Recent advances in azaborine chemistry

The chemistry of organoboron compounds has been primarily dominated by their use as powerful reagents in synthetic organic chemistry. Recently, the incorporation of boron as part of a functional target structure has emerged as a useful way to generate diversity in organic compounds. A commonly applied strategy is the replacement of a CC unit with its isoelectronic BN unit. In particular, the BN/CC isosterism of the ubiquitous arene motif has undergone a renaissance in the past decade. The parent molecule of the 1,2-dihydro-1,2-azaborine family has now been isolated. New mono- and polycyclic B,N heterocycles have been synthesized for potential use in biomedical and materials science applications. This review is a tribute to Dewar's first synthesis of a monocyclic 1,2-dihydro-1,2-azaborine 50 years ago and discusses recent advances in the synthesis and characterization of heterocycles that contain carbon, boron, and nitrogen.     

A 1,3-dihydro-1,3-azaborine debuts

We present the first synthesis and characterization of a 1,3-dihydro-1,3-azaborine, a long-sought BN isostere of benzene. 1,3-Dihydro-1,3-azaborine is a stable structural motif with considerable aromatic character as evidenced by structural analysis and its reaction chemistry. Single crystal X-ray analysis indicates bonding consistent with significant electron delocalization. 1,3-Dihydro-1,3-azaborines also undergo nucleophilic substitutions at boron and electrophilic aromatic substitution reactions. In view of the versatility and impact of aromatic compounds in the biomedical field and in materials science, the present study further expands the available chemical space of arenes via BN/CC isosterism.     

Theoretical studies of borazynes and azaborines

Four isomers of didehydroborazine, B3N3H4, borazyne, and three isomers of azaborine, C4H4BN, are studied by DFT, CCSD, and CCSD(T) computational methods. The singlets of 1,2-borazyne (I) and 1,4-borazyne (IV) have angles about the boron of ca. 150 degrees . In 1,2-azaborine (V), the angles are ca. 140 degrees , while the N angles are ca. 112 degrees except in IV (127 degrees ) and 1,4- azaborine (VII, 120 degrees ). These geometries are almost reversed in the triplets. The 1,3-borazyne (III) shows more bicyclic character than the corresponding m-benzyne, with an N-N distance of 1.7 A. In all cases I was found to be lower in energy than the 2,4-borazyne (II), III, and IV. The order of stability of the azaborines is V > VII > 1,3- azaborine (VI). The nucleus-independent chemical shift (NICS) indicates that all isomers of borazyne are less aromatic than benzene and all isomers of azaborine are about as aromatic as benzene. Time-dependent DFT (TD-DFT) is used to study the excited states of the singlets. The significant structural differences between the singlet and triplet states suggest long phosphoresence lifetimes.     

MNDO calculations on borazine derivatives. The substitution of one [HNBH] fragment for one [HCCH] fragment in benzene to form the azaborines and the nature of the cyclotrimer of the 1,2-isomer

