699-51-4

Usage

Uses

Used in Pharmaceutical Industry:
1,3-DIAZA-SPIRO[4.4]NONANE-2,4-DIONE is used as a potential drug candidate for the development of new medications. Its unique structure and properties make it a valuable tool in medicinal chemistry research and drug discovery, offering opportunities for the creation of innovative therapeutic agents.
Used in Organic Synthesis:
As a building block, 1,3-DIAZA-SPIRO[4.4]NONANE-2,4-DIONE is utilized in various organic synthesis processes. Its heterocyclic nature and spiro ring system provide a foundation for the construction of complex organic molecules, which can be further modified for specific applications.
Used as a Chelating Agent:
1,3-DIAZA-SPIRO[4.4]NONANE-2,4-DIONE has shown potential as a chelating agent in chemical reactions. Its ability to form stable complexes with metal ions can be leveraged in various applications, such as in the purification of metal catalysts or the development of new materials with specific properties.
Used as a Catalyst:
In addition to its chelating properties, 1,3-DIAZA-SPIRO[4.4]NONANE-2,4-DIONE has demonstrated potential as a catalyst in organic reactions. Its catalytic activity can be employed to enhance the efficiency and selectivity of various chemical processes, contributing to the advancement of chemical synthesis and manufacturing techniques.

InChI:InChI=1/C7H10N2O2/c10-5-7(3-1-2-4-7)9-6(11)8-5/h1-4H2,(H2,8,9,10,11)

Upstream product

• 461-72-3 2,4-imidazolidinedione 
• 120-92-3 cyclopentanone 
• 773837-37-9 sodium cyanide 
• 506-87-6 ammonium carbonate 
• 461-37-0 2,2,2-trifluoroethyl carbamate 
• 60421-23-0 cycloleucine methyl ester hydrochloride 
• 124-38-9 carbon dioxide 
• 49830-37-7 1-amino-1-cyanocyclopentane 
• 151-50-8 potassium cyanide 
• 143-33-9 sodium cyanide 

Downstream Products

• 52-52-8 1-amino-1-cyclopentanecarboxylic acid 
• 106663-31-4 3-[(Benzyl-ethyl-amino)-methyl]-1,3-diaza-spiro[4.4]nonane-2,4-dione 
• 106663-30-3 3-[(Benzyl-methyl-amino)-methyl]-1,3-diaza-spiro[4.4]nonane-2,4-dione 
• 15115-28-3 3-dibenzylaminomethyl-1,3-diaza-spiro[4.4]nonane-2,4-dione 
• 80355-07-3 3-benzyl-1,3-diazaspiro[4.4]nonane-2,4-dione 
• 83521-99-7 cyclopentanespiro-4'-imidazolidine-2',5'-dithione 
• 14109-98-9 cyclopentanespiro-5-(2-thiohydantoin) {cyclopentanespiro-5-(2-thioxoimidazolidin-4-one)} 
• 98334-44-2 4-thioxo-1,3-diaza-spiro[4.4]nonan-2-one 
• 554-68-7 triethylamine hydrochloride 
• 2927-49-3 3-(dichloro-fluoro-methylsulfanyl)-1,3-diaza-spiro[4.4]nonane-2,4-dione 
• 853574-48-8 C₁₁H₁₆N₂O₄ 

Relevant academic research and scientific papers

Structure-property relationship of 3-(4-substituted benzyl)-1,3-diazaspiro[4.4]nonane-2,4-diones as new potentional anticonvulsant agents. An experimental and theoretical study

The structure-property relationship of newly synthesized 3-(4-substituted benzyl)-1,3-diazaspiro [4.4]nonane-2,4-diones was studied by experimental and calculated methods. The prepared compounds were characterized by UV-Vis, FT-IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. The crystal structure was elucidated by single-crystal X-ray diffraction. The 3-benzyl-1,3-diazaspiro[4.4]nonane-2,4-dione crystallizes in triclinic P?1 space group, with two crystallographically independent molecules in the asymmetric unit. Cyclopentane ring adopts an envelope conformation. A three-dimensional crystal packing is governed by hydrogen N?H?O bonds, numerous C?H?O/N and C–H … π interactions between neighboring molecules. Density functional theory (DFT) calculations with B3LYP and M06-2X methods using 6–311++G(d,p) basis set were performed to provide structural and spectroscopic information. Comparisons between experimental and calculated UV-Vis spectral properties suggest that the monomeric form of the investigated spirohydantoins is dominant in all used solvents. The effects of substituents on the absorption spectra of spirohydantoins are interpreted by correlation of absorption frequencies with Hammett equation. The lipophilicities of the investigated molecules were estimated by calculation of their log P values. Some of the spirohydantoins synthesized in this work, exhibit the lipophilicities comparable to the standard medicine anticonvulsant drug Phenytoin. The results obtained in this investigation afford guidelines for the preparation of new derivatives of spirohydantoin as potential anticonvulsant agents and for better understanding the structure-activity relationship.

Synthesis and characterization of novel cycloalkanespiro-5-hydantoin phosphonic acids

A series of new cycloalkanespiro-5-hydantoin phosphonic acids have been synthesized and characterized. The mixture of [(2,4-dioxo-1,3-diazaspiro-alkane- 3-yl)-methyl]phosphonic acids and [(2,4-dioxo-1,3-diazaspiro-alkane-1,3-diyl) dimethyl]diphospho-nic acids was obtained from cycloalkanespiro-5-hydantoins, formaldehyde, and phosphorus trichloride in a molar ratio of 1:2:2, by a procedure modified by us. Their structures were proved by means of IR, 1H, 13C{1H} and 31P NMR spectroscopy. Copyright Taylor & Francis Group, LLC.

