5-(4-nitrophenyl)-2-furaldehyde -Drug Synthesis Database

【结构式】

【分子编号】63583

【品名】5-(4-nitrophenyl)-2-furaldehyde

【CA登记号】

【分子式】C₁₁H₇NO₄

【分子量】217.18092

【元素组成】C 60.83% H 3.25% N 6.45% O 29.47%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

Diazotization of 4-nitroaniline (I), followed by copper-catalyzed coupling of the resultant diazonium salt (II) with 2-furaldehyde (III) leads to 5-(p-nitrophenyl)-2-furancarboxaldehyde (IV) (1). Cyclization of semicarbazideacetic acid (V) by heating in aqueous sulfuric acid leads to 1-aminohydantoin (VI) (2). This is then condensed with aldehyde (IV) to furnish the furfurylidene aminohydantoin (VII) (1, 2). Treatment of (VII) with sodium methoxide gives rise to the corresponding sodium salt (1).

参考文献中间体

合成目标

【1】 Frimm, R.; Kovac, S.; Giller, S.A.; Furan derivatives. XXIII. Synthesis and absorption spectra of 5-(nitrophenyl)-2-furaldehyde derivatives. Chem Zvesti 1969, 23, 11-12, 916.
【2】 Snyder, H.R. Jr.; Davis, C.S.; Bickerton, R.K.; Halliday, R.P.; 1-[(5-Arylfurfurylidene)amino]hydantoins. A new class of muscle relaxants. J Med Chem 1967, 10, 5, 807.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15547	4-nitrophenylamine; p-Nitroaniline; 4-nitroaniline	100-01-6	C₆H₆N₂O₂	详情	详情
(II)	61431	4-nitrobenzenediazonium		C₆H₄N₃O₂	详情	详情
(III)	63582	2-furaldehyde		C₅H₄O₂	详情	详情
(IV)	63583	5-(4-nitrophenyl)-2-furaldehyde		C₁₁H₇NO₄	详情	详情
(V)	63584	2-[1-(aminocarbonyl)hydrazino]acetic acid		C₃H₇N₃O₃	详情	详情
(VI)	63585	1-amino-2,4-imidazolidinedione		C₃H₅N₃O₂	详情	详情
(VII)	63586	1-({(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}amino)-2,4-imidazolidinedione		C₁₄H₁₀N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In an alternative method, condensation of semicarbazide hydrochloride (I) with cyclohexanone (II) yields the semicarbazone (III). Subsequent reaction of (III) with ethyl chloroacetate (IV) in the presence of NaOMe gives rise to the cyclohexylidene aminohydantoin (V). Treatment of (V) with 5-(p-nitrophenyl)furfural (VI) under acidic conditions affords the furfurylidene aminohydantoin (VII). This is finally converted into the corresponding sodium salt employing methanolic NaOMe (3).

参考文献中间体

合成目标

【1】 Martin-Escudero Perez, U.; Izquierdo Sanjose, M.; Process for obtaining 1-[(5-(p-nitrophenyl)furfuryliden)amino]hydantoin and its sodium salt. ES 458000 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	23944	1-Hydrazinecarboxamide	563-41-7	CH₅N₃O	详情	详情
(II)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情
(III)	63587	2-cyclohexylidene-1-hydrazinecarboxamide		C₇H₁₃N₃O	详情	详情
(IV)	16601	ethyl chloroacetate; ethyl 2-chloroacetate	105-39-5	C₄H₇ClO₂	详情	详情
(V)	63588	1-(cyclohexylideneamino)-2,4-imidazolidinedione		C₉H₁₃N₃O₂	详情	详情
(VI)	63583	5-(4-nitrophenyl)-2-furaldehyde		C₁₁H₇NO₄	详情	详情
(VII)	63586	1-({(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}amino)-2,4-imidazolidinedione		C₁₄H₁₀N₄O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The title compound has also been obtained by solid phase synthesis. Bromoacetic acid (I) is coupled to hydroxymethyl polystyrene resin by means of DIC/DMAP to produce the bromoacetyl resin (II). Bromide displacement with tert-butyl carbazate (III) leads to the N-Boc hydrazino ester (IV), which is further deprotected to (V) employing trifluoroacetic acid. The hydrazinoacetic acid-bound resin (V) is then condensed with 5-(p-nitrophenyl)furfural (VI) to furnish hydrazone (VII). Acylation of resin (VII) with p-nitrophenyl chloroformate (VIII) produces the p-nitrophenyl carbamate (IX), which upon treatment with ammonia gives rise to the semicarbazone (X). Finally, concomitant intramolecular ring closure and resin cleavage of (X) produces the target aminohydantoin derivative (XI) (4, 5).

参考文献中间体

合成目标

【1】 Wilson, L.J.; Li, M.; Portlock, D.E.; Solid phase synthesis of 1-aminohydantoin libraries. Tetrahedron Lett 1998, 39, 29, 5135.
【2】 Portlock, D.E.; Li, M.; Wilson, L.J. (The Procter & Gamble Co.); Solid phase synthesis of 1-aminohydantoins. WO 9942450 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(II)	12309	methyl 2-bromoacetate; methyl bromoacetate	96-32-2	C₃H₅BrO₂	详情	详情
(III)	12091	1-Methylhydrazine; Monomethyl hydrazine	60-34-4	CH₆N₂	详情	详情
(IV)	63589	2-[2-(tert-butoxycarbonyl)hydrazino]acetic acid		C₇H₁₄N₂O₄	详情	详情
(V)	63590	2-hydrazinoacetic acid		C₂H₆N₂O₂	详情	详情
(VI)	63583	5-(4-nitrophenyl)-2-furaldehyde		C₁₁H₇NO₄	详情	详情
(VII)	63591	2-(2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid		C₁₃H₁₁N₃O₅	详情	详情
(VIII)	16605	4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene	7693-46-1	C₇H₄ClNO₄	详情	详情
(IX)	63592	2-(1-[(4-nitrophenoxy)carbonyl]-2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid		C₂₀H₁₄N₄O₉	详情	详情
(X)	63593	2-(1-(aminocarbonyl)-2-{(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}hydrazino)acetic acid		C₁₄H₁₂N₄O₆	详情	详情
(XI)	63586	1-({(E)-[5-(4-nitrophenyl)-2-furyl]methylidene}amino)-2,4-imidazolidinedione		C₁₄H₁₀N₄O₅	详情	详情

Extended Information