The three azaborine isomers with the formula C₄H₆BN, 1,2-, 1,4-, and 1,3-azaborine ( I , II , and III ), have been examined using MNDO (m odified n eglect of d iatomic o verlap) calculations. The most stable azaborine was I (heat of formation -8.147 kcal/mol), followed by II (+11.60 kcal/mol) and III (+16.64 kcal/mol). Qualitatively, although the π- and π*-orbitals calculated for the azaborines exhibited an ordering similar to that in benzene and borazine, the HOMO/LUMO energy differences (9.27, 9.68, and 8.44 eV, respectively) were smaller than was the difference calculated for borazine (12.81 eV), but of the same magnitude as the difference for benzene (9.76 eV). With the exception of borazine, each molecule had a π-orbital for the HOMO and a π*-orbital for the LUMO ; borazine's LUMO was a π*-orbital. The calculated shapes and atomic contributions for the π-and π*-orbitals of the azaborines were best described as “hybrids” of the π- and π*-orbitals of benzene and borazine. As was observed for the π- and π*-orbitals of borazine, the azaborines exhibited increased orbital density at the nitrogen atom in the π-bonding orbitals and at boron in the π-antibonding orbitals, as would be predicted from electronegativity considerations. Although I and II exhibited significant double- and single-bond localization, all of the ring bonds in III were delocalized. The delocalization in III was not uniform but, rather, resembled two inequivalent fused allyl systems. The cyclotrimer ( IV ) of 1,2-azaborine (heat of formation -44.07 kcal/mol), based purely on thermodynamic considerations, was predicted to form spontaneously from three monomer molecules with the concurrent loss of three molecules of dihydrogen. The cyclotrimers that could theoretically be produced from 1,2-azaborine without the loss of dihydrogen ( IVc and IVt ) were each calculated to be less stable (heats of formation +24.45, and +33.29 kcal/mol, respectively) than was the experimentally observed IV . The carbon molecules triphenylene ( TP ) and cis- and trans-4a,4b,8a,8b,12a,12b- hexahydrotriphenylene ( TPc and TPt ) (heats of formation +76.79, +101.6, and +103.1 kcal/mol, respectively) were each calculated to be less stable than were the azaborine cyclotrimer analogs, as was observed in comparisons of benzene with the azaborines and borazine.     

Synthesis of Novel Dispiro 1,4-Benzothiazine Hybrid Heterocycles Through 1,3-Dipolar Cycloaddition

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of acenaphthylene-1,2-dione or isatins and α-amino acids to (E)-methyl/ethyl 2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-2-ylidene)acetate led to the stereoselective formation of novel dispiro 1,4-benzothiazine hybrid heterocycles in good yields.     

A convenient synthesis of 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-, 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo-, and 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines

The reactions of 1-alkylamino-1-alkylthio-3-phenylpropene-3-thiones 3 with thiophosgene and phosgene in toluene, followed by treatment of the reaction mixture with triethylamine gave 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo- 4 , 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-4H-1,3-thiazines 5 , respectively in good to excellent yields. Similarly treatment of compounds 3 with N-arylimidoyl dichloride in benzene at room temperature gave 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines 6 in excellent yields. The reactions of compounds 3 with oxalyl chloride in toluene gave also 5 in good yields.     

Surface chemistry of monochlorinated and dichlorinated benzenes on Si(100)2x1: comparison study of chlorine content and isomeric effects

Using X-ray photoelectron spectroscopy (XPS) and temperature-programmed desorption (TPD), the room temperature (RT) adsorption and thermal evolution of monochlorobenzene (MCB) and 1,3-dichlorobenzene (1,3-DCB) on Si(100)2x1 have been investigated and compared with that of 1,2-dichlorobenzene (1,2-DCB) reported previously. Like 1,2-DCB, the C 1s features observed at 284.6 (C(1)) and 286.0 eV (C(2)) for both MCB and 1,3-DCB could be attributed to the C-H and C-Cl bonds, respectively. The C(1)/C(2) intensity ratios for MCB (5.0) and 1,3-DCB (2.0) are found to follow the stoichiometric ratios of the C-H to C-Cl bonds for MCB and 1,3-DCB, respectively, indicating that both MCB and 1,3-DCB adsorb on Si(100)2x1 molecularly with negligible C-Cl dissociation at RT, in marked contrast to the partial C-Cl dissociation found for 1,2-DCB. Unlike 1,2-DCB with two discernible Cl 2s features at 270.3 and 271.2 eV, a single Cl 2s feature at 271.2 eV is observed for MCB and 1,3-DCB, in accord with the single local chemical environment for Cl. The TPD results show that MCB undergoes molecular desorption exclusively, similar to that found for benzene. Both molecular desorption and recombinative HCl desorption are found for 1,3-DCB, similar to that for 1,2-DCB. Despite the different Cl contents and relative Cl locations on the benzene ring, both MCB and 1,3-DCB exhibit RT adsorption behavior remarkably similar to that of benzene. To explain the C-Cl dissociation observed for 1,2-DCB, we propose a possible transition state involving the Cl atoms located at more physically compatible positions with the surface Si dimers in order to facilitate the conversion of 1,2-DCB (preferentially over 1,3-DCB) to dissociated products at RT. However, the thermal evolution of 1,3-DCB is closer to that of 1,2-DCB than that of MCB and benzene. The breakage of C-Cl bonds is found to occur at a relatively low temperature of 425 K, which suggests a relatively low activation barrier for the dechlorination of 1,3-DCB adspecies. Calculated energetics for 1,4-DCB on Si(100)2x1 shows that double dechlorination is not as favorable a process as those for 1,2-DCB and 1,3-DCB.     

