- Decarboxylative alkynylation and cyanation of carboxylic acids using photoredox catalysis and hypervalent iodine reagents
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Alkynes and nitriles are important functional groups that serve as versatile building blocks in organic synthesis and find applications in material and medicinal sciences. A convenient and straightforward access to both classes of compounds under mild conditions is, therefore, highly desirable. Herein, we disclose the decarb-oxylative alkynylation and cyanation of broadly available carboxylic acids using photoredox catalysis and hyper-valent iodine reagents. Choices of both catalysts and reagents were crucial. Computational and experimental studies revealed two different possible mechanisms that are dictated by the oxidation potential of the reagents: radical for alkynylation, ionic for cyanation.
- Le Vaillant, Franck,Waser, Jér?me
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- A metal-free direct C (sp3)-H cyanation reaction with cyanobenziodoxolones
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A metal-free protocol of direct C(sp3)-H cyanation with cyanobenziodoxolones functioning as both cyanating reagents and oxidants was developed. Unactivated substrates, such as alkanes, ethers and tertiary amines, were thereby transformed to the corresponding nitriles in moderate to high yields. Mechanistic studies indicated that the cyanation proceeded with two potential pathways, which is highly dependent on the substrates: (1) a free radical case for alkanes and ethers and (2) an oxidative case for tertiary amines.
- Sun, Ming-Xue,Wang, Yao-Feng,Xu, Bao-Hua,Ma, Xin-Qi,Zhang, Suo-Jiang
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- From 2-aminomethyl-1,4-benzodioxane enantiomers to unichiral 2-cyano- and 2-carbonyl-substituted benzodioxanes via dichloroamine
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2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2-aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most part are never described as enantiomers or are inadequately characterized for enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)- and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group conversions in high yields without any racemization of the stereogenic benzodioxane C(2).
- Bolchi, Cristiano,Valoti, Ermanno,Straniero, Valentina,Ruggeri, Paola,Pallavicini, Marco
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- Room temperature decarboxylative cyanation of carboxylic acids using photoredox catalysis and cyanobenziodoxolones: a divergent mechanism compared to alkynylation
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The one-step conversion of aliphatic carboxylic acids to the corresponding nitriles has been accomplished via the merger of visible light mediated photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in high yields with natural and non-natural α-amino and α-oxy acids, affording a broad scope of nitriles with excellent tolerance of the substituents in the α position. The direct cyanation of dipeptides and drug precursors was also achieved. The mechanism of the decarboxylative cyanation was investigated both computationally and experimentally and compared with the previously developed alkynylation reaction. Alkynylation was found to favor direct radical addition, whereas further oxidation by CBX to a carbocation and cyanide addition appeared more favorable for cyanation. A concerted mechanism is proposed for the reaction of radicals with EBX reagents, in contrast to the usually assumed addition elimination process.
- Le Vaillant, Franck,Wodrich, Matthew D.,Waser, Jér?me
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- Synthesis and biological activity of novel carbacyclins having bicyclic substituents on the ω-chain
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A number of carbacyclins having bicyclic substituents on the ω-chain have been synthesized and tested for antiplatelet aggregation activity in vitro (against collagen-induced aggregation of rat platelet), for reduction of systemic blood pressure in vivo (ability to reduce the blood pressure in anesthetized rat by iv injection), and for cytoprotective activity (protection against ethanol-induced rat gastric lesion). The most effective compound for each activity was [3aS-[2E,3aα,4α(3R),5β,6aα]]-5-[hexahydro-5-hydroxy-4-[3-hydroxy-3-(2- indanyl)-1-propynyl]-2(1H)-pentalenylidene]pentanoic acid (compound 11a), while some 1,4-benzodioxan analogues had selectivity for organ-protective activity, and indan analogues showed selectivity in their antiaggregation activity.
- Tomiyama,Wakabayashi,Yokota
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- 2--2-IMIDAZOLINE HYDROCHLORIDE
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A new synthesis of 2--2-imidazoline hydrochloride from 2-cyano-benzodioxan is described and the previously claimed route to this compound is shown to give a formula isomer, ie. 2-methyl-2--2-imidazoline hydrochloride.
- Chapleo, Christopher B.,Myers, Peter L.
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- Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-Light Flavin Photocatalysis
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An operationally simple method is disclosed for the decarboxylative cyanation of aliphatic carboxylic acids at room temperature. Riboflavin tetraacetate, which is an inexpensive organic photocatalyst, promotes the oxidation of carboxylic acids upon visible-light activation. After decarboxylation, the generated radicals are trapped by TsCN, yielding the desired nitriles without any further additive, in a redox-neutral process. Importantly, this protocol can be adapted to flow conditions.
- Ramirez, Nieves P.,K?nig, Burkhard,Gonzalez-Gomez, Jose C.
