查看“︁自由基钟”︁的源代码

{{Citation style|time=2023-11-18T15:47:15+00:00}}
在[[化學|化学]]中，'''自由基钟'''是一种化学反应机理实验，有助于间接方法确定[[自由基]]反应的[[化学动力学|动力学]]。自由基钟化合物本身以已知的速率发生反应，这为确定另一个反应的速率提供了校准。

许多有机反应机制涉及到无法直接识别的中间体，但可以从反应中捕获并推断出这些中间体。 <ref name="Johnson">{{Cite journal |last=Johnson, C.C. |last2=Lippard, S.J. |last3=Liu, K.E. |last4=Newcomb, M. |year=1993 |title=Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase |journal=J. Am. Chem. Soc. |volume=115 |issue=3 |page=939–947 |doi=10.1021/ja00056a018}}</ref>当这些中间体是自由基时，它们的寿命可以从自由基钟实验推断出来。 <ref name="Roschek">{{Cite journal |last=Roschek, B. Jr. |last2=Tallman, K.A. |last3=Rector, C.L. |last4=Gillmore, J.G. |last5=Pratt, D.A. |last6=Punta, C. |last7=Porter, N.A. |year=2006 |title=Peroxyl Radical Clocks |journal=J. Org. Chem. |volume=71 |issue=9 |page=3527–3532 |doi=10.1021/jo0601462 |pmid=16626136}}</ref> <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}</ref>另一种可能更直接的方法涉及通过闪光光解和[[辐解|脉冲辐射解]]来生成和分离中间体，但这种方法非常耗时并且需要昂贵的设备。通过自由基时钟的间接方法，人们仍然可以获得相对或绝对速率常数，而不需要超出所研究的反应通常所需的仪器或设备。 <ref name="Moss">Moss, R.A.; Platz, M.; Jones, M. Reactive Intermediate Chemistry. Wiley, John & Sons, Incorporated, 2004. 127–128.</ref>

== 理论与技术 ==
自由基钟反应涉及具有已知[[速率常数]]的[[反应分子数|单分子]]自由基反应和具有未知速率常数的[[反应分子数|双分子]]自由基反应之间的竞争，以产生未重排和重排的产物。未重排自由基 U• 的重排继续形成具有已知速率常数 ( ''k'' <sub>r</sub> ) 的 R•（时钟反应）。这些自由基与[[化學捕捉|捕获剂]]AB 反应，分别形成未重排和重排产物 UA 和 RA。 <ref name="Yao">{{Cite journal |last=Fu, Y. |last2=Li, R.-Q. |last3=Liu, L. |last4=Guo, Q.-X. |year=2004 |title=Solvent effect is not significant for the speed of a radical clock |journal=Res. Chem. Intermed. |volume=30 |issue=3 |page=279–286 |doi=10.1163/156856704323034012 |s2cid=96038335}}</ref>

: <math chem="">\begin{array}{l}
 \ce{U. + AB ->[k_R] {UA} + B.} \\
 \bigg\downarrow{k_r} \\
 \ce{R. + AB -> {RA} + B.}
\end{array}</math>

两种产物的产率可以通过[[气相色谱法|气相色谱]]（GC）或[[核磁共振]]（NMR）测定。根据捕获剂的浓度、自由基时钟的已知速率常数以及产物的比率，可以间接建立未知的速率常数。

如果U• 和R• 之间存在[[化学平衡]]，则重排产物占主导地位。 <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFGriller,_D.Ingold,_K.U.1980">Griller, D.; Ingold, K.U. (1980). "Free-radical clocks". ''Acc. Chem. Res''. '''13''' (9): 317–323. [[DOI|doi]]:[[doi:10.1021/ar50153a004|10.1021/ar50153a004]].</cite></ref>由于[[反应分子数|单分子]]重排反应是一级反应，而[[反应分子数|双分子]]捕获反应是二级反应（均不可逆），因此未知速率常数 ( ''k'' <sub>R</sub> ) 可以通过以下公式确定： <ref>{{Cite journal |last=Newcomb, M. |year=1993 |title=Competition Methods and Scales for Alkyl Radical Reaction Kinetics |journal=Tetrahedron |volume=49 |issue=6 |page=1151–1176 |doi=10.1016/S0040-4020(01)85808-7}}</ref>

