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.

<ol>
	<li>Kamal, A., Reddy, K. L., Devaiah, V., Shankaraiah, N., Rao, M. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+Advances+in+the+Solid-Phase+Combinatorial+Synthetic+Strategies+for+the+Quinoxaline,+Quinazoline+and+Benzimidazole+Based+Privileged+Structures.">Recent Advances in the Solid-Phase Combinatorial Synthetic Strategies for the Quinoxaline, Quinazoline and Benzimidazole Based Privileged Structures.</a> Mini-Rev. Med. Chem. 6 (1), 71-89 (2006).</li><li>Spirkova, K., Stankovsky, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Some+Tricyclic+Annelated+Quinazolines.">Some Tricyclic Annelated Quinazolines.</a> Khim. Geterotsikl. Soedin. (10), 1388-1389 (1995).</li><li>Connolly, D. J., Cusack, D., O'Sullivan, T. P., Guiry, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Quinazolinones+and+Quinazolines.">Synthesis of Quinazolinones and Quinazolines.</a> Tetrahedron. 61 (43), 10153-10202 (2005).</li><li>Baba, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+on+Disease-Modifying+Antirheumatic+Drugs:+Synthesis+of+Novel+Quinoline+and+Quinazoline+Derivatives+and+Their+Anti-Inflammatory+Effect.">Studies on Disease-Modifying Antirheumatic Drugs: Synthesis of Novel Quinoline and Quinazoline Derivatives and Their Anti-Inflammatory Effect.</a> J. Med. Chem. 39 (26), 5176-5182 (1996).</li><li>Gama, Y., Shibuya, I., Simizu, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+and+Efficient+Synthesis+of+4-Dimethylamino-2-Glycosylaminoquinazolines+by+Cyclodesulfurization+of+Glycosyl+Thioureas+with+Dimethylcyanamide.">Novel and Efficient Synthesis of 4-Dimethylamino-2-Glycosylaminoquinazolines by Cyclodesulfurization of Glycosyl Thioureas with Dimethylcyanamide.</a> Chem. Pharm. Bull. 50 (11), 1517-1519 (2002).</li><li>Wakeling, A. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Specific+Inhibition+of+Epidermal+Growth+Factor+Receptor+Tyrosine+Kinase+by+4-Anilinoquinazolines.">Specific Inhibition of Epidermal Growth Factor Receptor Tyrosine Kinase by 4-Anilinoquinazolines.</a> Breast Cancer Res Treat. 38 (1), 67-73 (1996).</li><li>Verhaeghe, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+Antiplasmodial+Activity+of+New+4-Aryl-2-Trichloromethylquinazolines.">Synthesis and Antiplasmodial Activity of New 4-Aryl-2-Trichloromethylquinazolines.</a> Bioorg. Med. Chem. Lett. 18 (1), 396-401 (2008).</li><li>Kitano, Y., Suzuki, T., Kawahara, E., Yamazaki, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+Inhibitory+Activity+of+4-Alkynyl+and+4-Alkenylquinazolines:+Identification+of+New+Scaffolds+for+Potent+Egfr+Tyrosine+Kinase+Inhibitors.">Synthesis and Inhibitory Activity of 4-Alkynyl and 4-Alkenylquinazolines: Identification of New Scaffolds for Potent Egfr Tyrosine Kinase Inhibitors.</a> Bioorg. Med. Chem. Lett. 17 (21), 5863-5867 (2007).</li><li>Goel, R. K., Kumar, V., Mahajan, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quinazolines+Revisited:+Search+for+Novel+Anxiolytic+and+Gabaergic+Agents.">Quinazolines Revisited: Search for Novel Anxiolytic and Gabaergic Agents.</a> Bioorg. Med. Chem. Lett. 15 (8), 2145-2148 (2005).</li><li>Parhi, A. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antibacterial+Activity+of+Quinoxalines,+Quinazolines,+and+1,5-Naphthyridines.">Antibacterial Activity of Quinoxalines, Quinazolines, and 1,5-Naphthyridines.