Name: hydrolysis of a ni-schiff-base complex using conditions suitable for retention of acid-labile protecting groups
Uploaded: 2017-04-06T15:00:00.000+00:00
Duration: 6 min 44 s
Description: 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

במימון Slippery Rock האוניברסיטה. ברצוננו להודות ט בורון III (אוניברסיטת סלע חלקלק) ו ג הייני (אוניברסיטת פנסילבניה) על התובנות שלהם.

1. הידרוליזה של קומפלקס Ni-שיף-Base <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> ממיסים 1 מילימול של המתחם Ni-PBP-שיף-בסיס ב 40 מ&quot;ל של N, -dimethylformamide N (DMF) עם בוחש בה 250 מ&quot;ל עגול הבקבוק התחתון בטמפרטורת החדר. </li><li style=";text-align:right;direction:rtl"> להוסיף 60 מ&quot;ל של 0.2 פתרון EDTA מימית M, 4.5 pH. </li><li style=";text-align:right;direction:rtl"> שימוש בר ומערבבים מגנטי ומערבבים צלחת, ומערבבים הפתרון המשולב לילה. כמתחם שיף-בסיס הוא הידרוליזה, הצבע יהיה לעבור ממדיניות מוניטרית אדום עמוק ללבן. </li><li style=";text-align:right;direction:rtl"> לאחר השלמת התגובה כפי שצוין על ידי בהעדר כל צבע אדום, להעביר את התגובה משפך 250 מ&quot;ל separatory. </li><li style=";text-align:right;direction:rtl"> להוסיף 50 מ&quot;ל dichloromethane, מכסה את המשפך separatory, ומערבבים. מסננים את לשטוף אורגני לתוך מבחנה פסולת. חזור על תהליך זה שלוש פעמים כדי להסיר PBP וכל מורכבים Ni-PBP-שיף-בסיס שיורית. אסוף את השכבה המימית שנותרה בבקבוק תחתי עגול 250 מיליליטר. </li></ol> 2. הגנה Fmoc של Hydrolyzed חומצת אמינו <ol style=";text-align:right;direction:rtl"><li&gt; התאם את השכבה המימית המבודדת משלב 1.5 לעיל ל- pH 7 באמצעות סודיום ביקרבונט מוצק. בדוק מעת לעת pH באמצעות רצועות מבחן ה- pH. </li><li style=";text-align:right;direction:rtl"> הוספת 168 מ&quot;ג סודיום ביקרבונט (2.00 מילימול, 2 equiv) לפתרון ומערבבים בעזרת בר ומערבבים מגנטי ומערבבים צלחת. </li><li style=";text-align:right;direction:rtl"> ממיסים 337 אסתר Fmoc N -hydroxysuccinimide מ&quot;ג (1.00 מילימול, 1 equiv) בסכום מינימלי של dioxane (בערך 4 או 5 מ&quot;ל) ב בקבוקון 10 מ&quot;ל. העבר פתרון זה בתמיסה מימית ומערבבים במשך הלילה. </li><li style=";text-align:right;direction:rtl"> לאחר המאפשר תגובה לעורר לילה, להפוך לחומצה הפתרון שהתקבל ל- pH 2 עם 1 חומצה הידרוכלורית M. בדוק מעת לעת pH באמצעות רצועות מבחן ה- pH. </li><li style=";text-align:right;direction:rtl"> מעבירים את התגובה משפך 250 מ&quot;ל separatory ולהוסיף 50 אתיל אצטט מ&quot;ל. כיסוי או משפך separatory, לערבב היטב, ולאסוף את השכבה האורגנית בבקבוק מ&quot;ל Erlenmeyer 250. חזור על תהליך זה פעמיים נוספות, שילוב תמציות אורגניות. יבש את תמציות אורגניות בשילוב עם בערך 3 גרם של מגנזיום sulfate. </li><li style=";text-align:right;direction:rtl"> לרכז את התמציות אורגניות בשילוב באמצעות מאייד סיבובי כדי להרשות חומצת אמינו Fmoc המוגנת הגולמית. </li></ol>

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החוקרים אין לחשוף.

