Synthesis and antitumor evaluation of some new 1,3,4-oxadiazole-based heterocycles.

Publisher Summary This chapter discusses the chemistry of pyrazoles condensed to heteroaromatic five- and six-membered ring structures, and the synthesis of pyrazoloazines and its related compound. The synthesis of pyrazoles condensed to five-membered rings is analyzed along with the synthetic routes to ring systems. There exist three systems where pyrazoles are condensed to five-membered rings with one heteroatom. For pyrrolopyrazoles, a fourth isomerer is also possible. When the pyrazole ring is fused to a heterocyclic system in which the heteroatom is tetravalent, several isomeric structures can be drawn. The chemistry of pyrazoles condensed to six-membered rings can best be understood by assuming that the system consists of a five-membered π-excessive heterocyclic ring that is fused to a six-membered π-deficient ring. Thus, electrophilic reagents are expected to attack either the pyrazole nitrogens or carbons. On the other hand, nucleophilic reagents are expected to attack the six-membered ring. Pyrazoles condensed to a five-membered ring with one heteroatom have a π-deficient pyrazole and an electron-rich, five-membered ring.

Chemistry of Pyrazoles Condensed to Heteroaromatic Five- and Six-Membered Rings

Aiming to produce cyclized systems with potential bioactivity, a variety of fused and/or pendant thiophene, pyrazole, imidazole, thiazole, triazole, triazine, and coumarin systems were synthesized based on a cyanoacetic 2-[(benzoylamino)thi- oxomethyl] hydrazide precursor. The structure of the synthesized compounds was established based on elemental analysis and spectral data. The antibacterial and antifungal activities of the compounds are discussed and evaluated.

Synthesis, Structure Elucidation, and Biological Evaluation of Some Fused and/or Pendant Thiophene, Pyrazole, Imidazole, Thiazole, Triazole, Triazine, and Coumarin Systems Based on Cyanoacetic 2-[(Benzoylamino)thioxomethyl] Hydrazide

A series of novel thiobarbituric acid derivatives 3a–c , 5, and 12 were synthesized via the reaction of 4-benzoyl-1-cyanoacetylthiosemicarbazide ( 1 ) or its derivatives 2a–c , 9 with malonic acid and acetyl chloride. Coupling of thiobarbituric acid derivatives 3a-c and 5 with aromatic diazonium chlorides furnished a new series of the corresponding bisarylhydrazo-thiobarbituric dyes 4a–c . The reaction of 5 with cyclohexanone and sulfur under Gewald reaction condition afforded thieno[2,3-d]pyrimidine derivative 21 , that condensed with p-anisladehyde to give 5-arylidene thiobarbituric acid derivative 22 . The reaction of 1 with phenyl isothiocyanate afforded the non-isolable adduct 23 which was used as a key intermediate for the synthesis of polyfunctionally substituted thiazolidinone and thiobarbituric ring systems.

Synthesis and Reactions of Some New Thiobarbituric Acid Derivatives

4-Benzoyl-1-cyanoacetylthiosemicarbazide undergoes coupling reaction with aromatic diazonium chloride to afford (arylhydrazono)thiosemicarbazide, which was reacted with phenacyl bromide regioselectivity to afford the thiazoline. The (arylhydrazono)thiosemicarbazide could be transformed into the pyrazolo[1,5-a]triazine. Heterocyclization of 4-benzoyl-1-cyanoacetylthiosemicarbazide with α-haloketones (bromoacetone and phenacyl bromide), ethyl iodide, and ethyl bromoacetate furnished the pyrrylthiazoles, 1,2,4- triazole, and 1,3,4-thiadiazine. The latter was coupled with aromatic diazonium chloride to give the bis(arylhydrazono)‐thiadiazine. The mechanism for the formation of the title compounds was suggested and discussed.

Heterocyclic Synthesis with 4-Benzoyl-1-cyanoacetylthiosemicarbazide: Selective Synthesis of Some Thiazole, Triazole, Thiadiazine, Pyrrylthiazole, and Pyrazolo(1,5-a)triazine Derivatives

The reaction of isothiocyanates with 2‐cyanoethanoic acid hydrazide. A novel synthesis of 1,3,4‐thiadiazoles