</a> Bioorg. Med. Chem. Lett. 23 (17), 4968-4974 (2013).</li><li>Brown, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Chemistry of Heterocyclic Compounds, Volume 55: Quinazolines, Supplement I. , (1996).</li><li>Yang, C. -. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Color+Tuning+of+Iridium+Complexes+for+Organic+Light-Emitting+Diodes:+The+Electronegative+Effect+and+-Conjugation+Effect.">Color Tuning of Iridium Complexes for Organic Light-Emitting Diodes: The Electronegative Effect and -Conjugation Effect.</a> J. Organomet. Chem. 691 (12), 2767-2773 (2006).</li><li>Byford, A., Goadby, P., Hooper, M., Kamath, H. V., Kulkarni, S. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=O-Aminophenyl+Alkyl/Aralkyl+Ketones+and+Their+Derivatives.+Part+V.+An+Efficient+Synthetic+Route+to+Some+Biologically+Active+4-Substituted+Quinazolines.">O-Aminophenyl Alkyl/Aralkyl Ketones and Their Derivatives. Part V. An Efficient Synthetic Route to Some Biologically Active 4-Substituted Quinazolines.</a> Ind. J. Chem. 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. D., Eilander, J., Yoshida, M., Wang, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanistic+Study+of+a+Complementary+Reaction+System+That+Easily+Affords+Quinazoline+and+Perimidine+Derivatives.">Mechanistic Study of a Complementary Reaction System That Easily Affords Quinazoline and Perimidine Derivatives.</a> Eur. J. Org. Chem. (34), 7664-7674 (2014).</li><li>Wang, D. Z., Yoshida, M., George, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Theoretical+Study+on+the+Thermal+Decomposition+of+Thiourea.">Theoretical Study on the Thermal Decomposition of Thiourea.</a> Comput. Theoret. Chem. 1017, 91-98 (2013).</li><li>Zhang, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibitory+Effect+of+Hydrogen+Sulfide+on+Ozone-Induced+Airway+Inflammation,+Oxidative+Stress,+and+Bronchial+Hyperresponsiveness.">Inhibitory Effect of Hydrogen Sulfide on Ozone-Induced Airway Inflammation, Oxidative Stress, and Bronchial Hyperresponsiveness.</a> Am. J. Respir. Cell Mol. Biol. 52 (1), 129-137 (2015).</li><li>Yan, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-Pot+Synthesis+of+Cdxzn1-Xs-Reduced+Graphene+Oxide+Nanocomposites+with+Improved+Photoelectrochemical+Performance+for+Selective+Determination+of+Cu2+.">One-Pot Synthesis of Cdxzn1-Xs-Reduced Graphene Oxide Nanocomposites with Improved Photoelectrochemical Performance for Selective Determination of Cu2+.</a> RSC Adv. 3 (34), 14451-14457 (2013).</li><li>Keith, J. D., Pacey, G. E., Cotruvo, J. A., Gordon, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+Results+from+the+Reaction+of+Bromate+Ion+with+Synthetic+and+Real+Gastric+Juices.">Experimental Results from the Reaction of Bromate Ion with Synthetic and Real Gastric Juices.</a> Toxicology. 221 (2-3), 225-228 (2006).</li><li>Timchenko, V. P., Novozhilov, A. L., Slepysheva, O. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinetics+of+Thermal+Decomposition+of+Thiourea.">Kinetics of Thermal Decomposition of Thiourea.</a> Russ. J. Gen. Chem. 74 (7), 1046-1050 (2004).</li><li>Wang, S., Gao, Q., Wang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermodynamic+Analysis+of+Decomposition+of+Thiourea+and+Thiourea+Oxides.">Thermodynamic Analysis of Decomposition of Thiourea and Thiourea Oxides.</a> J. Phys. Chem. B. 109 (36), 17281-17289 (2005).</li></ol>

Except for the contents described in patent (pending), the authors have nothing else to disclose.

quinazolines تبديل، كنوع فريد من غير متجانسة، فقد كان معروفا لمجموعة متنوعة من الأنشطة البيولوجية، بما في ذلك المضادات الحيوية، ومضادات الاكتئاب 1، 2 المضادة للالتهابات، 3،4 مكافحة ارتفاع ضغط الدم، 3 المضادة للملاريا و 5 و مكافحة ورمي، 6 من بين أمور أخرى . ما هو quinazolines أكثر، 4 استبداله، على سبيل المثال، 4-أريل-quinazolines، مع النشاط المضادة للبالمتصورات 7 قد تم الاعتراف بها باعتبارها عامل نمو البشرة مستقبلات (EGFR) مثبطات التيروزين كيناز، 8 اكتئاب الجهاز العصبي المركزي و 9 و المضادات الحيوية ضد المكورات العنقودية المقاومة للميثيسيلين الذهبية ومقاومة للفانكومايسين المعوية البرازية. 10 لطيف واسعة من الأنشطة البيولوجية، تم استكشافها إلى حد كبير طرق الاصطناعية لquinazolines استبداله. وكمثال على ذلك، وبالفعل تم الإبلاغ عن أكثر من 25 طرق الاصطناعية لإعداد 4-phenylquinazolines 11 السمعةوتشمل وسائل resentative تشكيل 4-phenylquinazolines من 2 aminobenzophenones والفورماميد بحضور فلوريد البورون etherate (BF 3 · إت 2 O) 12 أو حمض الفورميك، 13 أو من ردود فعل 2-aminobenzophenones مع urotropine وbromoacetate الإيثيل، 14 أو رد الفعل مع ألدهيد وخلات الأمونيوم في وجود عامل مؤكسد. 15 مختلفة من ردود الفعل أعلاه باستخدام الرطوبة كاشف حساس (على سبيل المثال، BF 3 · إت 2 O) أو كاشف مكلفة (على سبيل المثال، urotropine وbromoacetate الإيثيل)، وهي طريقة سطحي التي يمكن بسهولة تحويل 2-aminobenzophenones في المناظرة 4-phenylquinazolines في سلفوكسيد ثنائي ميثيل ( DMSO) في وجود ثيوريا تم استكشافها. وتشير الدراسات الآلية على نطاق واسع على هذا التفاعل أنه هو رد فعل التكميلية التي ثيوريا يخضع التحلل الحراري لتشكيل carbodiimide وكبريتيد الهيدروجين، حيث يتفاعل carbodiimide مع 2-aminobenzophenone لتشكيل 4-phenylquinazolin-2 (1H) -imine المتوسط، بينما يستخدم DMSO ليس فقط كمادة مذيبة، ولكن أيضا كاشف لتوليد الحد كاشف عندما يتفاعل مع الهيدروجين التي تحتوي على الكبريت كبريتيد (الناشئة أيضا من ثيوريا). ثم، والاختزال التي تحتوي على الكبريت يقلل من 4 phenylquinazolin-2 (1H) -imine المتوسط ​​إلى تشكيل 4-فينيل-1،2-dihydroquinazolin-2-أمين أن يخضع القضاء على الأمونيا لتشكيل 4-phenylquinazoline. ويتم هذا التفاعل عادة في درجة حرارة 135-160 درجة مئوية، ويمكن أن يؤديها بسهولة عن طريق التقليدية التدفئة حمام الزيت على موقد أو تحت أشعة الميكروويف. ويتضح هذا التفاعل عموما في الشكل 1 أدناه. <img alt="الشكل 1" src="/files/ftp_upload/53662/53662fig1.jpg" /> الشكل 1: رد الفعل العام بين 2-aminobenzophenone وثيوريا في DMSO. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53662/53662fig1large.jpg" target="_blank">الرجاء انقر هنا لعرض نسخة أكبر من هذا الرقم.</a>

<table border="0" cellpadding="0" cellspacing="0" width="811">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">2-Aminobenzophenone</td>
			<td style="width:95px;">Alfa Aesar</td>
			<td style="width:105px;">A12580</td>
			<td style="width:395px;">98% purity, with tiny impurity as seen on Figure 1(A) in the manuscript.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Thiourea</td>
			<td style="width:95px;">Acros</td>
			<td style="width:105px;">138910010</td>
			<td>1 KG package, 99%, extra pure</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Dimethyl Sulfoxide</td>
			<td style="width:95px;">Acros</td>
			<td style="width:105px;">326880010</td>
			<td>Methyl sulfoxide, 99.7+%, Extra Dry, AcroSeal&#174;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">N,N-Dimethylformamide</td>
			<td style="width:95px;">Acros</td>
			<td style="width:105px;">348430010</td>
			<td>N,N-Dimethylformamide, 99.8%, Extra Dry over Molecular Sieve, AcroSeal&#174;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Ethyl Acetate</td>
			<td style="width:95px;">Acros</td>
			<td style="width:105px;">610170040</td>
			<td>Ethyl acetate, used as solvent for GC/MS analysis</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Preparative TLC plate</td>
			<td style="width:95px;">Sigma-Aldrich</td>
			<td style="width:105px;">Z740216 SIGMA</td>
			<td>PTLC (Preparative TLC) Glass Plates from EMD/Merck KGaA</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Rotavapor</td>
			<td style="width:95px;">Buchi</td>
			<td style="width:105px;">Rotavapor R-205</td>
			<td>Use to dry solvent</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Microwave Reactor</td>
			<td style="width:95px;">Biotage</td>
			<td style="width:105px;">Initiator+</td>
			<td>Use to carry out chemical reaction under microwave irradiation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hotplate</td>
			<td style="width:95px;">IKA</td>
			<td style="width:105px;">RCT basic</td>
			<td>use to carry out thermal chemical reaction</td>
		</tr>
	</tbody>
</table>

facile preparation of 4-substituted quinazoline derivatives

ورد في هذه الورقة هي طريقة بسيطة جدا لإعداد المباشر للمشتقات كينازولين 4 استبداله-من تفاعل بين استبداله 2-aminobenzophenones وثيوريا بحضور سلفوكسيد ثنائي ميثيل ([دمس]). هذا هو نظام رد فعل مكمل الفريد الذي ثيوريا يخضع التحلل الحراري لتشكيل carbodiimide وكبريتيد الهيدروجين، حيث يتفاعل السابقة مع 2-aminobenzophenone لتشكيل 4-phenylquinazolin-2 (1H) -imine المتوسط، في حين كبريتيد الهيدروجين يتفاعل مع DMSO لإعطاء methanethiol أو غيرها من جزيء المحتوية على الكبريت الذي يعمل عندئذ كعامل مختزل مكملة للحد من 4 phenylquinazolin-2 (1H) -imine المتوسط ​​إلى 4-فينيل-1،2-dihydroquinazolin-2-أمين. وفي وقت لاحق، والقضاء على الأمونيا من 4 فينيل 1،2-dihydroquinazolin-2-أمين تتيح استبدال مشتق كينازولين. عادة ما يعطي هذا رد فعل كينازولين مشتق كمنتج واحد الناشئة عن 2-aminobenzophenone كما رصدتها GC / MSتحليل، جنبا إلى جنب مع كمية صغيرة من الجزيئات التي تحتوي على الكبريت مثل كبريتيد ثنائي ميثيل، ميثيل ثالث كبريتيد، وما إلى ذلك رد فعل اكتمال عادة في 4-6 ساعة على 160 درجة مئوية في نطاق ضيق ولكن قد تستمر أكثر من 24 ساعة عندما نفذت في نطاق واسع. وناتج التفاعل يمكن تنقيته بسهولة عن طريق غسله بالماء DMSO تليها اللوني العمود أو رقيقة اللوني طبقة.

، يتم عرض تحليل GC من خليط التفاعل قبل التفاعل 5 ساعة بعد رد الفعل تحت أشعة الميكروويف، و 10 ساعة بعد رد الفعل تحت أشعة الميكروويف في 150 ° C في الشكل 2، والذي يوضح بشكل واضح في عملية رد الفعل هذا أنيق. وترد الأطياف كتلة 2-aminobenzophenone و 4 phenylquinazoline في الشكل (3) والشكل (4)، على التوالي. آلية واضحة للتفاعل بين 2-aminobenzophenone وثيوريا أن الشخص مع معرفة جيدة الكيمياء العضوية قد يظهر في الشكل 5 مسلمة. وعلى سبيل المقارنة، وترصد رد فعل في DMSO على موقد في 160 درجة مئوية مماثل GC / MS كما هو مبين في الشكل (6)، جنبا إلى جنب مع الطيف الكتلي من 4 phenylquinazolin-2 (1H) واحد ثانوي. واستنادا إلى العديد من الحقائق التجريبية، شرحا وافيا لتوليد 4-phenylquinazoline هو موضح في <strong&gt; الشكل (7). وتظهر الأطياف الشامل من ثاني كبريتيد ثنائي ميثيل (MeSSMe) وثالث كبريتيد ثنائي ميثيل (MeSSSMe) في الشكل رقم (8) والرقم 9 على التوالي. ويتضح من المقارنة بين رد الفعل بين 2-aminobenzophenone وثيوريا في DMF وفي DMF ولكن مع كمية صغيرة من DMSO في الشكل 10. على أساس تحليل GC / MS، فمن الواضح تماما أن تحويل ابتداء من المواد إلى المنتج هو الكمي تقريبا (الشكل 2). نظرا لفارق صغير من الوزن الجزيئي بين مواد البداية (على سبيل المثال، 2-aminobenzophenone، MW = 197، الوقت الاحتفاظ = 9.673 دقيقة) والمنتج من مشتقات كينازولين استبداله (على سبيل المثال، 4 phenylquinazoline، MW = 206، الوقت الاحتفاظ = 9.962 min)، ومرات الاحتفاظ البدء المواد والمنتجات على GC متشابهة جدا، ولكن لا يزال للانفصال. أكثر من 10 مختلفة 2-aminobenzophenones يكون النحلن اختبار لهذا التفاعل ويتم الحصول على نتائج مماثلة. 16

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.

إعداد سطحي المشتقات كينازولين 4 تبديل،

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

Nanyang Technological University

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

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.

توليف مشتقات المضادة للفيروسات عن طريق Tetrahydrocarbazole الضوئية وحمض حفز-CH Functionalization عبر الوسيط بيروكسيد (شيبس)

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 ...

Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization

Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and efficient synthesis of well-controlled fluorescent statistical glycopolymers using reversible addition-fragmentation chain-transfer (RAFT)-based polymerization is demonstrated. The synthesis starts with the preparation of &#946;-galactose-containing glycomonomer 2-lactobionamidoethyl methacrylamide obtained by reaction of lactobionolactone and N-(2-aminoethyl) methacrylamide (AEMA). 2-Gluconamidoethyl methacrylamide (GAEMA) is used as a structural analog lacking a terminal &#946;-galactoside. The following RAFT-mediated copolymerization reaction involves three different monomers: N-(2-hydroxyethyl) acrylamide as spacer, AEMA as target for further fluorescence labeling, and the glycomonomers. Tolerant of aqueous systems, the RAFT agent used in the reaction is (4-cyanopentanoic acid)-4-dithiobenzoate. Low dispersities (&#8804;1.32), predictable copolymer compositions, and high reproducibility of the polymerizations were observed among the products. Fluorescent polymers are obtained by modifying the glycopolymers with carboxyfluorescein succinimidyl ester targeting the primary amine functional groups on AEMA. Lectin-binding specificities of the resulting glycopolymers are verified by testing with corresponding agarose beads coated with specific glycoepitope recognizing lectins. Because of the ease of the synthesis, the tight control of the product compositions and the good reproducibility of the reaction, this protocol can be translated towards preparation of other RAFT-based glycopolymers with specific structures and compositions, as desired.

An efficient, three-step synthesis of RAFT-based fluorescent glycopolymers, consisting of glycomonomer preparation, copolymerization, and post-modification, is demonstrated. This protocol can be used to prepare RAFT-based statistical glycopolymers with desired structures.

إعداد سطحي والفعال للGlycopolymers نيون ثلاثي مكون عبر تسيطر عليها RAFT البلمرة

Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and ...

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled (functionalized) CNTs are used as stabilizers to produce Pickering type oil-in-water (O/W) emulsions. Lipids namely, Dimodan U and Phytantriol are used as emulsifiers, which in excess water self-assemble into the bicontinuous cubic Pn3m phase. This highly viscous phase is fragmented into smaller particles using a probe ultrasonicator in presence of conventional surfactant stabilizers or CNTs as done here. Initially, the CNTs (powder form) are dispersed in water followed by further ultrasonication with the molten lipid to form the final emulsion. During this process the CNTs get coated with lipid molecules, which in turn are presumed to surround the lipid droplets to form a particulate emulsion that is stable for months. The average size of CNT-stabilized nanostructured lipid particles is in the submicron range, which compares well with the particles stabilized using conventional surfactants. Small angle X-ray scattering data confirms the retention of the original Pn3m cubic phase in the CNT-stabilized lipid dispersions as compared to the pure lipid phase (bulk state). Blue shift and lowering of the intensities in characteristic G and G&#39; bands of CNTs observed in Raman spectroscopy characterize the interaction between CNT surface and lipid molecules. These results suggest that the interactions between the CNTs and lipids are responsible for their mutual stabilization in aqueous solutions. As the concentrations of CNTs employed for stabilization are very low and lipid molecules are able to functionalize the CNTs, the toxicity of CNTs is expected to be insignificant while their biocompatibility is greatly enhanced. Hence the present approach finds a great potential in various biomedical applications, for instance, for developing hybrid nanocarrier systems for the delivery of multiple functional molecules as in combination therapy or polytherapy.

We report on a smart application of carbon nanotubes for kinetic stabilization of lipid particles that contain self-assembled nanostructures in their cores. The preparation of lipid particles requires rather low concentrations of carbon nanotubes permitting their use in biomedical applications such as drug delivery.

إعداد سطحي من تجميعها الذاتي داخليا الدهن الجسيمات استقرت بواسطة أنابيب الكربون النانوية

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

بروتوكول لتوليف<em&gt; أورثو</em&gt; مشتقات الانيلين -trifluoromethoxylated

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Preparation of Biopolymer Aerogels Using Green Solvents

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers (gelatin, agar, cellulose), only recently have biomasses been recognized as an abundant source of chemically diverse macromolecules for functional aerogel materials. Biopolymer aerogels (pectin, alginate, chitosan, cellulose, etc.) exhibit both specific inheritable functions of starting biopolymers and distinctive features of aerogels (80-99% porosity and specific surface up to 800 m2/g). This synergy of properties makes biopolymer aerogels promising candidates for a wide gamut of applications such as thermal insulation, tissue engineering and regenerative medicine, drug delivery systems, functional foods, catalysts, adsorbents and sensors. This work demonstrates the use of pressurized carbon dioxide (5 MPa) for the ionic cross linking of amidated pectin into hydrogels. Initially a biopolymer/salt dispersion is prepared in water. Under pressurized CO2 conditions, the pH of the biopolymer solution is lowered to 3 which releases the crosslinking cations from the salt to bind with the biopolymer yielding hydrogels. Solvent exchange to ethanol and further supercritical CO2 drying (10 - 12 MPa) yield aerogels. Obtained aerogels are ultra-porous with low density (as low as 0.02 g/cm3), high specific surface area (350 - 500 m2/g) and pore volume (3 - 7 cm3/g for pore sizes less than 150 nm).

A new way for the production of biopolymer-based aerogels by carbon dioxide (CO2) induced gelation is shown. The technique utilizes pressurized carbon dioxide (5 MPa) for the production of biopolymer hydrogels and supercritical CO2 (12 MPa) to convert gels into aerogels. The only solvents needed besides CO2 are water and ethanol.

إعداد BIOPOLYMER Aerogels عن طريق المذيبات الخضراء

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

توليف سطحي من المذيلات تشبه دودة من الضوء المرئي وساطة التشتت البلمرة عن طريق Photoredox محفز

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Self-assembling Morphologies Obtained from Helical Polycarbodiimide Copolymers and Their Triazole Derivatives

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous networks, ribbons, worm-like aggregates, toroidal structures, and spherical particles) is described. These aggregates are morphologically influenced by extensive hydrophobic side chain-side chain interactions of the singular polycarbodiimide strands, as inferred by atomic force microscopy (AFM) and scanning electron microscopy (SEM) techniques. Polycarbodiimide-g-polystyrene copolymers (PS-PCDs) were prepared by a combination of synthetic methods, including coordination-insertion polymerization, copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) &#34;click&#34; chemistry, and atom transfer radical polymerization (ATRP). PS-PCDs were found to form specific toroidal architectures at low concentrations in CHCl3. To determine the influence of a more polar solvent medium (i.e., THF and THF/EtOH) on polymer aggregation behavior, a number of representative PS-PCD composites have been tested to show discrete concentration-dependent spherical particles. These fundamental studies are of practical interest to the development of experimental procedures for desirable architectures by directed self-assembly in thin film. These architectures may be exploited as drug carriers, whereas other morphological findings represent certain interest in the area of novel functional materials.

Here, we present a protocol to prepare and visualize secondary structures (e.g., fibers, toroidal architectures, and nano-spheres) derived from helical polycarbodiimides. The morphology characterized by both atomic force microscopy (AFM) and scanning electron microscopy (SEM) was shown to depend on molecular structure, concentration, and the solvent of choice.

الأشكال التضاريسية الذاتي تجميع تم الحصول عليها من حلزوني Polycarbodiimide البوليمر ومشتقاتها التريازول

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous ...

Facile Preparation of Ultrafine Aluminum Hydroxide Particles with or without Mesoporous MCM-41 in Ambient Environments

An aqueous suspension of nanogibbsite was synthesized via the titration of aluminum aqua acid [Al(H2O)6]3+ with L-arginine to pH 4.6. Since the hydrolysis of aqueous aluminum salts is known to produce a wide array of products with a wide range of size distributions, a variety of state-of-the-art instruments (i.e., 27Al/1H NMR, FTIR, ICP-OES, TEM-EDX, XPS, XRD, and BET) were used to characterize the synthesis products and identification of byproducts. The product, which was comprised of nanoparticles (10-30 nm), was isolated using gel permeation chromatography (GPC) column technique. Fourier transform infrared (FTIR) spectroscopy and powder X-ray diffraction (PXRD) identified the purified material as the gibbsite polymorph of aluminum hydroxide. The addition of inorganic salts (e.g., NaCl) induced electrostatic destabilization of the suspension, thereby agglomerating the nanoparticles to yield Al(OH)3 precipitate with large particle sizes. By utilizing the novel synthetic method described here, Al(OH)3 was partially loaded inside the highly ordered mesoporous framework of MCM-41, with average pore dimensions of 2.7 nm, producing an aluminosilicate material with both octahedral and tetrahedral Al (Oh/Td = 1.4). The total Al content, measured using energy-dispersive X-ray spectrometry (EDX), was 11% w/w with a Si/Al molar ratio of 2.9. A comparison of bulk EDX with surface X-ray photoelectron spectroscopy (XPS) elemental analysis provided insight into the distribution of Al within the aluminosilicate material. Furthermore, a higher ratio of Si/Al was observed on the external surface (3.6) as compared to the bulk (2.9). Approximations of O/Al ratios suggest a higher concentration of Al(O)3 and Al(O)4 groups near the core and external surface, respectively. The newly developed synthesis of Al-MCM-41 yields a relatively high Al content while maintaining the integrity of the ordered silica framework and can be used for applications where hydrated or anhydrous Al2O3 nanoparticles are advantageous.

An ultrafine aluminum hydroxide nanoparticle suspension was prepared via the controlled titration of [Al(H2O)]3+ with L-arginine to pH 4.6 with and without cage-effect confinement within mesoporous channels of MCM-41.

إعداد سهل من الجسيمات هيدروكسيد الألومنيوم متناهية الصغر مع أو بدون ميسوبورووس مسم-41 في البيئات المحيطة

An aqueous suspension of nanogibbsite was synthesized via the titration of aluminum aqua acid [Al(H2O)6]3+ with L-arginine to pH 4.6. Since the hydrolysis ...

Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high atomic and step economy. However, this functionality-directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required, producing a large amount of waste. Due to our interest in novel 1,3-butadiene synthesis, we describe the ruthenium-catalyzed olefination of electron-deficient alkenes using allyl acetate and without external oxidant. The reaction of 2-phenyl acrylamide and allyl acetate was chosen as a model reaction, and the desired diene product was obtained in 80% isolated yield with good stereoselectivity (Z,E/Z,Z = 88:12) under optimal conditions: [Ru(p-cymene) Cl2]2 (3 mol %) and AgSbF6 (20 mol %) in DCE at 110 &#186;C for 16 h. With the optimized catalytic conditions in hand, representative &#945;- and/or &#946;-substituted acrylamides were investigated, and all reacted smoothly, regardless of aliphatic or aromatic groups. Also, differently N-substituted acrylamides have proven to be good substrates. Moreover, we examined the reactivity of different allyl derivatives, suggesting that the chelation of acetate oxygen to the metal is crucial for the catalytic process. Deuterium-labeled experiments were also conducted to investigate the reaction mechanism. Only Z-selective H/D exchanges on acrylamide were observed, indicating a reversible cyclometalation event. In addition, a kinetic isotope effect (KIE) of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic C-H metalation step is probably involved in the rate-determining step.

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

The ruthenium-catalyzed olefination of electron-deficient alkenes with allyl acetate is described here. By using aminocarbonyl as a directing group, this external oxidant-free protocol has high efficiency and good stereo- and regioselectivity, opening a novel synthetic route to (Z,E)-butadiene skeletons.

إعداد فاسيل من (2<em&gt; Z</em&gt; 4<em&gt; E</em&gt;) - ديناميدس من قبل أوليفيناتيون من الكترون ناقصة ألكينس مع أليل خلات

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high ...

Preparation and Characterization of C60/Graphene Hybrid Nanostructures

Physical thermal deposition in a high vacuum environment is a clean and controllable method for fabricating novel molecular nanostructures on graphene. We present methods for depositing and passively manipulating C60 molecules on rippled graphene that advance the pursuit of realizing applications involving 1D C60/graphene hybrid structures. The techniques applied in this exposition are geared towards high vacuum systems with preparation areas capable of supporting molecular deposition as well as thermal annealing of the samples. We focus on C60 deposition at low pressure using a homemade Knudsen cell connected to a scanning tunneling microscopy (STM) system. The number of molecules deposited is regulated by controlling the temperature of the Knudsen cell and the deposition time. One-dimensional (1D) C60 chain structures with widths of two to three molecules can be prepared via tuning of the experimental conditions. The surface mobility of the C60 molecules increases with annealing temperature allowing them to move within the periodic potential of the rippled graphene. Using this mechanism, it is possible to control the transition of 1D C60 chain structures to a hexagonal close packed quasi-1D stripe structure.

Preparation and Characterization of C60/Graphene Hybrid Nanostructures

Here we present a protocol for the fabrication of C60/graphene hybrid nanostructures by physical thermal evaporation. Particularly, the proper manipulation of deposition and annealing conditions allow the control over the creation of 1D and quasi 1D C60 structures on rippled graphene.

إعداد وتوصيف ج60/Graphene الهجين النانو

Physical thermal deposition in a high vacuum environment is a clean and controllable method for fabricating novel molecular nanostructures on graphene. We ...