Linear Stepwise Synthesis of 2-(Naphthalen-1-yl)-2,3,5,6-tetrahydro-1H-isoquinolino[8,1,2-hij]quinazoline: A Novel Fused Heteroaromatic Framework

In this research investigation, a total of eighteen diverse tetra- and penta-lateral cyclic compounds were synthesized. These included 1,3,4-thiadiazole, thiazolidin-4-one (via an alternative method), 1,2,4-triazole, carbothioamide, thiazole-4-one, azetidin-2-one, and oxazole. The synthesis procedure entailed a sequence of reactions. The thiazolidine-4-one 1 was obtained by reaction p-aminobenzoic acid with thiosemicarbazide, followed by treatment with p-tolualdehyde to produce Schiff base 2. Reaction Schiff base 2 with mercaptoacetic acid in dry benzene was carried out to produce thiazolidine-4-one 3. In another synthesis pathway, the esterification of p-nitro benzoic acid with ethanol in the presence of sulfuric acid was obtained to formation of compound 4. Compound 4 was subsequently reacted with thiosemicarbazide, yielding compound 5. Cyclization of compound 5 was then achieved using 4% sodium hydroxide solution. This formed the 1,2,4-triazole heterocycle, designated compound 6. Thiosemicarbazone 7-9 were prepared by reaction of thiosemicarbazide with different aldehydes. Additionally, 2-substituted-1,3-thiazolidine-4-one derivatives 10-12 were synthesized through the reaction of thiosemicarbazone with chloroacetic acid in the presence of anhydrous sodium acetate. The Oxazole derivative 15 was obtained through a series of reactions starting with the reaction of p-amino benzoic acid with ethyl chloroacetate, resulting in compound 13. Compound 13 was then treated with urea to obtain compound 14, followed by a reaction with 4-phenyl phenacyl bromide to yield the final product, the Oxazole derivative 15. The 2-aminooxadiazole derivative 16 was synthesized by reaction urea with 4-bromoacetophenone which was reacted with 4-bromobenzaldehyde to produce Schiff base derivative 17. Finally, β-lactam 18 is obtained through reaction Schiff base with chloroacetyl chloride in the presence of triethyl amine. FT-IR, 1H-NMR, and 13C-NMR spectroscopy were used to confirm their proposed structures. Moreover, the antibacterial and antifungal activities of certain synthesized compounds, specifically 2,3,6,11,13,15,17, and 18, were assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans, demonstrating encouraging outcomes.Keywords: Antibacterial, antifungal activity, oxadaizole, heterocyclic derivatives, Oxazole.

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO2 in 6% H2SO4 in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K2CO3 and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.

A series of substituted and fused heterocyclic derivatives 2–17 were synthesized using 3,5-bis(4-methoxybenzylidene)-1-propylpiperidin-4-one (1) as starting material. Treatment of 1 with malononitrile or semicarbazide afforded compounds 2 and 3, respectively. Condensation of 1 with ethyl cyanoacetate afforded naphthyridine-3-carbonitrile derivative 4, which reacted with phosphorus pentachloride and phosphoryl chloride to give chloro derivative 5. Treatment of 5 with thiosemicarbazide afforded compound 6. The reaction of 1 with malononitrile gave cyano aminopyrane derivative 7 which was condensed with pyromellitic dianhydride, phthalic anhydride, succinic anhydride, or morpholine in glacial acetic acid to obtain imide derivatives 8–11. Additionally, the reaction of 7 with aromatic aldehydes gave derivatives 12a–12c. Acetylation of 7 with acetic anhydride in boiling acetic acid gave N-acetyl derivative 13 which was cyclized to pyridine derivative 14 by refluxing in dioxane in the presence of triethylamine. Treatment of 7 with hydrazine hydrate gave pyrazolo derivative 15. Finally, the reaction of 7 with triethyl orthoformate in the presence of acetic anhydride gave formimidate 16 which was treated with hydrazine hydrate to form N-amino derivative 17. Some of the synthesized compounds were examined in vitro for their antitumor activity against HepG-2, PC-3, and HCT-116 human carcinoma cell lines using MTT assay.

Synthesis of 3-benzazepines and azepino[4,5-b]heterocyclic ring systems via intramolecular Friedel–Crafts cyclization

Calculation of the thermodynamic properties and relative stabilities of aqueous acetic and chloroacetic acids, acetate and chloroacetates, and acetyl and chloroacetyl chlorides at high and low temperatures and pressures

In 1957, a new method for the synthesis of methylphosphonous dichloride, in high yield, by the reduction of the aluminum chloride – phosphorus trichloride – methyl chloride complex in diethyl phthalate solution by finely powdered antimony, was developed. That this is a general method for the synthesis of the more volatile alkylphosphonous dichlorides was demonstrated by the preparation, in good yield, of a series of compounds from the aluminum chloride – phosphorus trichloride complexes formed from ethyl chloride, n-propyl chloride, i-propyl chloride, n-butyl chloride, and s-butyl chloride. As expected, isomerization occurred in the case of the normal alkyl chlorides.

