Riconosciamo generosi fondi di start-up della State University di New York a Stony Brook, a sostegno di questo lavoro. Ringraziamo anche TOSOH F-Tech, Inc. per averci fornito TMSCF 3 reagenti per la sintesi di Togni reagente II.

1. Precursore Preparazione: Sintesi di metile 4- (N -hydroxyacetamido) benzoato (1a) <ol><li> Riduzione di metil 4-nitrobenzoato. <ol><li> Aggiungere 5,00 g di metil 4-nitrobenzoato (27,6 mmol, 1,00 equiv), 159 mg di 5% su carbone Rodio (Rh / C, 0.300 mol% Rh), e un fritto barra magnetica in un forno-essiccato 250 ml a due collo pallone a fondo tondo (essiccato a 150 ° C per 18 ore). NOTA: I reagenti possono essere pesati sotto atmosfera ambiente. Tuttavia, la reazione deve essere effettuata in atmosfera di azoto. </li><li> Collegare un collo del pallone di azoto / collettore del vuoto e tappare l&#39;altro collo con un setto. Eseguire tre cicli di vuoto-ricarica (cioè, il pompaggio di aria fuori del pallone e sostituendo il vuoto risultante con gas azoto) per sostituire l&#39;aria nel pallone con azoto. </li><li> Aggiungere 138 ml di tetraidrofurano anidro (THF, 0,200 M) al pallone di reazione mediante siringa ermetico. Fresco e mescolare le mixt reazioneure a 0 ° C per 15 min. </li><li> Aggiungere 1,47 ml di idrazina monoidrato (1,52 g, 30,4 mmol, 1,20 equiv) goccia a goccia alla miscela di reazione a 0 ° C utilizzando una siringa a tenuta d&#39;aria. Monitorare la reazione utilizzando una cromatografia su strato sottile (TLC). Utilizzare esano: acetato di etile (EtOAc) (4: 1 v / v, R f = 0,23) come eluente per sviluppare la TLC. </li><li> Quando metil 4-nitrobenzoato è completamente consumato, filtrare la miscela di reazione attraverso un breve pad di terra di diatomee (cioè, Celite, 5 g) in 60 ml di fritta imbuto Buchner con filtrazione sottovuoto. Lavare il filtro con EtOAc (20 ml x 3 volte). Concentrare il filtrato sotto vuoto usando un evaporatore rotante per permettere il benzoato di metile grezzo 4- (N -hydroxyamino), che è usato direttamente senza ulteriore purificazione. </li></ol></li><li> Protezione acetil di metil 4- (N -hydroxyamino) benzoato <ol><li> Aggiungere 2,55 g di bicarbonato di sodio (NaHCO3, 30,4 mmol, 1,20 equiv), tutto il greggiometil 4- (N -hydroxyamino) benzoato ottenuto dal passaggio precedente, e un fritto bar in una da 500 ml a due colli pallone a fondo del forno-essiccato. </li><li> Cap un collo con un setto e collegare un altro collo di un collettore di azoto / vuoto. Eseguire tre cicli di vuoto-ricarica per sostituire l&#39;aria nel pallone con azoto. </li><li> Aggiungere 138 ml di etere dietilico anidro (Et 2 O, 0,200 M) al pallone di reazione utilizzando una siringa a tenuta d&#39;aria. Raffreddare e agitare la miscela di reazione a 0 ° C per 15 min. </li><li> Preparare una soluzione di cloruro di acetile (2,17 ml, 2,39 g, 30,4 mmol, 1,20 equiv) in Et 2 O anidro (138 ml, 0,220 M). Aggiungere la soluzione alla miscela di reazione a 0 ° C utilizzando una pompa a siringa ad una velocità di 10,0 ml / h. </li><li> Al termine dell&#39;aggiunta, filtrare la miscela di reazione attraverso un breve pad di terra di diatomee (cioè, Celite, 5 g) in 60 ml di fritta imbuto Buchner con filtrazione sottovuoto. Lavare il filtro con EtOAc (20 ml x 3 volte). Concentrare ilfiltrato sotto vuoto usando un evaporatore rotante. </li><li> Purificare il prodotto grezzo con colonna cromatografia flash 35 eluendo con esano: EtOAc (4: 1 a 1: 1 (v / v)) (R f = 0,13, esano: EtOAc (4: 1 (v / v)) per ottenere 5,31 g di metil 4- (N -hydroxyacetamido) benzoato come un giallo solido (25,4 mmol, 92% di resa) luce. </li></ol></li></ol> 