Ab initioMODPOT/VRDDO/MERGE calculations on energetic compounds. IV. Nitrocubanes: Mononitro to octanitro quantum chemical calculations and electrostatic molecular potential contour maps

Ab initio MODPOT /VRDDO /MERGE calculations have been carried out for all the different position isomers of nitrocubane from mononitrocubane through octanitrocubane for a perfect symmetrical cubic cubane skeleton and for mononitrocubane through septanitrocubane for the almost cubic experimentally determined cubane skeleton. These calculations were carried out with our own rapid efficient ab initio programs which also incorporate a number of desirable computational strategies for calculations on large molecules. The skeletal total overlap population of the cubane skeleton (a theoretical index we showed years ago to be sensitive and predictive of stability of energetic molecular frameworks) indicates that successive nitration seems to increase the stability of the cubane skeleton. Successive nitration also seems to increase the total overlap population of the C? NO₂ bond. There are subtle differences depending on the exact positional isomer for a constant number of nitro groups—but the overall trend is definite. We have also generated electrostatic molecular potential contour (EMPC ) maps around these nitrocubanes. These maps are indicative of preferred positions of electrophilic and nucleophilic attack as a function of the number of nitro groups or their positions. These EMPC maps can also indicate, to a first approximation, a limit on how close these molecules may be able to approach each other in a crystal.     

Molecular calculations with the nonempirical ab initioMODPOT,VRDDO, and MODPOT/VRDDO procedures. XII. Carcinogenic 3-methylcholanthrene and its metabolites using a MERGE technique

Ab initio MODPOT/VRDDO/MERGE calculations were carried out on carcinogenic 3-methylcholanthrene (3-MCA) and its metabolites. The results for 3-MCA were compared to our earlier similar calculations for carcinogenic benzo(a)pyrene (BP). Both compounds 3-MCA and BP are carcinogenic and are metabolically activated by similar mechanisms but in different positions. Both the calculated wave functions for 3-MCA and BP and the electrostatic molecular potential contour maps generated from these wave functions correctly reflect the similarity of mechanisms of metabolic activation and the differences in position. Our calculated results both for BP and for 3-MCA reflect accurately their experimentally observed behavior. Thus this combination of theoretical techniques can be used with confidence to describe the behavior of the polycyclic aromatic hydrocarbons (PAH's) and their metabolites. The ab initio MODPOT/VRDDO method incorporates two very desirable options into our fast ab initio Gaussian programs: MODPOT –ab initio effective core model potentials—and a charge-conserving integral prescreening approximation which we named VRDDO (variable retention of diatomic differential overlap). For orbital energies and population analysis the MODPOT/VRDDO results agree to essentially three decimal places with completely ab initio calculations using the same valence atomic basis set. For this series of very closely related congeners our recent MERGE technique which allows reuse of integrals from a common skeletal fragment was used. The ab initio MODPOT/VRDDO/MERGE calculations were carried out for 3-MCA, 3-MCA oxides, 3-MCA dihydrodiols, and 3-MCA dihydrodiolepoxides. The metabolites investigated were 3-MCA 9,10-oxide; 3-MCA 7,8-oxide; 3-MCA 9,10-dihydrodiol [trans(axial, axial); trans(equatorial, equatorial); cis(axial, equatorial); cis(equatorial, axial)]; and 3-MCA 9,10-dihydrodiol–7,8-epoxide [for both conformations A and B of the dihydrodiol and for all stereoisomers of the dihydrodiolepoxides relative to below and above the plane: ααα, and ααβ αβα αββ βαα βαβ ββα and βββ (most stable)]. Calculations were also carried out for opening of the C₇? O? C₈ epoxide ring both towards C₇ and C₈ for the most stable isomer Aβββ (above the ring). Opening the epoxide ring between C₇ and O leads to a more stable intermediate than opening the epoxide ring between C₈ and O. Again, however, as with opening the epoxide ring in BP 7,8-dihydrodiol–9,10-epoxide there is no buildup of positive charge on C₇ in the 3-MCA metabolites as postulated by some cancer researchers, but rather the C₇ becomes slightly more negative. Nor is there a buildup of negative charge on the O atom, but rather it becomes slightly more positive. As the epoxide ring is opened further than 90° for the O? C₇? C₈ or O? C₈? C₇ angles, there appears to be a possible mixing of configurations that is being investigated further.     

