(S)-(+)-2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (S)-(+)-2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid
• 英文别名: (s)-(+)-2-t-Butyl-2-methyl-1,3-benzodioxol-4-carboxylic acid；(2S)-2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: OBKLBZDYLDXACZ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-2-aminocycloheptanol 、 (S)-(+)-2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成
  参考文献：
  名称：

  脂肪酶催化的（±）-反式和顺式-2-叠氮基环烷醇的动力学拆分。

  摘要：

  描述了脂肪酶催化的反式和顺式-2-叠氮基环烷醇的动力学拆分以及对映体纯的反式和顺式-2-氨基环烷醇的制备。筛选了四种脂肪酶，用于反式和顺式-2-叠氮基环烷醇的乙酰化。其中，假单胞菌属sp。脂肪酶（脂肪酶PS和脂肪酶AK，Amomo Pharmaceutical Co.）显示出最高的对映选择性。使用（S）-TBMB羧酸[（S）-2-叔丁基-2-甲基- 1,3-苯并二恶唑-4-羧酸]作为手性转化试剂。CD分析的结果证明N，O-双-（S）-TBMB羧化的顺-2-氨基环烷醇主要采用N-赤道构象。

  DOI：

  10.1271/bbb.63.2150
• 作为产物：
  描述：

  (+/-)-1-(2-tert-butyl-2-methyl-1,3-benzodioxol-4-yl)-2,2-difluoroethanone 在 1‐methyl‐2‐azaadamantane‐N‐oxyl 、 sodium tetrahydroborate 、 sodium chloride dihydrate 、 potassium bromide 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 、 异丙醇 为溶剂， 生成 (S)-(+)-2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid
  参考文献：
  名称：

  Reduction of acetophenones with methyl fluorines and a bulky group on the aromatic ring using microorganisms and related enzymes

  摘要：

  Whole-cell yeasts and mold-catalyzed reduction of two fluorinated acetophenone derivatives with very bulky substituents on ortho position of aromatic ring, (+/-)-1'-(2-tert-buty1-2-methyl-1,3-benzodioxo1-4-yl)-2',2'-difluoroethanone and (+/-)-1'-(2-tert-buty1-2-methyl-1,3-benzodioxol-4-yl)2',2',2'-trifluoroethanone were examined. On the former substrate, Geotrichum candidum NBRC 5767 showed high re-facially selective attack of hydride, while with Pichia angusta JCM 3620, complementary si-facially selective attack proceeded. G. candidum NBRC 5767 was revealed to be potent biocatalyst which provides (1'S)-alcohols from both substrates in a highly facially selective manner. Some unknown reductases were suggested responsible for those reductions, other than so far having been reported acetophenone reductase and trifluoromethyl ketone reductase from G. candidum, comparing the results obtained by applying those enzymes. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2012.06.010

文献信息

• Synthesis of (S)-(+)-2--butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid: A new type chiral derivation reagent for amines and alcohols
  作者：Yoshihiro Nishida、Hiroshi Ohrui、Hiroshi Meguro

  DOI：10.1016/s0040-4039(01)93763-3

  日期：1989.1

  A new chiral derivation reagent was developed for chiral amines and alcohols to determine the absolute configuration by circular dichroism and optical purity by 1H-NMR and liquid chromatography.

  开发了一种新的用于手性胺和醇的手性衍生试剂，可通过圆二色性确定绝对构型，并通过1 H-NMR和液相色谱确定光学纯度。
• Determination of the absolute configuration of monosaccharides using (+) or (−) 2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid and high-resolution 1H-n.m.r. spectroscopy
  作者：Yoshihiro Nishida、Mariko Kumagai、Akiko Kamiyama、Hiroshi Ohrui、Hiroshi Meguro

  DOI：10.1016/0008-6215(91)84086-t

  日期：1991.9

  3-benzodiazole-4-carboxylates. Their 1 H-n.m.r. signals, especially the strong singlet peaks of tert -Bu and Me groups in the 1-ester portion were diagnostic for the determination of the d,l -configuration and optical purity of monosaccharides.