2. Sintesi di metil 4- (N - (trifluorometossi) acetammido) benzoato (2a) <ol><li> Aggiungere 2,00 g di metil 4- (N -hydroxyacetamido) benzoato (1a) (9,56 mmol, 1,00 equiv), 311 mg di Cs 2 CO 3 (0,956 mmol, 10,0 mol%), 3,63 g di Togni reagente II (11,5 mmol, 1.20 equiv), e un fritto barra magnetica in un 250 ml pallone da forno secchi all&#39;interno di un vano portaoggetti (atmosfera di azoto). NOTA: Questa reazione può essere effettuata anche mediante tecniche di Schlenk fuori del cassetto portaoggetti. Attenzione: Pure reagente Togni II è l&#39;impatto e l&#39;attrito sensibile, fiamme liberes, scintille, e / o rettifica dovrebbe essere evitato. Strumenti morbidi e levigati devono essere utilizzati per le manipolazioni. Inoltre, la miscela di reazione deve essere agitata dietro uno schermo di sicurezza. 36 </li><li> Aggiungere 95,6 ml di essiccato e degassato cloroformio (CHCl3, 0,100 M) al pallone di reazione. </li><li> Chiudere la beuta con setto e agitare la miscela di reazione a 23 ° C sotto atmosfera di N 2 all&#39;interno o all&#39;esterno del vano portaoggetti per 16 ore. </li><li> Filtrare la miscela di reazione attraverso un imbuto filtrante per rimuovere eventuali residui solidi. Concentrare il filtrato sotto vuoto usando un evaporatore rotante. </li><li> Purificare il prodotto grezzo con cromatografia flash eluendo con esano: diclorometano (CH 2 Cl 2) (7: 3 a 0: 1 (v / v)) (R f = 0,44 (CH 2 Cl 2) permettere 2,51 g di metil 4- (N - (trifluorometossi) acetammido) benzoato (9,05 mmol, 95% resa). NOTA: Togni reagente II è accordo preparatozione alle procedure letteratura 37 e memorizzati nel cassetto portaoggetti congelatore a -35 ° C per mantenere la sua qualità per un lungo periodo di tempo. Questa reazione è ossigeno sensibile. Sebbene tutti i reagenti possono essere pesati sotto atmosfera ambiente a temperatura ambiente, la rimozione di tutto l&#39;ossigeno dal pallone di reazione è critica. Essiccato e degassato CHCl3 viene preparato mediante distillazione da CaH 2 in atmosfera di azoto seguita eseguendo tre cicli di congelamento-procedura pompa-disgelo. </li></ol> 3. Sintesi di Metil-4 Acetamido-3- (trifluorometossi) benzoato via OCF 3 -migration (3a) <ol><li> Aggiungere 2,51 g metile 4- (N - (trifluorometossi) acetammido) benzoato (9.05 mmol, 1,0 equiv), un fritto barra magnetica, e 9,05 ml di Meno 2 (1,00 m) in un recipiente a pressione da 50 ml. Tappare il recipiente con un tappo a vite. </li><li> Mescolare la miscela di reazione a 120 ° C dietro lo schermo di protezione per 20 ore. Attenzione: nitrometano Impureè esplosivo, quindi la miscela di reazione deve essere agitata dietro lo schermo di protezione. </li><li> Raffreddare la miscela di reazione di RT. </li><li> Trasferire la miscela di reazione in un pallone a fondo rotondo da 100 ml. </li><li> Concentrare la miscela di reazione sotto vuoto usando un evaporatore rotante. </li><li> Purificare il prodotto grezzo con cromatografia flash eluendo con esano: EtOAc (9: 1 a 7: 3 (v / v)) (R f = 0,51 esano: EtOAc (4: 1 (v / v)) per ottenere 2,13 g di metil 4-acetamido-3- (trifluorometossi) benzoato (7,69 mmol, 85%). NOTA: Questa reazione può essere condotta in atmosfera ambiente. Atmosfera di azoto non è necessaria. Un pallone a fondo tondo dotato di un condensatore acqua può essere utilizzata come un apparato reazione alternativa. </li></ol> 4. Caratterizzazione di nuovi prodotti <ol><li> Caratterizzare tutti i nuovi composti da 1 H, 13 spettroscopia NMR C e spettroscopia di massa ad alta risoluzione e utilizzare 19 spettroscopia NMR Fper caratterizzare composti contenenti atomi di fluoro. 34 </li></ol>