European solidarity is in high demand as the Covid-19 pandemic delivers a deep and asymmetric shock to EU economies and societies. Will there be sufficient supply? The European Council meeting of 17-21 July has agreed on a historic €750bn EU recovery fund. Yet, it has also exposed deep rifts among governments about the appropriate level and scope of European solidarity. The success of the agreement ultimately depends on voter attitudes. Will they support – and pay for – European solidarity or will they oppose it? We use new survey evidence (April 2020) to assess public support for European solidarity in 13 EU member states and the UK. Our analysis yields a number of important findings: support for solidarity varies by geographical distance, by issue, and by the perceived net-benefit to the own country; support is motivated by expectations of reciprocal benefit rather than feelings of moral obligation or common identity; in terms of instrumentation, most respondents prefer permanent EU arrangements of risk and burden sharing to ad hoc mutual assistance; a relative majority of respondents prefers a Europe that protects to a market Europe or a global Europe aspiring to international leadership. 1. Solidarity: high demand but short supply What’s new? In the wake of the coronavirus pandemic, European solidarity is in high demand, bringing back haunting memories – a déjà vu if there ever was one – from the 2010-2015 eurozone sovereign debt crisis and the 2015-2016 migration crisis, when the supply of solidarity remained meagre at best. Practically overnight, European institutions, from the Schengen open border agreement to the single market have come under siege. The freedom of movement was suspended, first by Austria and then by 21 more EU member states. The spread of the pandemic brought havoc first to Italy and Spain and then to Germany, the Netherlands and other member states. It exposed economic divergences that had been hidden behind the veil of a timid recovery in recent years. Some member states were much better placed to fight the downturn with discretionary fiscal measures than others, thus reinforcing the contentious quest for European solidarity. Trying times for EU solidarity, but there are silver linings too. Compared to the eurozone crisis, when EU leaders wavered to do the bare minimum to keep the EU together and to save the euro, the coronavirus crisis response proved more expedite and better coordinated. The ECB moved fast to contain interest rate spreads in the Eurozone in March. The member states agreed on a loan-based first aid package of 1 An earlier version of this article was published in mid-July as a Policy Brief, before the EU leaders reached a deal on July 21 on the bloc's long-term budget and economic recovery fund after four days of intense negotiations. 2 Lorenzo Cicchi is Research Associate at the Robert Schuman Centre for Advanced Studies and coordinator of the European Governance and Politics Programme; Philipp Genschel is Joint Professor of European Public Policy, Department of Political and Social Sciences and the Robert Schuman Centre of Advanced Studies; Anton Hemerijck is Professor of Political Science and Sociology, Department of Political and Social Sciences; Mohamed Nasr is PhD researcher, Department of Political and Social Sciences, European University Institute (EUI) and assistant lecturer at the Faculty of Economics and Political Science, Cairo University. 3 We would like to thank Stephan Shakespeare and Jonathan van Parys for stimulating feedback on the paper and generous support for the EUI-YouGov EU Solidarity Survey, as well as Waltraud Schelkle for comments. 540 billion Euros in April. In July, they passed an EU recovery package of 750 billion Euros, a large part of which is grants-based. While some have hailed this as a breakthrough towards more European solidarity, the fraught negotiations also revealed the divisiveness of the issue among government leaders anxious keep their voters happy. But how critical are voters really? When do they support and when do they oppose solidarity with other member states and why? Our analysis is based on the third iteration of the EUI-YouGov survey on Solidarity in Europe. The survey covers 13 EU member states and the UK. It was conducted in April 2020 at the height of the Corona pandemic in Europe. As in earlier (2018, 2019) renditions of the survey, it explores how support for European solidarity varies by issue (solidarity for what?), instrument (solidarity how?) and by member state (solidarity by whom for whom?). In addition, the 2020 survey contains questions on the ‘kind of society’ and the ‘kind of Europe’ citizens wish to live in. The dataset is available for download in Open Access from the EUI research repository through this link. 2. The multi-dimensional political space of (European) solidarity Solidarity as insurance. Organized solidarity provides the members of a community with an insurance mechanism against ‘bad luck’. This allows individual members to accept more risk, thereby enabling the group as a whole to pursue more ambitious goals and to more effectively defend its community cohesion under conditions of adversity. That is the overriding advantage of solidarity. Yet, this advantage only materializes in the long run and before the victims of bad luck are known. Once the veil of ignorance is lifted, and the identity of the victims is revealed, there are also short-run problems (as highlighted in the 2018 report): i. Solidarity is costly. It requires that group members pass some of their own physical, financial, human or organizational resources to other members of the community in order to improve the well-being, or reduce the suffering of these other members. Solidarity involves sharing in a real, that is material sense. In the short-run this may be perceived as a net-loss rather than a beneficial insurance premium for the long-run. ii. Solidarity is uneven. Solidarity involves transfers from better-off to less well-off members of the community. The transfers are zero-sum, at least in the short term. They flow from good risks to bad risks, from givers to takers, from net-contributors to net-beneficiaries with no immediate compensation. This may give rise to perceptions of inequity and unfairness. iii. Solidarity breeds the suspicion of moral hazard. Solidarity unburdens actors from the need to selfprotect against bad risks. This may induce careless or even openly exploitative and fraudulent behaviour that elicits unnecessary bad risks, i.e. risks that could have been avoided through appropriate self-protection, and this further increases the costs of solidarity. Even when victims act with all appropriate care, the sheer suspicion of carelessness can lead to distrust and denial of solidarity. There are solutions to each of these problems but they are ambiguous. To reduce the costs of solidarity, risk should be put on many shoulders. Hence, the risk pool should be relatively large. To avoid the same actors always ending up at the paying-end of the solidarity relation, the risk pool should be 4 Total sample size was 21779 adult respondents (2151 from the UK, 2014 from Denmark, 1005 from Finland, 2033 from France, 2004 from Sweden, 1007 from Greece, 1032 from Hungary, 2021 from Italy, 1013 from Lithuania, 1136 from the Netherlands, 1012 from Poland, 1017 from Romania, 2281 from Spain). Fieldwork was undertaken between 17 and 29 April 2020. The survey was carried out online. All figures are based on data taken from the YouGov survey. heterogeneous so as to increase the chances of turn-taking in solidary giving and taking. Yet, to reduce (the suspicion of) moral hazard, the risk pool should be small and homogeneous. People tend to trust people who are like them because they have more scruples before betraying their own kind. The EU is large and its societies are diverse. This makes European solidarity potentially very rewarding for all, but also very fragile. Does European solidarity exist? European solidarity is real. In the EUI-YouGov survey, we ask respondents on a 0-10 scale whether they think national governments should spend national resources only on their own country and the welfare of their own people or also on other EU countries and other people. We summarize the answers in Figure 1. The figure shows the country averages (left-panel) and maps these averages geographically (rightpanel). It shows two fairly coherent regional clusters: the least resourceful South-Eastern bloc of countries shows more willingness to pay for others, whereas the more resourceful North-Western bloc shows less willingness to pay. Support levels in the North-Western group fall below the European average (represented by the vertical dashed line) whereas the seven South-Eastern countries in our sample are above average. This chimes with the entrenched divisions in the European Council between Northern creditors and Southern debtors, the ‘Frugal Four’ and the ‘Friends of Cohesion’. Note, however, that the European average is fairly high and the spread around the average is fairly compressed. General support for solidarity varies from moderate (an average of 5 for Denmark) to moderately-high (average 7 for Romania). Hence, the overall picture is quite positive. Figure 1 – Support for spending national resources on other EU countries. The left-panel represents country averages with 95% confidence intervals. The right-panel represents the European map, where darker colours express more support for solidarity. The survey question is: “Some people think that the member states of the European Union should mostly spend their resources on their own countries and the welfare of their own people. Other people think that the member states of the European Union should pool their resources and spend them on all countries and all people across the whole of the European Union. What about you – on a scale of 0 to 10, where 0 means 'Spending resources 

