874-88-4Relevant articles and documents
Direct Trifluoromethoxylation without OCF3-Carrier through In Situ Generation of Fluorophosgene
Donnard, Morgan,Guérin, Thomas,Hanquet, Gilles,Leroux, Frédéric R.,Panossian, Armen,Saiter, Jérémy
supporting information, p. 3139 - 3147 (2021/06/26)
Owing to the high interest in the OCF3 group for pharmaceutical and agrochemical applications, trifluoromethoxylation received great attention in the last years with several new methods for this approach towards OCF3-comprising compounds. Yet, it most often requires the beforehand preparation of specific F3CO? transfer reagents, which can be toxic, expensive, unstable, and/or generate undesired side-products upon consumption. To circumvent this, the in-situ generation of gaseous fluorophosgene from triphosgene, its conversion by fluoride into the OCF3 anion, and the direct use of the latter in nucleophilic substitutions is an appealing strategy, which, although recently approached, has not been fully exploited. We disclose herein our efforts towards this aim.
Catalytic Halogen Bond Activation in the Benzylic C-H Bond Iodination with Iodohydantoins
Combe, Sascha H.,Hosseini, Abolfazl,Song, Lijuan,Hausmann, Heike,Schreiner, Peter R.
supporting information, p. 6156 - 6159 (2017/11/24)
This letter presents the side-chain iodination of electron-deficient benzylic hydrocarbons at rt using N-hydroxyphthalimide (NHPI) as radical initiator and 1,3-diiodo-5,5-dimethylhydantoin and 3-iodo-1,5,5-trimethylhydantoin (3-ITMH) as iodine source. Addition of a carboxylic acid increased the reactivity due to complex formation with and activation of 3-ITMH by proton transfer and halogen bond formation. No SEAr reactions were observed under the employed reaction conditions. Our method enables convenient product isolation and gives 50-72% yields of isolated products.
An efficient and selective method for the iodination and bromination of alcohols under mild conditions
Khazdooz, Leila,Zarei, Amin,Aghaei, Hamidreza,Azizi, Ghobad,Gheisari, Mohammad Mehdi
, p. 168 - 171 (2015/12/30)
A straightforward and effective procedure for the conversion of a variety of alcohols into the corresponding alkyl iodides and bromides is described using KX/P2O5 (X = I, Br). The reactions were easily carried out in acetonitrile under mild conditions. Using this method, the selective conversion of benzylic alcohols in the presence of aliphatic alcohols was achieved.
Reversed electron apportionment in mesolytic cleavage: The reduction of benzyl halides by SmI2
Yitzhaki, Offir,Hoz, Shmaryahu
, p. 9242 - 9248 (2015/06/16)
The paradigm that the cleavage of the radical anion of benzyl halides occurs in such a way that the negative charge ends up on the departing halide leaving behind a benzyl radical is well rooted in chemistry. By studying the kinetics of the reaction of substituted benzylbromides and chlorides with SmI2 in THF it was found that substrates para-substituted with electron-withdrawing groups (CN and CO2Me), which are capable of forming hydrogen bonds with a proton donor and coordinating to samarium cation, react in a reversed electron apportionment mode. Namely, the halide departs as a radical. This conclusion is based on the found convex Hammett plots, element effects, proton donor effects, and the effect of tosylate (OTs) as a leaving group. The latter does not tend to tolerate radical character on the oxygen atom. In the presence of a proton donor, the tolyl derivatives were the sole product, whereas in its absence, the coupling dimer was obtained by a SN2 reaction of the benzyl anion on the neutral substrate. The data also suggest that for the para-CN and CO2Me derivatives in the presence of a proton donor, the first electron transfer is coupled with the proton transfer. Reverse breakup: In the mesolytic cleavage of the radical anions of benzyl halides that are para-substituted by CN or CO2Me groups, the halogen departs, counterintuitively, as a radical and the benzyl system carries the negative charge (see figure).