: <math chem="">k_R = \frac{k_r [\ce{UA}]}\ce{[AB][RA]}</math>

== 时钟速率 ==
自由基钟反应背后的驱动力是它们的重新排列能力。 <ref name="Johnson">{{Cite journal |last=Johnson, C.C. |last2=Lippard, S.J. |last3=Liu, K.E. |last4=Newcomb, M. |year=1993 |title=Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase |journal=J. Am. Chem. Soc. |volume=115 |issue=3 |page=939–947 |doi=10.1021/ja00056a018}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFJohnson,_C.C.Lippard,_S.J.Liu,_K.E.Newcomb,_M.1993">Johnson, C.C.; Lippard, S.J.; Liu, K.E.; Newcomb, M. (1993). "Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase". ''J. Am. Chem. Soc''. '''115''' (3): 939–947. [[DOI|doi]]:[[doi:10.1021/ja00056a018|10.1021/ja00056a018]].</cite></ref>一些常见的自由基时钟是自由基环化、开环和 1,2-迁移。 <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFGriller,_D.Ingold,_K.U.1980">Griller, D.; Ingold, K.U. (1980). "Free-radical clocks". ''Acc. Chem. Res''. '''13''' (9): 317–323. [[DOI|doi]]:[[doi:10.1021/ar50153a004|10.1021/ar50153a004]].</cite></ref>两种流行的重排是 5-己烯基的环化和甲基环丙烷的开环： <ref name="Johnson" />
{| style="margin:1em auto;"
|[[File:Radical_Cyclization.svg|200x200px]]
|-
|[[File:Cyclopropyl_radical_clock_rearrangement.png|225x225px]]
|}
5-己烯基经历环化产生五元环，因为这[[熵|在熵]]和[[焓|焓上]]比六元环可能性更有利。 <ref name="Johnson">{{Cite journal |last=Johnson, C.C. |last2=Lippard, S.J. |last3=Liu, K.E. |last4=Newcomb, M. |year=1993 |title=Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase |journal=J. Am. Chem. Soc. |volume=115 |issue=3 |page=939–947 |doi=10.1021/ja00056a018}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFJohnson,_C.C.Lippard,_S.J.Liu,_K.E.Newcomb,_M.1993">Johnson, C.C.; Lippard, S.J.; Liu, K.E.; Newcomb, M. (1993). "Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase". ''J. Am. Chem. Soc''. '''115''' (3): 939–947. [[DOI|doi]]:[[doi:10.1021/ja00056a018|10.1021/ja00056a018]].</cite></ref> <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFGriller,_D.Ingold,_K.U.1980">Griller, D.; Ingold, K.U. (1980). "Free-radical clocks". ''Acc. Chem. Res''. '''13''' (9): 317–323. [[DOI|doi]]:[[doi:10.1021/ar50153a004|10.1021/ar50153a004]].</cite></ref>该反应的速率常数为2.3×10 <sup>5</sup>&nbsp;s <sup>-1</sup>于 298&nbsp;K. <ref name="Yao">{{Cite journal |last=Fu, Y. |last2=Li, R.-Q. |last3=Liu, L. |last4=Guo, Q.-X. |year=2004 |title=Solvent effect is not significant for the speed of a radical clock |journal=Res. Chem. Intermed. |volume=30 |issue=3 |page=279–286 |doi=10.1163/156856704323034012 |s2cid=96038335}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFFu,_Y.Li,_R.-Q.Liu,_L.Guo,_Q.-X.2004">Fu, Y.; Li, R.-Q.; Liu, L.; Guo, Q.-X. (2004). "Solvent effect is not significant for the speed of a radical clock". ''Res. Chem. Intermed''. '''30''' (3): 279–286. [[DOI|doi]]:[[doi:10.1163/156856704323034012|10.1163/156856704323034012]]. [[语义学者|S2CID]]&nbsp;[https://api.semanticscholar.org/CorpusID:96038335 96038335].</cite></ref>