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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.

A causa della mancanza di una procedura generale e user-friendly per la sintesi di areni trifluoromethoxylated, molti OCF composti aromatici 3 -non sono estremamente costosi. 34 La nostra strategia sposta un&#39;ampia tolleranza gruppo funzionale e fornisce un facile accesso alle varie areni trifluoromethoxylated. Questi composti potrebbero servire come mattoni importanti per la scoperta e lo sviluppo di nuovi prodotti farmaceutici, prodotti agrochimici, e materiali. Id...

Il trifluorometossi (OCF 3) gruppo ha fatto un profondo impatto sulla ricerca di vita e la scienza dei materiali in quanto la prima sintesi di trifluoromethyl dell&#39;etere nel 1935. 2 Grazie alla sua combinazione unica di alta elettronegatività (χ = 3.7) 3 ed eccellente lipofilia (Π x = 1.04), 4 il gruppo trifluorometossi ha trovato ampie applicazioni in medicina, agricoltura, industria e materiali. 5-10 Tuttavia, l&#39;introduzione facile del gruppo OCF 3 in molecole organiche, in particolare i composti aromatici, rimane una sfida importante nella chimica di sintesi. Nel corso degli ultimi decenni, gli sforzi per affrontare questa sfida ha portato allo sviluppo di una manciata di trasformazioni per la sintesi di areni trifluoromethoxylated 5-7,9-11 Questi includono (i) scambio di cloro / fluoro sui precursori trichlorinated;. 1,12 -17 (ii) deoxyfluorination di fluoroformiati; 18 </sup&gt; (iii) fluorodesulfurization ossidativo; 19-21 (iv) trifluoromethylation elettrofila di alcoli, 22-25 (v) trifluoromethoxylation nucleofila, 26-30, (vi) di transizione trifluoromethoxylation metallo-mediata di borato arilici e stannani, 31 e (vii ) trifluoromethoxylation radicale. 32,33 Tuttavia, molti di questi approcci sia soffrono di applicazione substrato scarsa o richiede l&#39;uso di reagenti altamente tossici e / o termicamente labili. Pertanto, a causa della mancanza di un metodo generale e di facile utilizzo per sintetizzare OCF 3 composti -aventi tenore, il potenziale del gruppo OCF 3 non è stata completamente sfruttata in chimica. Come parte del nostro interesse per reazioni trifluoromethoxylation, 34 descriviamo qui un protocollo a due fasi (cioè, O -trifluoromethylation radicale e OCF indotta termicamente 3 -migration) per la sintesi di metil 4-acetamido-3- (trifluorometossi) benzoato (3a) da metil 4- (N -hydroxyacetamido) benzoato (1a). La strategia è facile da usare e applicabili alla sintesi di una vasta gamma di orto derivati ​​dell&#39;anilina -trifluoromethoxylated.

