Dimethylamine-enamine

The reaction of the dimethylamine enamine of isobutyraldehyde with aryl isothiocyanates at or below 50°C leads to the iminotetrahydrothiazine-thiones 333 these compounds rearrange on heating to hexahydropyrimidine-2,6-dithiones 334 (equation 135)164... 

If the reflux period is extended, the enamine is destroyed and cyclohexyldimethyamine (1) is obtained as the major product (45.2 % yield, 4-hr. reflux). In addition, 1,2,3,4,5,6,7,8-octahydroacridine (2) is obtained in 4.8% yield. The unexpected formation o octa-hydroacridines from dimethylamine enamines is being investigated. 

Scheme 17.1 Formation of (a) proline-enamine (b) dimethylamine-enamine.

The yields ranged from 55% for the mixture of enamines formed from morpholine and methylisopropyl ketone to 94% for the enamine formed from dimethylamine and methyl t-butyl ketone. The hindered ketone 2,5-dimethylcyclopentanone could be converted to an enamine, but the more hindered ketone, 2,6-di-t-butylcyclohexanone, was inert. White and Weingarten 43) attribute the effectiveness of titanium tetrachloride in this reaction to its ability to scavenge water and to polarize the carbonyl bond. 

The enamine prepared from acetone and dimethylamine is shown here in its lowest-energy form. 

A number of products in which one of the naphthalene rings has been reduced have interesting pharmacological properties. Reaction of tetralone 30 with dimethylamine under TiCl catalysis produces the corresponding enamine (31). Reaction with formic acid at room temperature effects reduction of the... 

The reaction of thioaldehydes, generated from phosphonium ylides and sulphur with secondary amines such as dimethylamine, leads to thioamides. If the thioaldehydes possess a a-hydrogen atom enamines are produced (equation 103)326. 

Enamines or imines can form pyridines by cyclization to a nitrile group, as shown in the production of compound (48). Alternatively, the nitrogen atpm of the nitrile can be made more nucleophilic by attack on the carbon atom by an external nucleophile. Ammonia causes cyclization of the dienamines (53) (77JHC1077) and (54) (78JAP(K)786878l) in both cases, elimination of the amine introduces the extra double bond. Dimethylamine or piperidine cause cyclization of l-cyano-2,5,5-trimethylhex-l-en-3-yne to the f-butyl-pyridine (55). There are a few other examples of the synthesis of bicyclic compounds from... 

To a cooled pressure autoclave are added 288 gm (4.0 moles) of isobutyralde-hyde, 150 gm of potassium carbonate, 500 ml of xylene, and 200 gm (4.4 moles) of dimethylamine. The autoclave is sealed, and rocked, or stirred for 4 hr at 100°C, cooled, vented, and opened. The liquid is distilled to afford 122 gm of a forerun, b.p. 53°-87°C, and then 216 gm (55 %) of the enamine, b.p. 87°-88°C, n d° 1.4221. Less xylene and potassium carbonate gave poor results. In addition, if the distillation is not carried out immediately after the reaction, lower yields of the enamine are possible. 

The resulting enamine 25 then reacts with the Vilsmeier reagent 27, which results from DMF and phosphoryl chloride by way of intermediate 26 Elimination of hydrogen chloride leads to compound 28. Ring closure presumably occurs via intermediate 29. Rearomati/.ation with elimination of dimethylamine produces the desired quinoline 9. 

The formation of a-naphthols of type 189 from 1-alkyl-substituted salts 30, on heating with dimethylamine hydrochloride in ethanol, occurs by another mechanism and will be explained in Section III,C,4,b,i. The interaction of l-aryl-3-carboxy-substituted salts 62 with secondary amines in benzene is initiated probably as in the reaction of these salts with primary amines, and the attack by the secondary amine on position 3 is the primary step of this reaction. However, since protonation of the intermediate anion 190, a masked acyl anion, becomes difficult, an interaction of this anion with the carbonyl group of the benzophenone fragment occurs (86KGS125). The enamines 191 thus formed are usually hydrolyzed on purification, yielding five-membered cyclic acyloins 192. 

Dimethylamine reacts with cyclopentanone to yield an enamine. 

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