Variations on the Bergman Cyclization Theme: Electrocyclizations of Ionic Penta-, Hepta-, and Octadiynes.

The Bergman cyclization of (Z)-hexa-3-ene-1,5-diyne to form the aromatic diradical p-benzyne has garnered attention as a potential antitumor agent due to its relatively low cyclization barrier and the stability of the resulting diradical. Here, we present a theoretical investigation of several ionic extensions of the fundamental Bergman cyclization: electrocyclizations of the penta-1,4-diyne anion, hepta-1,6-diyne cation, and octa-1,7-diyne dication, leveraging the spin-flip formulation of the equation-of-motion coupled cluster theory with single and double substitutions (EOM-SF-CCSD). Though the penta-1,4-diyne anion exhibits a large cyclization barrier of +66 kcal mol-1, cyclization of both the hepta-1,6-diyne cation and octa-1,7-diyne dication along a previously unreported triplet pathway requires relatively low energy. We also identified the presence of significant aromaticity in the triplet diradical products of these two cationic cyclizations.

Enabling intensification of multiphase chemical processes with additive manufacturing.

Fixed bed supports of various materials (metal, ceramic, polymer) and geometries are used to enhance the performance of many unit operations in chemical processes. Consider first metal and ceramic monolith support structures, which are typically extruded. Extruded monoliths contain regular, parallel channels enabling high throughput because of the low pressure drop accompanying high flow rate. However, extruded channels have a low surface-area-to-volume ratio resulting in low contact between the fluid phase and the support. Additive manufacturing, also referred to as three dimensional printing (3DP), can be used to overcome these disadvantages by offering precise control over key design parameters of the fixed bed including material-of-construction and total bed surface area, as well as accommodating system integration features compatible with continuous flow chemistry. These design parameters together with optimized extrinsic process conditions can be tuned to prepare customizable separation and reaction systems based on objectives for chemical process and/or the desired product. We discuss key elements of leveraging the flexibility of additive manufacturing to intensification with a focus on applications in continuous flow processes and disperse, multiphase systems enabling a range of scalable chemistry spanning discovery to manufacturing operations.

A Multireference Ab Initio Study of the Diradical Isomers of Pyrazine.

Three diradical pyrazine isomers were characterized using highly correlated, multireference methods. The lowest lying singlet and triplet state geometries of 2,3-didehydropyrazine ( ortho), 2,5-didehydropyrazine ( para), and 2,6-didehydropyrazine ( meta) were determined. Two active reference spaces were utilized. The complete active space (CAS) (8,8) includes the σ and σ* orbitals on the dehydrocarbon atoms as well as the valence π and π* orbitals. The CAS (12,10) reference space includes two additional orbitals corresponding to the in-phase and out-of-phase nitrogen lone pair orbitals. Adiabatic and vertical gaps between the lowest lying singlet and triplet states, optimized geometries, canonicalized orbital energies, unpaired electron densities, and spin polarization effects were compared. We find that the singlet states of each diradical isomer contain two significantly weighted configurations, and the larger active space is necessary for the proper physical characterization of both the singlet and triplet states. The singlet-triplet splitting is very small for the 2,3-didehydropyrazine ( ortho) and 2,6-didehydropyrazine ( meta) isomers (+1.8 and -1.4 kcal/mol, respectively) and significant for the 2,5-didehydropyrazine ( para) isomer (+28.2 kcal/mol). Singlet geometries show through-space interactions between the dehydocarbon atoms in the 2,3-didehydropyrazine ( ortho) and 2,6-didehydropyrazine ( meta) isomers. An analysis of the effectively unpaired electrons suggests that the 2,5-didehydropyrazine ( para) isomer also displays through-bond coupling between the diradical electrons.

An Extended Multireference Study of the Singlet and Triplet States of the 9,10-didehydroanthracene Diradical.

The 9,10-didehydroanthracene is an aromatic diradical produced by the Bergman cyclization of a benzannulated 10-membered enediyne. It is a 1,4 diradical, similar to p-benzyne. Here we study the spin state occupancy of the ground state of 9,10-didehydroanthracene by employing multireference methods (MR-CISD and MR-AQCC) with different basis sets (cc-pVDZ and cc-pVTZ) and active space sizes (CAS (2,2) through CAS (8,8)). At the CAS (8,8) MR-AQCC/cc-pVDZ level of theory, we find a two-configurational singlet ground state with an adiabatic Δ EST of 6.13 kcal/mol. Unpaired electron density populations and dominant electronic configuration interactions were used to analyze the features of the 9,10-didehydroanthracene diradical.

An ab Initio Exploration of the Bergman Cyclization.

The Bergman cyclization is an important reaction in which an enediyne cyclizes to produce a highly reactive diradical species, p-benzyne. Enediyne motifs are found in natural antitumor antibiotic compounds, such as calicheammicin and dynemicin. Understanding the energetics of cyclization is required to better control the initiation of the cyclization, which induces cell death. We computed the singlet and triplet potential energy surfaces for the Bergman cyclization of (Z)-hex-3-ene-1,5-diyne using the CCSD and EOM-SF-CCSD methods. The triplet enediyne and transition state were found to have C2 symmetry, which contrasts with the singlet reactant and transition state that possess C2v symmetry. We analyzed the frontier orbitals of both cyclization pathways to explain the large energetic barrier of the triplet cyclization. Reaction energies were calculated using CCSD(T)/cc-pVTZ single-point calculations on structures optimized with CCSD/cc-pVDZ. The singlet reaction was found to be slightly endothermic (ΔHrxn = 13.76 kcal/mol) and the triplet reaction was found to be highly exothermic (ΔHrxn = -33.29 kcal/mol). The adiabatic singlet-triplet gap of p-benzyne, computed with EOM-SF-CCSD/cc-pVTZ, was found to be 3.56 kcal/mol, indicating a singlet ground state.