naphthoquinone; 1,4-Naphthoquinone -Drug Synthesis Database

【结构式】

【分子编号】16561

【品名】naphthoquinone; 1,4-Naphthoquinone

【CA登记号】130-15-4

【分子式】C₁₀H₆O₂

【分子量】158.15644

【元素组成】C 75.94% H 3.82% O 20.23%

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：(VIII)

1) The Diels-Alder cyclization of butadiene (I) with 2-methylbenzophenone (II) by means of acetic acid in refluxing toluene followed by oxidation with ceric ammonium nitrate gives 2-methyl-1,4-naphthoquinone (III), which by a new Diels-Alder cyclization with cyclopentadiene (IV) yields 4aalpha-methyl-1,4,4a,5,8,9a-hexahydro-1alpha,4alpha-methanoanthraquinone (V). The alkylation of (V) with 3,7,11,15-tetramethyl-2(E),6(E),10(E),14-hexadecatetraeanyl bromide (VI) by means of potassium tert-butoxide in THF affords the alkylated anthraquinone (VII), which is submitted to a retro Diels-Alder reaction in refluxing toluene containing dichlorodicyanobenzoquinone (DDQ) in order to obtain a simultaneous dehydrogenation. 2) The Diels-Alder cyclization of 1,4-naphthoquinone (VIII) with cyclopentadiene as before gives 1,4,4a,9a-tetrahydro-1,4-methanoanthraquinone (IX), which is alkylated with the alkyl bromide (VI) as before to yield the alkylated anthraquinone (X). The methylation of (X) with methyl iodide and potassium tert-butoxide affords the 9a-methylated anthraquinone (XI), which is finally submitted to a retro Diels-Alder reaction in refluxing toluene.

参考文献中间体

合成目标

【1】 Graul, A.; Castañer, J.; Menatetrenone. Drugs Fut 1996, 21, 6, 615.
【2】 Hamamura, K.; Iwama, T.; Seki, C.; Konishi, M. (Eisai Co., Ltd.); Preparation process of quinone deriv. and intermediate for the preparation thereof. EP 0613877 .
【3】 Hamamura, K.; Seki, C.; Konishi, M. (Eisai Co., Ltd.); Preparation process of naphthoquinone derivs. and intermediates for the preparation thereof. EP 0636598 .

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)	11579	1,3-Butadiene; Butadiene	106-99-0	C₄H₆	详情	详情
(II)	16555	2-methyl-2,5-cyclohexadiene-1,4-dione; 2-methylbenzo-1,4-quinone	553-97-9	C₇H₆O₂	详情	详情
(III)	16556	2-methyl-5,8-dihydro-1,4-naphthalenedione		C₁₁H₁₀O₂	详情	详情
(IV)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(V)	16558	(2R)-2-methyltetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4(9),6,13-triene-3,10-dione		C₁₆H₁₆O₂	详情	详情
(VI)	16559	(2E,6E,10E)-1-bromo-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene		C₂₀H₃₃Br	详情	详情
(VII)	16560	(2R,11S)-2-methyl-11-[(2E,6E,10E)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl]tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4(9),6,13-triene-3,10-dione		C₃₆H₄₈O₂	详情	详情
(VIII)	16561	naphthoquinone; 1,4-Naphthoquinone	130-15-4	C₁₀H₆O₂	详情	详情
(IX)	16562	tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,10-dione		C₁₅H₁₂O₂	详情	详情
(X)	16563	(2S)-2-[(2E,6E,10E)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl]tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,10-dione		C₃₅H₄₄O₂	详情	详情
(XI)	16564	(2R,11S)-2-methyl-11-[(2E,6E,10E)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl]tetracyclo[10.2.1.0(2,11).0(4,9)]pentadeca-4,6,8,13-tetraene-3,10-dione		C₃₆H₄₆O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 1,4-naphthoquinone (I) with bis(2-mercaptoethyl) ether (II) produces the bis-(dihydroxynaphthalene) adduct (III), which is spontaneously oxidized to the bis-napthoquinone derivative (IV). Then, cyclization of (IV) with further bis-mercapto ether (II) in DMF under a positive pressure of O2 leads to the target crown ether derivative.

参考文献中间体

合成目标

【1】 Huang, S.-T.; et al.; Efficient synthesis of "redox-switched" naphthoquinone thiol-crown ethers and their biological activity evaluation. Bioorg Med Chem 2002, 10, 6, 1947.

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)	16561	naphthoquinone; 1,4-Naphthoquinone	130-15-4	C₁₀H₆O₂	详情	详情
(II)	61651	Di-2-mercaptoethyl ether; 2-MERCAPTOETHYL ETHER; 2,2'-OXYDIETHANETHIOL; Di(2-mercaptoethyl) Ether; 2-Mercaptoethyl Ether; Bis(2-mercaptoethyl) ether; 2-Mercaptoethyl ether; 2,2'-Dithiodiethyl ether; (2,2'-OXYDIETHANETHIOL)	2150-02-9	C₄H₁₀OS₂	详情	详情
(III)	61652	2-[(2-{2-[(1,4-dihydroxy-2-naphthyl)sulfanyl]ethoxy}ethyl)sulfanyl]-1,4-naphthalenediol		C₂₄H₂₂O₅S₂	详情	详情
(IV)	61653	2-[(2-{2-[(1,4-dioxo-1,4-dihydro-2-naphthalenyl)sulfanyl]ethoxy}ethyl)sulfanyl]naphthoquinone		C₂₄H₁₈O₅S₂	详情	详情

Extended Information