A. David Rae

5-Nitrosalicylic Acid and its Proton-Transfer Compounds with Aliphatic Lewis Bases

The crystal structures of the proton-transfer compounds of 5-nitrosalicylic acid (5-nsa) with morpholine (morph), hexamethylenetetramine (hmt), and ethylenediamine (en) have been determined and their solid-state packing structures described. The compounds are [(morph)+(5-nsa)–] 1, [(hmt)+(5-nsa)–·H2O] 2, and [(en)2+2(5-nsa)–·H2O] 3. In all compounds, protonation of the hetero-nitrogen of the Lewis base occurs. With 1, the 5-nsa anions and the morpholine cations lie, respectively, in or across crystallographic mirror planes and are linked within the planes by hydrogen-bonding interactions through the aminium group and the carboxylic and phenolic oxygens of the anionic 5-nsa species giving a two-dimensional sheet polymer. Compound 2 is an unusual structure with the planar 5-nsa anions lying within pseudo mirror planes and cyclically linked by duplex water bridges through a single carboxylate oxygen into centrosymmetric dimers. The hmt cation molecules are disordered across the pseudo mirror and are strongly linked by N+–H···O hydrogen bonds only to the water molecules with peripheral weak hmt C–H···O hydrogen bonds extending the dimer within and between the dimer planes. Compound 3 is a network polymer comprised of the 5-nsa anions, the en dianions, and the water molecule in an extensive hydrogen-bonded structure.

The Modulated Crystal Structure of the Molecular Adduct of 2,4,6-Trinitrobenzoic Acid with 2,6-Diaminopyridine

The 1 : 1 adduct of 2,4,6-trinitrobenzoic acid (tnba) with 2,6-diaminopyridine (2,6-dap), [(2,6-dap)+(tnba)-], has been prepared and the low-temperature crystal structure has been determined by X-ray crystallography. A modulated structure has been identified and refined by using a stacking fault model that requires reflection data to be put on three scales depending on an index condition. Crystals are triclinic, space group P1–, with Z 8 in a cell of dimensions a 13.538(3), b 14.516(4), c 16.480(4) A; α 97.17(2), β 105.69(2), γ 106.09(2)˚. The structure involves proton transfer from the tnba molecule to the 2,6-dap molecule, with the resulting pyridinium proton and an amine proton interacting with the carboxyl oxygens of the tnba molecule in a primary cyclic hydrogen-bonding association. Additional peripheral hydrogen bonding completes a two-dimensional sheet structure.

The nature of halogen···halogen interactions and the crystal structure of 1,3,5,7-tetraiodoadamantane

An analysis of halogen ⋯ halogen (X ⋯ X) intermolecular interactions in crystals, using the Cambridge Structural Database (CSD). is presented. A total of 794 crystal structures yielded 1051 contacts corresponding to symmetrical and unsymmetrical X ⋯ X interactions of the type Cl ⋯ Cl, Br ⋯ Br, I ⋯ I, Cl ⋯ F, Br ⋯ F, I ⋯ F, Br ⋯ Cl, I ⋯ Cl and I ⋯ Br. These 1051 contacts are divided mainly into two categories, type I and type II depending upon the values of the two C–X ⋯ X angles θ1and θ2around the X atoms in a fragment of the type C–X ⋯ X–C. Type I contacts are defined as those in which θ1=θ2 while type II are defined as those in which θ1≅ 90° and θ2≅ 180°. Our results indicate that as the polarisability of the X atom increases, type II contacts become more significant than type I contacts and the X ⋯ X interaction may be more nearly considered to arise from specific attractive forces between the X atoms. A number of these concepts are succinctly illustrated in the crystal structure of 1,3,5,7-tetraiodoadamantane, 1. This structure has been reported to a very limited accuracy previously and the present work reveals an unusual twinned structure for this compound wherein the geometry of the stabilising I ⋯ I interactions is retained across the twin boundary. Compound 1 is tetragonal, space group I41/a, a= b = 7.1984(7) and c= 28.582(4)A, and Z = 4. The packing of the molecules in the crystal is controlled by I ⋯ I interactions. The supramolecular network of I ⋯ I connected molecules in crystalline 1 is closely related to that in adamantane-1,3,5,7-tetracarboxylic acid. Indeed, the stabilising nature of the I ⋯ I interactions is crucial for the crystallisation of 1 in this particular structure because otherwise, it should also have formed plastic crystals as do the analogous tetrachloro and tetrabromo derivatives.

