Medicines Dimethylformamide

Dimethylformamide has been measured in ambient air near a fibre plant and near waste facilities. It has rarely been found in water samples in the United States, other than at sewage treatment plants or in effluents of plants likely to have been using dimethylformamide. Levels measured were very low (WHO, 1991). It has been detected at low levels in drinking-water, surface water, wastewater and ambient air samples (United States National Library of Medicine, 1997). 

The benzodiazepine nucleus is a traditional pharmacophoric scaffold, which has been extensively studied, in medicinal chemistry. 1,4-benzodiazepinones can be readily synthesised by an intramolecular cycloaddition in N,N-dimethylformamide (DMF) under microwave heating conditions66. The synthetic approach summarised in Scheme 3.41 was performed using a microwave synthesiser especially designed for organic reactions. Both conventional heating and microwave heating conditions for the reactions were... 

The medicinal chemistry route used pyridine as the reaction solvent medium and, sodium hydride as the base. It was later recognized from solvent screening studies that the reaction pathway for the ring closure was solvent dependent. When dimethylformamide (DMF) was used as the solvent, an alternate cyclization pathway was observed (Scheme... 

The last step of the medicinal chemistry protocol consisted of coupling amine 2 and acid 3 using HATU (0-(7-Azabenzotriazol-l-yl)-N,N,N, N -tetramethyluronium hexafluorophosphate) in DMF (N,N-Dimethylformamide). After aqueous workup, the free base of final product 1 was first purified by column chromatography and then treated with HCl to afford drug candidate 1 as an amorphous HCl salt (Scheme 5.3). 

Figure 6.8. Plot of the time required for the solvent front to migrate 5 cm as a function of mobile phase composition for 2-propanol (1), N,N-dimethylformamide (2), 2,2,2-trifluoroethanol (3), methanol (4), acetone (5) and acetonitrile (6) in water on a Merck HPTLC RP-18 WF254s layer. (From ref. [95] Research Institute for Medicinal Plants).

Pol5miers of 1-vinyl-1,2,4-triazole are nontoxic, have a high hydrophiUc-ity, and a high hydrolysis stabiUty. Possible applications are in the food industry and medicine. Copolymers with of 2-hydroxyethyl methacrylate (HEMA) are used in biological and medical applications. They can be prepared in ethanol and AA -dimethylformamide (DMF) in the presence of 2,2 -azobisisobutyronitrile (AIBN) as the initiator. 

Perhaps the biggest impact will be over the use of solvents since many of the more common organic solvents are under threat from REACH these include N-methyl-2-pyrrolidone (NMP), dimethylformamide (DMF) and dime-thylacetamide (DMAc). (For more information on solvent substitution guides see Chapter 2, Tools for Facilitating more Sustainable Medicinal Chemistiy , by Helen Sneddon and James Sherwood s Chapter 3 on renewable solvent selection.) The electronics industry has also been subject to chemical legislation that aims to replace especially hazardous substances. RoHS (restriction on hazardous substances) targets certain chemicals, including lead, mercuiy, cadmium chromates and polybrominated flame retardants. ... 

---