スリッパリーロック大学が提供する資金。私たちは、彼らの洞察力のためにT・ボロン III（スリッパリーロック大学）とC・ハニー（ペンシルバニア大学）に感謝したいと思います。

ニッケル - シッフ塩基錯体の加水分解1。 <ol><li>室温で250 mLの丸底フラスコに撹拌しながらN、N-ジメチルホルムアミド（DMF）40mLにニッケルPBP-シッフ塩基錯体の1モルを溶解します。 </li><li> 0.2 M水性EDTA溶液、pH4.5中の60ミリリットルを加えます。 </li><li>磁気撹拌棒を使用し、プレートを攪拌、一晩組み合わせたソリューションをかき混ぜます。シッフ塩基錯体が加水分解されるように、色が白に深紅からシフトします。 </li><li>任意赤色着色の欠如によって示されるように反応が完了した後、250mLの分液漏斗に反応を転送します。 </li><li> 、50 mLのジクロロメタンを追加し、分液漏斗をキャップし、混合します。廃棄物のビーカーに有機洗浄液を排出します。 PBPと残留ニッケルPBP-シッフ塩基錯体を除去するために、このプロセスを3回繰り返します。 250mLの丸底フラスコに残った水層を集めます。 </li></ol>加水分解アミノ酸の2のFmoc保護<ol><li&gt;固体の重炭酸ナトリウムを用いてpHを7に上述のステップ1.5から単離し、水層を調整します。定期的にpH試験ストリップを用いてpHをチェックしてください。 </li><li>溶液に168 mgの重炭酸ナトリウム（2.00ミリモル、2当量）を添加し、磁気攪拌棒を用いて撹拌し、プレートを攪拌します。 </li><li> 10mLのバイアル中のジオキサンの最小量（約4または5 mL）中に337ミリグラムのFmoc Nヒドロキシスクシンイミドエステル（1.00ミリモル、1当量）を溶解。水溶液に、このソリューションを移し、一晩撹拌。 </li><li>反応物を一晩撹拌させた後、1 M塩酸でpH 2に、得られた溶液を酸性化します。定期的にpH試験ストリップを用いてpHをチェックしてください。 </li><li> 250mLの分液漏斗に反応を転送し、50mLの酢酸エチルを加えます。分液漏斗をキャップよく混合し、250 mLの三角フラスコに有機層を集めます。有機抽出物を組み合わせ、このプロセスをさらに2回繰り返します。マグネシウムsulfatの約3グラムと一緒にした有機抽出物を乾燥電子。 </li><li>粗製Fmoc-保護アミノ酸を得、ロータリーエバポレーターを使用して、合わせた有機抽出物を濃縮します。 </li></ol>

