2-bromo-6-(methylthio)purine | 139243-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-bromo-6-(methylthio)purine
• 英文别名: 2-Bromo-6-(methylsulfanyl)-7H-purine；2-bromo-6-methylsulfanyl-7H-purine
• CAS: 139243-95-1
• 化学式: C₆H₅BrN₄S
• 分子量: 245.103
• InChiKey: BNWRWPKXRAJBIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  309.7±52.0 °C(Predicted)
• 密度：
  2.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-二甲基乙酰胺 、 2-bromo-6-(methylthio)purine 在 叔丁基过氧化氢 、 potassium iodide 作用下， 反应 10.0h， 以94%的产率得到N-((2-bromo-6-(methylthio)-9H-purin-9-yl)methyl)-N-methylacetamide
  参考文献：
  名称：

  Transition-Metal-Free N9-Amidoalkylation of Purines with N,N-Dialkylamides

  摘要：

  A novel method for the selective N9-amidoalkylation of purines using N,N-dialkylamides as alkylation reagents via activation of sp(3) C-H bond adjacent to an amide nitrogen atom has been developed in the presence of KI and tert-butyl hydroperoxide (TBHP). This method was simple to operate and provided series of purine derivatives in moderate to excellent yield.

  DOI：

  10.1055/s-0036-1588134
• 作为产物：
  描述：

  2,6-二溴嘌呤 在 sodium hydrogensulfide 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 1.67h， 生成 2-bromo-6-(methylthio)purine
  参考文献：
  名称：

  Sodium salt glycosylation in the synthesis of purine 2'-deoxyribonucleosides: studies of isomer distribution

  摘要：

  A systematic study of 2-deoxyribonucleoside isomer distribution from the sodium salt glycosylation of substituted purines is reported. Reactions of 1-alpha-chloro-2-deoxy-3,5-di(p-toluyl)-erythro-pentofuranose with the sodium salts of purines in acetonitrile typically results in 9-beta and 7-beta regioisomers as major products in a ratio of about 4:1, results consistent with a S(N)2 reaction of base anion with the 1-alpha chlorosugar. However, the reaction with 2,6-dibromopurine (2) gave 9-beta and 9-alpha stereoisomers as major products in a 4:1 ratio. We have isolated and identified all nucleoside products from sodium salt glycosylations of several 2,6-disubstituted purines and 6-substituted purines. In addition to the major products, the 9-alpha and 7-alpha isomers were obtained in small yields in most cases. Rate studies showed that fastest glycosylations occurred with 2,6-bis(methylthio)purine (3). Glycosylations of 2,6-dichloropurine (1) and of 2 proceeded with nearly identical rates for the formation of the 9-beta isomers and with comparable rates for the formation of 7-beta and 9-alpha isomers, respectively. These observations indicate that the extent of sugar anomerization during glycosylation of 2 does not alone account for 9-alpha isomer formation, although, in a separate experiment, aging of chlorosugar solutions did increase the yield of 9-alpha product in the reaction. Studies of possible interconversion of isomers under the reaction conditions indicated that formation of the 9-alpha isomer from 2 was not the result of conversion of a kinetically favored (7-beta) isomer, nor was the 7-beta isomer from 1 derived from conversion of the 9-alpha isomer. We conclude that a combination of steric effect of the 6-bromo group and an as yet unidentified rate effect of the 2-bromo group is responsible for the significant yield of 9-alpha product from 2. The ability of substituents to enhance the rate and regioselectivity in the sodium salt glycosylation was evaluated with 2-bromo-6-(methylthio)purine (6). This base afforded the highest total nucleoside yield (86%) and the highest 9-beta isomer yield (68.3%) among all purines tested, suggesting a useful strategy to increase yield of intermediates that can be converted to biologically important purine 2'-deoxy-ribonucleosides.

