7-chloro-2,4-dihydroxy-2H-1,4-benzoxazin-3-one | 131761-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 7-chloro-2,4-dihydroxy-2H-1,4-benzoxazin-3-one
• 英文别名: 7-Chloro-2,4-dihydroxy-1,4-benzoxazin-3-one
• CAS: 131761-59-6
• 化学式: C₈H₆ClNO₄
• 分子量: 215.593
• InChiKey: CIVVWAHERGHLPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-2,4-dihydroxy-2H-1,4-benzoxazin-3-one 在 水 作用下， 以 甲醇 为溶剂， 生成 6-氯-苯并恶唑酮
  参考文献：
  名称：

  Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol

  摘要：

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.

  DOI：

  10.1021/jo00005a025
• 作为产物：
  描述：

  methyl 2-(5-chloro-2-nitrophenoxy)-2-methoxyacetate 在 palladium on activated charcoal sodium tetrahydroborate 、 三氯化硼 、 silver carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 7-chloro-2,4-dihydroxy-2H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol

  摘要：

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.

  DOI：

  10.1021/jo00005a025

文献信息

• ATKINSON, JEFFREY;MORAND, PETER;ARNASON, JOHN T.;NIEMEYER, HERMANN M.;BRA+, J. ORG. CHEM., 56,(1991) N, C. 1788-1800
  作者：ATKINSON, JEFFREY、MORAND, PETER、ARNASON, JOHN T.、NIEMEYER, HERMANN M.、BRA+

  DOI：——

  日期：——
• Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with .beta.-mercaptoethanol
  作者：Jeffrey Atkinson、Peter Morand、John T. Arnason、Hermann M. Niemeyer、Hector R. Bravo

  DOI：10.1021/jo00005a025

  日期：1991.3

  Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl alpha-(o-nitrophenoxy)-alpha-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group. A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring [R = MeO (1), t-Bu (6), Me (7), H (8), Cl (9), F (10), CO2Me (11a)]. The pK(a) values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series. They correlated well with sigma in a linear free energy relationship (LFER) yielding values of rho = 0.71 (with sigma-p) for pK(a1) (the hydroxamic acid) and rho = 1.6 (with sigma-m) for pK(a2) (the phenol). A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and sigma+ (rho = 1.1). The rates of hydroxamic acid reduction to lactams by beta-mercaptoethanol were also investigated. It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3-5) had measurable rates of reduction. H-1 NMR spectra recorded during this reaction in D2O buffers (pD9), however, showed that compounds 1, 2, 6-9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol. The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.