环丙基甲基自由基经历非常快速的开环重排，从而减轻[[環張力|环张力]]并且有利于热函。 <ref name="Johnson">{{Cite journal |last=Johnson, C.C. |last2=Lippard, S.J. |last3=Liu, K.E. |last4=Newcomb, M. |year=1993 |title=Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase |journal=J. Am. Chem. Soc. |volume=115 |issue=3 |page=939–947 |doi=10.1021/ja00056a018}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFJohnson,_C.C.Lippard,_S.J.Liu,_K.E.Newcomb,_M.1993">Johnson, C.C.; Lippard, S.J.; Liu, K.E.; Newcomb, M. (1993). "Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase". ''J. Am. Chem. Soc''. '''115''' (3): 939–947. [[DOI|doi]]:[[doi:10.1021/ja00056a018|10.1021/ja00056a018]].</cite></ref> <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFGriller,_D.Ingold,_K.U.1980">Griller, D.; Ingold, K.U. (1980). "Free-radical clocks". ''Acc. Chem. Res''. '''13''' (9): 317–323. [[DOI|doi]]:[[doi:10.1021/ar50153a004|10.1021/ar50153a004]].</cite></ref>该反应的速率常数为 8.6×10 <sup>7</sup>&nbsp;s <sup>-1</sup>于 298&nbsp;K. <ref>{{Cite journal |last=Bowry, V.W. |last2=Lusztyk, J. |last3=Ingold, K.U. |year=1991 |title=Calibration of a new horologery of fast radical "clocks". Ring-opening rates for ring- and α-alkyl-substituted cyclopropylcarbinyl radicals and for the bicyclo[2.1.0]pent-2-yl radical |journal=J. Am. Chem. Soc. |volume=113 |issue=15 |page=5687–5698 |doi=10.1021/ja00015a024}}</ref>

为了确定自由基反应的绝对速率常数，需要在一定时间范围内针对每组自由基（例如伯烷基）校准单分子时钟反应。 <ref name="Griller">{{Cite journal |last=Griller, D. |last2=Ingold, K.U. |year=1980 |title=Free-radical clocks |journal=Acc. Chem. Res. |volume=13 |issue=9 |page=317–323 |doi=10.1021/ar50153a004}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFGriller,_D.Ingold,_K.U.1980">Griller, D.; Ingold, K.U. (1980). "Free-radical clocks". ''Acc. Chem. Res''. '''13''' (9): 317–323. [[DOI|doi]]:[[doi:10.1021/ar50153a004|10.1021/ar50153a004]].</cite></ref>通过使用[[電子自旋共振|EPR 光谱]]，可以测量各种温度下[[反应分子数|单分子]]反应的绝对速率常数。 <ref name="Griller" /> <ref name="Moss">Moss, R.A.; Platz, M.; Jones, M. Reactive Intermediate Chemistry. Wiley, John & Sons, Incorporated, 2004. 127–128.</ref>然后可以应用[[阿伦尼乌斯方程]]来计算进行自由基时钟反应的特定温度的速率常数。

当使用自由基钟来研究反应时，存在一个隐含的假设，即自由基时钟的重排速率与确定重排反应速率时的速率相同。对环丁基甲基和5-己烯基在多种溶剂中的重排反应的[[计算化学|理论研究]]发现，它们的反应速率仅受溶剂性质的影响很小。 <ref name="Yao">{{Cite journal |last=Fu, Y. |last2=Li, R.-Q. |last3=Liu, L. |last4=Guo, Q.-X. |year=2004 |title=Solvent effect is not significant for the speed of a radical clock |journal=Res. Chem. Intermed. |volume=30 |issue=3 |page=279–286 |doi=10.1163/156856704323034012 |s2cid=96038335}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFFu,_Y.Li,_R.-Q.Liu,_L.Guo,_Q.-X.2004">Fu, Y.; Li, R.-Q.; Liu, L.; Guo, Q.-X. (2004). "Solvent effect is not significant for the speed of a radical clock". ''Res. Chem. Intermed''. '''30''' (3): 279–286. [[DOI|doi]]:[[doi:10.1163/156856704323034012|10.1163/156856704323034012]]. [[语义学者|S2CID]]&nbsp;[https://api.semanticscholar.org/CorpusID:96038335 96038335].</cite></ref>