  摘要（-）2-叔丁基-2-甲基-1,3-苯并二恶唑-4-羧酸与过-O-乙酰基-d-和1-葡萄糖基吡喃糖基溴的反应生成了非对映异构的过-O-乙酰化的吡喃糖基2-叔丁基-2-甲基-1,3-苯并二唑-4-羧酸酯。它们的1 Hn.mr信号，尤其是1-酯部分中叔-Bu和Me基团的强单峰峰，可用于确定单糖的d，l-构型和光学纯度。
• Study on the Application of the (<i>S</i>)-2-<i>tert</i>-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid-based On-line HPLC-Exciton CD Analysis to Acyclic 1,3-Diols
  作者：Syun-ichi SATO、Kumi SHIMIZU、Jeong-Hwan KIM、Eiichi AMI、Kazuaki AKASAKA、Hiroshi OHRUI

  DOI：10.1271/bbb.62.1822

  日期：1998.1

  The application of the on-line HPLC-exciton CD analysis with (S)-TBMB-carboxylic acid that simultaneously determined the enantiomeric composition and absolute configuration of vicinal diols, diamines and amino alcohols to 1,3-diols was studied. All optical isomers of di-O-(S)-TBMB-carbonyl-1,3-butanediols and 2,4-pentanediols were separated and their absolute configurations were determined without reference samples on line by HPLC.

  研究了在线HPLC-激发态圆二色谱（CD）分析应用于（S）-TBMB-羧酸，以同时确定邻位二醇、双胺和氨基醇至1,3-二醇的对映体组成和绝对构型。所有的光学异构体二-O-(S)-TBMB-羰基-1,3-丁二醇和2,4-戊二醇均被分离，其绝对构型在没有参考样品的情况下在线通过HPLC确定。
• Chemoenzymatic Synthesis of Both Enantiomers of 2-tert-Butyl-2-methyl-1,3-benzodioxole-4-carboxylic (TBMB) Acid
  作者：Toshinori Higashi、Chika Abe、Keiko Ninomiya、Takuya Machida、Nobuyuki Chishima、Shohei Taketomi、Miyu Furuta、Yoko Komaki、Yoshihiko Senba、Taeko Tokuda、Mitsuru Shoji、Takeshi Sugai

  DOI：10.1002/adsc.201000446

  日期：2010.10.4

  Both enantiomers of 2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic (TBMB) acid, which has a unique quaternary chiral center located on the acetal carbon, were prepared from a racemic ketone in which the carboxy group was replaced by a trifluoroacetyl group. First, reduction with fungi, Geotrichum candidum provided (2S,1′S)- and (2R,1′S)- 1′-(2-tert-butyl-2-methyl-1,3-benzodioxol-4-yl)-2′,2′,2′-trifluoroethanol

  由外消旋酮制备2-叔丁基-2-甲基-1,3-苯并二恶唑-4-羧酸（TBMB）酸的对映异构体，它们在乙缩醛碳上具有一个独特的季手性中心。基团被三氟乙酰基取代。首先，用真菌还原，白色念珠菌提供了（2 S，1 'S）-和（2 R，1 'S）-1'-（2-叔丁基-2-甲基-1,3-苯并二恶唑-4- yl）-2'，2'，2'-三氟乙醇的对映体选择性很高。乙酰化后，将所得非对映异构体混合物提交南极假丝酵母脂肪酶B催化的酯交换反应。该反应在缩醛碳的手性中心的影响下以立体选择性的方式进行，即使已从酯羰基碳上除去了六个原子。尽管两种底物在仲醇处具有相同的绝对构型，但一种立体异构体的反应速率比另一种异构体的反应速率高72倍。该差异反应性的原因主要归因于立体异构体之间的V max（app）的较大差异。产物乙酸盐和醇易于通过色谱分离，然后分别衍生为（R）-和（S）-TBMB酸，分别具有> 99.2％ee的酸。
• Synthesis and characterization of asymmetric o- and m-nitrobenzoic acids with a 1,3-benzodioxole skeleton
  作者：Masaya Suzuki、Yoshihiro Nishida、Yuya Ohguro、Yoshiko Miura、Akiko Tsuchida、Kazukiyo Kobayashi

  DOI：10.1016/j.tetasy.2003.10.030

  日期：2004.1

  A symmetric o- and m-nitrobenzoic acids with a 1,3-benzodioxole skeleton have been synthesized and characterized. The synthesis involved nitration at either the C-5 or C-6 position of 2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylate derived from catechol. These were then resolved with chiral solid-phased HPLC columns into each of enantiomers (>99% ee), which were characterized by circular dichroism. The (S)-enantiomers were also obtained by fractional crystallization of the precursor prior to the nitration. When applied as chiral derivation agents for alcohols and amines, m-nitrobenzoic acid showed notable ability to separate the enantiomers in both HPLC and NMR analyses. On the other hand, H-1 NMR and X-ray data of their ester and amide derivatives strongly suggested that the o-nitrobenzoic acid would serve as a fluorescent building block useful for the assembly of beta-peptide linkages with a defined conformation. (C) 2003 Elsevier Ltd. All rights reserved.