Name: facile preparation of 4-substituted quinazoline derivatives
Uploaded: 2016-02-15T14:00:00.000+00:00
Duration: 11 min 51 s
Description: Watch this Scientific Journal Video about Facile Preparation of 4-Substituted Quinazoline Derivatives at JoVE.com

The financial support from the National Science Foundation (NSF, grant number 0958901), the Robert Welch Foundation (Welch departmental grant BC-0022 and the Principal Investigator grant BC-1586), and the University of Houston-Clear Lake (FRSF grant) are greatly appreciated.

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B. 27 (4), 396-397 (1988).</li><li>Blazevic, N., Oklobdzija, M., Sunjic, V., Kajfez, F., Kolbah, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+Ring+Closures+of+Quinazoline+Derivatives+by+Hexamine.">New Ring Closures of Quinazoline Derivatives by Hexamine.</a> Acta Pharmaceut. Jugo. 25 (4), 223-230 (1975).</li><li>Panja, S. K., Saha, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recyclable,+Magnetic+Ionic+Liquid+Bmim[Fecl4]-Catalyzed,+Multicomponent,+Solvent-Free,+Green+Synthesis+of+Quinazolines.">Recyclable, Magnetic Ionic Liquid Bmim[Fecl4]-Catalyzed, Multicomponent, Solvent-Free, Green Synthesis of Quinazolines.</a> RSC Adv. 3 (34), 14495-14500 (2013).</li><li>Wang, Z. 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Except for the contents described in patent (pending), the authors have nothing else to disclose.

תגובה נקיה זה (כפי שמוצג באיור 2) מופיע מסקרן מאוד לתחילה כמו משקל המולקולרי של המוצר הוא גדל רק ב -9 ביחס לזה של חומר מוצא (כפי שמוצג באיור 3 ו איור 4). זה נשמע בלתי אפשרי בגלל המשקל האטומי של הפחמן הוא 12. סבירות מאוד, כניסתה של ...

Quinazolines להחליף, כסוג ייחודי של heterocycles, כבר ידוע עבור מגוון רחב של פעילויות ביולוגיות, כולל אנטיביוטיקה, 1 נגד דיכאון, 2 אנטי דלקתיות, 3,4 נגד מלריה נגד יתר לחץ דם, 3, 5 ו אנטי tumoral, 6 בין היתר . יתרה מזאת,-להחליף 4 quinazolines, למשל, 4-aryl-quinazolines, בעלי פעילות אנטי-plasmodial 7 הוכרו מעכבי טירוזין קינאז הקולטן לגורם הגדילה באפידרמיס (EGFR), 8 דיכאון CNS, 9 ואנטיביוטיקה נגד Staphylococcus methicillin עמידים aureus ו faecalis אנטרוקוקוס עמיד vancomycin. 10 בגלל הספקטרום הרחב של פעילויות ביולוגיות, שיטות סינטטיות עבור quinazolines להחליף נחקרו במידה רבה. כדוגמא, יותר מ -25 שיטות סינטטיות כבר דווחו לעריכה 4-phenylquinazolines. 11 נציגיםשיטות resentative כוללים היווצרות של 4-phenylquinazolines מ 2-aminobenzophenones ואת לפוראמיד בנוכחות etherate trifluoride בורון (BF 3 · Et 2 O) 12 או חומצה פורמית, 13 או מן התגובה של 2-aminobenzophenones עם urotropine אתיל bromoacetate, 14 או התגובה עם אלדהיד ו אמוניום אצטט בנוכחות סוכן חמצון. 15 שונה מן התגובות שלעיל באמצעות ריאגנט לחות רגיש (למשל, BF 3 · Et 2 O) או מגיב יקר (למשל, urotropine אתיל bromoacetate), שיטה קליל שיכול להמיר 2-aminobenzophenones בקלות לתוך המקביל 4-phenylquinazolines ב sulfoxide דימתיל ( DMSO) בנוכחות של thiourea נחקר. בהרחבה מחקרים מכניסטית על תגובה זו עולה כי היא תגובה משלימה שבו thiourea עובר פירוק תרמי לגבש carbodiimide ומימן גופרתי, שבו carbodiimide מגיב עם 2-aminobenzophenone לטופס 4-phenylquinazolin-2 (1H) -imine ביניים, תוך DMSO משמש לא רק כממיס, אלא גם מגיב לייצר המכילים גופרית צמצום מגיב כאשר הוא מגיב עם המימן גופרי (גם הנובעים thiourea). לאחר מכן, סוכני צמצום המכילים גופרית להפחית את 4-phenylquinazolin-2 (1H) -imine ביניים כדי ליצור 4-פניל-1,2-dihydroquinazolin-2-אמין כי עובר חיסול של אמוניה כדי ליצור 4-phenylquinazoline. התגובה זו מתבצעת בדרך כלל על טמפרטורה מ 135-160 מעלות צלזיוס, והוא יכול להתבצע בקלות על ידי אמצעי חימום אמבט שמנים מסורתי על פלטה חשמלית או תחת קרינת מיקרוגל. תגובה זו באה לידי ביטוי בדרך כלל באיור 1 להלן. <img alt="איור 1" src="/files/ftp_upload/53662/53662fig1.jpg" /> איור 1: תגובה כללית בין 2-aminobenzophenone וthiourea ב DMSO. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53662/53662fig1large.jpg" target="_blank">אנא לחץ כאן כדי לצפות בגרסה גדולה יותר של דמות זו.</a>

