Dimethyl ammonium iodide

Labelled [13C] and [14C]-A-octadecyl-A-[palmytoyloxyethyl]-lV,A-dimethyl ammonium iodide were prepared by reaction of (II) with 13CH3I and 14CH3I, respectively. Labelled [13C] and [14C]-lV-(2-hydro-xyethyl)-AyV-dimethyloctadecylammonium iodide were prepared by reaction of (I) with 13CH3I and 14CH3I, respectively. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

A method of synthesis which has been used generally in this series employed a Fischer reaction at an early stage to form the tetrahydrocarbazolone nucleus [59] (Scheme 7.2). We devised a second route employing the Fischer method in which the key intermediate was the cyclohexenone (22) (Scheme 7.3). This was readily prepared by treating the enolate of the methyl enol ether (21) with dimethyl(methylene)ammonium iodide [60] to form the Mannich base which was then condensed with 2-methylimidazole to give (22). 

Methy1propanaI N,N-dimethyl-N-ethyl-2-ammonium iodide, A033 2-Methyl-1,3-propanedicarboxylic acid, AH80... 

CH2=NMe2 I).21 A recent convenient preparation of the dimethyl-(methylene)ammonium iodide reagent from trimethylsilyl iodide and N,/V,/V, ZV -tetramethylenediamine22 could result in greater value in future being placed on this reaction for the preparation of terminal alkenes. 

Hooz, J. and Bridson, J. N. A method for the regiospecific synthesis of Mannich bases. Reaction of enolborinates with dimethyl (methylene) ammonium iodide, J. Am. ChertL Soc.. 95, 602, 1973. 

The salt is prepared efficiently by reaction oftrimethylamine with methylene iodide in dioxane ethanol. I he product (I) is then heated at about 150° for about 12 min. in tetrahydrothiophenc dioxide dimethyl(methylene)ammonium iodide (2) is obtained in 81 % yield. ... 

MANNlCil REAGENT Dimethyl(methyl-ene)ammonium iodide. 

MACROLIDES Nickel carbonyl. MANNICH BASIS Dimethyl(mcthylcnc)-ammonium iodide. 

Taking advantage of the experience gained with ammonium iodide/TFA for reduction of Met(O) residues, a new resin-cleavage-deprotection cocktail has been used that consists of TFA (81%), phenol (5%), thioanisole (5%), ethane-1,2-dithiol (2.5%), water (3%), dimethyl sulfide (2%), and ammonium iodide (1.5% w/w).P It was found to prevent oxidation of Met residues in the acid cleavage step that was observed to occur in considerable extents with other deprotection cocktails. 

Schreiber, J., Maag, H., Hashimoto, N., Eschenmoser, A. Dimethyl(methylene)ammonium iodide. Angew. Chem., Int. Ed. Engl. 1971,10, 330-331. 

Reaction with trimethylsiiyl ethers. Regioselective Mannich reactions are possible by reaction of dimethyl(methylene)ammonium iodide with trimethylsiiyl enolates and dienolates.2... 

Regiospecific synthesis of Mannich bases. Hooz and Bridson2 have described a new regiospecific3 synthesis of certain Mannich bases which involves first reaction of a trialkylborane with an a-diazoketone in THF to form an enol borinate (l)4 after evolution of nitrogen ceases, dimethyl(methylene)ammonium iodide (2) in DMSO is added. The Mannich base (3) is obtained in 85-100% yield after hydrolytic workup. Cosolvent DMSO is crucial for high yields. 

Trimethylsilyl enol ethers continue to be useful synthons for various aldol typeis,lb and Michael1 18 reactions. Their utility in part is due to their ease of regiospecific preparation, ease of cleavage and high reactivity. Danishefsky and coworkers have shown that silyl enol ethers react with dimethyl(methylene)ammonium iodide yielding Mannich bases.19 Otherwise inaccessible Mannich bases are accessible via the series below. 

Oimettiyiamnopyndine (DMAP) 361,433 Dimethyl copper ithium 280 Dknethyttormamlde DMF 211,229 Dimethyl(methylene)ammonium iodide (Esehenmoser s salt) 241 Dimethylpyrrazole chromium trioxide 76 Dimethyl sulfate 12 Dimethyl sutlide 79... 

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