6,7-dimethoxy-3,4-di-hydroisoquinolines were formed by the action of mercuric chloride on the thioureas (319)" or their S-methyl derivatives (320). " A recent paper by Klayman and his co-workers deals with the reactivity of S-methiodide derivatives of thioureas that are activated by electron-withdrawing groups towards hydroxylic compounds. "... 

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