Configurationally homogeneous diastereomers of a linear hexa(tertiary phosphine): Enantioselective self-assembly of a double-stranded parallel helicate of the type (P)-(Cu 3 (hexaphos) 2 )(PF 6 ) 3

Three configurationally homogeneous diastereomers of the linear hexa(tertiary phosphine) Ph2PCH2CH2P(Ph)CH2CH2P(Ph)CH2CH2P(Ph)CH2CH2P(Ph)CH2CH2PPh2 (hexaphos) have been isolated in enantiomerically pure form, namely (R,S,S,R)-, (R,S,S,S)-, and (S,S,S,S)-hexaphos. The strongly helicating (R,S,S,R)-(−) form of the ligand combines with copper(I) ions to generate by stereoselective self-assembly the P enantiomer of a parallel helicate of the type [Cu3(hexaphos)2](PF6)3, which has been characterized by x-ray crystallography. Theoretical modeling of the cation indicates that it is the relationship between the helicities of the two 10-membered rings containing the three copper ions, each of which has the twist-boat–chair–boat conformation, and the configurations of the three chiral, tetrahedral copper stereocenters of P configuration that determines the stereochemistry of the parallel and double α-helix conformers of the double-stranded trinuclear metal helicate.

Approaches to the Neurotrophically Active Natural Product 11-O-Debenzoyltashironin: A Chemoenzymatic Total Synthesis of the Structurally Related Sesquiterpene Khusiol

The sesquiterpenoid natural product 11-O-debenzoyltashironin (1, Scheme 1) and the corresponding benzoate ester tashironin (2) have been isolated from the pericaps of the eastern Asian plant Illicium merrillianum. The structures of these compounds were determined using NMR spectroscopic techniques, and the former was shown to induce neurite outgrowth in fetal rat cortical neurons at concentrations as low as 0.1 mm. As such and because of its compact and highly substituted tetracyclic structure, 11-O-debenzoyltashironin has attracted some attention as a synthetic target. In 2006 Danishefsky and co-workers reported the first and thus far only total synthesis of ( )-1, and two years later they described a modification of their elegant transannular Diels–Alder approach to the preparation of enantiomerically enriched variants of the intermediates associated with the original synthesis. Starting in 2007 Mehta and Maity have reported a series of impressive studies on the construction, in racemic form, of the tetracyclic core of compounds 1 and 2. This work, which employs a tandem oxidative dearomatization — intramolecular Diels–Alder (IMDA) reaction — ring-closing metathesis (RCM) sequence, has recently culminated in a total synthesis of ( )11-O-methyldebenzoyltashironin. No further work in the area has been described to date, and the lack of any reported structure–activity relationship studies is probably a reflection of the lengthy nature of the existing approaches to compound 1 and its congeners. In an effort to address this matter as well as the need to obtain the nonracemic forms of compound 1 and its congeners, we have begun exploring chemoenzymatic approaches to the tricyclic carbon framework of 11-O-benzoyltashironin. In this connection we now report the first enantioselective total synthesis of the sesquiterpenoid khusiol (3), a system that embodies the same 3,6,7,7-tetramethyloctahydro-3a,6a-ethanoindene framework encountered in compound 1 although possessing the opposite stereochemistry at C3. The starting material used in the present work was the cis-1,2-dihydrocatechol 4, which is readily obtained in approximately 80 % ee through the enzymatic cis dihydroxylation of p-iodotoluene. The assembly of the tricyclic core of khusiol (Scheme 2) followed a pathway established during a recently completed model study. Thus, the readily derived acetonide derivative 5 of diol 4 was converted, by metalation/trans-metalation protocols, into the corresponding cuprate, which was treated with the dienone 6, thereby producing, through a selective conjugate addition process, the a,b-unsaturated ketone 7 (60 %). While compound 7 failed to engage in an IMDA reaction upon heating, one of the epimeric alcohols (8), obtained by sodium borohydride mediated reduction of this enone, underwent the desired cycloaddition reaction on heating in mesitylene, thereby producing the epimerically pure tricyclic alcohol 9 (71 % yield based on recovered S-8) that incorporates the two contiguous quaternary carbon centers associated with target 3. Compound 9, the assigned structure of which is supported by single-crystal X-ray analyses of the corresponding 3,5-dinitrobenzoate and ketone (see the Supporting Information for details of the X-ray analysis of the latter), is presumably formed preferentially in the IMDA reaction because at the transition state for this process the hydroxy group associated with substrate R-8 resides on the exo-face of the developing cis-perhydroindene substructure. The next phase of the synthesis involved establishing a protocol for introducing the C3 methyl group. To these ends, compound 9 was oxidized to the corresponding ketone (99 %) using a mixture of pyridinium dichromate (PDC) and acetic acid. The resulting reaction mixture was subjected to hydrogenation, thus affording the saturated system 10 (99 %). Treatment of this compound with TMSOTf in the presence of triethylamine resulted in the formation of the kinetically favored silyl enol ether that was subjected to oxidation using a combination of IBX and MPO in DMSO. [a] M. K. Sharma, Prof. M. G. Banwell, Dr. A. C. Willis, Prof. A. D. Rae Research School of Chemistry, Institute of Advanced Studies The Australian National University Canberra ACT 0200 (Australia) Fax: (+61) 2-6125-8114 E-mail : mgb@rsc.anu.edu.au Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201100913. Scheme 1. Structures of compounds 1–4. Bz =benzoyl.