Electrophilic trifluoromethylation of arenes and N-heteroarenes using hypervalent iodine reagents

The reaction of hypervalent iodine trifluoromethylating reagents with a variety of arenes and N-heteroarenes gives access to the corresponding trifluoromethylated compounds. In comparative studies, 1-trifluoromethyl-1,3-dihydro-3,3-dimethyl-1,2-benziodoxole (2) proved to be the superior to 1-trifluoromethyl-1,2-benziodoxol-3-(¹H)-one (1) for the direct aromatic trifluoromethylation. Depending on the individual substrates, additives such as zinc bis(trifluoromethylsulfonyl)imide or tris(trimethylsilyl)silyl chloride proved helpful in promoting the reactions. In the case of nitrogen heterocycles a pronounced tendency for the incorporation of the trifluoromethyl group at the position adjacent to nitrogen was observed.     

New method for the annelation of a pyridine ring on derivatives of imidazole and benzimidazole

The interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-substituted (benz)imidazoles in benzene gave (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-imidazolium bromides and (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-benzimidazolium bromides which readily cyclize in the presence of base to form derivatives of 7,9-diarylpyrido[1,2-a]benzimidazole and 6,8-diarylpyrimidazo[1,2-a]pyridine. The effects of the nature of substituents in the benzene ring of the diarylbutenones and the substituent at N(1) in the (benz)imidazoles on the alkylation and cyclization reactions has been studied. The optimum conditions for the synthesis of the 5-R-4-hydroxy-2,4-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]benz-imidazol-10-ium, 5-R-2,4-diaryl-4-hydroxy-4,5-dihydro-3H-pyrido[1,2-a]benzimidazol-10-ium, and 5-R-2,4-diaryl-5H-pyrido[1,2-a]benzimidazol-10-ium have been found.     

1,2,4-Oxadiazoles from cycloreversions of oxadiazabicyclo[3.2.0]heptenes: 1-azetines as thiocyanate equivalents

1,3-Dipolar cycloaddition of nitrile oxides to 4-aryl-2-alkylthio-1-azetines gave a series of oxadiazabicyclo[3.2.0]heptenes as single diastereoisomers. Heating these cycloadducts in toluene resulted in an overall [2+2]-cycloreversion to give 5-alkylthio-3-aryl-1,2,4-oxadiazoles. In this process, the 1-azetine behaves as a thiocyanate equivalent. When the nitrile oxide substituent was 2-azidobenzene, the azide could be converted into a 1,2,3-triazole giving a (1,2,4-oxadiazolo)-(1,2,3-triazolo)-1,2-disubstituted benzene. 1,2,4-Oxadiazoles are sought after in medicinal chemistry and materials sciences.     

Expanding the functional group tolerance of cross-coupling in 1,2-dihydro-1,2-azaborines: Installation of alkyl,alkenyl, aryl,and heteroaryl substituents while maintaining a B−H bond

Palladium-catalyzed Negishi cross-coupling of 3-bromo-1-(tert-butyldimethylsilyl)-1,2-dihydro-1,2-azaborine while maintaining the B?H functionality has been demonstrated. 17 examples, including dialkylzinc, alkyl-, alkenyl-, aryl-, as well as nitrogen-, sulfur-, and oxygen-containing heteroaryl-zinc halide reagents have been coupled to generate new C(3) substituted 1,2-azaborines in moderate to excellent yields.     