<ol><li>Wang, J., Shi, T., Deng, G., Jiang, H., Liu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Highly+Enantio-+and+Diastereoselective+Mannich+Reactions+of+Chiral+Ni%28II%29+Glycinates+with+amino+sulfones.+Efficient+asymmetric+synthesis+of+aromatic+%CE%B1%2C%CE%B2-diamino+acids%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Highly Enantio- and Diastereoselective Mannich Reactions of Chiral Ni(II) Glycinates with amino sulfones. Efficient asymmetric synthesis of aromatic α,β-diamino acids.</a> J. Org. Chem. 73 (21), 8563-8570 (2011).</li>
<li>Wang, J., Lin, D., Zhou, S., Ding, X., Soloshonok, V. A., Liu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Asymmetric+synthesis+of+sterically+and+electronically+demanding+linear+%CF%89%2C-trifluoromethyl+containing+amino+acids+via+alkylation+of+chiral+equivalents+of+nucleophilic+glycine+and+alanine%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Asymmetric synthesis of sterically and electronically demanding linear ω,-trifluoromethyl containing amino acids via alkylation of chiral equivalents of nucleophilic glycine and alanine.</a> J. Org. Chem. 76 (2), 684-687 (2011).</li>
<li>Wang, J., Zhou, S., Lin, D., Ding, X., Jiang, H., Liu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Highly+diastereo-+and+enantioselective+synthesis+of+syn-%CE%B2%2C-substituted+tryptophans+via+asymmetric+Michael+addition+of+a+chiral+equivalent+of+nucleophilic+glycine+and+sulfonylindoles%5BTitle%5D)+AND+%22Chem.+Commun%22%5BJournal%5D)">Highly diastereo- and enantioselective synthesis of syn-β,-substituted tryptophans via asymmetric Michael addition of a chiral equivalent of nucleophilic glycine and sulfonylindoles.</a> Chem. Commun. 47 (29), 8355-8357 (2011).</li>
<li>Belokon, Y. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Highly+efficient+catalytic+synthesis+of+%CE%B1%2C-amino+acids+under+phase-transfer+conditions+with+a+novel+catalyst%2Fsubstrate+pair%5BTitle%5D)+AND+%22Angew.+Chem.+Int.+Ed%22%5BJournal%5D)">Highly efficient catalytic synthesis of α,-amino acids under phase-transfer conditions with a novel catalyst/substrate pair.</a> Angew. Chem. Int. Ed. 40 (10), 1948-1951 (2001).</li>
<li>Zhou, S., Wang, J., Lin, D., Zhao, F., Liu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Enantioselective+synthesis+of+2-substituted-tetrahydroisoquinolin-1-yl+glycine+derivatives+via+oxidative+cross-dehydrogenative+coupling+of+tertiary+amines+and+chiral+nickel%28II%29+glycinate%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Enantioselective synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives via oxidative cross-dehydrogenative coupling of tertiary amines and chiral nickel(II) glycinate.</a> J. Org. Chem. 78 (22), 11204-11212 (2013).</li>
<li>Belokon, Y. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+%CE%B1%2C-amino+acids+via+asymmetric+phase+transfer-catalyzed+alkylation+of+achiral+nickel%28II%29+complexes+of+glycine-derived+Schiff+bases%5BTitle%5D)+AND+%22J.+Am.+Chem.+Soc%22%5BJournal%5D)">Synthesis of α,-amino acids via asymmetric phase transfer-catalyzed alkylation of achiral nickel(II) complexes of glycine-derived Schiff bases.</a> J. Am. Chem. Soc. 125 (42), 12860-12871 (2003).</li>
<li>Ueki, H., Ellis, T. K., Martin, C. H., Soloshonok, V. A. <a target="_blank" href="http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200200688/abstract">Efficient large-scale synthesis of picolinic acid-derived nickel(II) complexes of glycine.</a> Eur. J. Org. Chem. 2003 (10), 1954-1957 (2003).</li>
<li>Dener, J. M., Fantauzzi, P. P., Kshirsagar, T. A., Kelly, D. E., Wolfe, A. B. <a target="_blank" href="http://pubs.acs.org/doi/abs/10.1021/op010204f">Large-scale syntheses of Fmoc-protected non-proteogenic amino acids: useful building blocks for combinatorial libraries.</a> Org. Process Res. Dev. 5 (4), 445-449 (2001).</li>
<li>Cruz, L. J., Beteta, N. G., Ewenson, A., Albericio, F. <a target="_blank" href="http://pubs.acs.org/doi/abs/10.1021/op049917z">&#34;One-pot&#34;, preparation of N-carbamate protected amino acids via the azide.</a> Org Process Res. Dev. 8 (6), 920-924 (2004).</li>
<li>Hart, J. R. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aHart%2C+JR+%22Ullmann%27s+Encyclopedia+of+Industrial+Chemistry%22">Ullmann's Encyclopedia of Industrial Chemistry</a>. , Wiley-VCH Verlag GmbH & Co. (2000).</li>
<li>Adamson, J. G., Blaskovich, M. A., Groenevelt, H., Lajoie, G. A. <a target="_blank" href="http://pubs.acs.org/doi/abs/10.1021/jo00010a050">Simple and convenient synthesis of tert-butyl ethers of Fmoc-serine, Fmoc-threonine, and Fmoc-tyrosine.</a> J. Org. Chem. 56 (10), 3447-3449 (1991).</li>
<li>Seyfried, M. S., Lauber, B. S., Luedtke, N. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Multiple-turnover+isotopic+labeling+of+Fmoc-+and+Boc-protected+amino+acids+with+oxygen+isotopes%5BTitle%5D)+AND+%22Org.+Lett%22%5BJournal%5D)">Multiple-turnover isotopic labeling of Fmoc- and Boc-protected amino acids with oxygen isotopes.</a> Org. Lett. 12 (1), 104-106 (2010).</li>
<li>Bonke, G., Vedel, L., Witt, M., Jaroszewski, J. W., Olsen, C. A., Franzyk, H. <a target="_blank" href="https://www.thieme-connect.de/DOI/DOI?10.1055/s-2008-1067171">Dimeric building blocks for solid-phase synthesis of α,-peptide-β,-peptoid chimeras.</a> Synthesis. 2008 (15), 2381-2390 (2008).</li>
</ol>

