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【结 构 式】

【分子编号】21032

【品名】3-hydroxy-4-nitrobenzaldehyde

【CA登记号】

【 分 子 式 】C7H5NO4

【 分 子 量 】167.12104

【元素组成】C 50.31% H 3.02% N 8.38% O 38.29%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

A synthesis of the racemic compound was later reported: 3-Hydroxy-4-nitrobenzaldehyde (I) was reduced to the benzyl alcohol (II) with NaBH4 and then converted to diacetate (III) with Ac2O in pyridine. Selective deacetylation of the aryl ester of (III) with KHCO3 in MeOH produced phenol (IV), which was then acylated with acetylsalicyloyl chloride (V) to yield (VI). The catalytic hydrogenation of the nitro group of (VI) in the presence of Raney-Ni was accompanied by migration of the salicyloyl unit to the amino group to yield salicylamide (VII) (accompanied by some byproduct resulting from the cleavage of the phenolic acetate). The resultant mixture of mono- and diacetate was converted to triol (VIII) by hydrolysis in aqueous NaOH. Then, the aminophenol ring of (VIII) was selectively oxidized with Fremy's salt to quinone (IX). Finally, the quinone was treated with H2O2 in the presence of NaHCO3 to furnish the racemic epoxide.

1 Matsumoto, N.; Iinuma, H.; Sawa, T.; Takeuchi, T.; Synthesis of anti-rheumatic agent epoxyquinomicin B. Bioorg Med Chem Lett 1998, 8, 21, 2945.
2 Matsumoto, N.; et al.; Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. I. Taxonomy, fermentation, isolation and antimicrobial activities. J Antibiot 1997, 50, 11, 900.
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) 21032 3-hydroxy-4-nitrobenzaldehyde C7H5NO4 详情 详情
(II) 21465 5-(hydroxymethyl)-2-nitrophenol C7H7NO4 详情 详情
(III) 21466 5-[(acetoxy)methyl]-2-nitrophenyl acetate C11H11NO6 详情 详情
(IV) 21467 3-hydroxy-4-nitrobenzyl acetate C9H9NO5 详情 详情
(V) 16900 2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride 5538-51-2 C9H7ClO3 详情 详情
(VI) 21469 5-[(acetoxy)methyl]-2-nitrophenyl 2-(acetoxy)benzoate C18H15NO8 详情 详情
(VII) 21470 4-[[2-(acetoxy)benzoyl]amino]-3-hydroxybenzyl acetate C18H17NO6 详情 详情
(VIII) 21471 2-hydroxy-N-[2-hydroxy-4-(hydroxymethyl)phenyl]benzamide C14H13NO4 详情 详情
(IX) 21472 2-hydroxy-N-[4-(hydroxymethyl)-3,6-dioxo-1,4-cyclohexadien-1-yl]benzamide C14H11NO5 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

3-Hydroxy-4-nitrobenzaldehyde (I) was treated with 1,3-propanediol (II) in the presence of p-toluenesulfonic acid to afford the corresponding acetal (III). Catalytic hydrogenation of the nitro group of (III) over Raney-Ni gave aniline (IV), which was then acylated with chloroacetyl chloride (V) in the presence of NaHCO3 to the chloroacetamide (VI). The acetal function of (VI) was hydrolyzed with HCl in aqueous MeOH, and subsequent cyclization of the chloroacetamide (VII) using K2CO3 in acetonitrile produced the formylbenzoxazinone (VIII). The target compound was then prepared by reductive condensation of aldehyde (VIII) with N-(4-chlorophenyl)piperazine (IX) in the presence of sodium triacetoxyborohydride and AcOH.

1 Brink, W.A.; Wustrow, D.J.; Belliotti, T.R.; et al.; A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: Discovery of a potential atypical antipsychotic agent. J Med Chem 1999, 42, 25, 5181.
2 Belliotti, T.; Wise, L.D.; Wustrow, D.J. (Pfizer Inc.); Benzoxazinone dopamine D4 receptor antagonists. EP 0906294; WO 9745419 .
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) 21032 3-hydroxy-4-nitrobenzaldehyde C7H5NO4 详情 详情
(III) 21034 5-(1,3-dioxan-2-yl)-2-nitrophenol C10H11NO5 详情 详情
(IV) 21035 (rac)-2-amino-5-(1,3-dioxan-2-yl)phenol C10H13NO3 详情 详情
(V) 11296 2-Chloroacetyl chloride; Chloroacetic chloride 79-04-9 C2H2Cl2O 详情 详情
(VI) 21037 2-chloro-N-[4-(1,3-dioxan-2-yl)-2-hydroxyphenyl]acetamide C12H14ClNO4 详情 详情
(VII) 21038 2-chloro-N-(4-formyl-2-hydroxyphenyl)acetamide C9H8ClNO3 详情 详情
(VIII) 21039 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde C9H7NO3 详情 详情
Extended Information