Synthesis of Di‐, Tri‐, and Tetrasubstituted Oxetanes by Rhodium‐Catalyzed OH Insertion and CC Bond‐Forming Cyclization

Oxetanes offer exciting potential as structural motifs and intermediates in drug discovery and materials science. Here an efficient strategy for the synthesis of oxetane rings incorporating pendant functional groups is described. A wide variety of oxetane 2,2‐dicarboxylates were accessed in high yields, including functionalized 3‐/4‐aryl‐ and alkyl‐substituted oxetanes and fused oxetane bicycles. Enantioenriched alcohols provided enantioenriched oxetanes with complete retention of configuration. The oxetane products were further derivatized, while the ring was maintained intact, thus highlighting their potential as building blocks for medicinal chemistry.     

Ring-opening reactions of oxetanes: A review of methodology development and synthetic applications

Ring-opening reactions of oxetanes yield important functionalized products depending upon the nature of nucleophiles as well as substitution pattern on the oxetane ring. Ring opening of oxetanes can be carried out under a variety of reaction conditions. In this review article, an up-to-date overview of major synthetic methodologies involved in the ring opening of oxetanes as well as their synthetic applications has been presented.     

Synthesis of Di‐, Tri‐, and Tetrasubstituted Oxetanes by Rhodium‐Catalyzed O?H Insertion and C?C Bond‐Forming Cyclization

Oxetanes offer exciting potential as structural motifs and intermediates in drug discovery and materials science. Here an efficient strategy for the synthesis of oxetane rings incorporating pendant functional groups is described. A wide variety of oxetane 2,2‐dicarboxylates were accessed in high yields, including functionalized 3‐/4‐aryl‐ and alkyl‐substituted oxetanes and fused oxetane bicycles. Enantioenriched alcohols provided enantioenriched oxetanes with complete retention of configuration. The oxetane products were further derivatized, while the ring was maintained intact, thus highlighting their potential as building blocks for medicinal chemistry.     

Highly Chemoselective Catalytic Coupling of Substituted Oxetanes and Carbon Dioxide

The chemoselective coupling of oxetanes and carbon dioxide to afford functional, heterocyclic organic compounds known as six‐membered cyclic carbonates remains a challenging topic. Here, an effective method for their synthesis relying on the use of Al catalysis is described. The catalytic reactions can be carried out with excellent selectivity for the cyclic carbonate product tolerating various (functional) groups present in the 2‐ and 3‐position(s) of the oxetane ring. The presented methodology is the first general approach towards the formation of six‐membered cyclic carbonates (6MCCs) through oxetane/CO₂ coupling chemistry. Apart from a series of substituted six‐membered cyclic carbonates, also the unprecedented room‐temperature coupling of oxetanes and CO₂ is disclosed giving, depending on the structural features of the substrate, a variety of five‐ and six‐membered heterocyclic products. A mechanistic rationale is presented for their formation and support for the intermediary presence of a carbonic acid derivative is given. The presented functional carbonates may hold great promise as building blocks in organic synthesis and the development of new, biodegradable polymers.     

Molecular calculations with the nonempirical ab initioMODPOT,VRDDO, and MODPOT/VRDDO procedures. IX. Carcinogenic benzo(a)pyrene and its metabolites using a MERGE technique

Ab initio MODPOT /VRDDO calculations have been carried out on carcinogenic benzo(a)pyrene and its metabolites. The MODPOT /VRDDO method incorporates two very desirable options into our fast ab initio Gaussian programs: MODPOT —ab initio effective core model potentials—and a charge-conserving integral prescreening approximation which we named VRDDO (variable retention of diatomic differential overlap). For orbital energies and population analyses the MODPOT /VRDDO results agree to essentially three decimal places with completely ab initio calculations using the same valence atomic basis set. For this series of very closely related congeners a new MERGE technique was implemented that allows reuse of integrals of a common skeletal fragment. Since our program computes integrals efficiently by blocks, reusing information common to the block, it was more difficult to implement a MERGE technique than for integral programs which calculate the integrals one-byone. The MODPOT /VRDDO calculations were performed for benzo(a)pyrene (BP), BP oxides, BP dihydrodiols, and BP dihydrodiol epoxides. The metabolites investigated were BP-7,8-oxide, BP-4,5-oxide, BP-7,8-dihydrodiol [cis(e, a), cis(a, e), trans(e, e), and trans(a, a)], and BP-7,8-dihydrodiol-9,10-epoxide [β,β,β (the most stable), β,β,α; α,α,β, and α,α,α all derived from cis-BP-7,8-dihydrodiol and β,α,β; α,β,β and α,β,β derived from trans-BP-7,8-dihydrodiol]. Several different conformations were calculated for each of the BP dihydrodiols and BP dihydrodiol epoxides. Calculations were carried out for the opening of the C₉—O—C₁₀ epoxide ring both toward C₉ and C₁₀ for the, most stable β,β,β isomer of BP-7,8-dihydrodiol-9,10-epoxide. Opening the epoxide ring between C₁₀ and O leads to a more stable intermediate than opening the epoxide ring between C₉ and C₁₀. However, there is no buildup of positive charge in C₁₀ as has been postulated by some cancer researchers, but rather the C₁₀ becomes slightly more negative. Nor is there a buildup of negative charge on the O atom. rather it becomes slightly less negative. As the epoxide ring is opened further than 90° for the O—C₉—C₁₀ or O—C₁₀—C₉ angles, there appears to be a possible mixing of configurations that is being investigated further.     

