بتمويل من جامعة زلق الصخرة. ونود أن نشكر T. البورون III (جامعة زلق روك) وC. هاني (جامعة بنسلفانيا) عن وجهات نظرهم.

1. التحلل من مجمع ني شيف-قاعدة <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> حل 1 مليمول مجمع ني PBP شيف القاعدي في 40 مل من N، N -dimethylformamide (DMF) مع التحريك في 250 مل قارورة أسفل جولة في درجة حرارة الغرفة. </li><li style=";text-align:right;direction:rtl"> إضافة 60 مل من 0.2 M حل EDTA مائي، ودرجة الحموضة 4.5. </li><li style=";text-align:right;direction:rtl"> باستخدام شريط مغناطيسي ويقلب لوحة، وإثارة الحل الجمع بين ليلة وضحاها. كما تحلل مجمع شيف قاعدة، ولون التحول من أحمر عميق إلى الأبيض. </li><li style=";text-align:right;direction:rtl"> بعد الانتهاء من رد فعل كما يدل على ذلك عدم وجود أي اللون الأحمر، ونقل رد فعل على قمع فصل 250 مل. </li><li style=";text-align:right;direction:rtl"> إضافة 50 مل ثنائي كلورو ميثان، حدا لقمع فصل، وتخلط. استنزاف غسل العضوية في كوب من النفايات. كرر هذه العملية ثلاث مرات لإزالة PBP وأي مجمع ني PBP شيف قاعدة المتبقية. جمع طبقة مائية المتبقية في 250 مل جولة أسفل القارورة. </li></ol> 2. حماية FMOC من تحلل الأحماض الأمينية <ol style=";text-align:right;direction:rtl"><li&gt; ضبط طبقة المائية المعزولة من الخطوة 1.5 المذكورة أعلاه لدرجة الحموضة 7 باستخدام بيكربونات الصوديوم الصلبة. تحقق درجة الحموضة بشكل دوري باستخدام شرائط اختبار درجة الحموضة. </li><li style=";text-align:right;direction:rtl"> إضافة 168 ملغ بيكربونات الصوديوم (2.00 ملمول، 2 م equiv) إلى حل ويحرك باستخدام شريط مغناطيسي ويقلب لوحة. </li><li style=";text-align:right;direction:rtl"> حل 337 ملغ FMOC N -hydroxysuccinimide استر (1.00 ملمول، 1 م equiv) في الحد الأدنى من ديوكسان (حوالي 4 أو 5 مل) في قارورة 10 مل. نقل هذا الحل إلى محلول مائي ويقلب بين عشية وضحاها. </li><li style=";text-align:right;direction:rtl"> بعد السماح للرد فعل لإثارة بين عشية وضحاها، يحمض المحلول الناتج لدرجة الحموضة 2 مع 1 M حمض الهيدروكلوريك. تحقق درجة الحموضة بشكل دوري باستخدام شرائط اختبار درجة الحموضة. </li><li style=";text-align:right;direction:rtl"> نقل رد فعل على قمع فصل 250 مل وإضافة 50 مل خلات الإيثيل. يضع حدا لقمع فصل، وتخلط جيدا، وجمع طبقة العضوية في قارورة مخروطي سعة 250 مل. كرر هذه العملية مرتين إضافية، والجمع بين مقتطفات العضوية. تجفيف مقتطفات العضوية جنبا إلى جنب مع ما يقرب من 3 غرام من المغنيسيوم sulfatه. </li><li style=";text-align:right;direction:rtl"> تركيز مقتطفات العضوية جنبا إلى جنب باستخدام المبخر الدوار على تحمل الخام الأحماض الأمينية FMOC المحمية. </li></ol>

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A., Kelly, D. E., Wolfe, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large-scale+syntheses+of+Fmoc-protected+non-proteogenic+amino+acids:+useful+building+blocks+for+combinatorial+libraries.">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://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&amp;#34;One-pot&amp;#34;,+preparation+of+N-carbamate+protected+amino+acids+via+the+azide.">&amp;#34;One-pot&amp;#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. 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الكتاب ليس لديهم ما يكشف.