<table><tbody><tr><td>2-Aminobenzophenone</td><td>Alfa Aesar</td><td>A12580</td><td>98% purity, with tiny impurity as seen on &lt;strong&gt;Figure 1(A)&lt;/strong&gt; in the manuscript.</td></tr><tr><td>Thiourea</td><td>Acros</td><td>138910010</td><td>1 kg package, 99%, extra pure</td></tr><tr><td>Dimethyl Sulfoxide</td><td>Acros</td><td>326880010</td><td>Methyl sulfoxide, 99.7+%, Extra Dry, AcroSeal&amp;reg;</td></tr><tr><td>&lt;em&gt;N,N&lt;/em&gt;-Dimethylformamide</td><td>Acros</td><td>348430010</td><td>&lt;em&gt;N,N&lt;/em&gt;-Dimethylformamide, 99.8%, Extra Dry over Molecular Sieve, AcroSeal&amp;reg;</td></tr><tr><td>Ethyl Acetate</td><td>Acros</td><td>610170040</td><td>Ethyl acetate, used as solvent for GC/MS analysis</td></tr><tr><td>Preparative TLC plate</td><td>Sigma-Aldrich</td><td>Z740216 SIGMA</td><td>PTLC (Preparative TLC) Glass Plates from EMD/Merck KGaA</td></tr><tr><td>Rotavapor</td><td>Buchi</td><td>Rotavapor R-205</td><td>Use to dry solvent</td></tr><tr><td>Microwave Reactor</td><td>Biotage</td><td>Initiator+</td><td>Use to carry out chemical reaction under microwave irradiation</td></tr><tr><td>Hotplate</td><td>IKA</td><td>RCT basic</td><td>use to carry out thermal chemical reaction</td></tr></tbody></table>

facile preparation of 4-substituted quinazoline derivatives

מדווחים במאמר זה היא שיטה פשוטה מאוד להכנה ישירה נגזרים quinazoline 4-להחליף מתגובה בין להחליף 2-aminobenzophenones ו thiourea בנוכחות sulfoxide דימתיל (DMSO). זוהי מערכת התגובה משלימים ייחודי שבו thiourea עובר פירוק תרמי לגבש carbodiimide ומימן גופרי, שבו מגיב לשעבר עם 2-aminobenzophenone לטופס 4-phenylquinazolin-2 (1H) -imine ביניים, תוך מימן גופרתי מגיב עם DMSO לתת מתאנתיול או מולקולה המכילה גופרית אחרת אשר לאחר מכן מתפקד בתור סוכן הפחתה משלים להפחית 4-phenylquinazolin-2 (1H) -imine ביניים לתוך 4-פניל-1,2-dihydroquinazolin-2-אמין. בהמשך לכך, חיסול אמוניה 4-פניל-1,2-dihydroquinazolin-2-אמין מקנה להחליף נגזרת quinazoline. תגובה זו בדרך כלל נותן quinazoline נגזרת כמוצר יחיד הנובעים-aminobenzophenone 2 כמו פיקוח על ידי GC / MSניתוח, יחד עם כמות קטנה של מולקולות המכילות גופרית כגון דיסולפיד דימתיל, דימתיל trisulfide, וכו התגובה כלל משלים ב 4-6 שעות ב 160 מעלות צלזיוס ב בקנה מידה קטן, אך עשוי להימשך יותר מ -24 שעות כאשר הן מבוצעות בקנה מידה גדול. מוצר התגובה יכול להיות מטוהרים בקלות באמצעות לשטוף מעליו DMSO עם מים ואחריו כרומטוגרפיה עמודה או כרומטוגרפיה בשכבה דקה.