著者は、開示することは何もありません。

上述のプロトコルは、穏やかなpH条件と2つの重要な工程を経て、この単離されたアミノ酸のその後のFmoc保護の下でのNi-シッフ塩基複合体からのアミノ酸骨格の単離を容易にするその能力において有用です。最初のステップは、複合体からのアミノ酸の放出を容易にするためにEDTAを含有するDMF /水の溶液を攪拌することを含みます。残留錯体または有機副生成物を容易に抽出して除去すること...

天然に見出される20個の天然アミノ酸のものとは異なる非天然アミノ酸（UAAの）軸受側鎖は、アプリケーションの広い範囲で有用性が見出されています。これらUAA年代の合成は、しかしながら、側鎖の構造及びアミノ酸骨格の立体化学に依存して困難であり得ます。ニッケルシッフ塩基錯体の文脈におけるグリシンのCH結合活性化はα、βジアミノ酸1,2または複素環式側鎖にフッ素化UAAのベアリングを含むアミノ酸誘導体の多様を生成するために使用されてきました。 3 非天然側鎖を添加した後、官能UAAのは、典型的には、塩酸4中で還流することによりシッフ塩基複合体から除去され、続いてイオン交換クロマトグラフィーを用いて単離されます。一般的に、効率的なながら、このプロトコルは、生成します固相ペプチド合成（SPPS）における使用には適さないかもしれMINO酸。 SPPSの性質は、酸不安定性側鎖保護基の存在を必要とし、典型的なニッケルシッフ塩基分解条件の強酸性の性質は、無傷のこれらの保護基でUAAの単離を防止することができます。我々の知る限り、唯一の代替的な分解方法が報告されている：高温でエチレンジアミン四酢酸（EDTA）およびヒドラジンの使用を、5つの条件自体は、フタルイミドのようないくつかの側鎖保護基には適さない場合があります。 <img alt="図1" src="/files/ftp_upload/55677/55677fig1.jpg" /> 図1のNi 2+、PBP、及びグリシン（Glyで）からのNi-PBP-Glyでの合成。 <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig1large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> </A&gt; 本明細書において、我々は、Ni-シッフ塩基錯体、ニッケルPBP-Glyを（ 図1）の加水分解のための方法を報告しています。 Ni 2+、グリシン、及びピリジン-2-カルボン酸（2-ベンゾイル-フェニル） -アミド（PBP）、6に由来するこの複合体は、UAAの様々な合成のために有用なプラットフォームであることが実証され、容易にされていますかアクセス可能な二段階の合成経路を使用して。この複合体7つの合成は、文献、先例高収率です。 6以下に説明する本発明者らの結果はUAAの軸受酸不安定性側鎖保護基と共に使用するのに適切な中性pH条件に弱酸性でEDTAを用いた加水分解条件の適用可能性を実証します。加水分解後、得られた水溶液は、Fmoc保護アミノ酸（ 図2）を産出するために標準的なFmoc保護条件に直ちに単離し、供することができます。 図2：加水分解およびNi-PBP-Glyをから分離アミノ酸ののFmoc保護。反応条件：I。 EDTA（12当量）を、pHが4.5、 II。 pH7の酢酸エチル洗浄、調整、 III。 Fmoc-OSuを（1当量）、 炭酸水素ナトリウム（2当量）を加えました。 <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig2large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a>