بروتوكول الموصوفة أعلاه هو مفيد في قدرته على تسهيل العزلة من العمود الفقري من الأحماض الأمينية من مجمع ني شيف قاعدة تحت ظروف الأس الهيدروجيني خفيفة وحماية FMOC لاحقة من هذه الأحماض الأمينية معزولة من خلال اثنين من الخطوات الحاسمة. الخطوة الأولى تنطوي على إثارة حل DMF / ا...

وقد وجدت الأحماض الأمينية غير طبيعية السلاسل الجانبية تحمل (UAA) والتي تختلف عن تلك التي والعشرين التي تحدث بشكل طبيعي الأحماض الأمينية الموجودة في الطبيعة فائدة في مجموعة واسعة من التطبيقات. توليف هذه لUAA، ومع ذلك، يمكن أن يكون صعبا اعتمادا على هيكل سلاسل الجانبية والفراغية من العمود الفقري من الأحماض الأمينية. وقد استخدم تفعيل تش بوند من الجلايسين في سياق النيكل مجمع شيف قاعدة لإنتاج مجموعة متنوعة من مشتقات الأحماض الأمينية بما في ذلك α، β-diamino الأحماض 1 وتحمل UAA في المفلورة 2 أو الحلقية غير المتجانسة سلاسل الجانب. 3 بعد إضافة غير طبيعية الجانب سلاسل، functionalized عادة تتم إزالة لUAA من مجمع شيف قاعدة من الجزر في حمض الهيدروكلوريك (4) ويتم عزل في وقت لاحق باستخدام التبادل الأيوني اللوني. في حين كفاءة عموما، هذا البروتوكول يولدالأحماض مينو التي قد تكون غير صالحة للاستخدام في الحالة الصلبة الببتيد التوليف (SPPS). طبيعة SPPS يتطلب وجود جماعات حمض عطوب جانب سلسلة حماية والطبيعة الحمضية بقوة من الظروف ني شيف قاعدة التحلل النموذجية يمنع عزل في UAA مع هذه الجماعات حماية سليمة. على حد علمنا، تم الإبلاغ عن واحد فقط طريقة التحلل البديل: استخدام ثنائي أمين الإيثيلين رباعي حمض الخل (EDTA) والهيدرازين في درجات حرارة مرتفعة، 5 الشروط التي أنفسهم قد لا تكون مناسبة لبعض جنبا إلى سلسلة تحمي جماعات مثل phthalimides. <img alt="شكل 1" src="/files/ftp_upload/55677/55677fig1.jpg" /> الشكل 1: توليف ني PBP-الغليسين من ني 2+، PBP، وجليكاين (الغليسين). <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig1large.jpg" target="_blank">الرجاء انقر هنا لمشاهدة نسخة أكبر من هذا الرقم.</a> </<html> و&gt; هنا، ونحن التقرير وسيلة لالتحلل من مجمع ني شيف قاعدة، ني PBP-الغليسين (الشكل 1). وقد تجلى هذا المجمع، والمستمدة من ني 2+، الجلايسين، والبيريدين-2-متيل حمض (2-بيروكسايد-فينيل) -amide (PBP) (6)، لتكون منبرا مفيدا لتوليف مجموعة متنوعة من وUAA وبسهولة يمكن الوصول إليها باستخدام طريق الاصطناعية من خطوتين. 7 توليف هذا المجمع هو في ارتفاع العائد سوابق أدب. 6 نتائجنا الموضحة أدناه توضح مدى انطباق شروط التحلل استخدام EDTA في حموضة أقل ما يقال لظروف الأس الهيدروجيني محايدة مناسبة للاستخدام مع تأثير حمض عطوب جانب سلسلة UAA لحماية الفئات. وبعد التحلل، ومحلول مائي الناتجة يمكن عزل ويتعرضون على الفور لشروط الحماية FMOC القياسية لتحمل الأحماض الأمينية FMOC المحمية (الشكل 2). س: المحافظة على together.within الصفحات = &quot;1&quot;&gt; <img alt="الشكل 2" src="/files/ftp_upload/55677/55677fig2.jpg" /> الشكل 2: التحلل وFMOC الحماية من الأحماض الأمينية المعزولة من ني PBP-الغليسين. شروط التفاعل: ط. EDTA (12 م equiv)، ودرجة الحموضة 4.5. ثانيا. إيثيل غسل خلات والتكيف مع درجة الحموضة 7؛ ثالثا. FMOC-جامعة ولاية أوهايو (1 EQUIV)، NaHCO 3 (2 EQUIV). <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig2large.jpg" target="_blank">الرجاء انقر هنا لمشاهدة نسخة أكبر من هذا الرقم.</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

