Ca++-modulators. Unusual highly stereospecific hantzsch-like cyclization: first authenticated example of 2-chloromethylene-1,2,3,4-tetrahydropyridine

Frigerio, M.; Zaliani, Andrea; Riva, Carlo Ruga; Palmisano, Giovanni; Pilati, Tullio; Gandolfi, C.

doi:10.1016/s0040-4039(00)82340-0

Cited by 14 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formation of a similar exocyclic C=C bond was noted only on trying to alkylate N-substituted 1,4-dihydropyridines in the presence of a strong base (lithium diisopropylamide) [20] capable of deprotonating a methyl group. In some cases the presence of 2-methylene-1,2,3,4-tetrahydropyridines was also demonstrated as an intermediate products in the Hantzsch synthesis of N-substituted, as well as N-unsubstituted, dihydropyridines according to [21][22][23][24].…”

mentioning

confidence: 99%

Electrochemical oxidation of 4-monoalkyl-substituted 1,4-dihydropyridines

Turovska

Goba

Turovskis

et al. 2008

Chem Heterocycl Comp

View full text Add to dashboard Cite

The electrochemical oxidation of 4-monoalkyl-substituted 1,4-dihydropyridines has been studied in an aprotic medium and in the presence of pyridine. In an aprotic medium the products of oxidation are both 4-alkyl-substituted and 4-unsubstituted pyridines or mixtures of them. On oxidation in acetonitrile of 4- 2,3, were obtained in addition to the oxidized forms. In the presence of base the products of preparative electrolysis of the studied compounds were 4-alkyl-substituted pyridines. The exception was the 4-i-Prsubstituted dihydropyridine which was dealkylated on oxidation even in the presence of base.Dihydropyridines are one of the most investigated classes of organic compounds. The synthesis and reactions of 1,4-dihydropyridines have been examined in detail in reviews [1][2][3][4]. Many compounds of this series possess pharmacological activity. A series of pharmaceuticals [5] has been developed based mainly on 4-arylsubstituted 1,4-dihydropyridines. Antioxidant properties have also been confirmed for the heterocycle itself in reactions with various radicals [6,7]. On the other hand study of the redox reaction of the dihydropyridine ring is also important for the reason that its oxidation is the main metabolism of dihydropyridines.The attention of electrochemists is mainly attracted [8][9][10][11][12][13] by the oxidation of 4-methyl-, 4-aryl-1,4-dihydropyridines or those unsubstituted in position 4. In all the mentioned cases proton is split off from the position 4 of the ring on oxidation. N Me H Me R H COOMe MeOOC 1-5 1 R = Me, 2 R = Et, 3 R = n-Pr, 4 R = i-Pr, 5 R = i-Bu

show abstract

mentioning

confidence: 99%

Electrochemical oxidation of 4-monoalkyl-substituted 1,4-dihydropyridines

Turovska

Goba

Turovskis

et al. 2008

Chem Heterocycl Comp

View full text Add to dashboard Cite

show abstract

“…The best method for preparing 2a and also the unsymmetrically 3,5-disubstituted 1,4-DHP 2c proved to be a two stage synthesis (Scheme 1, method C) by initial synthesis of the 2-(10-methyl-10H-phenothiazin-3-ylmethylene)acetoacetic acid esters 3a,b and subsequent cyclization with methyl β-aminocrotonate. The corresponding ylidene derivatives 3a,b were prepared by refluxing acetoacetic acid esters with the 10-methyl-10H-phenothiazine-3-carbaldehyde 1 in benzene in the presence of piperidine acetate with azeotropic distillation of water [16].…”

mentioning

confidence: 99%

4-(10-Methyl-10H-phenothiazin-3-yl)-1,4-dihydropyridines, 4,5-dihydroindeno[1,2-b]-and 5,5-dioxo-4,5-dihydrobenzo-thieno[3,2-b]pyridines

Vı̄gante

Tirzītis

Tirzīte

et al. 2007

Chem Heterocycl Compd

View full text Add to dashboard Cite

Keywords: 10-methyl-10H-phenothiazin-3-carbaldehyde, 1,4-dihydropyridine, Hantzsch synthesis, 4-(10-methyl-10H-phenothiazin-3-yl)-5-oxo- 1H-4,5-dihydroindeno[1,2-b]pyridine.Highly effective coronary dilators [1, 2] and hypotensive agents [3] have already been discovered amongst 4-aryl-and 4-hetaryl-1,4-dihydropyridines (1,4-DHP) but this has not diminished the synthesis of novel 1,4-DHP's with the aim of finding compounds having an altered profile of pharmacological properties. It is known that the 1,4-DHP structure can be regarded as a pharmacophoric group or "special structure" and the variation of the substituent in the DHP ring might be expected to give a selective action of the 1,4-DHP on various cell membrane receptors [4].The antioxidant activity of 1,4-DHP has been investigated [5, 6] and its correlation with pharmacological properties discussed [7,8]. It was found that the exchange of an o-nitrophenyl group at position 4 of the 1,4-DHP for a polycyclic heterocyclic substituents (xanthone, azaxanthen-9-one, thioxanthen-9-one) had a marked effect on inotropic and vasodilator activity [9, 10]. 1,4-DHP and 4,5-dihydro-indenopyridines containing lipophilic and bulky substituents show inhibitory activity on glutathione-S-transferase [11].At the same time, phenothiazine derivatives can possess high antioxidant, antiradical, neuroprotective, and antitumor activity [12,13]. In recent years phenothiazine derivatives have been investigated as neuroprotectors of nerve cells in Alzheimer [14] and Creutzfeld-Jakob deseases [15]. In combination this encouraged us to synthesize 1,4-DHP derivatives having the two pharmacotropic groups (1,4-DHP and phenothiazine) in the same molecule.To prepare the novel series of monocyclic 1,4-DHP 2, 5-oxo-4H-dihydroindeno[1,2-b]pyridines 5, and also 5,5-dioxo-4,5-dihydrobenzothieno[3,2-b]pyridines 8 we have employed different modifications of the Hantzsch synthesis using 10-methyl-10H-phenothiazine-3-carbaldehide 1 as the aldehyde component. Hence the 1,4-DHP 2b was prepared in 42% yield by refluxing the aldehyde 1 with acetoacetic ester and ammonia in ethanol (Scheme 1, method A). The corresponding dimethyl ester of the 1,4-DHP-3,4-dicarboxylic acid 2a was __________________________________________________________________________________________

show abstract

Ethyl 4-Chloroacetoacetate

Jackson

2001

Encyclopedia of Reagents for Organic Synthesis

View full text Add to dashboard Cite

Ca++-modulators. Unusual highly stereospecific hantzsch-like cyclization: first authenticated example of 2-chloromethylene-1,2,3,4-tetrahydropyridine

Cited by 14 publications

References 9 publications

Electrochemical oxidation of 4-monoalkyl-substituted 1,4-dihydropyridines

Electrochemical oxidation of 4-monoalkyl-substituted 1,4-dihydropyridines

4-(10-Methyl-10H-phenothiazin-3-yl)-1,4-dihydropyridines, 4,5-dihydroindeno[1,2-b]-and 5,5-dioxo-4,5-dihydrobenzo-thieno[3,2-b]pyridines

Ethyl 4-Chloroacetoacetate

Contact Info

Product

Resources

About