Journal of Chemical Research

Dr Paul Watts is a reader in organic chemistry at The University of Hull and since graduating from the University of Bristol, where he completed a PhD in bio-organic natural product synthesis, he has led the Micro Reactor Group at Hull. In this role, he has published 90 papers, and he regularly contributes to the field by way of invited book chapters, review articles, and keynote lecturers on the subject of micro reaction technology in organic synthesis.

Dr Charlotte Wiles is the Chief Technology Officer at Chemtrix BV, and has been actively researching within the area of micro reaction technology for 10 years, starting with a PhD entitled Micro reactors in organic chemistry, which she obtained from The University of Hull in 2003. In the past decade, she has authored many scientific papers and review articles, recently co-authoring a book on the subject of micro reaction technology in organic synthesis. More recently, she has tailored her experience to the development and evaluation of commercially available continuous flow reactors, systems and peripheral equipment.

This review article explains the advantages of micro reactors and flow reactors as tools for conducting organic synthesis and describes how the technology may be used in research and development as well as production. A selection of examples is taken from the literature to illustrate how micro reactors enables chemists to perform their reactions more efficiently than when using batch processes.

Aldehydes or ketones react readily in one-pot with isatoic anhydride and ammonium salts in the presence of tris-(hydrogensulfato)boron to produce the corresponding 2,3-dihydroquinazolin-4(1H)-ones in high yields under solvent-free conditions. The use of tris(hydrogensulfato)boron makes this process quite simple, more convenient and environmentally friendly. 2,3-Dihydroquinazolin-4(1H)-one derivatives have interesting biological and pharmacological activities.

1-(3-Methoxybenzoyl)-3,6-diphenyl-1,4-dihydro-1,2,4,5-tetrazine was prepared from 3-methoxybenzoyl chloride and 3,6-diphenyl-1,2(or 1,4)-dihydro-1,2,4,5-tetrazine, and its structure was determined by X-ray diffraction. This reaction yields the title compound rather than 1-(3-methoxybenzoyl)-3,6-diphenyl-1,2-dihydro-1,2,4,5-tetrazine. The central tetrazine ring of the title compound exhibits a boat conformation and therefore, is not homoaromatic.

A simple efficient one-pot three-component condensation for synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones in good to excellent yields using 2-thienylboronic acid as a catalyst was described.

A new pentacyclic triterpene, 3β,11β-dihydroxyfriedelane was isolated from leaves of Maytenus robusta Reissek (Celastraceae) together with other four known compounds: 3-oxofriedelane (friedelin), 3β-hydroxyfriedelane, 3-oxo-29-hydroxyfriedelane and 3-oxo-11β-hydroxyfriedelane. The structure and chemical conformation of the new friedelane triterpene were established by ¹H and ¹³C NMR, including the 2D experiments, HSQC, HMBC, COSY and NOESY.

An efficient procedure has been developed for the synthesis of new chiral cholic acid molecular tweezer artificial receptors by linking an unsymmetrically disubstituted urea to methyl deoxycholate via a carbonate chain using microwave irradiation. The structures of these new receptors were confirmed by ¹H NMR, IR, MS spectra and elemental analysis. Their binding properties were examined by UV-Vis spectra titration. The preliminary results indicate that these molecular tweezers not only recognised anions, but also showed good enantioselectivity for D-amino acid methyl esters.

An efficient oxidative desulfurisation of thioamides by CuBr/TBHP is reported. Thioamides containing alkyl or aryl on the nitrogen undergo desulfurisation and give amides with good yields. Thioamides not containing substituent on the nitrogen undergo desulfurisation and give 1,2,4-thiadiazoles in moderate to good yields.

B₂O₃/Al₂O₃ has been found to be a new and highly efficient heterogeneous catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones by the Biginelli reaction under solvent-free conditions. 3,4-Dihydropyrimidin-2(1H)-ones have important pharmacological and biological activities.

