Philip R. Lowe

Synthesis of 1-alkoxy-2-alkyl-benzimidazoles from 2-nitroanilines via tandem N-alkylation-cyclization-O-alkylation

Abstract Substituted 2-nitroanilines react with benzylic, allyl and alkyl halides to give 2-aryl-1-benzyloxy-, 1-allyloxy-2-vinyl- and 1-alkoxy-2-alkyl-benzimidazoles, in a one-pot cascade process involving 1-alkylation-cyclization-O-alkylation. 2-Aryl-1-benzyloxy- and 1-allyloxy-2-vinyl- derivatives are obtained in high yields (79–98%), while with simple alkyl halides, yields of the benzimidazoles are substrate dependent. An X-ray crystal structure of 2,4-dimethyl-1-ethoxybenzimidazole is presented.

Crystal structure and molecular modelling of the antimicrobial drug pentamidine

The solid-state conformation of pentamidine, a drug effective against Pneumocystis carinii pneumonia, is shown by X-ray diffraction to be flat and extended; molecular modelling shows that a more curved conformation could bind to the minor groove of DNA spanning four base pairs.

Structural studies on bio-active compounds. Part 12. Tautomerism and conformation of aryl-substituted 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones in the solid phase and in solution

The tautomerism of a series of aryl-substituted 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones has been studied in deuteriochloroform solution by 1H n.m.r. techniques and, in the case of 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione and 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione, in the solid state by X-ray crystallography. Of these compounds, most exist between 80 and 95% in the enolised form in solution and 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione adopts this tautomer in the crystal. However, 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione is present as the diketone in the solid phase and enolises very slowly in solution. 1-(6-Benzoyloxy-2-hydroxyphenyl)-3-hydroxy-3-phenylprop-2-en-1-one is shown by 1H n.m.r. spectroscopy possibly to adopt a ‘coiled’ conformation in solution in deuteriochloroform.

A T-shaped selenenyl halide

The title selenenyl halide complex, 3-iodo-2-phenyl-3H-3-selenaindazole, C(12)H(9)IN(2)Se, has an almost planar conformation and a nearly ideal T-shape for the Se(INC) moiety [Se-I 2.8122 (12), Se-C 1.881 (7) and Se-N2 2.051 (6) A; C-Se-N 79.6 (3), C-Se-I 96.8 (2) and N-Se-I 176.17 (17) degrees ]. This arrangement, together with the two selenium lone pairs, leads to a distorted trigonal-bipyrimidal geometry about the Se atom. Intermolecular interactions are largely limited to stacking forces.

A new amidrazone derivative with anti­mycobacterial activity

Of a series of pyridine-2-carboxamidrazone derivatives with activity against mycobacteria, the N(1)-[4-(1,1-dimethylpropyl)benzylidene] derivative reported here, C(18)H(22)N(4), is one of the most active. The predicted E isomer about the C11=N12 double bond is confirmed and intramolecular hydrogen bonding involving both amino H atoms helps to keep the molecule flat. The same donor and acceptor atoms also form intermolecular hydrogen bonds.

Reassignment of the stereochemistry of oblonginine

Abstract The stereochemistry of the steroidal alkaloid oblonginine from Veratrum oblongum (Chinese name Changgenglilu), previously reported to possess the structure (22R,25S)-22,26-epiminocholest-5-en-3β-ol, was re-examined using X-ray crystallography and high resolution NMR spectroscopy and reassigned with regard to C-22 and C-25. Therefore, oblonginine has the structure (22S,25R)-22,26-epiminocholest-5-en-3β-ol.

Classical Packing and Stacking in 6-Phenyl-5-azauracil

Although probably not incorporated directly into nucleic acids, the title compound, 6-phenyl-1,3,5-triazine-2,4(1H,3H)-dione (C9H7N3O2), resembles the pyrimidine bases in such nucleic acids. In the solid state, molecules base pair about a centre of symmetry into a dimer arrangement along the a axis and are linked firmly in the c direction by an N1—H1⋯O4 interaction related by the glide plane. The remaining intermolecular forces are achieved by the alternate stacking of phenyl and triazine rings in columns along the b axis.

DCMCIT, an analogue of the antitumour drugs mitozolomide and temozolomide

The crystal structure of 3-(2-chloroethyl)-N,N-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-d]-1,2 ,3,5- tetrazine-8-carboxamide, (1), C9H11C1N6O2, an analogue of the novel bicyclic antitumour agents mitozolomide (2) and temozolomide (3), has been determined at 290 K. Although, as in structures (2) and (3), the imidazotetrazinone ring system is essentially planar, the substitution of the--CONH2 group at C8 by a--CON(CH3)2 group in (1) negates the possibility of forming an intramolecular hydrogen bond at either N7 or N1 and thus allows rotation of this group about the C8-C81 bond by ca 45 degrees.

Regioselective deacylation of 2,4-diacylaminopyrimidine derivatives by Lewis acids and crystal structures of two products

Deacylation of 2,4-diacylamino derivatives of pyrimethamine and related diaminopyrimidines with tin(II) chloride or zinc chloride, in ethanol or propan-2-ol, affords 2-acyl-4-aminopyrimidines exclusively. Regioselective 4-deacylation was observed by 1H NMR spectroscopy and established by crystallographic analysis of the 2,4-dipropionylpyrimidine 11 and the corresponding 4-amino-2-propionylpyrimidine deacylation product 17. The latter exists in the solid state as an unusual base-pair dimer linked by two pairs of equivalent hydrogen bonds.

Antitumour imidazotetrazines. Part 5. Crystal and molecular structure of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3h)-one (mitozolomide)

The structure of the novel bicyclic antitumour agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (Mitozolomide) has been investigated by single-crystal X-ray diffraction methods. The compound crystallizes in the triclinic space group P in a cell of dimensions a= 7.003(4), b= 8.680(4), c= 16.041(9)A, α= 93.76(5), β= 93.99(5), γ= 92.08(7)° with Z= 4. The structure was solved by direct methods and refined using full-matrix least-squares calculations, which at convergence produced a final R index of 0.052 for the 3 244 observed data. The two independent molecules per asymmetric unit are rotamers about the C(8)–C(81) and C(8)′–C(81)′ bonds, the orientation of the carbamoyl group in one rotamer facilitating an intramolecular hydrogen bond of the type N–H ⋯ N. With the exception of the chloroethyl side chain, both molecules are approximately planar and intermolecular hydrogen bonds hold groups of four molecules together around the centre of symmetry.