الأحماض الأمينية غير طبيعية، والأحماض الأمينية التي تحتوي على وظائف جنبا إلى سلسلة لا ينظر عادة في الطبيعة، تم العثور على نحو متزايد في تسلسل الببتيد الاصطناعية. تركيب بعض الأحماض الأمينية غير طبيعية وغالبا ما تتضمن استخدام السلائف تتألف من شيف قاعدة استقرت كاتيون النيكل. يمكن تثبيت غير طبيعية جنبا إلى سلاسل على العمود الفقري الأحماض الأمينية الموجودة في هذا المجمع شيف قاعدة. الناتجة من الأحماض الأمينية غير طبيعي ويمكن بعد ذلك تكون معزولة عن ذلك باستخدام التحلل المعقد للشيف قاعدة، وعادة عن طريق استخدام الجزر في المحاليل الحمضية بقوة. هذه الظروف الحمضية للغاية قد يزيل حمض عطوب جانب سلسلة حماية الفئات اللازمة لالأحماض الأمينية غير طبيعية لاستخدامها في الحالة الصلبة الببتيد التوليف بمساعدة الميكروويف. في هذا العمل، ونحن تقديم والتحلل كفاءة وحماية FMOC اللاحقة من الأحماض الأمينية معزولة عن مجمع قاعدة ني شيف. شروط التحلل الواردة في هذا العمل هي مناسبة لاستبقاء الصورة حمض عطوببيئة تطوير متكاملة سلسلة حماية الفئات ويمكن أن تكون قابلة للتكيف مع مجموعة متنوعة من ركائز الأحماض الأمينية غير طبيعية.

افترضنا أن إزالة ني 2+ من مجمع ني PBP-الغليسين يمكن أن تسمح لالتحلل المائي الفعال للشيف قاعدة دون الحاجة لظروف الأس الهيدروجيني قاسية. كما EDTA هو عامل خالب غير مكلفة ومدروسة، 10 افترضنا أن إضافة EDTA إلى حل ني PBP-الغليسين من شأنه أن يسهل ع...

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

هنا، نقدم والتحلل كفاءة وحماية FMOC اللاحقة من الأحماض الأمينية معزولة عن مجمع ني شيف قاعدة. شروط التحلل المقدمة هنا هي مناسبة للاستخدام عند الحاجة الاحتفاظ مجموعات حماية حمض عطوب جنبا إلى سلسلة. قد تكون هذه التقنية قابلة للتكيف مع مجموعة متنوعة من ركائز الأحماض الأمينية غير طبيعية.

التحلل من شيف-قاعدة ني مجمع الظروف عن طريق مناسبة للاحتباس حماية المجموعات حمض عطوب

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

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9.6K Views.  Slippery Rock University.  هنا، نقدم والتحلل كفاءة وحماية FMOC اللاحقة من الأحماض الأمينية معزولة عن مجمع ني شيف قاعدة. شروط التحلل المقدمة هنا هي مناسبة للاستخدام عند الحاجة الاحتفاظ مجموعات حماية حمض عطوب جنبا إلى سلسلة. قد تكون هذه التقنية قابلة للتكيف مع مجموعة مت...

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

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications.
In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

To deliver cancer drugs to tumor sites with high specificity and reduced side effects, new methods based on nanoparticles are required. Here, we describe disulfide cross-linked micelles that can be easily prepared by hydrogen peroxide-mediated oxidation and are able to dissociate efficiently under a reducing tumor environment to release payloads.

مقاربة سطحية وكفاءة لإنتاج المذيلات عكسية ثاني كبريتيد عبر ربط

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. ...