ניתוח GC של תערובת תגובה לפני התגובה, 5 שעות לאחר התגובה תחת קרינת מיקרוגל, ו -10 שעות לאחר התגובה תחת קרינת מיקרוגל ב 150 מעלות צלזיוס מוצגים באיור 2, אשר ממחישה היטב את תהליך התגובה מסודר זה. ספקטרה ההמונית של 2-aminobenzophenone ו -4-phenylquinazoline <str...

Watch this Scientific Journal Video about Facile Preparation of 4-Substituted Quinazoline Derivatives at JoVE.com

Facile Preparation of 4-Substituted Quinazoline Derivatives

A protocol for facile preparation of 4-substituted quinazoline derivatives from 2-aminobenzophenones, thiourea and dimethyl sulfoxide is presented.

הכנה קלילה של נגזרי Quinazoline 4-הוחלפו

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted ...

facile-preparation-of-4-substituted-quinazoline-derivatives

Universidad San Sebastian

Research

JoVE Journal

Chemistry

11.8K Views.  University of Houston-Clear Lake. A protocol for facile preparation of 4-substituted quinazoline derivatives from 2-aminobenzophenones, thiourea and dimethyl sulfoxide is presented.

Video: Facile Preparation of 4-Substituted Quinazoline Derivatives

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

שינויו Functionalization של קבוצת guanidine ידי מבשרי תפורות

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

Biochemistry

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

סינתזה של נגזרות אנטי Tetrahydrocarbazole ידי פוטו וFunctionalization CH זרז חומצה באמצעות חמצניים ביניים (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

הכנת N-(2-alkoxyvinyl) sulfonamides N- tosyl-1,2,3-triazoles, הבאים ההמרה ל שהוחלפו Phthalans ו- Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

הכנת יציב Aziridinium Bicyclic יונים, פתיחת הטבעת שלהם לסינתזה של Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

A convenient synthetic route for spirocyclic heterocycles is well sought after due to the molecule&#39;s potential use in biological systems. By means of solid-phase synthesis, regenerating Michael (REM) linker strategies, and 1,3-dipolar cycloaddition, a library of structurally similar heterocycles, both with and without a spirocyclic center, can be constructed. The main advantages of the solid-support synthesis are as follows: first, each reaction step can be driven to completion using a large excess of reagents resulting in high yields; next, the use of commercially available starting materials and reagents keep the costs low; finally, the reaction steps are easy to purify via simple filtration. The REM linker strategy is attractive because of its recyclability and traceless nature. Once a reaction scheme is completed, the linker can be reused multiple times. In a typical solid-phase synthesis, the product contains either a part of or the whole linker, which can prove undesirable. The REM linker is &#34;traceless&#34; and the point of attachment between the product and the polymer is indistinguishable. The high diastereoselectivity of the intramolecular 1,3-dipolar cycloaddition is well documented. Limited by the insolubility of the solid support, the reaction progression can only be monitored by a change in the functional groups (if any) via infrared (IR) spectroscopy. Thus, the structural identification of intermediates cannot be characterized by conventional nuclear magnetic resonance (NMR) spectroscopy. Other limitations to this method stem from the compatibilities of the polymer/linker to the desired chemical reaction scheme. Herein we report a protocol that allows for the convenient production of spirocyclic heterocycles that, with simple modifications, can be automated with high-throughput techniques.

Here we present a protocol to demonstrate an efficient method for the synthesis of spirocyclic heterocycles. The five-step process utilizes solid-phase synthesis and regenerating Michael linker strategies. Generally difficult to synthesize, we present a customizable method for the synthesis of spirocyclic molecules otherwise inaccessible to other modern approaches.

מוצק-שלב הסינתזה של Oximes Spirocyclic [4.4]

A convenient synthetic route for spirocyclic heterocycles is well sought after due to the molecule&#39;s potential use in biological systems. By means of ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

סינתזה יעילה של מרכזי הפחמן הדו הדו באמצעות התוספת המשלים של מונואורגאורומטוזיס

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it efficient in both time and resources and utilizes water as the solvent. 3-Aminocrotononitrile or an appropriate &#945;-cyanoketone is combined with an aryl hydrazine and dissolved in 1 M HCl. The mixture is then heated in a microwave reactor at 150 &#176;C, typically for 10-15 min. The product can be readily obtained by basifying the solution with 10% NaOH and isolating the desired compound with a simple vacuum filtration. The use of water as a solvent in this reaction lends to its ease and utility in production, and this method is easily reproducible with a variety of functional groups. Typical isolated yields range from 70-90%, and reactions can be performed on the milligram to gram scale with little to no change in observed yields. Some of the applications of these molecules and their derivatives include pesticides, anti-malarials, and chemotherapeutics, among many others.