<table><tbody><tr><td>5% Rhodium on carbon</td><td>Aspira Scientific</td><td>300835</td><td>5% wt% dry loading</td></tr><tr><td>Hydrazine monohydrate</td><td>Sigma-Alderich</td><td>13696HMV</td><td>Reagent grade, 98%</td></tr><tr><td>Acetyl chloride</td><td>Alfa Aesar</td><td>10176887</td><td>98%</td></tr><tr><td>Sodium bicarbonate</td><td>Fisher Scientific</td><td>134826</td><td>Chemical pure</td></tr><tr><td>Cesium carbonate</td><td>Alfa Aesar</td><td>12887</td><td>99.9%, metals basis</td></tr><tr><td>Togni Reagent II</td><td></td><td></td><td>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><td>Tetrahydrofuran</td><td>BDH</td><td>BDH1149-4LG</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Diethyl Ether</td><td>Fisher Scientific</td><td>148221</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Chloroform</td><td>Fisher Scientific</td><td>141739</td><td>Dried over CaH&lt;sub&gt;2&lt;/sub&gt; and distilled</td></tr><tr><td>Nitromethane</td><td>Alfa Aesar</td><td>J03z053</td><td>Dried over CaSO&lt;sub&gt;4&lt;/sub&gt; and distilled</td></tr><tr><td>Silica gel</td><td>SILICYCLE</td><td>60514</td><td>40-63 &amp;micro;m (230-400 mesh)</td></tr><tr><td>Celite</td><td>EMD</td><td>2012040674</td><td>Not acid washed</td></tr></tbody></table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

Le molecole portanti trifluorometossi gruppo (OCF 3) spesso show desiderato proprietà farmacologiche e biologiche. Tuttavia, la sintesi di composti aromatici facile trifluoromethoxylated rimane una sfida formidabile nella sintesi organica. Approcci convenzionali spesso soffrono di portata substrato povero, o richiedono l&#39;uso di, manico difficili da altamente tossici, e / o reattivi termicamente labili. Qui riportiamo un protocollo di facile utilizzo per la sintesi di metil 4-acetamido-3- (trifluorometossi) benzoato utilizzando 1-trifluorometil-1,2-benziodoxol-3 (1H) -one (Togni reagente II). Trattamento metil 4- (N -hydroxyacetamido) benzoato (1a) con Togni reagente II in presenza di una quantità catalitica di carbonato di cesio (Cs 2 CO 3) in cloroformio a RT prestata metil 4- (N - (trifluorometossi) acetammido) benzoato (2a). Questo intermedio è stato poi convertito nel prodotto finale metil 4-acetamido-3- (trifluoromethoxy) benzoato (3a) in nitrometano a 120 ° C. Questa procedura è generale e può essere applicato alla sintesi di un ampio spettro di orto derivati ​​dell&#39;anilina -trifluoromethoxylated, che potrebbe servire come utili blocchi sintetici per la scoperta e lo sviluppo di nuovi prodotti farmaceutici, prodotti agrochimici e materiali funzionali.

Metil 4- (N -hydroxyacetamido) benzoato (1a) è stato sintetizzato nel 92% isolato resa attraverso una procedura in due fasi (ad esempio, la riduzione metil 4 nitrobenzoato con idrazina utilizzando 5% Rh / C come catalizzatore per formare metil 4- ( N -hydroxyamino) benzoato, seguita da protezione acetil della idrossilammina risultante). O- Trifluoromethylation di 1a con Togni reagente II in presenza di quantità catal...

Watch this Scientific Journal Video about Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives at JoVE.com

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Protocollo per la sintesi di<em&gt; Ortho</em&gt; Derivati ​​all&#39;anilina -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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9.9K 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.

Sintesi di hypervalent iodonio Alchinile triflati per l&#39;applicazione di Generazione Cyanocarbenes

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

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Chimica

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.

La modifica e funzionalizzazione del gruppo Guanidine da precursori su misura

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

Biochimica

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.

Sintesi di derivati ​​antivirale Tetrahydrocarbazole da fotochimica e acido-catalizzata CH funzionalizzazione via intermedi perossidi (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 ...

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zempl&#233;n.

Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme activity monitoring. Especially for glucose type structures previous syntheses proved to be challenging and low yielding. Our novel approach employs indoxylic acid esters as precious intermediates to yield a considerable number of indoxyl glycosides in good yields.

Sintesi di indoxyl-glicosidi per il rilevamento di glicosidasi Attività

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are ...

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.

