o-Dihydroxybenzene; Catechol; Pyrocatechol -Drug Synthesis Database

【结构式】

【分子编号】11599

【品名】o-Dihydroxybenzene; Catechol; Pyrocatechol

【CA登记号】120-80-9

【分子式】C₆H₆O₂

【分子量】110.11244

【元素组成】C 65.45% H 5.49% O 29.06%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(I)

The cyclization of catechol (I) with 2-chloroacrylonitrile (II) by means of K2CO3 in acetone gives 2-cyanobenzo-1,4-dioxane (III), which is hydrolyzed with ethanol and HCl to the corresponding iminoether (IV) Finally, this compound is cyclized with ethylenediamine (V) in cool ethanol.

参考文献中间体

合成目标

【1】 Myers, P.L.; Chapleo, C.B.; 2-[2-(1,4-Benzodioxanyl)]-2-imidazoline hydrochloride. Tetrahedron Lett 1981, 22, 48, 4839-42.
【2】 Chapleo, C.B.; Myers, P.L. (Reckitt & Colman Pharmaceuticals); Imidazoline deriv.. GB 2068376 .
【3】 Hillier, K.; Idazoxan hydrochloride. Drugs Fut 1983, 8, 9, 778.

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)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(II)	12372	2-Chloroacrylonitrile	920-37-6	C₃H₂ClN	详情	详情
(III)	36171	2,3-dihydro-1,4-benzodioxine-2-carbonitrile		C₉H₇NO₂	详情	详情
(IV)	36172	ethyl 2,3-dihydro-1,4-benzodioxine-2-carboximidoate		C₁₁H₁₃NO₃	详情	详情
(V)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

A synthesis of (+)-(R)-flesinoxan has been described: The nitration of pyrocatechol (I) with nitric acid gives 3-nitrocatechol (II), which is cyclized with epichlorohydrin (III) and acylated with acetic anhydride, yielding 2-(acetoxymethyl)-5-nitro-1,4-benzodioxan (IV). The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding amine (V), which is cyclized with bis(2-chloroethyl)amine in refluxing chlorobenzene to afford the piperazine (VI). The reaction of (VI) with N-(4-fluorobenzoyl)aziridine (VII) by means of triethylamine in refluxing acetone gives racemic flesinoxan (VIII), which is then submitted to a carefully controlled enzymatic acetylation with Amano P-30 lipase, which acetylates the (R)-isomer selectively. After separation of the nonesterified compound, the acetate is hydrolyzed to give an enriched product, which is submitted to a new enzymatic esterification to improve the optical purity.

参考文献中间体

合成目标

【1】 Ghazal, N.B.; Ennis, M.D.; The synthesis of (+)- and (-)-flesinoxan: Application of enzymatic resolution methodology. Tetrahedron Lett 1992, 33, 42, 6287.

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)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(II)	11600	3-Nitro-1,2-benzenediol		C₆H₅NO₄	详情	详情
(III)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(IV)	11602	(5-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl acetate		C₁₁H₁₁NO₆	详情	详情
(V)	11603	(5-amino-2,3-dihydro-1,4-benzodioxin-2-yl)methyl acetate		C₁₁H₁₃NO₄	详情	详情
(VI)	11604	(5-piperazino-2,3-dihydro-1,4-benzodioxin-2-yl)methyl acetate		C₁₅H₂₀N₂O₄	详情	详情
(VII)	11605	1-Aziranyl(4-fluorophenyl)methanone		C₉H₈FNO	详情	详情
(VIII)	11606	4-fluoro-N-(2-[4-[2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-5-yl]piperazino]ethyl)benzamide		C₂₂H₂₆FN₃O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The intermediate phenylenediamine derivative (VI) has been obtained as follows: The reaction of 2-[2-(2-methoxyethoxy)ethoxy]ethanol (I) with Ts-Cl and NaOH in THF/water gives the tosylate (II), which is condensed with pyrocatechol (III) by means of K2CO3 in methanol, yielding the aryl ether (IV). The nitration of (IV) with HNO3 in acetic acid affords the dinitro derivative (V), which is finally reduced to the target phenylenediamine intermediate (VI) with hydrazine in ethanol catalyzed by Pd/C.

参考文献中间体

合成目标

【1】 Sessler, J.L.; Miller, R.A.; Harriman, A.M. (Pharmacyclics, Inc.; University of Texas System); Radiation sensitization using texaphyrins. US 5622946 .