הפרוטוקול המתואר לעיל הנו שימושי ביכולתה להקל על הבידוד של עמוד שדרת חומצת אמינו מתסביך Ni-שייף-בסיס בתנאי pH קלים והגנה עוקבת Fmoc של חומצת אמינו מבודדת זו דרך שני שלבים קריטיים. השלב הראשון כולל ערבוב פתרון DMF / מים המכיל EDTA כדי להקל שחרור חומצת אמינו מהמתחם. תוצרי לוואי ...

חומצות אמינו לא טבעיות שרשרות צד נושאת (של UAA) כי שונות מאלו של עשרים חומצות אמינו נמצאו באופן טבעי בטבע מצאו שירות בתוך טווח רחב של יישומים. סינתזה של UAA של אלה, עם זאת, יכול להיות קשה תלוי במבנה-שרשראות הצד ואת סטראוכימיה של עמוד השדרה חומצת אמינו. הפעלת הקשר CH של גליצין בהקשר של מתחם שיף-בסיס ניקל נעשה שימוש כדי לייצר מגוון של נגזרים חומצת אמינו כולל α, חומצות-diamino β 1 ונושאת של UAA fluorinated 2 או בצד שרשראות heterocyclic. 3 לאחר תוספת של שרשרות צד לא טבעיות, פונקציונלי UAA של כלל מוסרים מהמתחם שייף-הבסיס ידי ריפלוקס חומצה הידרוכלורית 4 ובהמשך המבודד באמצעות כרומטוגרפיה-חילוף יונים. אמנם בדרך כלל יעיל, פרוטוקול זה מייצרחומצות המינים שעשויות להיות מתאים לשימוש סינתזת פפטיד מוצק שלב (SPPS). אופי SPPS מחייב נוכחות של הגנה על קבוצות שרשרת בצד חומצה-רָפִיף ואת אופי חומצי מאוד של תנאי הפירוק טיפוסי Ni-שיף-בסיס מונע בידוד של UAA של עם קבוצות הגנה אלה ללא פגע. למיטב ידיעתנו, רק אחד שיטת פירוק אלטרנטיבה דווחה: שימוש בחומצת ethylenediaminetetraacetic (EDTA) ו הידרזין בטמפרטורות גבוהות, 5 תנאים עצמם לא יכולים להיות מתאימים כמה שרשרת בצד הגנה על קבוצות כגון phthalimides. <img alt="איור 1" src="/files/ftp_upload/55677/55677fig1.jpg" /> איור 1: סינתזה של Ni-PBP-גלאי מ Ni 2+, PBP, ו גליצין (גלאי). <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/55677/55677fig1large.jpg" target="_blank">אנא לחץ כאן כדי להציג גרסה גדולה יותר של דמות זו.</a> </<html> a&gt; בזאת, אנו מדווחים על שיטה הידרוליזה של קומפלקס Ni-שיף-בסיס, Ni-PBP-גלאי (איור 1). מורכבות זו, נגזרת Ni 2+, גליצין, וחומצה קרבוקסילית-פירידין-2 (2-בנזואיל-פניל) -amide (PBP), 6 הודגמה להיות פלטפורמה שימושית עבור סינתזה של מגוון UAA של והוא בקלות נגיש באמצעות מסלול סינטטי שני שלבים. סינתזה 7 של מורכבות זו היא-precedented ספרות בתשואה גבוהה. 6 התוצאות שלנו מפורטות להלן להדגים את תחולת התנאים הידרוליזה ניצול EDTA ב במתינות חומצי לתנאי pH ניטראליים המתאים לשימוש עם הגנה על קבוצות השרשרת בצד החומצה-יציבה בעמידתו של UAA. בעקבות הידרוליזה, הפתרון מימי וכתוצאה אפשר לבודד נתון מייד לתנאי הגנת Fmoc תקן להרשות חומצת אמינו-מוגנת Fmoc (איור 2). o: לשמור-together.within-page = &quot;1&quot;&gt; <img alt="איור 2" src="/files/ftp_upload/55677/55677fig2.jpg" /> איור 2: הידרוליזה Fmoc-הגנה של חומצת אמינו מבודדת מן Ni-PBP-גלאי. תנאי תגובה: i. EDTA (12 equiv), pH 4.5; ii. אתיל אצטט לשטוף וכוונון ל- pH 7; iii. Fmoc-אוס (1 equiv), NaHCO 3 (2 equiv). <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/55677/55677fig2large.jpg" target="_blank">אנא לחץ כאן כדי להציג גרסה גדולה יותר של דמות זו.</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