Preparazione di N-(2-alkoxyvinyl) sulfamidici da N- tosyl-1, 2,3-triazoli e successiva conversione di Phthalans sostituito e fenetilamine

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

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Chemoselective preparazione di 1-Iodoalkynes, 1,2-Diiodoalkenes e 1,1,2-Triiodoalkenes basato sull'iodurazione ossidativo degli alchini terminali

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. Yet maleimide-based conjugates display limited stability in vivo because the succinimidyl thioether linkage can undergo a retro-Michael reaction. This, of course, can lead to the release of the radioactive payload or its exchange with thiol-bearing biomolecules in circulation. Both of these processes can produce elevated activity concentrations in healthy organs as well as decreased activity concentrations in target tissues, resulting in reduced imaging contrast and lower therapeutic ratios. In 2018, we reported the creation of a modular, stable, and easily accessible phenyloxadiazolyl methyl sulfone reagent &#8212; dubbed &#8216;PODS&#8217; &#8212; as a platform for thiol-based bioconjugations. We have clearly demonstrated that PODS-based site-selective bioconjugations reproducibly and robustly create homogenous, well-defined, highly immunoreactive, and highly stable radioimmunoconjugates. Furthermore, preclinical experiments in murine models of colorectal cancer have shown that these site-selectively labeled radioimmunoconjugates exhibit far superior in vivo performance compared to radiolabeled antibodies synthesized via maleimide-based conjugations. In this protocol, we will describe the four-step synthesis of PODS, the creation of a bifunctional PODS-bearing variant of the ubiquitous chelator DOTA (PODS-DOTA), and the conjugation of PODS-DOTA to the HER2-targeting antibody trastuzumab.

In this protocol, we will describe the synthesis of PODS, a phenyoxadiazolyl methyl sulfone-based reagent for the site-selective attachment of cargos to the thiols of biomolecules, particularly antibodies. In addition, we will describe the synthesis and characterization of a PODS-bearing bifunctional chelator and its conjugation to a model antibody.

Sintesi e Bioconjugation di tiolo-reattive reagenti per la creazione del sito-selettivamente per volta efattori

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. ...

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate in a direct aza-Michael reaction with tricarbonyl(tropone)iron under solvent-free conditions. Less nucleophilic aniline derivatives and more hindered secondary amines add efficiently to the cationic tropone complex formed by protonation of tricarbonyl(tropone)iron. While the protocol utilizing the cationic complex is less efficient overall for accessing the aza-Michael adducts than the direct, solvent-free addition to the neutral complex, it allows the use of a broader range of amine nucleophiles. Following protection of the amine of the aza-Michael adduct as a tert-butyl carbamate, the diene is decomplexed from the iron tricarbonyl fragment upon treatment with cerium(IV) ammonium nitrate to provide derivatives of 6-aminocyclohepta-2,4-dien-1-one. These products can serve as precursors to diverse compounds containing a seven-membered carbocyclic ring. Because the demetallation requires protection of the amine as a carbamate, the aza-Michael adducts of secondary amines cannot be decomplexed using the protocol described here.

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.

Preparazione di 6-aminociclohepta-2,4-dien-1-one Derivati via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate ...

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

3-Aroyl-N-hydroxy-5-nitroindoles were synthesized by cycloaddition of 4-nitronitrosobenzene with a conjugated terminal alkynone in a one-step thermal procedure. Preparation of the nitrosoarene and of the alkynones were adequately reported and respectively through oxidation procedures on the corresponding aniline and on the alkynol.

Una sintesi diretta, regiosesesesese ed economica di 3-Aroyl-N-idrossicco-5-nitroindoles di Cycloaddition di 4-Nitronidobenzee con alchinoni

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ...