Synthesis and solid-state characterisation of 4-substituted methylidene oxindoles

Background

4-substituted methylidene oxindoles are pharmacologically important. Detailed analysis and comparison of all the interactions present in crystal structures is necessary to understand how these structures arise. The XPac procedure allows comparison of complete crystal structures of related families of compounds to identify assemblies that are mainly the result of close-packing as well as networks of directed interactions.

Results

Five 4-substituted methylidene oxindoles have been synthesized by the Knoevenagel condensation of oxindole with para-substituted aromatic aldehydes and were characterized in the solid state by x-ray crystallography. Hence, the structures of (3E)-3-(4-Bromobenzylidene)-1,3-dihydro-2H-indol-2-one, 3a, (3E)-3-(4-Chlorobenzylidene)-1,3-dihydro-2H-indol-2-one, 3b, (3E)-3-(4-Methoxybenzylidene)-1,3-dihydro-2H-indol-2-one, 3c, (3E)-3-(4-Methylbenzylidene)-1,3-dihydro-2H-indol-2-one, 3d and (3E)-3-(4-Nitrobenzylidene)-1,3-dihydro-2H-indol-2-one, 3e, were elucidated using single crystal X-ray crystallography.

Conclusions

A hydrogen bonded dimer molecular assembly or supramolecular construct was identified in all the crystal structures examined along with a further four 1D supramolecular constructs which were common to at least two of the family of structures studied. The 1D supramolecular constructs indicate that once the obvious strong interaction is satisfied to form hydrogen bonded dimer it is the conventionally weaker interactions, such as steric bulk and edge-to-face interactions which compete to influence the final structure formation.

     

Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ-oxaphospholes

The reaction of ethyl propiolate with triphenylphosphine (Ph₃P) in the presence of N-alkylisatins led to ethyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-4-carboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones in good yield. The reaction of dialkyl acetylenedicarboxylates with Ph₃P in the presence of N-alkylisatins led to dialkyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-3,4-dicarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones and alkyl 4-(alkoxy)-5-oxo-2,5-dihydro-3-furancarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones.     

The reaction of aromatic dialdehydes with enantiopure 1,2-diamines: an expeditious route to enantiopure tricyclic amidines

The condensation of enantiopure 1,2-diamines with terephthalaldehyde, isophthalaldehyde or 2-iodo-, 2-alkyl- or 2-aryl-1,3-benzenedialdehydes in toluene followed by treatment with NBS in dichloromethane gives direct access to enantiopure 1,4-, and 1,3-di(4,5-dihydro-1H-imidazol-2-yl)benzenes (diamidines). The condensation of o-phthalaldehyde, and other ortho-disubstituted aromatic dialdehydes, with enantiopure 1,2-diamines, without NBS, gives enantiopure 3,5-dihydro-2H-imidazol-[2,1]-isoindoles.     

Low energy electron and O- reactions in films of O2 coadsorbed with benzene or toluene

A detailed understanding of nascent reactive events leading to DNA damage is required to describe ionizing radiation effects on living cells. These early, sub-picosecond events involve mainly low energy (E < 20 eV) secondary electrons (SE), and low energy (E < 5 eV) secondary ion (and neutral) fragments; the latter are created either by the primary radiation, or by SE via dissociative electron attachment (DEA). While recent work has shown that SE initiate DNA strand break formation via DEA, the subsequent damage induced by the DEA ion fragments in DNA, or its basic components is unknown. Here, we report 0-20 eV electron impact measurements of anion desorption from condensed films containing O2 and either benzene (C6H6), or toluene (C6H5CH3); these molecules represent the most fundamental structural analogs of pyrimidine bases. Our experiments show that all of the observed OH- yields are the result of reactive scattering of 1-5 eV O- fragments produced initially by DEA to O2. These O- reactions involve hydrogen abstraction from benzene or toluene, and result in the formation of benzyl radicals, or toluene radicals centered on either the ring or exocyclic methyl group. O- scatters over nm distances comparable to DNA dimensions, and reactions involve a transient anion collision complex. Anion desorption is found to depend on both, the temperature of hydrocarbon film formation (morphology), and the order of overlayer adsorption, e.g. O2 on benzene, or benzene on O2. Our measurements support the notion that in irradiated DNA similar secondary-ion reactions can be initiated by the abundant secondary electrons, and may lead to clustered damage.     

