Lithium diisopropylamide二异丙基氨基锂

规格: 2.0 M solution in THF/n-heptane(12:25), SpcSeal
CAS: 4111-54-0
产品编号: H81992
MDL: MFCD00064449
品牌: INFI

产品介绍

二异丙基氨基锂(LDA)是有机合成中应用非常广泛的有位阻非亲核性强碱试剂,常常用来生成碳负离子和烯醇离子等。LDA广泛地应用于醛、酮和酯的烯醇化反应,生成的烯醇离子经硅衍生物或者磺酰基捕获后生成相应的硅醚或者磺酸酯。该反应一般在低温下数分钟内完成,反应条件非常温和,不对其它官能团产生明显的影响。

合成工艺

传统工艺是从金属锂出发,先制备丁基锂,再与二异丙胺反应,得到二异丙基氨基锂,需要两步反应,且工业化买到的丁基锂一般为正己烷溶液,所得产品中含有正己烷,无法制得其他规格的产品。通过前期的研究积累,开发一步法工艺,即从金属锂出发,不经过丁基锂,得到二异丙基氨基锂,且制得了多种规格的产品。

应用实例

1.TBAJ-587是抗结核药物贝达喹啉(BDQ)的类似物,带有二芳基喹啉骨架,保留了高活性,毒性较小,并且比母体分子具有更好的药代动力学特征,已进入I期临床试验。文章报道了以LDA作为碱,基于协同Li/Li双金属体系的TBAJ-587不对称合成,反应可以合成5g规格,经过简单的重结晶后,以99.9:0.1 er得到产物。该方案的实施可以辅助完成临床药物生产的需求[1]。

图片来源于期刊:The Journal of Organic Chemistry Article ASAP. doi.org/10.1021/acs.joc.3c00705.


2.鲁索曲波帕(Lusutrombopag)是一种可口服的血小板生成素受体激动剂,用于治疗慢性肝病。文章开发一种一锅法合成鲁索曲波帕的关键羧酸中间体的工艺。首先3,5-二氯苯甲酸经LDA锂化,再甲酰化,然后与2-膦酰基丙酸三乙酯进行HWE烯化反应。该方法可进行千克级生产,产量高,避免分离中间体的繁琐程序[2]。

图片来源于期刊: Organic Process Research & Development 2020, 24, 2651-2656.

参考文献

[1] The Journal of Organic Chemistry Article ASAP. doi.org/10.1021/acs.joc.3c00705.

[2] Organic Process Research & Development 2020, 24, 2651-2656.