Design, synthesis and anticancer activities of novel otobain derivatives
Li, Zhongzhou,Su, Hui,Yu, Weiwei,Li, Xinjun,Cheng, Hao,Liu, Mingyao,Pang, Xiufeng,Zou, Xinzhuo
, p. 277 - 287 (2015/12/30)
A series of novel racemic otobain derivatives was designed and synthesised using 2-piperonyl-1,3-dithianes in the conjugate addition-alkylation to 5H-furan-2-one, followed by cationic cyclisation. All the synthesised compounds were consequently evaluated for their anticancer activity against several human cancers in vitro. The efficacy of the most active compound 27g was comparable with etoposide, with IC50 values ranging from 1.06 μM to 4.16 μM in different cancer cell lines. Notably, compound 27g strongly induced cell cycle arrest and increased the expression of mitosis-specific markers MPM-2 and phosphorylated histone H3, but it did not trigger cell apoptosis. Further a colony formation assay showed that compound 27g effectively inhibited the anchor growth of lung cancer cells in a dose-dependent manner. More importantly, compound 27g at 40 mg kg-1 significantly suppressed tumour volume (P 0.01) and tumour weight (P 0.05) in a human lung cancer cell xenograft mouse model without causing systematic toxicity in mice. Our findings indicated that compound 27g has significant potential for further drug development.
A direct transformation of Aryl Aldehydes to Benzyl Iodides Via reductive iodination
Ruso, Jayaraman Sembian,Rajendiran, Nagappan,Kumaran, Rajendran Senthil
, p. 39 - 43 (2014/03/21)
A facile transformation of aryl aldehydes to benzyl iodides through one-pot reductive iodination is reported. This protocol displays remarkable functional group tolerance and the title compound was obtained in good to excellent yield.
Optimization of novel indole-2-carboxamide inhibitors of neurotropic alphavirus replication
Sindac, Janice A.,Barraza, Scott J.,Dobry, Craig J.,Xiang, Jianming,Blakely, Pennelope K.,Irani, David N.,Keep, Richard F.,Miller, David J.,Larsen, Scott D.
, p. 9222 - 9241 (2014/01/06)
Neurotropic alphaviruses, which include western equine encephalitis virus (WEEV) and Fort Morgan virus, are mosquito-borne pathogens that infect the central nervous system causing acute and potentially fatal encephalitis. We previously reported a novel series of indole-2-carboxamides as alphavirus replication inhibitors, one of which conferred protection against neuroadapted Sindbis virus infection in mice. We describe here further development of this series, resulting in 10-fold improvement in potency in a WEEV replicon assay and up to 40-fold increases in half-lives in mouse liver microsomes. Using a rhodamine123 uptake assay in MDR1-MDCKII cells, we were able to identify structural modifications that markedly reduce recognition by P-glycoprotein, the key efflux transporter at the blood-brain barrier. In a preliminary mouse PK study, we were able to demonstrate that two new analogues could achieve higher and/or longer plasma drug exposures than our previous lead and that one compound achieved measurable drug levels in the brain.
ARBOVIRUS INHIBITORS AND USES THEREOF
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Page/Page column 60, (2012/10/08)
The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.
Synthesis and bladder smooth muscle relaxing properties of substituted 3-amino-4-aryl-(and aralkyl-)cyclobut-3-ene-1,2-diones
Butera, John A.,Jenkins, Douglas J.,Lennox, Joseph R.,Sheldon, Jeffrey H.,Norton, N. Wesley,Warga, Dawn,Argentieri, Thomas M.
, p. 2495 - 2501 (2007/10/03)
We have reported on the design, synthesis, and biological characterization of (R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3- ethyl-benzonitrile (1),1 a novel, potent, and selective adenosine 5′-triphosphate-sensitive
Selective functionalisation of hydrocarbons by nitric acid and aerobic oxidation catalysed by N-hydroxyphthalimide and iodine under mild conditions
Minisci, Francesco,Recupero, Francesco,Gambarotti, Cristian,Punta, Carlo,Paganelli, Roberto
, p. 6919 - 6922 (2007/10/03)
Alkylbenzenes are selectively functionalised to the corresponding acetates by nitric aerobic oxidation catalysed by N-hydroxyphthalimide and iodine. With cyclohexane the oxidation leads to a mixture of cyclohexyl acetate and trans-2-iodocyclohexyl acetate. The mechanism is discussed.