Investigations of the reactivity of “kick‐started” oxetanes in photoinitiated cationic polymerization

The ability of certain alkyl substituted epoxides to accelerate the photoinitiated cationic ring‐opening polymerizations of oxetane monomers by substantially reducing or eliminating the induction period altogether has been termed by us “kick‐starting.” In this communication, the rates of photopolymerization of several model “kick‐started” oxetane systems were quantified and compared with the analogous biscycloaliphatic epoxide monomer, 3,4‐epoxycyclohexylmethyl 3′,4′‐epoxycyclohexanecarboxylate (ERL). It has been found that the “kick‐started” systems undergo photopolymerization at rates that are at least two‐fold faster than ERL. These results suggest that “kick‐started” oxetanes could replace ERL in many applications in which high speed ultraviolet induced crosslinking photopolymerizations are carried out. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 586–593     

Cu(OTf)2/NBS Promoted Cyclization of 1-Cinnamyl Alcohol-o-Carboranes: An Efficient Approach for Synthesis of o-Carboranes Substituted Oxetanes

The Cu(OTf)₂/NBS promoted cyclization of 1-cinnamyl alcohol-o-carboranes for synthesis of o-carborane substituted oxetanes has been developed. A series of substituted oxetanes has been synthesized with moderate to good yields, which would be an important synthon for design novel reactions in oxetane chemistry as well as carborane chemistry.     

Studies on The Application of The Paternò-Büchi Reaction to The Synthesis of Novel Fluorinated Scaffolds

In the context of new scaffolds obtained by photochemical reactions, Paternò-Büchi reactions between heteroaromatic, trifluoromethylphenyl ketone and electron rich alkenes to give oxetanes are described. A comprehensive study has then been carried out on the reaction of aromatic ketones with fluorinated alkenes. Depending on the substitution pattern at the oxetane ring, a metathesis reaction is described as a minor side process to give mono fluorinated alkenes. Overall, this last reaction corresponds to a photo-Wittig reaction and yield amid isosteres. In order to explain the uncommon regioselectivity of the Paternò-Büchi reaction with these alkenes, electrostatic-potential derived charges (ESP) have been determined. In a second computational study, the relative stabilities of the typical 1,4-diradical intermediates of the Paternò-Büchi reaction have been determined. The results well explain the regioselectivity. Further transformations of the oxetanes or previous functionalization of the fluoroalkenes open perspectives for oxetanes as core structures for biologically active compounds.     

Synthesis and in vitro evaluation of taxol oxetane ring D precursors

A series of potential taxoid substrates was prepared in radiolabeled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways.     

Directed ring-opening of 1,5-dioxaspiro[3.2]hexanes: selective formation of 2,2-disubstituted oxetanes

1,5-Dioxaspiro[3.2]hexanes undergo ring-opening reactions with many heteroatom nucleophiles to provide alpha-substituted-beta'-hydroxy ketones. However, certain Lewis acidic nucleophiles provide 2,2-disubstituted oxetanes. Herein, the results of reactions of 3-phenyl-1,5-dioxaspiro[3.2]hexane with a variety of nitrogen-containing heteroaromatic bases are reported. There appears to be a correlation between the pK(a) of the nucleophile and the reaction outcome with more acidic nucleophiles providing 2,2-disubstituted oxetanes. Moreover, the mode of ring opening can be directed toward the substituted oxetane by the addition of a Lewis acid. These results are rationalized by calculation of stationary points on the potential energy surfaces for the various possible reaction pathways using ab initio molecular orbital methods.     

