Synthesis of N-pyridyl azoles using a deprotometalation-iodolysis-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells

International audienc

Main group multiple C-H/N-H bond activation of a diamine and isolation of a molecular dilithium zincate hydride : experimental and DFT evidence for Alkali metal-zinc synergistic effects

The surprising transformation of the saturated diamine (iPr)NHCH2CH2NH(iPr) to the unsaturated diazaethene [(iPr)NCH=CHN(iPr)](2-) via the synergic mixture nBuM, (tBu)(2)Zn and TMEDA (where M = Li, Na; TMEDA = N, N,N',N'-tetramethylethylenediamine) has been investigated by multinuclear NMR spectroscopic studies and DFT calculations. Several pertinent intermediary and related compounds (TMEDA)Li[(iPr)NCH2CH2NH(iPr)]Zn(tBu)(2) (3), (TMEDA)Li[(iPr)NCH2CH2N(iPr)]Zn(tBu) (5), {(THF)Li[(iPr)NCH2CH2N(iPr)]Zn(tBu)}(2) (6), and {(TMEDA)Na[(iPr)NCH2CH2N(iPr)]Zn(tBu)}(2) (11), characterized by single-crystal X-ray diffraction, are discussed in relation to their role in the formation of (TMEDA)M[(iPr)NCH=CHN(iPr)]Zn(tBu) (M = Li, 1; Na, 10). In addition, the dilithio zincate molecular hydride [(TMEDA)Li](2)[(iPr)NCH2CH2N(iPr)]Zn(tBu)H 7 has been synthesized from the reaction of (TMEDA)Li[(iPr)NCH2CH2NH(iPr)]Zn(tBu)(2) 3 with nBuLi(TMEDA) and also characterized by both X-ray crystallographic and NMR spectroscopic studies. The retention of the Li-H bond of 7 in solution was confirmed by Li-7-H-1 HSQC experiments. Also, the Li-7 NMR spectrum of 7 in C6D6 solution allowed for the rare observation of a scalar (1)J(Li-H) coupling constant of 13.3 Hz. Possible mechanisms for the transformation from diamine to diazaethene, a process involving the formal breakage of four bonds, have been determined computationally using density functional theory. The dominant mechanism, starting from (TMEDA)Li[(iPr)NCH2CH2N(iPr)]Zn(tBu) (4), involves the formation of a hydride intermediate and leads directly to the observed diazaethene product. In addition the existence of 7 in equilibrium with 4 through the dynamic association and dissociation of a (TMEDA)LiH ligand, also provides a secondary mechanism for the formation of the diazaethene. The two reaction pathways (i.e., starting from 4 or 7) are quite distinct and provide excellent examples in which the two distinct metals in the system are able to interact synergically to catalyze this otherwise challenging transformation

Forced labor as a criminal punishment

Piespiedu darbs Latvijā tiek piemērots jau trīspadsmit gadus, taču joprojām nav rimušas diskusijas, kas saistītas ar piespiedu darba piemērošanu praksē un problēmjautājumiem. Aktualitāti joprojām nezaudē arī fakts, ka Latvijā aizvien ir viens no lielākajiem rādītājiem attiecībā uz ieslodzīto personu skaitu uz 100 000 iedzīvotājiem. Tas rosina domāt par to, vai Latvijā tiek pilnībā izmantotas visas iespējas, ko sniedz piespiedu darba kā kriminālsoda piemērošana. Autore piedāvā ieskatu galvenajos secinājumos: 1)jākonkretizē Krimināllikumā iekļautais jēdziens „darbnespējīga persona”; 2)būtu vēlams izstrādāt kritērijus, pēc kuriem noteikt piespiedu darba stundu skaitu, jo šobrīd motivāciju tam veido tikai tiesnešu un prokuroru subjektīvs viedoklis; 3)Kriminālprocesa likumā iekļaut punktu, kas uzliktu par pienākumu tiesnešiem spriedumā iekļaut pienāku notiesātajai personai noteiktā laikā ierasties Valsts probācijas dienestā; 4)u.c. Atslēgvārdi: kriminālsods, piespiedu darbs, piemērošana, izpilde, Valsts probācijas dienests, arests