Two 4-amino-N-bromoalkylphthalimide derivatives were prepared by the reduction of 4-nitro-N-bromoalkylphthal-imides and SnCl₂ and reacted with calix[4]azacrown to give two new 4-aminophthalimido-N-alkyl-calix[4]azacrown derivatives. They were characterised by IR, ¹H NMR, ¹³C NMR and HRMS and shown to adopt a cone conformation, 4-aminophthalimido-N-alkyl-calix[4]azacrown may provide a potential fluorescent probe for Cu²⁺.

An easy and efficient method for the synthesis of novel deoxycholic acid bis-1,3,4-thiadiazol-carbamate derivatives under microwave irradiation has been developed. Twelve new methyl 3α,12α-bis-[(5-aryl-1,3,4-thiadiazol-2-yl) carbamoyloxy]-cholan-24-oates were obtained in better yield (78–91%) and shorter time (15–22 min). Their structures were identified by ¹H NMR, IR, MS spectra and elemental analyses.

The three-component reaction involving chromone-3-carbaldehyde, 4-hydroxycoumarin and cyclohexyl isocyanide produces furocoumarin and biscoumarin derivatives. Formation of the latter compound seems to involve cyclohexylamine. Cyclohexyl isocyanide was found to act as a masked source of cyclohexylamine.

A ternary Cd(II) complex with a tripodal ligand tris[2-(N-ethyl)benzimidazylmethyl]amine (Etntb) and salicylate, [Cd (Etntb)(salicylate)(DMF)](NO₃)·DMF, has been synthesised. Its crystal structure reveals that the central Cd(II) atom is seven-coordinated. The DNA-binding properties of the Cd(II) complex have been investigated by spectrophotometric methods and viscosity measurements, and the results suggest that the Cd(II) complex binds to DNA via an intercalation binding mode.

An efficient synthesis of a series of stilbenes is reported using 4-nitrotoluene and substituted arylaldehydes as starting materials in the presence of Cs₂CO₃ and polyethylene glycol under solvent-free microwave irradiation. Compared with conventional method, this strategy exhibited higher stereoselectivity, shorter reaction times and has a lower environmental impact.

A series of novel derivatives of 7-phenyl-8H-benzo[h]indeno[1,2-b]quinolin-8-ones were synthesised directly by one-pot three-component reaction of indanedione, α-naphthylamine and various substituted arylaldehydes under solvent-free conditions using ultrasonic irradiation as a clean source of energy. This fast method provided the products in high yields (70–93%) and low reaction times (10–75 min).

A new acetylation procedure has been applied to 13 aryl-methyl ethers using boron chemistry. In this procedure, demethylation of aryl-methyl ethers and acetylation of the resulting phenols were combined into one procedure in order to shorten the number of stages and to achieve easy purification. Eleven known with/without bromine and two new [bis(3,4-diacetoxyphenyl)methanone and 5,5'-methylenebis(1,2-diacetoxy-3,4-dibromobenzene) (a natural bromophenol's acetylated derivative)] acetylated arene compounds were synthesised from their methoxy derivatives by this method. The effectiveness of the method was illustrated by producing an acetylated natural bromophenol from its methyl ether. The phenol form was obtained by hydrolysing the acetylated natural bromophenol. Thus, the advantage of this method in the natural product chemistry of phenolic compounds was confirmed.

An MCM-41-immobilised bidentate nitrogen platinum complex (MCM-41-2N-Pt) was very conveniently synthesised from commercially available and cheap 3-(2-aminoethylamino)propyltrimethoxysilane by immobilisation on the mesoporous silica nanoparticles, MCM-41, followed by reaction with potassium chloroplatinite. It was found that the MCM-41-2N-Pt complex is a highly efficient catalyst for the hydrosilylation of olefins with triethoxysilane and can be easily recovered and reused several times without significant loss of activity.

An efficient synthesis of a 2-deoxy-2-acetonyl sugar from its corresponding natural sugar by methallylation of the 2–iodo sugar is reported. The simplified procedure eliminated the need to carry out the reaction under strictly controlled conditions, giving an efficient route for the synthesis of 2-deoxy-2-acetonyl sugar under ordinary laboratory conditions.