Intermolecular oxonium ylide mediated synthesis of medium-sized oxacycles

Detailed in this account are our efforts toward efficient oxacycle syntheses. Two complementary approaches are discussed, with both employing chemoselective allyl ether activation and rearrangement as the key step. Vinyl substituted oxiranes and oxetanes provide a single step access to dihydropyrans and tetrahydrooxepines. Oxiranes proved to be poor substrates, while oxetanes were slightly better. An alternative approach using substituted allyl ethers proved successful and addressed the limitations encountered in the ring expansions.     

Ab initio MRD-CI calculations for breaking a chemical bond in a molecule in a crystal or other solid environment. III. Me2N?NO2 decomposition of dimethylnitramine in a large crystalline environment

Recently we extended our strategy for MRD-CI (multireference double excitation-configuration interaction) calculations, based on localized/local orbitals and an “effective” CI Hamiltonian, for molecular decompositions of large molecules to breaking a chemical bond in a molecule in a crystalline or other solid environment. Our technique begins with an explicit quantum chemical SCF calculation for a reference molecule surrounded by a number of other molecules in the multipole environment of more distant neighbors. The resulting canonical molecular orbitals are then localized, and the localized occupied and virtual orbitals in the region of interest are included explicitly in the MRD-CI with the remainder of the occupied localized orbitals being folded into an “effective” CI Hamiltonian. The MRD-CI calculations are then carried out for breaking a bond in the reference molecule. This method is completely general in that the space treated explicitly, as well as the surrounding space, may contain voids, defects, deformations, dislocations, impurities, dopants, edges and surfaces, boundaries, etc. Dimethylnitramine is the smallest prototype of the energetic R₂N—NO₂ nitramines, such as the 6-member ring RDX or the 8-member ring HMX. Decomposition of energetic compounds is initiated in the solid by a breaking of the target bond. Thus, it is crucial to know the difference in energy between breaking a bond in an isolated energetic molecule versus in the molecule in a solid. In the present study, we have carried out MRD-CI calculations for the Me₂N—NO₂ dissociation of dimethylnitramine in a dimethylnitramine crystal. The cases we investigated were one dimethylnitramine molecule (surrounded by 53 and 685 neighboring dimethylnitramine molecules represented by multipoles), three dimethylnitramine molecules, and three dimethylnitramine molecules (surrounded by 683 neighbors). All multipoles were cumulative atomic multipoles up through quadrupoles. The MRD-CI calculations on dimethylnitramine required large numbers of reference configurations from which were allowed all single and double excitations.     

Hybrid acrylate‐oxetane photopolymerizable systems

Simultaneous free radical and cationic photopolymerizations of mixtures of multifunctional acrylate and oxetane monomers were carried out to provide hybrid interpenetrating network polymers. The use of “kick‐started” oxetanes in which oxetane monomers are accelerated by the use of small amounts of certain highly substituted epoxides provides dual independent radical and cationic systems with similar rates of photopolymerization leading to homogeneous interpenetrating networks. The combined photopolymerizations are very rapid and afford crosslinked network films that are colorless, hard, and transparent. The networks display no indications of phase separation. The use of this technology in various applications such as coatings, 3D imaging, and for composites is discussed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 594–601     

Transposition des oxirannes-ethanols par l'intermediaire d'alcoxyetains

Oxiraneethoxytributyltins prepared from the corresponding oxiraneethanols, on heating at ～ 200° gave, after demetalation with isophthallic acid, 2-oxetanemethanols and/or 3-oxolanols. As appears from about thirty rearrangements the choice between oxetane and oxolane formation is dependent on: (1) the relative degree of substitution of the oxirane ring; cyclization occuring predominantly at the more substituted carbon; and (2) the configuration of the oxirane ring, when both its ends are equally substituted; cis form being more suitable for generation of the smaller ring. The reaction is shown to proceed with inversion of configuration at the site of oxygen attack. The results of attempts to perform the rearrangement in dilute-phase or through alkaline metal alkoxides in various media support the conclusion that there is a large contribution by electrophilic assistance to the oxirane opening. Such assistance can be efficiently provided by a tin atom in a push-pull mechanism which accomodates all the facts. The present method of oxiraneethanol rearrangement may offer a convenient route to functional oxetanes.     