The first synthesis and X-ray structures of polyfluorinated 1,2-, 2,3- and 2,4a-dihydro-1,3-diazafluorenes

Acetic acid-catalyzed condensation of 2-amino-3-(1-imino-2,2,2-trifluoroethyl)-1,1,4,5,6,7-hexafluoroindene (1b) with acetone and cyclopentanone gives 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-2,3-dihydro-1,3-diazafluorene (2a) and 5,6,7,8,9,9-hexafluoro-4-trifluoromethyl-2,3-dihydro-1,3-diazafluorene-2-spiro-1′-cyclopentane (3a) together with small amounts of 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-1,2-dihydro-1,3-diazafluorene (2b) and 5,6,7,8,9,9-hexafluoro-4-trifluoromethyl-1,2-dihydro-1,3-diazafluorene-2-spiro-1′-cyclopentane (3b), respectively. When acted upon by (CH₃)₂SO₄ compounds 2, 3 were converted into corresponding fluorine-containing 1-methyl-1,2-dihydro-1,3-diazafluorenes 6, 7. 4a-Chloro-5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-2,4a-dihydro-1,3-diazafluorene (8) has been synthesized by the interaction of compound 2 with SOCl₂. Solution of compound 2 as well as 8 in CF₃SO₃H-CD₂Cl₂ generated 5,6,7,8,9,9-hexafluoro-2,2-dimethyl-4-trifluoromethyl-1,2,3,4-tetrahydro-1,3-diazafluorene-4-yl cation (2c). The structures of compounds 2, 3, 6-8 have been determined by single crystal X-ray diffraction.     

Analysis of 1,2(2,3)- and 1,3-positional isomers of diacylglycerols from vegetable oils by reversed-phase high-performance liquid chromatography

Separation of 1,2(2,3)- and 1,3-positional isomers of diacylglycerols (DAG) from vegetable oils by reversed-phase high-performance liquid chromatography (RP-HPLC) is investigated. The method is based on isocratic elution using 100% acetonitrile and UV detection at 205 nm. The following elution order of DAG molecular species is identified: 1,3-dilinolein < 1,2-dilinolein < 1,3-dimyristin < 1-oleoyl-3-linoleoyl-glycerol < 1,2-dimyristoyl-rac-glycerol < 1(2)-oleoyl-2(3)-linoleoyl-glycerol < 1-linolenoyl-3-stearoyl-glycerol < 1(2)-linolenoyl-2(3)-stearoyl-glycerol < 1,3-diolein < 1-palmitoyl-3-oleoyl-glycerol < 1,2-dioleoyl-sn-glycerol < 1(2)-palmitoyl-2(3)-oleoyl-glycerol < 1-linoleoyl-3-stearoyl-glycerol < 1,3-dipalmitin < 1(2)-linoleoyl-2(3)-stearoyl-glycerol < 1-oleoyl-3-stearoyl-glycerol < 1,2-dipalmitoyl-rac-glycerol < 1-palmitoyl-3-stearoyl-sn-glycerol < 1,3-distearin < 1,2-distearoyl-rac-glycerol. Linearity is observed over three orders of magnitude. Limits of detection and quantitation range 0.2-0.7 microg/mL for 1,3-dilinolein to 0.6-1.9 microg/mL for 1,2-dioleoyl-sn-glycerol, respectively. Precision and accuracy of the method are also demonstrated. The method is developed to separate mixtures of DAG molecular species produced from edible oils.     

