Multistep batch-flow hybrid synthesis of a terbinafine precursor

A three-step batch-flow hybrid process has been developed for an expeditious synthesis of the enynol key intermediate of antifungal terbinafine. This procedure involves consecutive organometallic steps without the necessity of any in-line purification: after a metalation by n-butyllithium, a selective addition of the lithium salt was elaborated followed by a Grignard reaction resulting in a high yield of 6,6-dimethylhept-1-en-4-yn-3-ol. Moreover, as an alternative to tetrahydrofuran, cyclopentyl methyl ether was used as solvent implementing a safe, sustainable, yet selective synthetic process. Even on a laboratory-scale, the optimized batch-flow hybrid process had a theoretical throughput of 41 g/h. Furthermore, the newly developed process provides an efficient synthesis route to the key-intermediate, while making acrolein obsolete, minimizing side-products, and enabling safe and convenient scale-up.

Criminal Law Measures Providing for the Treatment of Socially Significant Diseases: a Mandatory Application or a Selective Addition

Modern society faces a serious problem of preserving the health of people. Currently, there are some wide-spread diseases that are highly dangerous because they are easily transmitted and have a high mortality rate. These diseases compose a group of socially significant diseases, their list is approved by the Decree of the RF Go­vernment of Dec. 1, 2004 No. 715. One of the key institutes of counteracting the spread of socially significant diseases is the institute of criminal law measures. A number of clauses of the RF Criminal Code regulate mandatory treatment of criminally liable persons. The use of criminal law measures is regulated by Art. 72.1, 73, 79, 82.1 and Ch. 15 of the RF Criminal Code, while Art. 18 of the RF Penitentiary Code determines the procedure of using medical measures to treat persons sentenced to punishments involving isolation from the society. However, the non-mandatory and ambiguous procedure of prescribing mandatory treatment for socially significant di­seases through criminal law means creates difficulties in organizing a comprehensive approach to treating such diseases. In the process of their research, the authors ascertained that it is necessary to adopt an uncompromising approach in prescribing treatment of a socially significant disease by using criminal law measures to a person suffering from such a disease. This goal could be achieved by replacing the phrase «could hold accountable» to «holds accountable» in the clauses of Art. 72.1, 73 and 79 of the RF Criminal Code. It is suggested that the legal limitation of the use of mandatory treatment for convicts isolated from the society should be abolished by elimina­ting the words «which is connected with danger to themselves or other persons» from Part 2, Art. 18 of the RF Penitentiary Code. Related problems arise during the mandatory treatment of psychiatric disorders that are socially significant diseases too. Thus, the elimination of legal problems of treating socially significant diseases through criminal law measures will increase the effectiveness of criminal legislation from the standpoint of its social function — the protection of the society and its representatives.

Unexpected Radical Telomerisation of Vinylidene Fluoride with 2-Mercaptoethanol

The radical telomerisation of vinylidene fluoride (VDF) with 2-mercaptoethanol as chain transfer agent (CTA) was studied to synthesise fluorinated telomers which bear a hydroxy end-group, such as H(VDF)nS(CH2)2OH, under thermal (di-tert-butyl peroxide as the initiator) or photochemical initiations. A careful structural study of a typical H-VDF-S(CH2)2OH telomer was performed by 1H and 19F NMR spectroscopy. These analytical methods allowed us to explore the selective addition of the thiyl radical onto the hydrogenated side of VDF, and the telomer containing one VDF unit was obtained selectively. Surprisingly, for higher [VDF]o initial concentrations, a monoadduct telomer was produced as well as PVDF homopolymer. This feature was related to the fast consumption of the CTA. The kinetics of radical telomerisation led to a quite high transfer constant of the CTA (40 at 140 °C) that evidences the formation of a monoadduct as the only telomer formed.