With Mannich bases

Similar reactions described in [116] involve the interaction of o-PDA 1 with Mannich bases 130 (Scheme 4.42). The authors showed that for a 1 1 ratio of the... 

C. W., Synthesis of phenethylamines from phcnylaceionitrilcs obtained by alkylation of cyanide ion with Mannich bases from phenols and ocher bcnzylamincs. Tetrahedron, 29, 1931, 197.3. 

Diamino-5-benzylpyrimidines and analogues antibacterial agents. II. C-AIkylation of pyrimidines with Mannich bases and application to the synthesis of trimetoprim and analogues, J. Med. Chem.. 23,379. 1980 see also J. Med. Chem.. 23, 384 and 5.35. 1980. 

Von Strandtman, M., Cohen, M. P., Puch-alski, C., and Shavel J.. Jr., Reaction of phos-phoranes with Mannich bases. Synthesis of a-substituted-P-arylacrylic acids via the Wittig reaction, J. Org. Chem., 33, 4306, 1968. 

Brown, H.C., Kabalka, G. W Rathkc,, M. W and Rogic, M. M., Reaction of orga-noboranes with Mannich bases. A convenient prtxiedure for the alkylation of cyclic and bi-cyclic ketones via hydroboration, J. Am. Chem. Soc., 90, 4166, 1968. 

Both the above mechanisms are proposed in the literature with Mannich bases of nitroalkanes the substitution is clearly favored by the steric hindrance of the amine moiety, thus suggesting path 1, - whereas NMR studies on the reaction of P-amino-ketones with hydroxy coumarins do not reveal the presence of vinyl ketone intermediates. lodomethylated phenolic Mannich bases arc also claimed to react according to path 2, although the formation as by-products of dimers and methylene-bis-derivatives accounts for the participation of methylenequinone intermediates in the process. "... 

Okuda, T. and Maisumoto, U., Alkylation with Mannich bases. V. Mannich reaction of acyl-l-naphthols, YakugakuZasshi, 79, 1140, 1959 C/tem. Ahstr., 54.. 34.62, 1960. 

Strekowski, L., Alkylation of 2,4-dioxopyri-dines with Mannich bases. Bull. Akad Pol. Sd.. 21, 257, 1973 Chem. Ahmr.. 79,53252, 1973,... 

Ivanov. B. E., Zheltukhin, V. F., and Valitova, L. A.. Mechanism of the reaction of trie-thylphosphite with Mannich bases, in Khim. Primen. Fosfororg. Soedin.. Tr. 4th Konf., 1972, 204 Chem. Ahstr., 78, 135260, 1973. 

Metal Ions Affording Chelates with Mannich Bases ... 

A second challenge is the toxitity potential of some prodrugs, namely, a toxic metabolite formed from the promoiety or a reactive metabolic intermediate generated during the activation of some bioprecursors. The former case is illustrated by the liberation of formaldehyde, as seen with Mannich bases or some double esters [1,4]. The latter case involves a very few known examples of failed bioprecursors whose activation was via a reactive and toxic intermediate. Thus, arylacetylenes were examined as potential bioprecursors of nonsteroidal anti-inflammatory agents [1]. Although the nature of the final (and stable) metabolite (an arylacetic add) was known, researchers at the time were not aware that the metabolic pathway involved an intermediate and highly reactive ketene. 

Reactions of enamine (20) with Mannich bases, with esters of a, -unsaturated acids and with acrylonitrile take place under more severe conditions as compared to the similar reactions of cyclohexane enamines. 

Several improvements in the synthesis of emetine and its derivatives have been reported. Condensation of the dihydroisoquinoline (6) with Mannich bases (7 R = Et, Me, H) afforded the key intermediates (8) for syntheses of emetine, C(3)-noremetine, and C(3)-bisnoremetine. Condensation of the ketone (8 R = Et) with the Wittig reagent (9) yielded 2,3-dehydro-O-methylpsychotrine (10) or its dihydro-compound according to the conditions. The preparation of... 

Historically, Mannich bases have provided ready access to enone systems by 3-elimination of the amino group. A library of anti-leishmanial chalcones was prepared by a Heck reaction with Mannich bases serving as an enone precursor. 

The Stetter procedure [22, 23] is an excellent route to 1,4-diketones. Here, cyanide anion, or more often a thiazolium ylide, catalyses the addition of an aldehyde to an a,p-unsaturated ketone or a precursor thereof, e.g. a Mannich base. For example, the reaction of pyridine-4-carbaldehyde with Mannich base 11, catalysed by the ylide from 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide 12, produces the 1,4-diketone 13, from which the central thiophene ring of 14 can be constructed (Scheme 12) [24]. Comparable thiazolium yUde catalysis... 

Diene syntheses with Mannich bases a-Spiroketones s. lA, 824 Oxiranes from ketones and diazo compounds... 

Reaction of nitroacetic ester with Mannich bases... 

In the syntheses of the second group, the formation of the AD fragments takes place by the reaction of cyclic 1,3-diketones with Mannich bases containing ring A and a side chain with the potential Cg-Cg, C j, and atoms (Schemes 53 and 54). In the third group of syntheses, the formation of rings B and C takes place in the diene condensations of bicyclic dienynes with maleic anhydride and some of its derivatives (Scheme 55). 

Messinger P, Kusuma K. Alkylation of active methylene group of sulfones with Mannich-bases. Synthesis 1980 (7) 565-566. 

Sulphone syntheses based upon sulphinic acids include addition to activated alkenes, " condensation of salts RSOz Na" with Mannich bases or with an aldehyde and a urea or a thiourea in a Mannich-type reaction, and reaction with a diazoalkane benzhydryl p-tolyl sulphone is formed... 

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