חומצות אמינו לא טבעיות, חומצות אמינו המכילות פונקציות שרשרת צד לא נראות לרוב בטבע, נמצאות יותר ויותר רצפים פפטיד סינטטיים. סינתזה של כמה חומצות אמינו לא טבעיות כוללת בדרך כלל את השימוש מבשר מורכב שייף-בסיס התייצב ידי קטיון ניקל. ניתן להתקין בצד שרשראות טבעי על עמוד השדרה חומצת אמינו הנמצאת במתחם שיף-בסיס זה. חומצת האמינו טבעי וכתוצאה מכך יכול להיות מבודד אז הידרוליזה באמצעות מורכבות זו של בסיס שיף, בדרך כלל על ידי העסקת ריפלוקס בתמיסה חומצית מאוד. תנאים חומציים ביותר אלה עשויים להסיר שרשרת הצד רָפִיף-חומצה הגנה על קבוצות הכרחי חומצות אמינו לא טבעיות כדי לשמש סינתזה פפטיד מוצק שלב מיקרוגל בסיוע. בעבודה זו, אנו מציגים הידרוליזה יעיל והגנה Fmoc הבאות של חומצת אמינו מבודדת מתסביך בסיס Ni-שיף. תנאים הידרוליזה שהוצגו בעבודה זו מתאימים שמירה של ים חומצה-רָפִיףIDE-שרשרת הגנה על קבוצות ועשויות להיות להתאמה למגוון של מצעי חומצות אמינו לא טבעיים.

החוקרים שיערו כי הסרת Ni 2+ מהמתחם Ni-PBP-גלאי עלולה לאפשר הידרוליזה מימית יעיל של בסיס שיף ללא צורך בתנאים קשים pH. כמו EDTA הוא סוכן chelating זול היטב למד, 10 שיערנו כי תוספת של EDTA לפתרון של Ni-PBP-גלאי יקל קלאציה של יוני Ni 2+, ובכך לקדם הידרו...

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

כאן, אנו מציגים הידרוליזה יעיל והגנה Fmoc הבאות של חומצת אמינו מבודדת מתסביך Ni-שיף-בסיס. תנאים הידרוליזה שהוצגו כאן מתאימים לשימוש כאשר השמירה של קבוצות הגנה חומצה-רָפִיף בצד שרשרת נדרשת. טכניקה זו עשויה להיות להתאמה למגוון של מצעי חומצות אמינו לא טבעיים.

הידרוליזה של תנאי Ni-שיף-Base מורכבים באמצעות מתאים שמירת חומצה-רָפִיף קבוצות הגנה

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

Universidad San Sebastian

Research

JoVE Journal

Biochemistry

9.6K Views.  Slippery Rock University.  כאן, אנו מציגים הידרוליזה יעיל והגנה Fmoc הבאות של חומצת אמינו מבודדת מתסביך Ni-שיף-בסיס. תנאים הידרוליזה שהוצגו כאן מתאימים לשימוש כאשר השמירה של קבוצות הגנה חומצה-רָפִיף בצד שרשרת נדרשת. טכניקה זו עשויה להיות להתאמה למגוון של מצעי חומצות אמ?...

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.

גישה קלילה ויעילה לייצור ההפיך דיסולפיד צולב Micelles

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.

פרידה של Aldehydes, קטונים תגובתי תערובות באמצעות פרוטוקול החילוץ ביסולפאט

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 מטאפיתזה על ידי הזרזים התומכים בסיליקה באמצעות מתודולוגיה של כימיה אורגנומתכתית של פני השטח

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.

הכנת SNS קובלט (II) מכלולי מודל מודלים של הכבד אלכוהול דהידרוגנאז

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

הגנה על אלכוהולים

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;" />

הכנת חומצות קרבוקסיליות: הידרוליזה של ניטרילים

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.

חומצה הלידים לחומצות קרבוקסיליות: הידרוליזה

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.

קבוצות הגנה על אלדהידים וקטונים: מבוא

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;" />

אצטלים ותיואצטלים כקבוצות הגנה על אלדהידים וקטונים

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;" />

אמידים לחומצות קרבוקסיליות: הידרוליזה

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