On the polymorphism of benzocaine; a low- temperature structural phase transition for form (II)

A low-temperature structural phase transition has been observed for form (II) of benzocaine (BZC). Lowering the temperature doubles the b-axis repeat and changes the space group from P2(1)2(1)2(1) to P112(1) with gamma now 99.37 degrees. The structure is twinned, the twin rule corresponding to a 2(1) screw rotation parallel to a. The phase transition is associated with a sequential displacement parallel to a of zigzag bi-layers of ribbons perpendicular to b*. No similar phase transition was observed for form (I) and this was attributed to the different packing symmetries of the two room-temperature polymorphic forms.

N-Oxide-bridged complexes of cobalt(II) and nickel(II) with 2-acetylpyridine 1-oxide oxime (pro). X-ray crystal structure of the dimeric complex [Co(pxo)(CH3OH)Cl2]2

The X-ray structure is reported for the dimeric complex [Co(pxo)(CH3OH)Cl2]2 involving the bidentate N-oxide ligand 2-acetylpyridine 1-oxide oxime (pxo). The complex is monoclinic, C2/c, a = 19.328(6), b = 9.810(4), c = 15.561(6) A, β = 126.94(2)°, Z = 4. The centrosymmetric dimer is N-oxide-bridged. Each cobalt has a six-coordinate NO3Cl2 environment, produced by O,N coordination from one pxo, bridging N-oxide bonding from a second pxo, terminal chlorides, and coordinated CH3OH. Attempted preparations of other 1:1 pxo complexes, using a range of solvents, generally yielded some previously reported 2:1 complexes of the type M(pxo)2X2. However, the complexes Ni(pxo)Cl2·H2O and Co(pxo)Cl2 were also obtained, and, on the basis of magnetic, spectroscopic and X-ray powder diffraction measurements, the complexes appear to have six-coordinate structures, involving chloride-bridged chains of N-oxide-bridged dimer molecules.