Ab initio molecular orbital study of energies and conformers of 3,4-dihydro-1,2-dithiin, 3,6-dihydro-1,2-dithiin, 4H-1,3-dithiin,and 2,3-dihydro-1,4-dithiin

Optimized geometries and energies for 3,4-dihydro-1,2-dithiin ( 1 ), 3,6-dihydro-1,2-dithiin ( 2 ), 4H-1,3-dithiin ( 3 ), and 2,3-dihydro-1,4-dithiin ( 4 ) were calculated using ab initio 6-31G* and MP2/6-31G*//6-31G* methods. At the MP2/6-31G*//6-31G* level, the half-chair conformer of 4 is more stable than those of 1 , 2 , and 3 by 2.5, 3.5, and 3.6 kcal/mol, respectively. The half-chair conformers of 1 , 2 , 3 , and 4 are 2.9, 7.1, 2.0, and 5.6 kcal/mol, respectively, more stable than their boat conformers. The calculated half-chair structures of 1 – 4 are compared with the calculated chair conformer of cyclohexane and the half-chair structures for cyclohexene, 3,4-dihydro-1,2-dioxin ( 5 ), 3,6-dihydro-1,2-dioxin ( 6 ), 4H-1,3-dioxin ( 7 ), and 2,3-dihydro-1,4-dioxin ( 8 ). © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1064–1071, 1998     

Syntheses, structures, luminescence and electrochemistry of benzene- and biphenyl-centered bis- and tris-1,3,2-diazaboroles and -1,3,2-diazaborolidines

Reaction of 1,4-bis(dibromoboryl)benzene (1a) with 2 equiv. of the diazabutadiene tBuN=CH-CH=NtBu and subsequent reduction of the obtained bis(1,3,2-diazaborolium)salt 2a with sodium amalgam afforded the 1,4-bis(1,3,2-diazaborolyl)benzene 3a. Similarly, 1,3-bis(dibromoboryl)benzene (1b), 1,3,5-tris(dibromoboryl)benzene (1c) and 4,4'-bis(dibromoboryl)biphenyl (1d) were converted into compounds 3b, 3c and 3d which contain two or three diazaborolyl substituents at the arene core. Treatment of precursors 1a,b,d with two equiv. or with three equiv. of N,N'-di-tert-butylethane-1,2-diamine in the presence of an excess of NEt3 gave rise to the diazaborolidine derivatives 4a-4d. Reaction of 1,3-bis(diiodoboryl)benzene with two equivalents of N,N'-dimethylethane-1,2-diamine in the presence of NEt3 furnished the corresponding 1,3-bis(diazaborolidinyl)benzene 4e. The novel compounds were characterized by elemental analyses and spectroscopy (1H, 13C, 11B NMR, MS). The molecular structures of 3c, 4a and 4e were eludicated by X-ray-diffraction analyses. In addition to this, the oxidative cyclovoltammograms and blue emission spectra of these novel compounds were discussed. Here, the electronic communication between boron heterocycles on the different spacer-units and the luminescence of the oligo-diazaborolylarenes were of interest.     

Straightforward synthesis of 4,5-bifunctionalized 1,2-oxazinanes via Lewis acid promoted regio- and stereo-selective nucleophilic ring-opening of 3,6-dihydro-1,2-oxazine oxides

Functionalized 1,2-oxazinanes are interesting and valuable heterocycles with potential applications in synthetic and medicinal chemistry. A straightforward strategy for quick access to unprecedented trans-4-hydroxyl-5-azido/cyano/amino 1,2-oxazinanes are developed: N-COR 3,6-dihydro- 1,2-oxazine oxides are prepared with ease from related dihydro- 1,2-oxazines and opened by nucleophiles TMSN₃, TMSCN and aryl/alkyl amines. Appropriate Lewis acid catalysts are found playing a vital role for both reaction rate and regioselectivity. The N-COR group can be removed under mild conditions to provide highly desirable NH 1,2-oxazinanes inaccessible via previous methods.