Chemical Name Lithium Diisopropylamide
CAS Number 4111-54-0
EC Number 223-893-0
Beilstein Registry Number 3655042
MDL Number MFCD00064449
Synonym 2-Propanamine,N-(1-methylethyl)-,lithiumsaltDIISOPROPYLAMINOLITHIUMDisotatLDALDA THF COMPLEXLITHIUM DIISOPROPYLAMIDELITHIUM DIISOPROPYLAMIDE THF COMPLEXLITHIUM DIISOPROPYLAMIDE, 1.8M SOLUTION IN THF/HEPTANE/ETHYLBENZENELITHIUM DIISOPROPYLAMIDE, 10 WT. % SOLUT ION IN MINERAL OILLITHIUM DIISOPROPYLAMIDE, 10 WT. % SUSPE NSION IN HEXANESLITHIUM DIISOPROPYLAMIDE, 2.0M SOLUTION IN HEPTANE/THF/ETHYLBENZENELITHIUM DIISOPROPYLAMIDE, 2M SOLUTION IN THF/HEPTANELITHIUM DIISOPROPYLAMIDE, 2M SOLUTION IN THF/N-HEPTANELITHIUM DIISOPROPYLAMINELITHIUMDIISOPROPYLAMIDE,2MSOLUTIONINTETRAHYDROFURAN/HEPTANE/ETHYLBENZENELithium diisopropylamide solutionLithium diisopropylamide solution, ~2 M in THF/heptane/ethylbenzeneLithiu
PubChem Substance ID 2724682
Reaxys-RN 906717
Merck Number 3196
Chemical Name Translation 二异丙基氨基锂
LabNetwork Molecule ID LN00163930
InChI InChI=1S/C6H14N.Li/c1-5(2)7-6(3)4;/h5-6H,1-4H3;/q-1;+1
GHS Symbol
Signal word Danger
WGK Germany 3
Safety Statements
  • S16 Keep away from sources of ignition - No smoking 远离火源,禁止吸烟;
  • S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice 眼睛接触后,立即用大量水冲洗并征求医生意见;
  • S33 Take precautionary measures against static discharges 对静电采取预防措施;
  • S36/37/39 Wear suitable protective clothing, gloves and eye/face protection 穿戴适当的防护服、手套和眼睛/面保护;
  • S43 In case of fire use ... (indicate in the space the precise type of fire-fighting equipment. If water increases the risk add -?Never use water) 着火时使用(指明具体的消防器材种类,如果用水增加危险,注明“禁止用水”
  • S45 In case of accident or if you feel unwell seek medical advice immediately (show the label where possible) 发生事故时或感觉不适时,立即求医(可能时出示标签);
  • S60 This material and its container must be disposed of as hazardous waste 该物质及其容器必须作为危险废物处置;
  • S61 Avoid release to the environment. Refer to special instructions/safety data sheet 避免释放到环境中,参考特别指示/安全收据说明书;
  • S62 If swallowed, do not induce vomiting: seek medical advice immediately and show this container or label where possible 吞食后不要催吐:立即求医并出示该容器或标签;
  • S9 Keep container in a well-ventilated place 保持容器在通风良好的场所;
    Risk Statements
    • R11 Highly flammable 非常易燃
    • R14 Reacts violently with water 遇水会猛烈反应
    • R14/15 Reacts violently with water, liberating extremely flammable gases 遇水剧烈反应,释放出高度可燃气体
    • R15 Contact with water liberates extremely flammable gases 遇水会释放出极端易燃的气体
    • R17 Spontaneously flammable in air 在空气中能够自燃
    • R19 May form explosive peroxides 可能生成易爆的过氧化物质
    • R34 Causes burns 会导致灼伤
    • R35 Causes severe burns 会导致严重灼伤
    • R37 Irritating to respiratory system 刺激呼吸道
    • R40 Limited evidence of a carcinogenic effect 有限证据表明其致癌作用
    • R48/20
    • R50/53
    • R51/53
    • R62 Possible risk of impaired fertility 有削弱生殖能力的危险
    • R63 Possible risk of harm to the unborn child 可能危害未出生婴儿
    • R65 Harmful: may cause lung damage if swallowed 若吞咽可能伤害肺部器官
    • R67 Vapours may cause drowsiness and dizziness 蒸汽可能导致嗜睡和昏厥
      Precautionary statements
      • P210 Keep away from heat/sparks/open flames/hot surfaces. — No smoking. 远离热源/火花/明火/热的表面。——禁止吸烟。
      • P222 Do not allow contact with air. 不要与空气接触。