  DOI：

  10.1021/jo00032a038

文献信息

• C–H Amination of Purine Derivatives via Radical Oxidative Coupling
  作者：Zheng Luo、Ziyang Jiang、Wei Jiang、Dongen Lin

  DOI：10.1021/acs.joc.8b00066

  日期：2018.4.6

  An oxidative coupling reaction between purines and alkyl ethers/benzyl compounds was developed to synthesize a series of N9 alkylated purine derivatives using n-Bu4NI as a catalyst and t-BuOOH as an oxidant. This protocol uses commercially available, inexpensive catalysts and oxidants and has a wide range of substrates with a simple operation.

  开发了嘌呤与烷基醚/苄基化合物之间的氧化偶联反应，以n -Bu 4 NI为催化剂，t -BuOOH为氧化剂，合成了一系列N9烷基化的嘌呤衍生物。该方案使用可商购的，廉价的催化剂和氧化剂，并具有操作简单的多种底物。
• Transition-Metal-Free N9-Amidoalkylation of Purines with N,N-Dialkylamides
  作者：Dongen Lin、Saiyu Xu、Zheng Luo、Ziyang Jiang

  DOI：10.1055/s-0036-1588134

  日期：——

  A novel method for the selective N9-amidoalkylation of purines using N,N-dialkylamides as alkylation reagents via activation of sp(3) C-H bond adjacent to an amide nitrogen atom has been developed in the presence of KI and tert-butyl hydroperoxide (TBHP). This method was simple to operate and provided series of purine derivatives in moderate to excellent yield.
• Sodium salt glycosylation in the synthesis of purine 2'-deoxyribonucleosides: studies of isomer distribution
  作者：Catherine Hildebrand、George E. Wright

  DOI：10.1021/jo00032a038

  日期：1992.3

  A systematic study of 2-deoxyribonucleoside isomer distribution from the sodium salt glycosylation of substituted purines is reported. Reactions of 1-alpha-chloro-2-deoxy-3,5-di(p-toluyl)-erythro-pentofuranose with the sodium salts of purines in acetonitrile typically results in 9-beta and 7-beta regioisomers as major products in a ratio of about 4:1, results consistent with a S(N)2 reaction of base anion with the 1-alpha chlorosugar. However, the reaction with 2,6-dibromopurine (2) gave 9-beta and 9-alpha stereoisomers as major products in a 4:1 ratio. We have isolated and identified all nucleoside products from sodium salt glycosylations of several 2,6-disubstituted purines and 6-substituted purines. In addition to the major products, the 9-alpha and 7-alpha isomers were obtained in small yields in most cases. Rate studies showed that fastest glycosylations occurred with 2,6-bis(methylthio)purine (3). Glycosylations of 2,6-dichloropurine (1) and of 2 proceeded with nearly identical rates for the formation of the 9-beta isomers and with comparable rates for the formation of 7-beta and 9-alpha isomers, respectively. These observations indicate that the extent of sugar anomerization during glycosylation of 2 does not alone account for 9-alpha isomer formation, although, in a separate experiment, aging of chlorosugar solutions did increase the yield of 9-alpha product in the reaction. Studies of possible interconversion of isomers under the reaction conditions indicated that formation of the 9-alpha isomer from 2 was not the result of conversion of a kinetically favored (7-beta) isomer, nor was the 7-beta isomer from 1 derived from conversion of the 9-alpha isomer. We conclude that a combination of steric effect of the 6-bromo group and an as yet unidentified rate effect of the 2-bromo group is responsible for the significant yield of 9-alpha product from 2. The ability of substituents to enhance the rate and regioselectivity in the sodium salt glycosylation was evaluated with 2-bromo-6-(methylthio)purine (6). This base afforded the highest total nucleoside yield (86%) and the highest 9-beta isomer yield (68.3%) among all purines tested, suggesting a useful strategy to increase yield of intermediates that can be converted to biologically important purine 2'-deoxy-ribonucleosides.