<table><tbody><tr><td>Ni-PBP-Gly</td><td></td><td></td><td>Synthesized from published protocol</td></tr><tr><td>DMF</td><td>Fisher</td><td>D119-4</td><td></td></tr><tr><td>EDTA</td><td>Fisher</td><td>S311-100</td><td></td></tr><tr><td>Dichloromethane</td><td>Acros</td><td>AC610050040</td><td></td></tr><tr><td>Sodium Bicarbonate</td><td>Fisher</td><td>S233-500</td><td></td></tr><tr><td>Fmoc-OSu</td><td>Chem-Impex</td><td>&quot;00147&quot;</td><td></td></tr><tr><td>Dioxane</td><td>Fisher</td><td>D111-500</td><td></td></tr><tr><td>Hydrochloric Acid</td><td>Fisher</td><td>A144-500</td><td></td></tr><tr><td>Ethyl Acetate</td><td>Acros</td><td>AC610060040</td><td></td></tr><tr><td>Magnesium Sulfate</td><td>Fisher</td><td>M65-500</td><td></td></tr><tr><td>ZEOPrep 60ECO Silica Gel</td><td>ZEOChem</td><td></td><td></td></tr><tr><td>Hexanes</td><td>Fisher</td><td>3200250.650.443</td><td></td></tr><tr><td>Chromatography Column</td><td></td><td></td><td></td></tr><tr><td>pH Test Strips</td><td></td><td></td><td></td></tr><tr><td>Rotary Evaporator</td><td></td><td></td><td></td></tr><tr><td>250 mL Separatory Funnel</td><td></td><td></td><td></td></tr><tr><td>250 mL Round Bottom Flask</td><td></td><td></td><td></td></tr><tr><td>Stir Bar</td><td></td><td></td><td></td></tr><tr><td>Stir Plate</td><td></td><td></td><td></td></tr></tbody></table>

hydrolysis of a ni-schiff-base complex using conditions suitable for retention of acid-labile protecting groups

非天然アミノ酸は、一般に自然界に見られない側鎖官能基を含むアミノ酸は、ますます合成ペプチド配列に見出されます。いくつかの非天然アミノ酸の合成は、多くの場合、ニッケルカチオンによって安定化シッフ塩基からなる前駆体の使用を含みます。非天然側鎖がこのシッフ塩基複合体に見出されるアミノ酸骨格上にインストールすることができます。得られた非天然アミノ酸は、その後、典型的には、強酸性溶液中で還流を採用することにより、シッフ塩基の加水分解を用いて、この複合体から単離することができます。これらの高度に酸性の条件は、マイクロ波アシスト固相ペプチド合成に使用される非天然アミノ酸のために必要な酸に不安定な側鎖保護基を除去することができます。本研究では、効率的な加水分解およびNi-シッフ塩基複合体から単離されたアミノ酸のその後のFmoc保護を提示します。この作品で提示加水分解条件は、酸に不安定なSの保持に適していますIDE鎖保護基および非天然アミノ酸の種々の基材に適応することができます。

私たちは、Ni-PBP-Glyを複合体からのニッケル2+の除去は厳しいpH条件を必要とせずにシッフ塩基の効率的な水加水分解される可能性がありという仮説を立てました。 EDTAは、安価でよく研究キレート剤であるように、10は、我々は、Ni-PBP-Glyでの溶液にEDTAの添加は、それによって複合体の加水分解を促進すること、のNi 2+イオンのキレー?...