可以通过连接到自由基时钟的取代基类型来调整自由基时钟的速率以增加或减少。在下图中，显示了自由基钟反应的速率，以及时钟上附加的各种取代基。 <ref name="Johnson">{{Cite journal |last=Johnson, C.C. |last2=Lippard, S.J. |last3=Liu, K.E. |last4=Newcomb, M. |year=1993 |title=Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase |journal=J. Am. Chem. Soc. |volume=115 |issue=3 |page=939–947 |doi=10.1021/ja00056a018}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFJohnson,_C.C.Lippard,_S.J.Liu,_K.E.Newcomb,_M.1993">Johnson, C.C.; Lippard, S.J.; Liu, K.E.; Newcomb, M. (1993). "Radical Clock Substrate Probes and Kinetic Isotope Effect Studies of the Hydroxylation of Hydrocarbons by Methane Monooxygenase". ''J. Am. Chem. Soc''. '''115''' (3): 939–947. [[DOI|doi]]:[[doi:10.1021/ja00056a018|10.1021/ja00056a018]].</cite></ref>{{Failed verification|date=2011年2月}}</link><sup class="noprint Inline-Template" style="white-space:nowrap;">&#x5B;''[[wikipedia:可供查證|<span title="The material near this tag failed verification of its source citation(s). (February 2011)">验证失败</span>]]''&#x5D;</sup>
{| class="wikitable"
| colspan="3" |[[File:Radical_cyclization_substituted.png|315x315px]]</img>
|-
! X
!Y
!''k'' (s <sup>-1</sup> )
|-
|苯基
|苯基
|5x10 <sup>7</sup>
|-
|甲氧基
| H
| 1.4×10 <sup>5</sup>
|-
|甲氧基
|氰基
|2.5×10 <sup>8</sup>
|-
|氰基
|H
| 1.6×10 <sup>8</sup>
|}
通过在自由基钟的一般类别及其上的特定取代基中进行选择，可以选择具有适合研究具有宽范围速率的反应的速率常数的自由基钟。反应速率范围为 10 <sup>-1</sup>至 10 <sup>12</sup>&nbsp;M <sup>−1</sup>&nbsp;s <sup>-1</sup>已使用自由基钟进行了研究。 <ref name="Roschek">{{Cite journal |last=Roschek, B. Jr. |last2=Tallman, K.A. |last3=Rector, C.L. |last4=Gillmore, J.G. |last5=Pratt, D.A. |last6=Punta, C. |last7=Porter, N.A. |year=2006 |title=Peroxyl Radical Clocks |journal=J. Org. Chem. |volume=71 |issue=9 |page=3527–3532 |doi=10.1021/jo0601462 |pmid=16626136}}<cite class="citation journal cs1" data-ve-ignore="true" id="CITEREFRoschek,_B._Jr.Tallman,_K.A.Rector,_C.L.Gillmore,_J.G.2006">Roschek, B. Jr.; Tallman, K.A.; Rector, C.L.; Gillmore, J.G.; Pratt, D.A.; Punta, C.; Porter, N.A. (2006). "Peroxyl Radical Clocks". ''J. Org. Chem''. '''71''' (9): 3527–3532. [[DOI|doi]]:[[doi:10.1021/jo0601462|10.1021/jo0601462]]. [[PubMed|PMID]]&nbsp;[https://pubmed.ncbi.nlm.nih.gov/16626136 16626136].</cite></ref>

== 使用示例 ==
自由基钟用于用萘钠还原烷基卤化物的反应烯酮、维蒂希重排、 二烷基汞化合物的还原消除反应、二环氧乙烷二羟基化和亲电氟化。 

== 參考文獻 ==
{{reflist}}

== 外部链接 ==
* [http://www.scs.uiuc.edu/chem/research/organic/seminar_extracts/2005_2006/06_Wang.pdf RADICAL CLOCKS: MOLECULAR STOPWATCHES FOR TIMING RADICAL REACTIONS]
* [https://archive.today/20121210064633/http://euch6f.chem.emory.edu/radical.html Radical Clock Reactions]

[[Category:化学动力学]]
[[Category:自由基]]