      • P231+P232
      • P240 Ground/bond container and receiving equipment. 与地面接触/连接集装箱和接受设备。
      • P241 Use explosion-proof electrical/ventilating/lighting/…/equipment. 使用防爆电气/通风/照明/ .../设备。
      • P260 Do not breathe dust/fume/gas/mist/vapours/spray. 不要吸入粉尘/烟/气体/烟雾/蒸汽/喷雾。
      • P261 Avoid breathing dust/fume/gas/mist/vapours/spray. 避免吸入粉尘/烟/气体/烟雾/蒸汽/喷雾。
      • P264 Wash hands thoroughly after handling. 处理后要彻底洗净双手。
      • P273 Avoid release to the environment. 避免释放到环境中。
      • P280 Wear protective gloves/protective clothing/eye protection/face protection. 戴防护手套/防护服/眼睛的保护物/面部保护物。
      • P301+P330+P331
      • P302+P334
      • P303+P361+P353
      • P304+P340
      • P305+P351+P338
      • P310 Immediately call a POISON CENTER or doctor/physician. 立即呼救解毒中心或医生/医师。
      • P321 Specific treatment (see … on this label). 具体治疗(见本标签上的)。
      • P363 Wash contaminated clothing before reuse. 被污染的衣服洗净后方可重新使用。
      • P370+P378
      • P405 Store locked up. 上锁保管。
      • P422 Store contents under… 存储目录在…之下。
      • P501 Dispose of contents/container to..… 处理内容物/容器.....
        Hazard statements
        • H225 Highly flammable liquid and vapour 高度易燃液体和蒸气
        • H226 Flammable liquid and vapour 易燃液体和蒸气
        • H228 Flammable solid 易燃固体
        • H250 Catches fire spontaneously if exposed to air 暴露于空气自发着火
        • H261 In contact with water releases flammable gas 与水接触时释放可燃气体。
        • H302 Harmful if swallowed 吞食有害
        • H304 May be fatal if swallowed and enters airways 吞食和进入呼吸道可能致命
        • H314 Causes severe skin burns and eye damage 导致严重的皮肤灼伤和眼睛损伤
        • H335 May cause respiratory irritation 可能导致呼吸道刺激
        • H336 May cause drowsiness or dizziness 肯能导致嗜睡或头晕
        • H351 Suspected of causing cancer 怀疑致癌
        • H361 Suspected of damaging fertility or the unborn child 怀疑对生育能力或未出生婴儿造成伤害
        • H373 May causes damage to organs through prolonged or repeated exposure 长期或频繁接触可能会损伤器官
        • H400 Verytoxictoaquaticlife 对水生生物毒性非常大。
        • H410 Verytoxictoaquaticlifewithlonglastingeffects 对水生生物毒性非常大并具有长期影响。
        • H411 Toxictoaquaticlifewithlonglastingeffects 对水生生物有毒性并具有长期影响。
          Personal Protective Equipment Faceshields, full-face respirator (US), Gloves, Goggles, multi-purpose combination respirator cartridge (US)
          Hazard Codes 4.3F,CF,C,NF;C;N
          UN Number 3399
          Packing Group II
          Storage condition 0-10储存温度2-8°C2-8°C0-10°C
          Hazard Class 4.3/3
          Restrict 危险品
        • ⑴.常温下为白色固体,温度升至0 ℃以上就不稳定。溶于Et2O、THF、DME、HMPA。它的己烷或戊烷溶液在室温下能够稳定放置几周时间,它与THF的复合物在环己烷和庚烷中相当稳定。
        • ⑵. 有广泛用途的金属化碱性试剂,用于Aldol缩合,烷基乙酸、二烷基乙酸、内酯,a,b-不饱和酮等的a-烷化,合成醛和硝基烷;从醛合成酮;合成b-羟酸;三取代烯的立体选择合成;制不对称酮的烯醇锂盐;制溴甲基锂;亚硝胺的锂化,3-甲基吡啶的甲基锂化;吲哚的合成;氯代酸酯的环化;苯乙烯还原成乙苯。
        • ⑶. 是有机合成中应用非常广
        • 非常有名的大位阻强碱,用于形成碳负离子。
        • {ALD} Merck: 14,3196
        • 4111-54-0 H81992 Lithium diisopropylamide二异丙基氨基锂

          化学属性

          Vapor Density >;1 (vs air)
          Boiling Point 65 °C
          Flash Point -20°C(lit.)
          Solubility 分解
          Appearance liquid
          Stability 对湿度敏感
          Density 0.7469
          Mol. Formula C6H14LiN
          Mol. Weight 107.12
          pH :A

          *以上化合物性质及应用等信息仅供参考