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.

الفصل بين الألدهيدات والكيتونات رد الفعل من الخلائط استخدام بروتوكول استخراج بيكبريتيت

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

Chemistry

Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry

With this protocol, a well-defined singlesite silica-supported heterogeneous catalyst [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is designed and prepared according to the methodology developed by surface organometallic chemistry (SOMC). In this framework, catalytic cycles can be determined by isolating crucial intermediates. All air-sensitive materials are handled under inert atmosphere (using gloveboxes or a Schlenk line) or high vacuum lines (HVLs, &#60;10-5 mbar). The preparation of SiO2-700 (silica dehydroxylated at 700 &#176;C) and subsequent applications (the grafting of complexes and catalytic runs) requires the use of HVLs and double-Schlenk techniques. Several well-known characterization methods are used, such as Fourier-transform infrared spectroscopy (FTIR), elemental microanalysis, solid-state nuclear magnetic resonance spectroscopy (SSNMR), and state-of-the-art dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP-SENS). FTIR and elemental microanalysis permit scientists to establish the grafting and its stoichiometry. 1H and 13C SSNMR allows the structural determination of the hydrocarbon ligands coordination sphere. DNP SENS is an emerging powerful technique in solid characterization for the detection of poorly sensitive nuclei (15N, in our case). SiO2-700 is treated with about one equivalent of the metal precursor compared to the amount of surface silanol (0.30 mmol&#183;g-1) in pentane at room temperature. Then, volatiles are removed, and the powder samples are dried under dynamic high vacuum to afford the desired materials [(&#8801;Si-O-)Hf(&#951;2&#960;-MeNCH2)(&#951;1-NMe2)(&#951;1-HNMe2)]. After a thermal treatment under high vacuum, the grafted complex is converted into metal imido silica complex [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)]. [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] effectively promotes the metathesis of imines, using the combination of two imine substrates, N-(4-phenylbenzylidene)benzylamine, or N-(4-fluorobenzylidene)-4-fluoroaniline, with N-benzylidenetert-butylamine as substrates. A significantly lower conversion is observed with the blank runs; thus, the presence of the imido group in [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is correlated to the catalytic performance.

A new group IV metal catalyst for imine metathesis is prepared by grafting amine metal complex onto dehydroxylated silica. Surface metal fragments are characterized using FT-IR, elemental microanalysis, and solid-state NMR spectroscopy. Further dynamic nuclear polarization surface enhanced NMR spectroscopy experiments complement the determination of the coordination sphere.

Imine Metathesis بواسطة المحفزات المدعومة من السيليكا باستخدام منهجيه الكيمياء فلزي السطحية

With this protocol, a well-defined singlesite silica-supported heterogeneous catalyst [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is designed and prepared ...

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.

إعداد SNS Cobalt (II) المجمعات نموذج بينسر من الكبد الكحول ديهيدروجيناز

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

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

حماية الكحول

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

Education

JoVE Core

Organic Chemistry

Unit 1

Alcohols and Phenols

KEY TERMS AND CONCEPTS

Preparation of Carboxylic Acids: Hydrolysis of Nitriles

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 base-catalyzed conditions, carboxylate anions (R&#8211;COO&#8722;) are formed.
<img alt="Figure1" src="/files/ftp_upload/13085/13085_PT_Figure_1.svg" style="text-align: center; height: 56px;" />
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="Figure2" src="/files/ftp_upload/13085/13085_PT_Figure_2.svg" style="text-align: center; height: 46px;" />

تحضير أحماض الكربوكسيليك: التحلل المائي للنتريل

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 ...

Carboxylic Acids

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&#8211;oxygen &#960; bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid as the substitution product.&#160;
<img alt="Figure1" src="/files/ftp_upload/12361/12361_PT_Figure_1_.svg" style="text-align: center; height: 200px;" />
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.

