Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives

1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained.

Effects of culture conditions on larval growth and survival of stalked barnacles (Pollicipes pollicipes).

Pollicipes pollicipes (Crustacea: Scalpelliformes) is a highly prized food in Portugal and Spain and con- sequently a species of considerable interest to aqua- culture. Surprisingly, however, larval culture conditions for this barnacle have not been opti- mized. This study investigated the effects of temper- ature, diet, photoperiod and salinity on the growth and survival of P. pollicipes larvae. Temperature had a significant effect on specific growth rate (2.6–5.9% total width per day, from 11 to 24°C), reducing mean development time to the cyprid from 25 days at 11 °C to 10 days at 24°C, although this was accompanied by a significant increase in mortality to over 90% above 22°C. Mid- range temperatures (15–20°C) maximized total survival (19–31% respectively). Algal diets of Tetra- selmis suecica, T. suecica/Skeletonema marinoi and S. marinoi/Isochrysis galbana did not affect specific growth rate significantly, but survival (on average 39% in 15 days) and the proportion of high-quality healthy cyprids was significantly higher on the lat- ter two diets (11–15% of initial number of larvae). Photoperiod did not significantly affect the survival, although specific growth rate was significantly higher at 24:0 and 16:8 L:D. Salinity (20– 40 g L 1 range) did not affect growth and survival significantly. The best growth and survival were accomplished using rearing temperatures of 15–20°C, daily feeding with T. suecica/S. marinoi or I. galbana/S. marinoi and a photoperiod of 24:0 L:D.