4-Chlorophenyl thiocyanate -Drug Synthesis Database

【结构式】

【分子编号】10198

【品名】4-Chlorophenyl thiocyanate

【CA登记号】3226-37-7

【分子式】C₇H₄ClNS

【分子量】169.6342

【元素组成】C 49.56% H 2.38% Cl 20.9% N 8.26% S 18.9%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

A synthesis for [benzene-U-14C]-tiludronate has been described: The chlorination of [U-14C]-acetanilide (I) with tetrabutylammonium iodotetrachloride gives the corresponding 4-chloro derivative (II) (along with some of the 2-chloro isomer). The hydrolysis of (II) with concentrated HCl at 60 C yields the chloroaniline (III), which is converted to the corresponding diazonium salt (IV) with NaNO2 and HCl. The reaction of (IV) with ferric thiocyanate affords the labeled 4-chlorophenylthiocyanate (V), which is condensed with the lithium salt of methylenebis(phosphonic acid)tetraisopropyl ester (VI) in THF to yield 4-chlorophenylsulfanylmethylenebis(phosphonic acid)tetraisopropyl ester (VII). Finally, this compound is hydrolyzed with concentrated HCl or aqueous NaOH.

参考文献中间体

合成目标

【1】 Ellames, G.J.; Burgos, A.; Synthesis of disodium [benzene-U-C-14]-(4-chlorophenylthio)methylene diphosphonate, [benzene-U-C-14]-tiludronate. J Label Compd Radiopharm 1995, 36, 11, 1071.

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)	10194	N-Phenylacetamide; Acetanilide	103-84-4	C₈H₉NO	详情	详情
(I)	44610			C₈H₉NO	详情	详情
(II)	10195	N-(4-Chlorophenyl)acetamide	539-03-7	C₈H₈ClNO	详情	详情
(II)	44611			C₈H₈ClNO	详情	详情
(III)	10196	4-Chlorobenzenaminium chloride		C₆H₇Cl₂N	详情	详情
(III)	44612			C₆H₇Cl₂N	详情	详情
(IV)	10197	4-Chlorobenzenediazonium chloride		C₆H₄Cl₂N₂	详情	详情
(IV)	44613			C₆H₇Cl₂N	详情	详情
(V)	10198	4-Chlorophenyl thiocyanate	3226-37-7	C₇H₄ClNS	详情	详情
(V)	44614			C₇H₄ClNS	详情	详情
(VI)	10199	[Bis(diisopropoxyphosphoryl)methyl]lithium		C₁₃H₂₉LiO₆P₂	详情	详情
(VII)	10200	Diisopropyl [(4-chlorophenyl)sulfanyl](diisopropoxyphosphoryl)methylphosphonate		C₁₉H₃₃ClO₆P₂S	详情	详情
(VII)	44615			C₁₉H₃₃ClO₆P₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

By cleavage of the 7-methoxy-9-oxoxanthene-2-carboxylic acid (I) with AlCl3 in xylene to give 7-hydroxy-9-oxoxanthene-2-carboxylic acid (II), which is then esterified with ethanol and anhydrous HCl to the corresponding ethyl ester (III). This product is treated first with ethylene oxide (A) in DMF, and finally hydrolyzed with NaOH in ethanol-water. The condensation of 2-chloro-5-nitrobenzoic acid (IV) with 4-methoxyphenol (V) by means of K2CO3, Cu and Cu2I2 in n-pentanol gives 2-(4-methoxyphenoxy)-5-nitrobenzoic acid (VI), which is cyclized with concentrated H2SO4 to 7-methoxy-2-nitroxanthone (VII). The reduction of the nitro group of (VII) with SnCl2 in concentrated HCl yields 7-methoxy-2-aminoxanthone (VIII). Finally, this product is treated first with NaNO2 - HCl, then with NaCN and finally hydrolyzed with H2SO4 to afford 7-methoxy-9-oxoxanthene-2-carboxylic acid.

参考文献中间体

合成目标

【1】 Castaner, J.; Blancafort, P.; AH 7725. Drugs Fut 1976, 1, 7, 313.
【2】 Bays, D.E.; Xanthone derivatives.. DE 2058295; FR 2073425; GB 1312620; US 3706768 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10393	Oxirane; Ethylene oxide	75-21-8	C₂H₄O	详情	详情
(I)	40469	7-methoxy-9-oxo-9H-xanthene-2-carboxylic acid		C₁₅H₁₀O₅	详情	详情
(II)	40470	7-hydroxy-9-oxo-9H-xanthene-2-carboxylic acid		C₁₄H₈O₅	详情	详情
(III)	40471	ethyl 7-hydroxy-9-oxo-9H-xanthene-2-carboxylate		C₁₆H₁₂O₅	详情	详情
(IV)	10198	4-Chlorophenyl thiocyanate	3226-37-7	C₇H₄ClNS	详情	详情
(V)	32744	4-methoxyphenol	150-76-5	C₇H₈O₂	详情	详情
(VI)	40466	2-(4-methoxyphenoxy)-5-nitrobenzoic acid		C₁₄H₁₁NO₆	详情	详情
(VII)	40467	2-methoxy-7-nitro-9H-xanthen-9-one		C₁₄H₉NO₅	详情	详情
(VIII)	40468	2-amino-7-methoxy-9H-xanthen-9-one		C₁₄H₁₁NO₃	详情	详情

Extended Information