هاليدات الحمض إلى أحماض الكربوكسيليك: التحلل المائي

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

Carboxylic Acid Derivatives

Protecting Groups for Aldehydes and Ketones: Introduction

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
<img alt="Figure1" src="/files/ftp_upload/12844/12844_PT_Figure_1.svg" style="text-align: center; height: 60px;" />
The aldehydes and ketones can be selectively protected in the presence of other carbonyl groups such as esters or acids based upon their reactivity. This is important for the manipulation of one functional group over the other.
For instance, when carrying out a reduction reaction in the presence of an ester and a ketone, the ketone will always be preferentially reduced to alcohol. In order to achieve the selective reduction of an ester to an alcohol while keeping the ketone unaffected, the ketone group needs to be protected (Figure 2, first step). After the ketone is protected, the ester is reduced to an alcohol using LiAlH4 (Figure 2, second step). Finally, the ketone is regenerated by removing the protecting group (Figure 2, third step).
<img alt="Figure2" src="/files/ftp_upload/12844/12844_PT_Figure_2.svg" style="text-align: center; height: 215px;" />
Acetals and thioacetals are the most commonly used protecting groups for aldehydes and ketones and can be easily removed. In addition, they are resistant to chemical species such as nucleophiles, or reducing and oxidizing agents.

مجموعات حماية الألدهيدات والكيتونات: مقدمة

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired ...

Aldehydes and Ketones

Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones

Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals readily can be protected from undergoing undesirable reactions. For instance, if a compound contains a ketone and an ester group, the ketone can be protected by converting it into acetal. On the other hand, the ester does not form acetal; hence it can be subjected to the desired reaction, and in&#160;the end, the ketone can be deprotected.
<img alt="Figure1" src="/files/ftp_upload/12333/12333_Figure_1.svg" style="opacity: 0.9; text-align: center; height: 200px;" />
The sulfur-containing analogs of acetals are called thioacetals that&#160;can act as an efficient protecting group for aldehydes and ketones. The thioacetals are stable in acidic conditions. Due to this, they cannot be deprotected by acid hydrolysis. Instead, mercuric chloride in aqueous acetonitrile is used for its deprotection.
<img alt="Figure2" src="/files/ftp_upload/12333/12333_Figure_2.svg" style="text-align: center; height: 55px;" />
Apart from acting as protecting groups, thioacetals also play a major role in organic synthesis, especially in reduction reactions. Thioacetals can undergo desulfurization in the presence of Raney nickel and hydrogen to form hydrocarbons.
<img alt="Figure3" src="/files/ftp_upload/12333/12333_Figure_3.svg" style="text-align: center; height: 55px;" />

الأسيتال والثيوأسيتال كمجموعات حماية للألدهيدات والكيتونات

Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, ...

Amides to Carboxylic Acids: Hydrolysis

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more electrophilic. Next, water acts as a nucleophile and attacks the carbonyl carbon to form a tetrahedral intermediate. Further, deprotonation of the tetrahedral intermediate gives a neutral tetrahedral addition intermediate. Subsequent protonation of the amino nitrogen converts the amino group into a better leaving group. In the next step, the carbonyl group is re-formed with the departure of ammonia as a leaving group. A final deprotonation step yields a carboxylic acid.
<img alt="Figure1" src="/files/ftp_upload/12372/12372_PT_Figure_1_.svg" style="text-align: center; height: 225px;" />
The formation of ammonium ion drives the equilibrium favoring the product formation.
Base-promoted hydrolysis: 
Base-promoted hydrolysis is another nucleophilic acyl substitution reaction, where hydroxide acts as a nucleophile. Amides undergo hydrolysis when heated under basic aqueous solutions to produce carboxylic acid.
The base-promoted mechanism involves a nucleophilic attack by the hydroxide ion at the amide carbonyl carbon to form a tetrahedral intermediate. In the second step, the carbonyl group is reconstructed with the departure of an amide ion as a leaving group. Next, deprotonation yields a carboxylate ion and ammonia. This step drives the reaction to completion, which pushes the equilibrium towards the product. A final step involves acidification of the carboxylate ion to give free acid.
<img alt="Figure2" src="/files/ftp_upload/12372/12372_PT_Figure_2.svg" style="text-align: center; height: 200px;" />

أميدات إلى أحماض الكربوكسيليك: التحلل المائي

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires ...