ونحن نعترف أموال لبدء سخية من جامعة ولاية نيويورك في ستوني بروك في دعم هذا العمل. كما نشكر TOSOH F-تك، شركة لتزويدنا TMSCF 3 كاشف لتركيب Togni الكاشف الثاني.

1. السلائف التحضير: توليف الميثيل 4- (N -hydroxyacetamido) بنزوات (1A) <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> تخفيض الميثيل 4-nitrobenzoate. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إضافة 5.00 غرام من الميثيل 4-nitrobenzoate (27.6 مليمول، 1.00 EQUIV)، 159 ملغ من 5٪ الروديوم على الكربون (ره / C، 0.300 مول ره٪)، والمغناطيسي ضجة بار إلى المجفف فرن 250 مل سنتين جولة الرقبة من أسفل القارورة (المجففة على 150 درجة مئوية لمدة 18 ساعة). يمكن أن يكون وزنه الكواشف تحت الغلاف الجوي المحيط: ملاحظة. ومع ذلك، يحتاج رد فعل التي يتعين الاضطلاع بها في جو من النيتروجين. </li><li style=";text-align:right;direction:rtl"> ربط العنق واحدة من القارورة إلى النيتروجين / فراغ متعددة ولحد الرقبة أخرى مع الحاجز. تنفيذ ثلاث دورات فراغ عبوة (أي ضخ الهواء من القارورة واستبدال ينتج عن ذلك من فراغ مع غاز النيتروجين) ليحل محل الهواء في قارورة مع غاز النيتروجين. </li><li style=";text-align:right;direction:rtl"> إضافة 138 مل رباعي هيدرو الفوران اللامائية (THF، 0.200 M) إلى دورق التفاعل باستخدام حقنة محكم. بارد ويحرك mixt رد فعللدى عودتهم إلى 0 درجة مئوية لمدة 15 دقيقة. </li><li style=";text-align:right;direction:rtl"> إضافة 1.47 مل من الهيدرات الهيدرازين (1.52 غرام، 30،4 مليمول، 1.20 EQUIV) قطرة قطرة إلى خليط التفاعل عند 0 درجة مئوية باستخدام حقنة محكم. رصد رد فعل باستخدام اللوني طبقة رقيقة (TLC). استخدام hexanes: خلات الإيثيل (EtOAc) (4: 1 ت / ت، و R = 0.23) باعتبارها شاطف لتطوير TLC. </li><li style=";text-align:right;direction:rtl"> عندما يتم استهلاك الميثيل 4-nitrobenzoate تماما، تصفية خليط التفاعل من خلال لوحة قصيرة من الأرض دياتومي (أي Celite، 5 غ) في 60 مل فريت بوخنر قمع باستخدام الترشيح فراغ. غسل فلتر مع EtOAc (20 مل × 3 مرات). تركيز الراشح في الخلاء باستخدام المبخر الدوار على تحمل الميثيل الخام 4- (N -hydroxyamino) بنزوات، والذي يستخدم مباشرة دون مزيد من التنقية. </li></ol></li><li style=";text-align:right;direction:rtl"> حماية الاسيتيل من الميثيل 4- (N -hydroxyamino) بنزوات <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إضافة 2.55 غرام من بيكربونات الصوديوم (NaHCO 3، 30.4 مليمول، 1.20 EQUIV)، كل النفط الخام4- الميثيل (N -hydroxyamino) بنزوات تم الحصول عليها من الخطوة السابقة، وعلى بقضيب إلى 500 مل يومين جولة الرقبة من أسفل القارورة المجفف الفرن. </li><li style=";text-align:right;direction:rtl"> سقف واحد الرقبة مع الحاجز وربط العنق أخرى لمشعب النيتروجين / فراغ. تنفيذ ثلاث دورات فراغ عبوة ليحل محل الهواء في قارورة مع غاز النيتروجين. </li><li style=";text-align:right;direction:rtl"> إضافة 138 مل ايثر اللامائية (ET 2 O، 0.200 M) إلى دورق التفاعل باستخدام حقنة محكم. بارد ويحرك خليط التفاعل في 0 درجة مئوية لمدة 15 دقيقة. </li><li style=";text-align:right;direction:rtl"> إعداد محلول كلوريد الأسيتيل (2.17 مل، 2.39 غرام، 30،4 مليمول، 1.20 EQUIV) في اللامائية إت 2 O (138 مل، 0.220 M). إضافة حل لخليط التفاعل في 0 ° C باستخدام مضخة الحقن بمعدل 10.0 مل / ساعة. </li><li style=";text-align:right;direction:rtl"> في نهاية بالإضافة إلى ذلك، تصفية خليط التفاعل من خلال لوحة قصيرة من الأرض دياتومي (أي Celite، 5 غ) في 60 مل فريت بوخنر قمع باستخدام الترشيح فراغ. غسل فلتر مع EtOAc (20 مل × 3 مرات). تركيزالترشيح في الخلاء باستخدام المبخر الدوار. </li><li style=";text-align:right;direction:rtl"> تنقية الناتج الخام مع عمود فلاش اللوني 35 يبلغ حجمه مع hexanes: EtOAc (4: 1-1: 1 (ت / ت)) (R F = 0.13، hexanes: EtOAc (4: 1 (ت / ت)) على تحمل 5.31 ز من الميثيل 4- (N -hydroxyacetamido) بنزوات بمثابة ضوء أصفر صلبة (25.4 مليمول، 92٪ العائد). </li></ol></li></ol> 2. تجميع الميثيل 4- (N - (trifluoromethoxy) acetamido) بنزوات (2A) <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إضافة 2.00 غرام من الميثيل 4- (N -hydroxyacetamido) بنزوات (1A) (9.56 ملمول، 1.00 EQUIV)، 311 ملغ من جيم 2 CO 3 (0،956 ملمول، 10.0٪ مول)، 3.63 غرام من Togni كاشف II (11،5 مليمول، 1.20 EQUIV)، والمغناطيسي ضجة بار إلى 250 مل دورق كروي المجفف فرن داخل صندوق قفازات (الغلاف الجوي النيتروجين). ملاحظة: يمكن أيضا أن هذا رد فعل يتعين القيام بها باستخدام تقنيات Schlenk خارج صندوق قفازات. الحذر: الصرفة Togni الكاشف الثاني هو التأثير والاحتكاك الحساسة اللهب المكشوفالصورة، ينبغي تجنب الشرر، و / أو طحن. وينبغي استخدام الأدوات الناعمة والمصقولة للتلاعب. بالإضافة إلى ذلك، يجب أن يحرك خليط التفاعل وراء درع السلامة. 36 </li><li style=";text-align:right;direction:rtl"> إضافة 95.6 مل من الكلوروفورم المجففة ونزع الغاز (CHCl 3، 0.100 M) إلى دورق التفاعل. </li><li style=";text-align:right;direction:rtl"> سقف القارورة مع الحاجز ويقلب الخليط التفاعل عند 23 درجة مئوية تحت N 2 الغلاف الجوي سواء داخل أو خارج صندوق قفازات لمدة 16 ساعة. </li><li style=";text-align:right;direction:rtl"> تصفية خليط التفاعل من خلال قمع مرشح لإزالة أي بقايا صلبة. تركيز الراشح في الخلاء باستخدام المبخر الدوار. </li><li style=";text-align:right;direction:rtl"> تنقية الناتج الخام مع عمود فلاش اللوني يبلغ حجمه مع hexanes: ثنائي كلورو ميثان (CH 2 الكلورين 2) (7: 3-0: 1 (ت / ت)) (R و = 0.44 (CH 2 الكلورين 2) على تحمل 2.51 غرام من الميثيل 4- (N - (trifluoromethoxy) acetamido) بنزوات (9.05 ملمول، 95٪ العائد). ملاحظة: Togni الكاشف الثاني مستعدة اتفاقجي للإجراءات الأدب 37 وتخزينها في الثلاجة صندوق قفازات عند -35 درجة مئوية إلى الحفاظ على جودته لفترة طويلة من الزمن. رد الفعل هذا هو الأوكسجين حساسة. على الرغم من أن جميع الكواشف يمكن أن يكون وزنه في ظل أجواء المحيطة في RT، وإزالة كل الأكسجين من القارورة رد فعل أمر بالغ الأهمية. المجففة ونزع الغاز CHCl 3 تعده لتقطير من CAH 2 تحت أجواء النيتروجين يليها إجراء ثلاث دورات من إجراءات تجميد مضخة ذوبان الجليد. </li></ol> 3. تجميع الميثيل 4-Acetamido-3- (trifluoromethoxy) بنزوات عبر OCF 3 -migration (3A) <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إضافة 2،51 ز الميثيل 4- (N - (trifluoromethoxy) acetamido) بنزوات (9.05 ملمول، 1.0 EQUIV)، المغناطيسي ضجة بار، و9.05 مل من مينو 2 (1.00 M) في وعاء ضغط 50 مل. سقف السفينة مع غطاء المسمار. </li><li style=";text-align:right;direction:rtl"> يحرك الخليط التفاعل عند 120 ° C وراء درع السلامة لمدة 20 ساعة. تحذير: النيتروميثان نجسغير المتفجرة، لذلك ينبغي أن يحرك خليط التفاعل وراء درع السلامة. </li><li style=";text-align:right;direction:rtl"> يبرد الخليط رد فعل على RT. </li><li style=";text-align:right;direction:rtl"> نقل خليط التفاعل إلى 100 مل دورق كروي. </li><li style=";text-align:right;direction:rtl"> تركيز خليط التفاعل في الخلاء باستخدام المبخر الدوار. </li><li style=";text-align:right;direction:rtl"> تنقية الناتج الخام مع عمود فلاش اللوني يبلغ حجمه مع hexanes: EtOAc (9: 1-7: 3 (ت / ت)) (R و = 0.51 hexanes: EtOAc (4: 1 (ت / ت)) على تحمل 2.13 غرام من الميثيل 4-acetamido-3- (trifluoromethoxy) بنزوات (7.69 ملمول، 85٪). ملاحظة: يمكن أن يتم هذا التفاعل في ظل أجواء المحيطة. ليس مطلوبا جو النيتروجين. A دورق كروي مجهزة مكثف المياه يمكن أن تستخدم بمثابة جهاز التفاعل بديل. </li></ol> 4. توصيف المنتجات الجديدة <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> تميز جميع المركبات الجديدة بنسبة 1 H، 13 C NMR الطيفي وعالية الدقة التحليل الطيفي الجماعية واستخدام 19 F NMR الطيفيلتوصيف المركبات التي تحتوي على ذرات الفلور 34 </li></ol>

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M. <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+polyfluoro+aromatic+ethers+-+a+facile+route+using+polyfluoroalkoxides+generated+from+carbonyl+and+trimethysilyl+compounds.">Synthesis of polyfluoro aromatic ethers - a facile route using polyfluoroalkoxides generated from carbonyl and trimethysilyl compounds.</a> Inorg. Chem. 34, 6085-6092 (1995).</li><li>Kolomeitsev, A. A., Vorobyev, M., Gillandt, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Versatile+application+of+trifluoromethyl+triflate.">Versatile application of trifluoromethyl triflate.</a> Tetrahedron Lett. 49, 449-454 (2008).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+deeper+insight+into+direct+trifluoromethoxylation+with+trifluoromethyl+triflate.">A deeper insight into direct trifluoromethoxylation with trifluoromethyl triflate.</a> J. Fluorine Chem. 131, 200-207 (2010).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+and+direct+trifluoromethoxylation+of+aliphatic+substrates+with+2,4-dinitro(trifluoromethoxy)benzene.">A new and direct trifluoromethoxylation of aliphatic substrates with 2,4-dinitro(trifluoromethoxy)benzene.</a> Adv. Synth. Catal. 352, 2831-2837 (2010).</li><li>Huang, C. H., Liang, T., Harada, S., Lee, E., Ritter, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Silver-mediated+trifluoromethoxylation+of+aryl+stannanes+and+arylboronic+acids.">Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.</a> J. Am. Chem. Soc. 133, 13308-13310 (2011).</li><li>Rozen, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+fluorinations+by+reagents+containing+the+OF+group.">Selective fluorinations by reagents containing the OF group.</a> Chem. Rev. 96, 1717-1736 (1996).</li><li>Venturini, F., 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=Direct+trifluoro-methoxylation+of+aromatics+with+perfluoro-methyl-hypofluorite.">Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite.</a> J. Fluorine Chem. 140, 43-48 (2012).</li><li>Hojczyk, K. N., Feng, P., Zhan, C., Ngai, M. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethoxylation+of+arenes:+synthesis+of+ortho-trifluoromethoxylated+aniline+derivatives+by+OCF3+migration.">Trifluoromethoxylation of arenes: synthesis of ortho-trifluoromethoxylated aniline derivatives by OCF3 migration.</a> Angew. Chem. Int. Ed. 53, 14559-14563 (2014).</li><li>Still, W. C., Kahn, M., Mitra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+chromatographic+technique+for+preparative+separations+with+moderate+Resolution.">Rapid chromatographic technique for preparative separations with moderate Resolution.</a> J. Org. Chem. 43, 2923-2925 (1978).</li><li>Fiederling, N., Haller, J., Schramm, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Notification+about+the+Explosive+Properties+of+Togni's+Reagent+II+and+One+of+Its+Precursors.">Notification about the Explosive Properties of Togni's Reagent II and One of Its Precursors.</a> Org. Process Res. Dev. 17, 318-319 (2013).</li><li>Matousek, V., Pietrasiak, E., Schwenk, R., Togni, A. <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+hypervalent+iodine+reagents+for+electrophilic+trifluoromethylation.">One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.</a> J. Org. Chem. 78, 6763-6768 (2013).</li></ol>

The authors declare no competing financial interests.

ونظرا لعدم وجود إجراء عام وسهلة الاستعمال لتركيب أرينية trifluoromethoxylated، العديد من OCF 3 المحتوية على المركبات العطرية هي مكلفة للغاية. 34 استراتيجيتنا إزاحة التسامح مجموعة وظيفية واسعة ويوفر سهولة الوصول إلى مختلف أرينية trifluoromethoxylated. هذه المركبات يمكن أن تكون...

وtrifluoromethoxy جعلت (OCF 3) مجموعة لها تأثير عميق على البحوث الحياة وعلوم المواد منذ التوليف الأول من الأثير ترايفلوروميثيل في عام 1935. 2 نظرا لمزيج فريد من كهربية عالية (χ = 3.7) 3 وبالانجذاب ممتاز (Π س = وقد وجدت 1.04)، 4 مجموعة trifluoromethoxy تطبيقات واسعة في مجال الطب، والزراعة، وصناعة مواد 5-10 ومع ذلك، لا يزال مقدمة سطحي من مجموعة OCF 3 في الجزيئات العضوية، وخاصة المركبات العطرية، تحديا كبيرا في الكيمياء الاصطناعية. على مدى العقود القليلة الماضية، أدت الجهود لمواجهة هذا التحدي في تطوير حفنة من التحولات لتركيب أرينية trifluoromethoxylated 5-7،9-11 هذه تشمل (ط) تبادل الكلور / الفلور على السلائف trichlorinated؛ 1،12 -17 (ب) deoxyfluorination من fluoroformates (18)؛ </سوب&gt; (ج) fluorodesulfurization الأكسدة، 19-21 (د) trifluoromethylation أليف الإلكترونات من الكحول، 22-25 (V) trifluoromethoxylation أليف النواة، 26-30، (السادس) الانتقال بوساطة المعادن trifluoromethoxylation من بورات أريل وstannanes (31)؛ و (السابع ) trifluoromethoxylation راديكالية. 32،33 ومع ذلك، فإن العديد من هذه الطرق إما يعانون من سوء نطاق الركيزة أو تتطلب استخدام الكواشف شديدة السمية و / أو عطوب حراريا. لذلك، نظرا لعدم وجود طريقة عامة وسهلة الاستعمال لتجميع OCF 3 مركبات فيتامين، وإمكانات مجموعة OCF 3 لم تستغل بالكامل في الكيمياء. كجزء من مصلحتنا في التفاعلات trifluoromethoxylation، 34 وصفنا هنا بروتوكول من خطوتين (أي O راديكالية -trifluoromethylation وOCF التي يسببها حراريا 3 -migration) لتركيب الميثيل 4-acetamido-3- (trifluoromethoxy) بنزوات (3A) من الميثيل 4- (N -hydroxyacetamido) بنزوات (1A). الاستراتيجية هي سهلة لتشغيل وتنطبق على تركيب مجموعة واسعة من أورثو مشتقات الأنيلين -trifluoromethoxylated.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">5% Rhodium on carbon</td>
			<td style="width:71px;">Aspira Scientific</td>
			<td style="width:119px;">300835</td>
			<td style="width:167px;">5% wt% dry loading</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">hydrazine monohydrate</td>
			<td style="width:71px;">Sigma-Alderich</td>
			<td style="width:119px;">13696HMV</td>
			<td style="width:167px;">Reagent grade, 98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Acetyl chloride</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">10176887</td>
			<td style="width:167px;">98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Sodium bicarbonate</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">134826</td>
			<td style="width:167px;">Chemical pure</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Cesium carbonate</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">12887</td>
			<td style="width:167px;">99.9%, metals basis</td>
		</tr>
		<tr height="148">
			<td height="148" style="height:148px;width:216px;">Togni Reagent II</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Prepared according to the literature procedure (ref 37). Caution: Pure Togni reagent II is impact and friction sensitive, treat it with great care (see ref. 36).</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Tetrahydrofuran</td>
			<td style="width:71px;">BDH</td>
			<td style="width:119px;">BDH1149-4LG</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Diethyl Ether</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">148221</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">Chloroform</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">141739</td>
			<td style="width:167px;">Dried over CaH2 and distilled</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">nitro methane</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">J03z053</td>
			<td style="width:167px;">Dried over CaSO4 and distilled</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Silica gel</td>
			<td style="width:71px;">SILICYCLE</td>
			<td style="width:119px;">60514</td>
			<td style="width:167px;">40-63 &#181;m (230-400 mesh)</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Cilite</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">2012040674</td>
			<td style="width:167px;">Not acid washed</td>
		</tr>
	</tbody>
</table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

جزيئات تحمل trifluoromethoxy (OCF 3) مجموعة غالبا ما تظهر المطلوب الخصائص الدوائية والبيولوجية. ومع ذلك، والتوليف سطحي من المركبات العطرية trifluoromethoxylated لا يزال يشكل تحديا هائلا في التركيب العضوي. وغالبا ما تعاني الأساليب التقليدية من سوء نطاق الركيزة، أو تتطلب استخدام عالية السمية، والتعامل مع يصعب، و / أو الكواشف عطوب حراريا. هنا، ونحن التقرير بروتوكول سهل الاستعمال لتركيب الميثيل 4-acetamido-3- (trifluoromethoxy) بنزوات باستخدام 1-ترايفلوروميثيل-1،2-benziodoxol-3 (1 H) واحد (Togni كاشف II). علاج الميثيل 4- (N -hydroxyacetamido) بنزوات (1A) مع Togni الكاشف الثاني في وجود كمية الحفاز من السيزيوم كربونات (CS 2 3 CO) في الكلوروفورم في RT تمنح الميثيل 4- (N - (trifluoromethoxy) acetamido) بنزوات (2A). هذا المتوسط ​​ثم تم تحويلها إلى الميثيل المنتج النهائي 4-acetamido-3- (trifluoromethoxy) بنزوات (3A) في النيتروميثان في 120 ° C. هذا الإجراء هو عام ويمكن تطبيقها على تركيب مجموعة واسعة من أورثو مشتقات الأنيلين -trifluoromethoxylated، والتي يمكن أن تكون مفيدة لبنات البناء الاصطناعية لاكتشاف وتطوير الأدوية الجديدة والكيماويات الزراعية، والمواد الفنية.

تم توليفها الميثيل 4- (N -hydroxyacetamido) بنزوات (1A) في العائد معزولة 92٪ من خلال إجراء خطوتين (أي الحد الميثيل 4-nitrobenzoate مع الهيدرازين باستخدام 5٪ ره / C كمحفز لتشكيل الميثيل 4- ( N -hydroxyamino) بنزوات، تليها حماية الاسيتيل من هيدروكسيل الناتج). ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

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.

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

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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9.8K Views.  State University of New York at Stony Brook. 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.

Video: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

توليف Hypervalent Iodonium Alkynyl Triflates لتطبيق توليد Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

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 ...

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

والمباشر، المرحلة المبكرة بروتوكول Guanidinylation لتوليف مجمع تحتوي على أمينوغوانيدين المنتجات الطبيعية

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST-1 بمثابة محفز غير المتجانسة للتوليف ونيلين

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

A Protocol for the Production of Gliadin-cyanoacrylate Nanoparticles for Hydrophilic Coating

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray coating. These nanoparticles are produced by the polymerization reaction of alkyl cyanoacrylate on the surface of cereal protein (gliadin) molecules. Alkyl cyanoacrylate is a monomer that instantly polymerizes at RT when it is applied to the surface of materials. Its polymerization reaction is initiated by the trace amounts of weakly basic or nucleophilic species on the surface, including moisture. Once polymerized, the polymerized alkyl cyanoacrylates show a strong affinity with the object materials because nitrile groups are in the backbone of poly (alkyl cyanoacrylate). Proteins also work as initiator for this polymerization because they contain amine groups that can initiate the polymerization of cyanoacrylate. If aggregated protein is used as an initiator, protein aggregate is surrounded by the hydrophobic poly(alkyl cyanoacrylate) chains after the polymerization reaction of alkyl cyanoacrylate. By controlling the experimental condition, particles in the nanometer range are produced. The produced nanoparticles readily adsorb to the surface of most materials including glass, metals, plastics, wood, leather, and fabrics. When the surface of a material is sprayed with the produced nanoparticle suspension and rinsed with water, the micellar structure of nanoparticle changes its conformation, and the hydrophilic proteins are exposed to the air. As a result, the nanoparticle-coated surface changes to hydrophilic.

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic. The produced nanoparticle is an assembly of gliadin-cyanoacrylate diblock copolymers. Spray coating with the produced nanoparticle changes the surface of target material to a hydrophilic surface.

بروتوكول لإنتاج الجسيمات النانوية غليادين-cyanoacrylate لمع الماء طلاء

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

تخليق البروتين Bioconjugates<em&gt; عبر</em&gt; سيستين-maleimide الكيمياء

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

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 ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5&#39;-[CUA CGG AAU CAU]-3&#39; containing zero, one, or two modifications located at the C2&#39;-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2&#39;-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

This article provides a detailed procedure on the solid-phase synthesis, purification, and characterization of dodecamers of RNA modified at the C2&#39;-O-position. UV-vis and circular dichroism photometric analyses are used to quantify and characterize structural aspects, i.e., single-strands or double-strands.

بروتوكول لتجميع المرحلة الصلبة من أوليغوميرس من الحمض النووي الريبي تحتوي على 2&#39;-<em&gt; O</em&gt; -thiofenylmethyl تعديل وتوصيف عن طريق التعميم ديكرويسم

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

توليف وتحليل الطيف الكتلي اليغو-بيبتويدس

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges, since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for the simultaneous extraction of metabolites, proteins, and lipids (MPLEx) from the same soil sample was created by adapting a solvent-based approach. This MPLEx protocol has proven to be both simple and robust for many sample types, even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations.

A protocol is presented for simultaneously extracting metabolites, proteins, and lipids from a single soil sample, allowing reduced sample preparation times and enabling multi-omic mass spectrometry analyses of samples with limited quantities.

بروتوكول مبليكس لمتعدد omic تحاليل عينات التربة

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and ...

بروتوكول لتوليف

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