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)	53327	Methyl Triglycol	112-35-6	C₇H₁₆O₄	详情	详情
(II)	53328	2-[2-(2-methoxyethoxy)ethoxy]ethyl 4-methylbenzenesulfonate	n/a	C₁₄H₂₂O₆S	详情	详情
(III)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(IV)	53329	1,2-bis{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}benzene; 2-{2-[2-(2-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}phenoxy)ethoxy]ethoxy}ethyl methyl ether	n/a	C₂₀H₃₄O₈	详情	详情
(V)	53330	1,2-bis{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}-4,5-dinitrobenzene; 2-{2-[2-(2-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}-4,5-dinitrophenoxy)ethoxy]ethoxy}ethyl methyl ether	n/a	C₂₀H₃₂N₂O₁₂	详情	详情
(VI)	53331	2-amino-4,5-bis{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}phenylamine; 4,5-bis{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}-1,2-benzenediamine	n/a	C₂₀H₃₆N₂O₈	详情	详情

合成路线4

该中间体在本合成路线中的序号：

Proxodolol (V) was obtained as shown in Scheme 21696501a: Monoalkylation of pyrocatechol with chloroacetic acid gives 2-hydroxyphenoxyacetic acid (I), which is cyclized on heating into 1,4-benzodioxan-2-one (II). Condensation of (II) with acetamidoxime, giving 2-methyl-5-(2-hydroxyphenoxymethyl)-1,2,4-oxadiazole (III), followed by alkylation with epichlorohydrin yields the corresponding diether (IV), which smoothly reacts with tert-BuNH2, and the amine (V) is converted into its hydrochloride by reaction with HCl.

参考文献中间体

合成目标

【1】 Mashkovski, M.D.; Sokolov, S.D.; Vinogradova, S.M.; Yuzhakov, S.D.; Yermakova, V.N.; Proxodolol. Drugs Fut 1997, 22, 5, 499.
【2】 Sokolov, S.D.; Vinogradova, S.M.; Azarevich, O.G.; Berg, M.V.; Mashkovski, M.D.; Yuzhakov, S.D.; Morozov, A.V. (Center for Chemistry of Drugs); The hydrochlorides of derivs. of 5-phenoxymethyl-1,2, 4-oxadiaxole, possessing beta- and alpha-adrenoblocking activities. SU 1132505 .
【3】 Sokolov, S.D.; Vinogradova, S.M.; Azarevich, O.G. (Center for Chemistry of Drugs); The method for producing of 5-(2-hydroxyphenoxymethyl)-1,2,4-oxadiazoles. SU 1139129 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
	11847	2-Chloroacetic acid; Chloroacetic Acid	79-11-8	C₂H₃ClO₂	详情	详情
	64134	N'-hydroxyethanimidamide		C₂H₆N₂O	详情	详情
(I)	16894	2-Hydroxyphenoxyacetic acid; o-Hydroxyphenoxyacetic acid; 2-(2-hydroxyphenoxy)acetic acid	6324-11-4	C₈H₈O₄	详情	详情
(II)	16895	1,4-BENZODIOXAN-2-ONE; 1,4-benzodioxin-2(3H)-one	4385-48-2	C₈H₆O₃	详情	详情
(III)	16896	2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenol		C₁₀H₁₀N₂O₃	详情	详情
(IV)	16897	2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenyl 2-oxiranylmethyl ether; 3-methyl-5-[[2-(2-oxiranylmethoxy)phenoxy]methyl]-1,2,4-oxadiazole		C₁₃H₁₄N₂O₄	详情	详情
(V)	16898	1-(tert-butylamino)-3-[2-[(3-methyl-1,2,4-oxadiazol-5-yl)methoxy]phenoxy]-2-propanol hydrochloride		C₁₇H₂₆ClN₃O₄	详情	详情

合成路线5

该中间体在本合成路线中的序号：(I)

The enantiomerically pure benzodioxane derivative (VIII) was obtained in a straightforward route including five steps starting from pyrocatechin (I). Racemic (VI) was then resolved by means of crystallization with (-)-O,O'-dibenzoyl-L-tartaric acid.

参考文献中间体

合成目标

【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072.
【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
(I)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	28714	2,3-dihydro-1,4-benzodioxin-2-ylmethanol	3663-82-9	C₉H₁₀O₃	详情	详情
(IV)	20959	2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate		C₁₆H₁₆O₅S	详情	详情
(V)	20960	3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol		C₁₂H₁₇NO₃	详情	详情
(VI)	28715	3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情
(VII)	16186	(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid		C₁₈H₁₄O₈	详情	详情
(VIII)	28716	3-chloro-N-[(2R)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl]-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情

Extended Information