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, dipyrrinones, and pharmaceuticals. Additionally, restricted rotation of these systems often results in highly to moderately fluorescent systems as observed in 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidin-3-ones, xanthoglows, pyrroloindolizinedione analogs, BODIPY analogs, and the phenolic and imidazolinone ring systems of Green Fluorescent Protein (GFP). This manuscript describes an inexpensive and operationally simple method of performing a Claisen-Schmidt condensation to generate a series of fluorescent pH dependent pyrazole/imidazole/isoindolone dipyrrinone analogs. While the methodology illustrates the synthesis of dipyrrinone analogs, it can be translated to produce a wide range of conjugated bicyclic aromatic compounds. The Claisen-Schmidt condensation reaction utilized in this method is limited in scope to nucleophiles and electrophiles that are enolizable under basic conditions (nucleophile component) and non-enolizable aldehydes (electrophile component). Additionally, both the nucleophilic and electrophilic reactants must contain functional groups that will not inadvertently react with hydroxide. Despite these limitations, this methodology offers access to completely novel systems that can be employed as biological or molecular probes.

The Claisen-Schmidt condensation reaction is an important methodology for the generation of methine-bridged conjugated bicyclic aromatic compounds. Through utilizing a base-mediated variant of the aldol reaction, a range of fluorescent and/or biologically relevant molecules can be accessed through a generally inexpensive and operationally simple synthetic approach.

Protocollo per la sintesi di

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Sintesi di hypervalent iodonio Alchinile triflati per l'applicazione di Generazione Cyanocarbenes

La modifica e funzionalizzazione del gruppo Guanidine da precursori su misura

Sintesi di derivati antivirale Tetrahydrocarbazole da fotochimica e acido-catalizzata CH funzionalizzazione via intermedi perossidi (CHIPS)

Sintesi di indoxyl-glicosidi per il rilevamento di glicosidasi Attività

Preparazione di N-(2-alkoxyvinyl) sulfamidici da N- tosyl-1, 2,3-triazoli e successiva conversione di Phthalans sostituito e fenetilamine

Chemoselective preparazione di 1-Iodoalkynes, 1,2-Diiodoalkenes e 1,1,2-Triiodoalkenes basato sull'iodurazione ossidativo degli alchini terminali

Sintesi e Bioconjugation di tiolo-reattive reagenti per la creazione del sito-selettivamente per volta efattori

Preparazione di 6-aminociclohepta-2,4-dien-1-one Derivati via Tricarbonyl(tropone)iron

Una sintesi diretta, regiosesesesese ed economica di 3-Aroyl-N-idrossicco-5-nitroindoles di Cycloaddition di 4-Nitronidobenzee con alchinoni

Sintesi di pirazolo dipendente dal pH, imidazolo e fluorofori di Isoindolone Dipyrrinone usando un approccio di condensazione claisen-schmidt

Protocollo per la sintesi di

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Esplora Altri Video

Capitoli in questo video

Sintesi di hypervalent iodonio Alchinile triflati per l'applicazione di Generazione Cyanocarbenes

La modifica e funzionalizzazione del gruppo Guanidine da precursori su misura

Sintesi di derivati ​​antivirale Tetrahydrocarbazole da fotochimica e acido-catalizzata CH funzionalizzazione via intermedi perossidi (CHIPS)

Sintesi di indoxyl-glicosidi per il rilevamento di glicosidasi Attività

Preparazione di N-(2-alkoxyvinyl) sulfamidici da N- tosyl-1, 2,3-triazoli e successiva conversione di Phthalans sostituito e fenetilamine

Chemoselective preparazione di 1-Iodoalkynes, 1,2-Diiodoalkenes e 1,1,2-Triiodoalkenes basato sull'iodurazione ossidativo degli alchini terminali

Sintesi e Bioconjugation di tiolo-reattive reagenti per la creazione del sito-selettivamente per volta efattori

Preparazione di 6-aminociclohepta-2,4-dien-1-one Derivati via Tricarbonyl(tropone)iron

Una sintesi diretta, regiosesesesese ed economica di 3-Aroyl-N-idrossicco-5-nitroindoles di Cycloaddition di 4-Nitronidobenzee con alchinoni

Sintesi di pirazolo dipendente dal pH, imidazolo e fluorofori di Isoindolone Dipyrrinone usando un approccio di condensazione claisen-schmidt

Sintesi di derivati antivirale Tetrahydrocarbazole da fotochimica e acido-catalizzata CH funzionalizzazione via intermedi perossidi (CHIPS)