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

1-Aryl-1H-pyrazole-5-amines are prepared from aryl hydrazines combined with either 3-aminocrotononitrile or an &#945;-cyanoketone in a 1 M HCl solution using a microwave reactor. Most reactions are done in 10-15 minutes and pure product can be obtained via vacuum filtration with typical isolated yields of 70-90%.

הכנת בעזרת מיקרוגל של 1-Aryl-1H-קורטידול-5-amines

A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it ...

Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.

New routes for the synthesis of nitrogen-containing heterocycles utilizing cercosporin as a metal-free photocatalyst were developed.

צרקוספורין-פוטוזרז [4 + 1]-ו [4 + 2]-אוספים שנתיים של האזובחות בתנאים מתונים

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. ...

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of functionalized nitrogen-containing target compounds through the regiocontrolled ring-opening of C-substituted aziridines. Despite the tremendous progress in aziridine synthesis over the past decade, accessing contiguous bisaziridines efficiently remains difficult. Therefore, we were interested in synthesizing contiguous bisaziridines bearing an electronically diverse set of N-substituents beyond the single aziridine backbone for regioselective ring-opening reactions with diverse nucleophiles. In this study, chiral contiguous bisaziridines were prepared by organocatalytic asymmetric aziridination of chiral (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde with N-Ts-O-tosyl or N-Boc-O-tosyl hydroxylamine as the nitrogen source in the presence of (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as a chiral organocatalyst. Also demonstrated here are representative examples of regioselective ring-opening reactions of contiguous bisaziridines with a variety of nucleophiles such as sulfur, nitrogen, carbon, and oxygen, and the application of contiguous bisaziridines to the synthesis of multi-substituted chiral pyrrolidines by Pd-catalyzed hydrogenation.

Contiguous bisaziridines containing non-activated and activated aziridines were synthesized by asymmetric organocatalytic aziridinations and then subjected to chemoselective ring-opening reactions under acidic or basic conditions. The non-activated aziridine ring opens with less reactive nucleophiles under acidic conditions, whereas the activated aziridine ring opens with more reactive nucleophiles under basic conditions.

הכנת ביסאזירידינים רציפים לתגובות פתיחת טבעת רגיוזלקטיביות

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of ...

<meta charset="utf8"></head><body>סינתזה של נוזלים יוניים מבוססי קינולין ליישומים אנטי-מיקרוביאליים

Green Synthesis of Quinoline-Based Ionic Liquid

The ever-growing menace of Antimicrobial Resistance (AMR) jeopardizes the potency of the prevailing antibiotics against the relentlessly sprouting infections spawned by bacteria, viruses, parasites as well as fungi, posing a great threat to human health and well-being. In this regard, several novel molecules have proved their mettle, with Ionic Liquids (ILs) being one of the most eco-friendly, non-volatile, and thermally stable alternatives to the existing antimicrobials, possessing high solvating potential as well as low vapor pressure. Moreover, the utilization of these entities in both stabilizing as well as destabilizing protein structures and enhancing enzymatic activity has further raised their potential in the biomedical industry. With this in view, we present the green synthesis and characterization of quinoline-based IL, owing to its immense antimicrobial potency, with low cytotoxicity and great artificial chaperone activity. Here, maneuvering the one-pot synthesis approach in solvent-free, greener reaction conditions not only ameliorated the reaction efficiency but also augmented the chemical yield. The purity of the synthesized IL was corroborated using 1H Nuclear Magnetic Resonance (NMR), 13C NMR, and Infrared (IR) spectroscopy. The biological potential of the synthesized compound is further validated by analyzing its Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties and authenticated using disc diffusion assay.

<meta charset="utf8"></head><body>מחבר זרקור: קידום מחקר עמידות מיקרוביאלית עם גישות חדשניות ותרכובות סינתטיות

In the present work, we elucidate the green synthesis of quinoline-based Ionic Liquid (IL), namely, 1-Hexadecylquinolin-1-ium bromide {[C16quin]Br} by mixing quinoline with an excess of 1-Bromohexadecane, along with its detailed characterization using Nuclear Magnetic Resonance and Infrared spectroscopic measurements.