Dimethyl methylene

The three examples in Table 9 show Mannich reactions with 7V,A -dimethyl(methylene)im-inium salts. In the case of 5, a d.r. (exo/endo) 20 80 of the products was reported3 0. 

An interesting example for the modification of steroids by the addition of 5a-cholestanes to an Af(V-dimethyl(methylene)iminium salt with good stereoselectivity has been reported7. 

REGIOSELECTIVE MANNICH CONDENSATION WITH DIMETHYL(METHYLENE)AMMONIUM TRIFLUOROACETATE 1-DIMETHYLAMINO-4-METHYL-3-PENTANONE... 

The less highly substituted Mannich bases can also be prepared directly from ketones and dimethyl(methylene)ammonium trifluoroacetate by the procedure reported here, which takes advantage of the isomerization of Mannich bases in trifluoroacetic acid. (In acetic acid the Mannich bases undergo elimination of dimethylamine to give a-methylene ketones.) This method is rapid and affords products having an isomeric purity of at least 90% without difficult separations. The 49-57% yield of l-(di-methylamino)-4-methyl-3-pentanone obtained with this procedure compares favorably with the overall yields of amino ketones prepared by the indirect routes mentioned previously. 

Butanone, 4-(dimethylamino)-3,3-dimethyl- (8, 9) (53921-82-7) Dimethyl(methylene)ammonium trifluoroacetate Ammonium, di-methylmethylene-, salt with trifluoroacetic acid (1 1) (8) ... 

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). 

Treatment of Af-monosnbstitnted acetamides as well as aryl or alkyl methyl ketoximes 441 with dimethyl(methylene)ammoninm chloride 442 in the presence of phosphorus oxychloride offers two promising, straightforward and generally applicable routes to 2-bis(dimethylaminomethyl)acetamides 443 as a result of the formation of unidoyl chlorides as intermediates (equation 188). 

Reaction with indoles,5 Reaction with N,N-dimethyl(methylene)ammonium chloride is superior to reaction under conventional Mannich conditions for functionalization of various indoles. 

An important extension of these reactions is the Mannich reaction, in which aminomethyl-ation is achieved by the combination of formaldehyde, a secondary amine and acetic acid (Scheme 24). The intermediate immonium ion generated from formaldehyde, dimethyl-amine and acetic acid is not sufficiently reactive to aminomethylate furan, but it will form substitution products with alkylfurans. The Mannich reaction appears to be still more limited in its application to thiophene chemistry, although 2-aminomethylthiophene has been prepared by reaction of thiophene with formaldehyde and ammonium chloride. The use of N,(V-dimethyl(methylene) ammonium chloride (Me2N=CH2 CF) has been recommended for the (V.A-dimethylaminomethylation of thiophenes (83S73). 

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. 

Camphor has two dissimilar chiral centres (C-l and C-U) and therefore four enantiomorphs might be expected. But only one pair of enantiomers is known. This is due to the fact that only the ois-form is possible trans fusion of the gem-dimethyl-methylene bridge to cyclohexane ring is impossible. Thus only the enantiomers of cis-isomer are known. 

Aus Tetramethylphosphoniumbromid erhalt man mit Natriumamid in Tetrahydrofuran bei geeigneter Wahl der Reaktionsbedingungen kein Methylenphosphoran, sondern Tri-methylphosphan-(dimethyl-methylen-phosphoranylimid)712 ... 

Analoge Verbindungen erhalt man auch bei der Alkylierung von Phosphan-phosphano-imiden und bei der Protonierung von Trimethylphosphan-(dimethyl-methylen-phosphor-anylimid)746 747 z.B. ... 

Trimethyl- -(dichlor-methyl-silylimid) E2, 118 Trimethyl- -(dirnethylaluminiumimid) E2, 116 Trimethyl- -dimethylarsinoimid E2, 1 15 Trimethyl- -(dimethyl-fluor-silylimid) E2, 118 Trimethyl- -(dimethyl-methylen-phnsphoranyl-imid) E2, 114, 119... 

Bis[dw-butyLphosphano] tellurium replaces norbornadiene, cycloheptatriene, acetonitrile, and dimethyl(methylene)oxosulfurane in chromium, molybdenum, and tungsten complexes. The P —Te compound acts as a bidentate ligand with the two phosphorus atoms coordinated to the metal atom1. The tetracarbonylchromium complex [R = CH(CH3)J can be recrystallized without loss of tellurium2. 

However, practically no evidence was presented for such an unusual structure. In spite of the statement that this structure will be confirmed later, such a publication has not appeared, although the authors continued to discuss this problem 152). Very recently Bacskai and Lap-porte 153) repeated and extensively studied this problem and, on the basis of careful analytical work reported in detail, concluded that the 1,3 structure was erroneous. Thus, polyisobutenes obtainable with certain Ziegler-Natta type catalyst combinations also have the well known structure of alternating gem.-dimethyl-methylene groups. This conventional structure was established as early as 1940 by Thomas et al 154) in contrast to the contention of the Russian authors 155) ascribing this discovery to Rudenko in 1951. 

In steps 5 and 6 of Scheme 6.1 the torand backbone is built up from two molecules of ketone 9 via Mannich salt 10. Together these reactions constitute the most efficient method known so far for the synthesis of fused pyridines from cyclic ketones. The key intermediates involved in the transformation of 9 to 11 are shown in Scheme 6.7. In Protocol 5, ketone 9 reacts with /V,/V-dimethyl(methylene)ammonium chloride in acetonitrile.21 The HC1 salt of the resulting Mannich compound 10 precipitates from this solvent and the relatively pure product is isolated from the reaction mixture by filtration. 

V,/V-Dimethyl(methylene)ammonium chloride, 6.31 g, 67.4 mmol moisture sensitive, irritant... 

Add the 5-benzylidene-2,3,5,6,7,8-hexahydroacridin-4(1 W)-one,/V,A/-dimethyl-(methylene)ammonium chloride, and acetonitrile to the flask. Stir the reaction mixture at room temperature under N2 for 36 h. 

Boric acid is known to complex starch (see Section IV), and the same complexation takes place with the starch-iodine complexes. Figure 29 diagrams the assumed position of attached boric acid.159 As with starch, starch blue is capable of sorbing some dyes (Acridine Orange, Methylene Blue, and 1,9-dimethyl-methylene blue).225 This phenomenon is discussed in more detail in the accompanying article (p. 345). 

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. 

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