Synthesis and reactions of some derivatives of 1,2-dihydrothiazolo [3,2-a]pyridinium salts

The condensation of 2-mercaptopyridine, 2-mercapto-4-methylpyridine, and 2-mercapto-6-methylpyridine with -bromoacetaldehyde and its diethyl acetal has given cyclic products (3-hydroxy- and 3-ethoxy-2,3-thiazolo[3,2-a]pyridinium salts), from which cyanine dyes have been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1254–1257, September, 1973.     

Synthesis and complete 1H and 13C assignments of thiazolo[3,2-a]quinolinium derivatives

Several hitherto unknown thiazolo[3,2-a]quinolinium salts derivatives were prepared and characterized. Two-dimensional high field nmr methods were employed to make complete assignments of the proton and carbon nmr spectra for these compounds.     

The mass spectra of some 1H-imidazo[1,2-a]pyrrolo[3,2-e]pyridines

We report here the mass spectral fragmentations of some derivatives of a new heterocyclic system 1H-imidazo[1,2-a]pyrrolo[3,2-e]pyridine. These compounds combine structural features of 1H-pyrrolo[2,3-b]pyridines and imidazo[1,2-a]pyridines, but follow fragmentation pathways similar to the former.     

Electrochemical and electron spin resonance studies of selected benzazolo[3,2-a]quinolinium salts

The electrochemical reduction of the chloride or perchlorate salts of benzazolo[3,2-a]quinolinium ion and several of its analogues is reported. The compounds studied are the perchlorate salt of 3-nitrobenzothiazolo-and 3-nitro-9-methoxybenzothiazolo[3,2-a]quinolinium, and the chloride salts of 7-ethyl-, 3-nitro-7-methyl-, 3-nitro-7-ethyl-, 3-nitro-7-isopropyl-, 3-nitro-7-butyl- and 3-nitro-7-benzylbenzimidazolo[3,2-a]-quinolinium, respectively. Cyclic voltammetry of the corresponding 3-nitrobenzothiazolo[3,2-a]quinolinium derivatives in N,N-dimethylformamide shows an irreversible peak potential at -0.6 and a quasi-reversible peak at -(1.2–1.3) volts, respectively, relative to the standard calomel electrode. In contrast, the corresponding 3-nitrobenzimidazolo[3,2-a]quinolinium derivatives show, in general, reversible peaks at near -0.8 and -(1.2–1.4) volts, respectively. Upon electrolytic reduction, only the nitro-substituted derivatives produced observable electron paramagnetic resonance electron spin resonance spectra. This observation is explained in terms of the stabilization of the radicals produced by the nitro group. Theoretical MM+/AM1/UHF calculations support the idea that the larger nitrogen splitting is caused by N-12 and the minor splittings by N-7 in the benzimidazolo[3,2-a]quinolinium ion series.     

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines,Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3′,2′:4,5]pyrimido[1,2-a]azepines

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.     

First synthesis of 4H-furo[3,2-f]pyrrolo[1,2-a][1,4]diazepines

The synthetic pathway leading to 4-H-furo[3,2-f]pyrrolo[1,2-a][1,4]diazepines is described in five steps starting from 2-hydroxyketones via 2-amino-3-furonitriles.     

Oxazolo[3,2-a]pyridinium and oxazolo[3,2-a]pyrimidinium salts in organic synthesis

The methods for the synthesis of oxazolo[3,2-a]pyridinium and oxazolo[3,2-a]pyrimidinium salts and their reactivities are reviewed. Both systems exhibit ambident properties in reactions with nucleophiles; depending on the substituents and the reagents, both the oxazole and azine rings can undergo opening and transformations. A number of new methodologies involving oxazolopyridinium and oxazolopyrimidinium salts for the design of functionalized oxazoles, imidazoles, fused pyrroles, and other heterocyclic systems are generalized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 831–848, April, 2008.     

Photochemical synthesis of 7H-indolo[1,2-a]quinolinium salts - a new ring system

Photodehydrocyclization of 1-phenyl-2-/2-arylethenyl/-3,3-dialkyl-3H-indolium cations leads in very good yield to 7H-indolo[1,2-a]quinolinium cations.     