The pseudo symmetric structure of bis(dicyclohexylammonium) bis(oxalatotriphenylstannate)

The asymmetric unit of bis(dicyclohexylammonium) bis(oxalatotriphenylstannate) [Cc: a = 14.669(4) Å, b = 12.764(2) Å, c = 32.198(9) Å, β= 95.14(1)°, Z = 4] consists of two [(cyclo-C6H11)2NH2]+ / [(C6H5)3Sn(O2CCO2)]- ion-pairs that are linked by hydrogen bonds into a pseudo centrosymmetric dinuclear entity. The tin atoms in the stannates show cis-C3SnO2 trigonal bipyramidal coordination geometries. The structure can also be described either as two c-glide related substructures of pseudo C1 symmetry, or as an occupancy modulation that keeps half the asymmetric units of a 1: 1 disordered P21/c parent structure for which a´ = a/2, b´ = b/2 and c´ = c. The pseudo symmetry suggests a mechanism for stacking faults and twinning, which have been taken into consideration in refining the structure. The two dicyclohexylammonium counterions are locally disordered.

Revisiting the crystal structure and thermal properties of NaMgAl(oxalate)3·9H2O/Cr(III): an extraordinary spectral hole-burning material

We have reinvestigated the crystal structure and thermal properties of NaMgAl(oxalate)(3) x 9 H(2)O. In the thermal gravimetric analysis the steps of dehydration and decomposition/oxidation yield a mass change that is commensurate with 9 water molecules of hydration. Dehydration steps occur at 127, 171, and 201 degrees C whereas the oxalate ligand decomposes in steps at 403 and 424 degrees C with a final oxidation step at 692 degrees C. A refinement of the single crystal X-ray diffraction data taken at 200 K affirms the P3c1 space group with nine water molecules of hydration and unit cell parameters a = b = 16.7349(2) A and c = 12.6338(1) A with Z = 6. The structures can be described in terms of modulations of an idealised Z = 1 structure in P3lm. T-Cycle experiments of spectral holes in the R(1)-line yield a single Gaussian barrier with T(0) +/- sigma(T) of 46 +/- 21 K and three barriers with 40 +/- 12, 70 +/- 10, 107 +/- 5 K for perprotonated and partially deuterated (46%) NaMgAl(oxalate)(3) x 9 H(2)O/Cr(III) 0.5%, respectively.

Specificity in template syntheses of hexaaza-macrobicyclic cages: [Pt(Me5-tricosatrieneN6)]4+ and [Pt(Me5-tricosaneN6)]4+

The racemic C3 hexadentate cage complex, [Pt(Me5-tricosatrieneN6)]Cl4 (1,5,9,13,20-pentamethyl-3,7,11,15,18,22-hexaazabicyclo[7.7.7]tricosa- 3,14,18-triene)platinum(IV) tetrachloride), was synthesised stereospecifically and regiospecifically from a reaction of the bis-triamine template [Pt(tamc)2]Cl4 (bis[1,1,1-tris(aminomethyl)ethane]- platinum(IV) tetrachloride) with formaldehyde and then propanal, in acetonitrile under basic conditions. Largely, one racemic diastereoisomer was obtained in a surprisingly high yield (approximately 50%), even though the molecule has seven chiral centres. The origins of the stereoselective synthesis are addressed. The crystal structure of [Pt(Me5-tricosatrieneN6)]-(ZnCl4)1.5Cl.2H2O showed that all three imines were attached to one tame fragment with a chiral amine site ([symbol: see text] SSS, delta RRR) and a chiral methine carbon site ([symbol: see text] RRR, delta SSS) on each ligand strand. The PtN6(4+) moiety had a slightly distorted octahedral configuration with the two types of Pt-N bonds related to the imine and the amine donors, 2.050(7) and 2.072(6) A, respectively. Treatment with sodium borohydride (15 s, 20 degrees C) at pH approximately 12.5 reduced the imine groups, but not the Pt(IV) ion, producing a C3 saturated ligand complex [Pt(Me5-tricosaneN6)]Cl4 ((1,5,9,13,20- pentamethyl-3,7,11,15,18,22- hexaazabicyclo[7.7.7]tricosane)platinum(IV)tetrachloride). X-ray crystallographic analysis showed that the average Pt-N bond distance in the cation increased upon imine reduction to 2.10 (av) A. The cyclic voltammograms of the two cage complexes displayed irreversible two-electron reduction waves in aqueous media and a approximately 0.3 V shift to more positive potentials compared to that of the smaller cavity sar (3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) analogue. After reduction, net dissociation of one strand of the cage was also evident, to give unstable square planar Pt(II) macrocyclic products.