EU solidarity in times of Covid-19

Der Beitrag berichtet anhand neuer Umfrageergebnisse (April 2020) über die öffentliche Zustimmung zu EU-Solidarität in 13  EU-Mitgliedstaaten und in Großbritannien. Die Analyse ergibt u. a. diese Erkenntnisse: Die Befürwortung variiert je nach geografischer Entfernung, Problematik und empfundenem Nettonutzen für das eigene Land ; sie ist eher durch die Erwartung gegenseitigen Nutzens motiviert als durch Gefühle moralischer Verpflichtung oder gemeinsamer Identität ; die meisten Befragten bevorzugen dauerhafte EU-Vereinbarungen zur Risiko- und Lastenteilung gegenüber einzelfallbasierter Ad-hoc-Hilfe ; eine relative Mehrheit zieht ein beschützendes Europa einem marktschaffenden oder einem globalen Europa mit internationalem Führungsanspruch vor.

Mohamed Nasr

Papers

The reaction of isothiocyanates with 2‐cyanoethanoic acid hydrazide. A novel synthesis of 1,3,4‐thiadiazoles

EU solidarity in times of Covid-19

EU-Solidarität in Zeiten von Covid-19

The motivated electorate: Voter uncertainty, motivated reasoning, and ideological congruence to parties

Voter perceptions of parties’ left–right positions: The role of party strategies