Oxazolo[3,2-a]pyridinium salts

The first synthesis of the aromatic oxazolo[3,2-a]pyridinium ring system has been accomplished by the cyclization of 1-acetonyl- or 1-phenacyl-2-pyridones. Through use of the analogous quinolones and 2-(p-bromophenacyl)-1-isoquinolone, benzologs of the new system have been prepared.     

Thiazolo [3,2-a] pyridinium salts

The sulfides formed by the reaction of α-halo ketones or α-halo acetals with 2-mercaptopyridine may be cyclized in good yield to form thiazolo[3, 2-a]pyridinium salts. The presence of chloro or nitro substituents on the pyridine ring does not interfere with the synthesis. Nitration of 3-methylthiazolo[3, 2-a]pyridinium perchlorate has been found to occur at position 8.     

Hexahydrobenzothiazolo[3,2-a]pyridinium salts

Salts of hexahydrobenzothiazolo[3,2-a]pyridine are obtained by exchange reactions. Anions are placed in the order [(NC)₂CCHC(CN)₂]- > ClO₄ ^–>I₃ ^–>Br^– according to the ability to displace each other. X-ray structural and spectroscopic studies establish the cis-attachment of the thiazolidine and cyclohexane rings in the hexahydrobenzothiazolo [3,2-a]pyridinium salts studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1682–1688, December, 1988.     

New synthesis of 5,6-dihydrothiazolo[3,2-b][1,2,4]triazoles

Russian Journal of Organic Chemistry -     

Diazepines. III. Synthesis of 4H-Pyrrolo[1,2-a] thieno[3,2-f] [1,4] diazepines

The synthesis of 4H-pyrrolo[1,2-a]thieno[3,2-f] [1,4]diazepines ( 8 ) is described. Phthal-imidomethylfurans 1 were treated with bromine-methanol to give the dihydrofurans 2 , which were hydrolyzed and then liydrogenated over Raney nickel or with zinc-acetic acid to afford the 1,4-diketones 5 . Condensation of 2-amino-3-benzoylthiophenes 6 with 5 gave 3-benzoyl-2-pyrrolylthiopenes 7 . The removal of the phthaloyl group from 7 with hydrazine hydrate and ring closure to the diazepine ring yielded the new heterocycles 8 .     

Synthese und Eigenschaften von Thiazolo[3,2-a]pyrimidinen und Thiazolo [3,2-a] pyrrolo [2,3-d]pyrimidinen

From the alkali-catalysed reaction of thiouracil with bromoacetaldehyde diethyl acetal three products are isolated in nearly the same quantity: 2-(2, 2-diethoxyethylthio)-uracil ( 2 ) and two cyclization products: 3 , a thiazolo[3, 2-a]pyrimidin-5-one, and 4 , athiazolo[3, 2-a]pyrimidin7-one. By warming with acid both 2 and 4 yield 3 . Rearrangement of 4 to 3 proceeds also by heating the hydrochloride. Similar cyclizations leading to thiazolo[3, 2-d]pyrrolo[2, 3-d]pyrimidin-5-ones are also described. Bromine substitutes 3 in position 6. The bromo derivative 6 on treatment with primary or secondary amines affords 7-amino compounds.     

Synthesis of imidazo[1,2-a]pyridine-6-carbohydrazides and 1H-pyrido[1,2-a]pyrimidine-7-carbohydrazides

The one-pot, multicomponent synthesis of imidazopyridine and pyridopyrimidine fused heterocyclic systems from readily available diamines, l,l-bis(methylthio)-2-nitroethene, cyanoacetohydrazide and aromatic aldehydes in good to high yields is described. This protocol has the advantages of simple work-up, mild reaction conditions, absence of catalyst and provides an entry point to fused heterocyclic structures.     

Synthesis of 1H-imidazo[1,2-a]imidazole

The synthesis and structure analysis of the unknown 1H-imidazo[1,2-a]imidazole ( 1 ) is described. The preparation involves alkylation of 2-aminoimidazole with bromoacetaldehyde diethyl acetal and subsequent hydrolysis and cyclization with hydrochloric acid. The structure was characterized by mass spectrometry and by ¹H-, ¹⁵N- and ¹³C-nmr of 1 and by ¹H-nmr of its 1-benzyl derivative 8 . An independent synthesis of 8 was accomplished via cyclization of 2-(N-dichloroethyl-N-benzyl)aminoimidazole ( 11 ).