Watch this Scientific Journal Video about Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups at JoVE.com

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

ここで、我々は、効率的な加水分解およびNi-シッフ塩基複合体から単離されたアミノ酸のその後のFmoc保護を提示します。酸不安定性側鎖保護基の保持が必要な場合、ここに提示加水分解条件は、使用するのに適しています。この技術は、非天然アミノ酸の種々の基材に適応することができます。

酸に不安定な保護基を保持するのに適したNi-シッフ塩基錯体の使用条件の加水分解

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide ...

hydrolysis-ni-schiff-base-complex-using-conditions-suitable-for

Research

JoVE Journal

Biochemistry

9.6K ビュー.  Slippery Rock University. ここで、我々は、効率的な加水分解およびNi-シッフ塩基複合体から単離されたアミノ酸のその後のFmoc保護を提示します。酸不安定性側鎖保護基の保持が必要な場合、ここに提示加水分解条件は、使用するのに適しています。この技術は、非天然アミノ酸の種々の基材に適応することができます。 

ビデオ: Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer by generating a charged structure provides an opportunity to use extraction as a simple purification technique. By combining the use of a miscible organic solvent with saturated sodium bisulfite, aldehydes and reactive ketones can be successfully transformed into charged bisulfite adducts that can then be separated from other organic components of a mixture by the introduction of an immiscible organic layer. Here, we describe a simple protocol for the removal of aldehydes, including sterically-hindered neopentyl aldehydes and some ketones, from chemical mixtures. Ketones can be separated if they are sterically unhindered cyclic or methyl ketones. For aliphatic aldehydes and ketones, dimethylformamide is used as the miscible solvent to improve removal rates. The bisulfite addition reaction can be reversed by basification of the aqueous layer, allowing for the re-isolation of the reactive carbonyl component of a mixture.

Here, we present a protocol to remove aldehydes and reactive ketones from mixtures by a liquid-liquid extraction protocol directly with saturated sodium bisulfite in a miscible solvent. This combined protocol is rapid and facile to perform. The aldehyde or ketone can be re-isolated by the basification of the aqueous layer.

アルデヒドおよびケトン類の反応性の重亜硫酸塩の抽出のプロトコルを使用して混合物からの分離

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer ...

化学

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each possessing two sulfur and one nitrogen donor atom functionalities (SNS) and based on bis-imidazole or bis-triazole compounds) are metallated with CoCl2&#183;6H2O to afford tridentate SNS pincer cobalt(II) complexes. Preparation of the cobalt(II) model complexes for liver alcohol dehydrogenase is facile. Based on a quick color change upon adding the CoCl2&#183;6H2O to acetonitrile solution that contains the ligand precursor, the complex forms rapidly. Formation of the metal complex is complete after allowing the solution to reflux overnight. These cobalt(II) complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH). The complexes are characterized using single crystal X-ray diffraction, electrospray mass spectrometry, ultra-violet visible spectroscopy, and elemental analysis. To accurately determine the structure of the complex, its single crystal structure must be determined. Single crystals of the complexes that are suitable for X-ray diffraction are then grown via slow vapor diffusion of diethyl ether into an acetonitrile solution that contains the cobalt(II) complex. For high quality crystals, recrystallization typically takes place over a 1 week period, or longer. The method can be applied to the preparation of other model coordination complexes and can be used in undergraduate teaching laboratories. Finally, it is believed that others may find this recrystallization method to obtain single crystals beneficial to their research.

Preparation of SNS CobaltII Pincer Model Complexes of Liver Alcohol Dehydrogenase

The preparation of SNS pincer cobalt(II) model complexes of liver alcohol dehydrogenase is presented here. The complexes can be prepared by reacting the ligand precursor with CoCl2&#183;6H2O and can then be recrystallized by allowing diethyl ether to slowly diffuse into an acetonitrile solution that contains the cobalt complex.

SNSコバルト(II)の製造用肝アルコール脱水素酵素のピンサーモデル複合体

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each ...

