Substitution of HMPT by the cyclic urea DMPU as a cosolvent for highly reactive nucleophiles and bases

Abstract

The cyclic urea DMPU ( N , N'-dimethyl-N, N'-propylene urea= 1,3-dimethyl-2-0x0-hexahydropyrimidine) is shown to exhibit the same effects as HMPT in oxirane-opening with Li-acetylide, in a Wittig olefination, in the double deprotonation of a nitroalkane, in the Michael addition of Li-dithiane to cyclohexenone, and in selective generations of certain enolates (Schemes 1-7). DMPU might therefore be a safe substitute of the carcinogenic HMPT as a cosolvent with unique properties in diverse types of reactions.Hexamethylphosphoric triamide (HMPT) is extensively used in research laboratories due to its unique properties as a dipolar aprotic solvent [l] and its superior ability to form cation-ligand complexes [ 2 ] . However, in recent years HMPT has been sholvn to be a carcinogen in animal tests even at low concentrations [3] and 'it was concluded that HMPA ranks in the super league of experimental carcinogens and must be considered as potentially posing a serious risk to man, even at the scale of use in a laboratory ' [4]. The need for a safe substitute is thus indispensable. Tetrasubstituted ureas1)2) appeared to us especially attractive since their properties are similar to those of HMPT. We were particularly interested in a cosolvent which a) would be compatible with highly nucleophilic and basic reagents3), and b) could be employed at dry-ice temperature or below. We reportFor a review on tetramethylurea, see [5]; for a more recent survey of tetrasubstituted ureas as solvents see [6]. A few other solvents, cosolvents, and/or complexing agents have also been studied; for example tetraalkylsulfamides [7] and N, N, N', N'-tetramethylethylenediamine (TMEDA) 181.Other solvents such as dimethyl sulfoxide (acidic) or 1-methyl-2-pyrrolidinone (both acidic and electrophilic) were thus not suitable.

On the preparation of cyclopentadienes by a novel homolytic annulation of but-3-en-1-ones with alkynes mediated by samarium diiodide

“…Use of the more stable precursor enone 6c again led to annulated product. Employment of DMPU as a co-solvent in place of the highly toxic HMPA 19,20 greatly slowed the reaction. After 3 days of stirring, the reaction mixture was still deep blue.…”

The Urea Renaissance

“…[1b] Urea and its derivatives were, however, largely bypassed by the major developments of organic chemistry in the 20th century. With a few exceptions, for example, the urea/ hydrogen peroxide complex (UHP), [2] or the cyclic urea cosolvent 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), [3] ureas rarely featured as tools or targets in organic synthesis. Ureas lacked the natural ubiquity of amides, the reactivity of esters, and the versatility of carbamates, and therefore languished on the dark fringes of the carbonyl functional world.…”

Tools and techniques for solvent selection: green solvent selection guides

“…Only the most recent safety datasheets contain this information and it is not widely known at the time of writing [59]. Despite being recommended as an alternative solvent decades before the solvent selection guides of the pharmaceutical industry existed, the urea derivative dimethyl propylene urea (DMPU) has not become a prominent green solvent, but may also be worth considering for certain types of chemistry [60,61].…”