Catalytic reactions of oxetanes with protonic reagents and aprotic reagents leading to novel polymers

This paper reports new addition reactions of oxetanes with certain protonic reagents such as carboxylic acid, phenol, and thiol, and with certain aprotic reagents such as acyl chloride, thioester, phosphonyl dichloride, silyl chloride, and chloroformate using quaternary onium salts as catalysts. The kinetic study of the addition reactions of oxetanes was also investigated. These new addition reactions were applicable to the synthesis of new polymers. These polyaddition systems could also construct both polymer main chains and reactive side chains. The alternating copolymerization of oxetanes with carboxylic anhydride was performed. Furthermore, it was found that anionic ring‐opening polymerization of oxetanes containing hydroxy groups proceeded to afford the hyperbranched polymer (HBP) with an oxetanyl group and many hydroxy groups at the ends of the polymer chains. Alkali developable photofunctional HBPs were synthesized by the polyaddition of bis(oxetane)s or tris(oxetane)s, and their patterning properties were examined, too. The photo‐induced cationic polymerization of the polymers with pendant oxetanyl groups and the thermal curing reactions of polyfunctional oxetanes (oxetane resins) were also examined to give the crosslinking materials quantitatively. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 709–726, 2007     

Ab-Initio MRD-CI calculations for breaking a chemical bond in a molecule in a crystal or other solid environment. II.H3C—NO2 decomposition of nitromethane in a nitromethane crystal with voids

Recently we extended our strategy for MRD-CI (multireference double excitation-configuration interaction) calculations based on localized/local orbitals and an “effective” CI Hamiltonian for molecular decompositions of large molecules to breaking a chemical bond in a molecule in a crystal or other solid environment. Our technique involves solving a quantum chemical ab-initio SCF explicitly for a system of a reference molecule surrounded by a number of other molecules in the multipole environment of more distant neighbors. The resulting canonical molecular orbitals are then localized and the localized occupied and virtual orbitals in the region of interest are included explicitly in the MRD-CI with the remainder of the occupied localized orbitals being folded into an “effective” CI Hamiltonian. The MRD-CI calculations are carried out for breaking a bond in the reference molecule. This method is completely general. The space treated explicitly quantum chemically and the surrounding space can have voids, defects, deformations, dislocations, impurities, dopants, edges and surfaces, boundaries, etc. We previously applied this procedure successfully to the H₃C? NO₂ bond dissociation of nitromethane in a nitromethane crystal with extensive testing of the number of molecules that have to be included explicitly in the SCF and how many molecules have to be represented by more distant multipoles. The results indicated that it took more energy to dissociate the H₃C? NO₂ bond when the nitromethane molecule was in the crystal than it did to dissociate that bond in the free nitromethane molecule. In this present study we have investigated the effect of voids (both in the nitromethane molecules treated explicitly in the SCF and those in the environment represented by multipoles) on the calculated H₃C? NO₂ bond dissociation energies.     

The Synthesis,Characterization, and Photoinitiated Cationic Polymerizaton of Difunctional Oxetanes

Abstract

Seven novel difunctional oxetane monomers have been prepared and characterized using standard spectroscopic techniques. The photoinitiated cationic polymerization of these seven monomers was carried out and their reactivity compared to a typical diepoxide monomer. In these studies the reactivities of the various oxetane monomers were evaluated and compared by three different techniques: gel time measurements, differential scanning photocalorimetry, and real time infrared spectroscopy. It was observed that the difunctional oxetanes are generally more reactive than their structurally similar epoxide counterparts in photoinitiated cationic polymerization.     

Enhancing cationic ring‐opening photopolymerization of cycloaliphatic epoxides via dark cure and oxetanes

Due to the longevity of the cationic active centers, cationic ring‐opening photopolymerization can continue after illumination ceases. In addition, substantial reactivity enhancement for epoxides is realized through copolymerization with oxetanes. Here, the separate reactions of epoxide and oxetane moieties were resolved during illumination and subsequent dark cure via real‐time Raman spectroscopy. Using oxetane additives, reactivity and conversion of 3,4‐epoxycyclohexylmethyl‐3′,4′‐epoxycyclohexane carboxylate (EEC) were improved during illumination and subsequent dark cure through modulation of the initial formulation viscosity and selection of the oxetane secondary functional groups. The largest enhancement in reactivity occurred with secondary groups comprising either aliphatic chains with their flexibility or hydroxyls with their chain‐transfer capacity. In contrast, oxetanes containing UV‐absorbing phenyl rings reduced the initiation efficiency, and difunctional oxetanes suppressed overall conversion through additional crosslinking. Although bulk conversion was directly related to initial formulation viscosity, the impact of the oxetane secondary functional groups was greater. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1436–1445