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supporting information
(2019/03/08)
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- Characterization of an indole-3-acetamide hydrolase from alcaligenes faecalis subsp. parafaecalis and its application in efficient preparation of both enantiomers of chiral building block 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid
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Both the enantiomers of 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid are valuable chiral synthons for enantiospecific synthesis of therapeutic agents such as (S)-doxazosin mesylate, WB 4101, MKC 242, 2,3-dihydro-2-hydroxymethyl-1,4-benzodioxin, and N-[2,4-oxo-1,3-thiazolidin-3-yl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide. Pharmaceutical applications require these enantiomers in optically pure form. However, currently available methods suffer from one drawback or other, such as low efficiency, uncommon and not so easily accessible chiral resolving agent and less than optimal enantiomeric purity. Our interest in finding a biocatalyst for efficient production of enantiomerically pure 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid lead us to discover an amidase activity from Alcaligenes faecalis subsp. parafaecalis, which was able to kinetically resolve 2,3-dihydro-1,4-benzodioxin-2-carboxyamide with E value of >200. Thus, at about 50% conversion, (R)-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid was produced in >99% e.e. The remaining amide had (S)-configuration and 99% e.e. The amide and acid were easily separated by aqueous (alkaline)-organic two phase extraction method. The same amidase was able to catalyse, albeit at much lower rate the hydrolysis of (S)-amide to (S)-acid without loss of e.e. The amidase activity was identified as indole-3-acetamide hydrolase (IaaH). IaaH is known to catalyse conversion of indole-3-acetamide (IAM) to indole-3-acetic acid (IAA), which is phytohormone of auxin class and is widespread among plants and bacteria that inhabit plant rhizosphere. IaaH exhibited high activity for 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which was about 65% compared to its natural substrate, indole-3-acetamide. The natural substrate for IaaH indole-3-acetamide shared, at least in part a similar bicyclic structure with 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which may account for high activity of enzyme towards this un-natural substrate. To the best of our knowledge this is the first application of IaaH in production of industrially important molecules.
- Mishra, Pradeep,Kaur, Suneet,Sharma, Amar Nath,Jolly, Ravinder S.
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- New imidazoline/α2-adrenoceptors affecting compounds-4(5)-(2-aminoethyl)imidazoline (dihydrohistamine) derivatives. Synthesis and receptor affinity studies
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Compilation of agmatine structure and imidazoline moiety leads to a new group of imidazoline/α2-adrenoceptor ligands, 4(5)-(2-aminoethyl)imidazoline derivatives. In this study the exploration of previously unknown 4(5)-(2-aminoethyl)imidazolines including the analogues of reported imidazoline and α2-aderenoceptors ligands: clonidine, rilmenidine, idazoxan, efaroxan, antazoline, tracizoline is described. The synthesis of a variety of novel 4(5)-(2-aminoethyl)imidazolines and their I 1, I2, α2-adrenoceptors affinities are reported.
- Treder, Adam P.,Andruszkiewicz, Ryszard,Zgoda, W?odzimierz,Walkowiak, Aleksandra,Ford, Celeste,Hudson, Alan L.
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scheme or table
p. 156 - 167
(2011/03/18)
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- Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof
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A pharmaceutical composition comprising idazoxan or derivatives and their therapeutically acceptable salts, racemates, optically active isomers and polymorphs.
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- Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof
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Pharmaceutical composition comprising 5 to 20% of an idazoxan salt or of idazoxan hydrate, 10 to 40% of microcrystalline cellulose, 1 to 5% of lubricant, 0.1 to 0.5% of colloidal silica and from 29.5% to 84.8% of lactose, with respect to the total mass.
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(2008/06/13)
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- Substituted heterocyclic compounds, method for preparing and compositions containing same
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The invention relates to compounds of formula (I): wherein: R1, R2and R3are as defined in the description, X is as defined in the description, Y represents an oxygen atom, a sulphur atom, a C(H)qgroup, SO or SO2, n is equal to from 0 to 5, A represents a NR5R6group, and medicinal products containing the same which are useful in treating or in preventing melatoninergic disorders.
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- N-(Dialkylamino-2 ethyl) 2,3-dihydro 1,4-benzodioxin 2-carboximidamides-2: Synthesis and pharmacological activities
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In connection with the structure of piperoxan 1 and the recently described pharmacological properties of N-(diethylamino-2 ethyl) 2,3-dihydro 1,4-benzodioxin 2-carboximidamide 2a (R = C2H5, R' = H) and of idazoxan 3, different structural analogues have been prepared. These derivatives showed marked antiarrhythmic properties leading to the disappearance of extrasystoles and to a persistent regularization of the cardiac rhythm of rabbits perfused with aconitine. In addition, sedative effects have been detected using classical tests.
- Davrinche,Nguyen-Tri-Xuong,Reynaud,Arnould-Guerin,Tran,Rinjard,Pieri
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p. 397 - 401
(2007/10/02)
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- 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles useful as antihypertensives and platelet aggregation inhibitors
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2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula: STR1 wherein R1, and R2 and R3 are independently selected from the group consisting of hydrogen, and alkyl (1-6C), and wherein n is an integer equal to 0, 1 or 2, and the pharmaceutically acceptable acid addition salts thereof, are α2 blockers and thus are useful as affectors of the CNS, specifically as platelet aggregation inhibitors and as antihypertensives.
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- 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles
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2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula STR1 wherein R1 and R2 are each independently selected from the group consisting of hydrogen, alkyl, optionally substituted phenyl, and optionally substituted phenyl
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- 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles useful as antidepressants
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2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula: STR1 wherein R1, and R2 and R3 are independently selected from the group consisting of hydrogen, and alkyl, and wherein n is an integer equal to 0, 1 or 2, and the pharmaceutically acceptable acid addition salts thereof, are useful as antidepressants.
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- 2-(1,4-Benzodioxan-2-ylalkyl)benzimidazoles useful as anti-depressants
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Compounds of the formula STR1 and the pharmaceutically acceptable, non-toxic salts thereof, wherein: R is hydrogen, lower alkyl, or benzyl; X is a substitution for hydrogen at any position in the benzene ring and is selected from the group consisting of lower alkyl, lower alkoxyl, benzyl and halo; m is an integer from 0 to 4; and n is an integer from 0 to 2; are novel. These compounds have been shown to be α2 blockers, and are, therefore, anti-depressants.
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