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics (DCAF)

Elimination of harmful antibodies from organisms is a valuable approach for the intervention of antibody-associated diseases, such as Dengue hemorrhagic fever and autoimmune diseases. Since thousands of antibodies with different epitopes are circulating in blood, no universal method, except for the dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF), was reported to target specific harmful antibodies. The development of DCAF molecules makes significant contribution to the progress of targeted therapy, which were demonstrated to eliminate the antibody dependent enhancement (ADE) effect in a Dengue virus (DENV) infection model and to boost the acetylcholine receptor activity in a myasthenia gravis model. Here, we describe a protocol for the synthesis of a DCAF molecule (DCAF1), which can selectively block 4G2 antibody to attenuate ADE effect during Dengue virus infection, and illustrate the binding of DCAF1 to 4G2 antibody by an ELISA assay. In our method, DCAF1 is synthesized by the conjugation of a hydrazine derivative of a Fc-III peptide and a recombinant expressed long &#945;-helix with antigenic sequence through native chemical ligation (NCL). This protocol has been successfully applied to DCAF1 as well as other DCAF molecules for targeting their cognate antibodies.

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics DCAF

Development of a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF) is novel for the elimination of harmful antibodies. Here, we describe a detailed protocol for the synthesis of DCAF1 molecule, which can selectively block 4G2 antibody to eliminate antibody dependent enhancement effect during Dengue virus infection.

抗原ペプチドとFc-III模倣体(DCAF)の二重機能コンジュゲートによる標的抗体遮断

Elimination of harmful antibodies from organisms is a valuable approach for the intervention of antibody-associated diseases, such as Dengue hemorrhagic ...

免疫・感染学

Molecular Orbital (MO) Theory

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes featuring the ligand 1,1&#39;-bis(diphenylphosphino)ferrocene (dppf): M(dppf)Cl2, where M = Ni or Pd. While both of these transition metal complexes are 4-coordinate, they exhibit different geometries at the metal center. Using molecular orbital (MO) theory in conjunction with 1H NMR and Evans method, we will determine the geometry of these two compounds.

Molecular Orbital MO Theory: Predicting Geometry of Transition Metal Complexes

分子軌道 (MO) 理論

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes ...

Education

JoVE Science Education

無機化学

Preparation of Carboxylic Acids: Hydrolysis of Nitriles

Nitriles (R–CN) can be converted into carboxylic acids (R–COOH) upon treatment with aqueous acids, i.e., upon hydrolysis of nitriles. Under base-catalyzed conditions, carboxylate anions (R–COO−) are formed.
<img alt="Hydrolysis reaction mechanism diagram, showing conversion of nitrile to carboxylic acid with arrows." src="/files/ftp_upload/13085/13085_PT_Figure_1.svg" style="text-align: center; height: 56px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction facilitates a two-step conversion of haloalkanes to carboxylic acids. Here, haloalkanes are first converted to nitriles using sodium cyanide via an SN2 reaction. The resultant nitrile is then hydrolyzed to yield carboxylic acids bearing one more carbon than the haloalkane used. The reaction uses dimethyl sulfoxide, alcohols, or water as solvents. As the process involves the SN2 mechanism, tertiary alkyl halides are seldom used.
<img alt="Organic synthesis reaction sequence; diagram illustrating nucleophilic substitution to carboxylic acid." src="/files/ftp_upload/13085/13085_PT_Figure_2.svg" style="text-align: center; height: 46px;" data-altupdatedat="1747908711000" data-alt="Figure2">

カルボン酸の調製:ニトリルの加水分解

Nitriles (R&#8211;CN) can be converted into carboxylic acids (R&#8211;COOH) upon treatment with aqueous acids, i.e., upon hydrolysis of nitriles. Under ...