An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries

An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting as an Aurora kinase A inhibitor was discovered with a combination of rational design, parallel synthesis using the procedures developed, in silico and in vitro screenings.

Towards understanding intermolecular interactions in hydantoin derivatives: the case of cycloalkane-5-spirohydantoins tethered with a halogenated benzyl moiety

A series of cycloalkane-5-spirohydantoins bearing a halogeno substituted benzyl group (X = Cl and Br) in position 3 has been synthesized and their structures (1-6) have been determined by a single crystal X-ray diffraction method. These compounds have multiple functional groups, which allow greater competition and/or cooperation among the different intermolecular interactions in the formation of their crystal structures. The molecules are linked together by paired N-H?O hydrogen bonds in R22(8) rings, while the C-H?O interactions lead to their further association into double chains. The contribution of the cycloalkyl ring depends on its conformational flexibility and the multiple C-H donor implications. In the case of compounds 1-4 bearing the cyclopentyl or the cyclohexyl ring, halogen bonding (X?O) interactions give rise to a supramolecular pseudo-hexagonal network. In addition, the C-H?X interactions with a higher degree of multifurcation at the halogen acceptor have an important role in the formation of the crystal structure. Regarding compounds 5 and 6 with the cycloheptane ring, the X?O interaction is absent, and along with the C-H?X interactions, these compounds realize an alternative crystal structure with an emphasis on the X?π interactions. The lattice energies of all these crystal structures, as well as the intermolecular pair energies, have been calculated using PIXEL and further partitioned into coulombic, dispersive, polarization and repulsive factors. The crystal structures have also been subjected to Hirshfeld surface analysis which reveals that approximately 75% of the close contacts correspond to relatively weak interactions. The application of both concepts has provided a new insight into the relationship between the molecular interactions and crystal structures of the hydantoin derivatives.

A Sustainable, Semi-Continuous Flow Synthesis of Hydantoins

Hydantoins are an important class of heterocycles with applications in pharmacy, agriculture, and as intermediates in organic synthesis. Traditional synthetic procedures to access hydantoins are target oriented with multiple synthetic steps and often use reagents that are not commercially available or sustainable. Herein, an efficient process is described for accessing hydantoins starting from commercially available amines using consecutive gas–liquid transformations (oxygen, carbon dioxide). This semi-continuous process produced ten benzylic/aliphatic hydantoins in good overall yields (52–84 %).

Direct chemical derivatization of natural plant extract: Straightforward synthesis of natural plant-like hydantoin

The direct chemical derivatization of natural plant extracts that would enable the straightforward synthesis of natural plant-like molecules seemed to be far from reality due primarily to the inherently complex chemical property of the extract. After mode

Microwave-assisted synthesis of functionalized spirohydantoins as 3-D privileged fragments for scouting the chemical space

Fragment-based drug design has been successfully applied to a large set of proteins, however in order to expand this concept to the most demanding targets, such as protein-protein interactions, it is required to enrich current fragment libraries with new and original 3D privileged fragments. Our goal was to develop a rapid microwave-assisted synthesis of 27 new privileged spirohydantoin fragments. Among them 24 compounds showed a high water solubility. These molecules were plotted according to the normalized principal moments of inertia of their minimized conformers, and most of the compounds were prone to occupy under-populated regions of the triangular plot. Finally we demonstrated that the hydantoin ring can be selectively N-monoalkylated providing the access to rapid functionalization for further elaboration.

AMIDOALKYLPIPERAZINYL DERIVATIVES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES

The invention relates to novel amidoalkylpiperazinyl derivatives of tricyclic heterocyclic systems of general formula (I), wherein Z represents -NH- and X represents -S-, or Z represents -S- and X represents >C=C1 represents H or -CH3, R6 and R7 both represent H, n is an integer from 0 to 4 inclusive, G represents a cyclic amide or imide moiety, and optical isomers, geometric isomers, and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of the central nervous system disorders.

Microwave-assisted synthesis of cycloalkanespirohydantoins and piperidinespirohydantoins as precursors of restricted α-amino acids

Cycloalkanespirohydantoins 3 and piperidinespirohydantoins 4 were synthesized from cycloalkanones 9 and piperidones 10 under microwave-assisted conditions. Results are compared with those obtained under thermal conditions. Cycloalkanespirohydantoins 3 were N-protected with Boc group and hydrolyzed under basic conditions to obtain five, six and seven-membered ring restricted α-amino acids 12 in very good overall yields (76-94%). ARKAT USA, Inc.

New polyamides based on 1,3-bis(4-carboxy phenoxy) propane and hydantoin derivatives: Synthesis and properties

Six new polyamides 5a-f containing flexible trimethylene segments in the main chain were synthesized through the direct polycondensation reaction of 1,3-bis(4-carboxy phenoxy) propane 3 with six derivatives of hydantoins 4a-f in a medium consisting of N-methyl-2-pyrrolidone, triphenyl phosphite, calcium chloride and pyridine. The polycondensation reaction produced a series of novel polyamides in high yield with inherent viscosities between 0.30-0.47 dL/g. The resulted polymers were fully characterized by means of FT-IR, 1H-NMR spectroscopy, elemental analyses, inherent viscosity, solubility tests and gel permeation chromatography (GPC). Thermal properties of these polymers were investigated by using thermal gravimetric analysis (TGA) and differential thermal gravimetry (DTG). The glass-transition temperatures of these polyamides were recorded between 130 and 155 °C by differential scanning catorimetry (DSC), and the 5% weight loss temperatures were ranging from 325 to 415 °C under nitrogen. 1,3-bis(4-Carboxy phenoxy) propane 3 was prepared from the reaction of 4-hydroxy benzoic acid 1 with 1,3-dibromo propane 2 in the presence of NaOH solution.