JoVE Core

有機化学

ユニット １

カルボン酸

KEY TERMS AND CONCEPTS

カルボン酸の調製: ニトリルの加水分解

Protection of Alcohols

This lesson delves into the concept of protection and deprotection of a functional group fundamental to synthetic organic chemistry. These phenomena are explained in the context of aliphatic and aromatic alcohols.
<h4>Protection</h4>
It defines a protecting group as the masking agent to make the more reactive species inert to a given set of conditions. This concept is depicted via the illustration of liquid flow through different outlets in an assembly of pipes. The analogy helps to understand the role of a protecting group in reaction selectivity, as in the case of the organolithium alkylation of a halide in the presence of a competing acidic alcohol group. The example shows how protection of the alcohol group helps to achieve the alkylation of the halide. Popular protecting groups for alcohols include the trialkylsilyl family for nucleophiles or carbon and nitrogen bases and the tetrahydropyranyl (THP) group for strong bases. In the former example, the halide of the trialkylsilyl derivative reacts with the alcohol in the presence of a nucleophilic catalyst to generate a trialkylsilyl ether.
<h4>Deprotection</h4>
Every protection is followed by deprotection after the intended reaction. The deprotection restores the system to its native state. In protection with trialkylsilyl groups, deprotection is achieved using fluoride salts like tetra-n-butylammonium fluoride (TBAF) that are soluble in organic solvents. Here, the re-protonation of the oxygen regenerates the native alcohol. In the case of protection with THP, deprotection is achieved using acid hydrolysis.
<h4>Principle of design</h4>
The lesson also elucidates the principles behind the design of a protecting group using an illustration of a house under varying external weather conditions. It demonstrates the selectivity offered by a protecting group in a specific environment. For instance, THP protects alcohol from strong bases. The acetal formed in this case is stable towards bases but susceptible to acid hydrolysis.
Apart from the reaction conditions, the reactivity of the molecule to be protected also plays a key role in designing a suitable protecting group. For example, methyl ethers&#8217; ability to protect phenols is found inappropriate for aliphatic alcohols. Here, the stability of the corresponding leaving groups during deprotection plays a key role. For example, the alkoxides, unlike phenoxides, are poor leaving groups for deprotection with hydrogen bromide.
The following table summarizes the various protection/deprotection groups for different types of alcohols and related conditions:
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Protecting group</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Structure</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Protects</td>
			<td style="color: black; border: 1px solid black; text-align: center;">From</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Protection</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Deprotection</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Trialkylsilyl (R3Si&#8211;), 
			e.g., TBDMS</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Me3Si&#8211;OR 
			(Me3C)Me2Si&#8211;OR</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Nucleophiles, 
			C or N bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">R3SiCl, 
			base</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H+, H2O, 
			or F&#8722;</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Tetrahydropyranyl 
			(THP)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure1" src="/files/ftp_upload/11927/Figure_1-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Strong bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">3,4-Dihydropyran, 
			H+</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H+, H2O</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Benzyl ether 
			(OBn)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure2" src="/files/ftp_upload/11927/Figure_2-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Almost everything</td>
			<td style="color: black; border: 1px solid black; text-align: center;">NaH, BnBr</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H2, Pd/C, 
			or HBr</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Methyl ether 
			(ArOMe)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure3" src="/files/ftp_upload/11927/Figure_3-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Phenols 
			(ArOH)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">NaH, MeI, or 
			(MeO)2SO2</td>
			<td style="color: black; border: 1px solid black; text-align: center;">BBr3, HBr, HI, 
			Me3SiI</td>
		</tr>
	</tbody>
</table>

Protection and Deprotection of Alcohols and Phenols

アルコールの保護

This lesson delves into the concept of protection and deprotection of a functional group fundamental to synthetic organic chemistry. These phenomena are ...

アルコール類とフェノール類

Acid Halides to Carboxylic Acids: Hydrolysis

Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid as the substitution product. 
<img alt="Organic reaction mechanism, diagram, showing nucleophilic substitution and product formation steps." src="/files/ftp_upload/12361/12361_PT_Figure_1_.svg" style="text-align: center; height: 200px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction produces a very strong acid, HCl, as a by-product. Therefore, a base such as pyridine is used in the reaction, which reacts with HCl to form pyridinium chloride. This process neutralizes the acid and prevents undesired side reactions.

酸性ハロゲン化物からカルボン酸へ:加水分解

Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction ...

酸に不安定な保護基を保持するのに適したNi-シッフ塩基錯体の使用条件の加水分解

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カルボン酸の調製:ニトリルの加水分解

アルコールの保護

アルコールの保護

カルボン酸の調製:ニトリルの加水分解

酸性ハロゲン化物からカルボン酸へ:加水分解

酸性ハロゲン化物からカルボン酸へ:加水分解