Ru(II)-catalyzed one-pot synthesis of polysubstituted spirofluorene-indenes via [3 + 2] annulation and then intramolecular Friedel-Crafts alkylation has been achieved. The simple method provides a broad scope of aryl ketones and internal alkynes, achieving PAHs skeletons in moderate to good yields.

In this work Azo compound was synthesized through a diazo-coupling reaction (A1) (4-((4,5-diphenyl-1H-imidazol-2-yl)diazenyl)aniline). The diazotization process of 4-aminoaniline with 4,5-diphenyl-1H-imidazol as coupling component was described ,then Schiff bases[AB1-AB3] prepared from condensation of the free amino group in the azo compound with many aromatic aldehydes by using ETOH as solvent. Cyclization of Schiff bases with Chloro acetyl chloride in the presence of tri ethyl amine give the corresponding β-lactam derivatives [L1-L3].All these compounds were identified by Spectral techniques (FT-IR, 1H-NMR, 13C-NMR) and followed by (TLC) and melting points of them.

A series of seven novel azetedinones 4a-g have been synthesized by cyclocondensation of various Schiff bases of phenothiazine with chloroacetyl chloride in presence of triethylamine. Various Schiff bases of phenothiazine were synthesized by condensation of 2-hydrazinyl-1-(10H-phenothiazin-10-yl)ethanone 2 with various aryl aldehydes. Compound 2 was synthesized by reacting 2-chloro-1-(10H-phenothiazin-10-yl) ethanone 1 with hydrazine hydrate. The synthesized compounds were characterized by IR, 1H-NMR and mass spectra. The titled compounds were evaluated for anti-tubercular, anti-bacterial, anti-fungal and anti-inflammatory activity by Lowenstein-Jensen medium method, cup plate method, disc diffusion method and carrageenan induced paw edema method, respectively. All the seven compounds 4a-g at a concentration of 100, 10 and 1 mg/L showed inhibition against the growth of Mycobacterium tuberculosis. Compounds showed good anti-bacterial activity against Staphylococcus aureus and Bacillus subtilis. Compound 4e showed equipotent antibacterial activity with streptomycin standard and showed better anti-bacterial activity against gram positive bacteria profile than gram negative bacteria. Zone of inhibition was not found for the compounds against Escherichia coli and Pseudomonas aeruginosa. Compounds 4a-g exhibited good antifungal activity against Aspergillus species and no activity against Candida albicans. None of the reported compounds showed promising anti-inflammatory activity. Key words: Azetidinones, anti-tubercular, anti-bacterial, anti-fungal, inflammation

The reaction of resorcinol with ethylacetoacetate yielded the 7‐hydroxy‐4‐methyl coumarin (1), which on treatment with benzidine gives 1‐(4ʹ‐amino‐biphenyl‐4‐yl)‐7‐hydroxy‐4‐methyl‐1H‐quinolin‐2‐one (2). 1‐{4ʹ‐[(Substituted benzylidene)‐amino]‐biphenyl‐4‐yl}‐7‐hydroxy‐4‐methyl‐1H‐quinolin‐2‐one (3a‐j) were obtained by reacting 1‐(4ʹ‐amino‐biphenyl‐4‐yl)‐7‐hydroxy‐4‐methyl‐1H‐quinolin‐2‐one (2) with different substituted aromatic aldehydes in presence of glacial acetic acid by microwave irradiation. The compound 1‐{4ɴ‐[(substituted benzylidene)‐amino]‐biphenyl‐4‐yl}‐7‐hydroxy‐4‐methyl‐1H‐quinolin‐2‐one (3a‐j) on cyclization with chloro acetyl chloride in presence of triethylamine as catalyst under microwave irradiation furnished 1‐{4ʹ‐[3‐chloro‐2‐(substituted phenyl)‐4‐oxo‐azetidin‐1‐yl]‐biphenyl‐4‐yl}‐7‐hydroxy‐4‐methyl‐1H‐quinolin‐2‐one (4a‐j). Purity of synthesized compounds was checked by TLC and the structures were elucidated by their IR, 1H NMR, Mass and elemental analysis data. The synthesized compounds were screened for anticonvulsant activity.

Synthetic analogs of indoles and azetidinones are reported to possess various pharmacological activities such as anti-inflammatory, antidepressant, neuroleptic, cytotoxic, antitubercular, antihypercholesterolemic, antioxidant activities along with wide range of antimicrobial activity. Isatin (indole-2, 3-dione) on treatment with o-phenelynediamine in presence of ethanol and glacial acetic acid gave 6H-indolo(2, 3 b)quinoxaline [M1] which on treatment with ethylchloroacetate gave Ethyl [6H-indolo(2, 3 b)quinoxaline)-1-acetate [M2] which on amination with hydrazine hydrate afforded 6H-indolo(2, 3 b)quinoxaline-1-acetic acid hydrazide[M3]. New series of N-(3-chloro-2 oxo-4 aryl azetidine-1-yl)-2-[6H-indolo (2, 3 b) quinoxaline-6-yl] acetamides[M4] were synthesized by condensation of 6H-indolo (2, 3b) quinoxaline-1-acetic acid with different aromatic aldehydes to produce a series of schiff s bases. β-lactam moiety was incorporated on Schiff s base through cycloaddition reaction using chloroacetyl chloride in presence of triethyl amine. The synthesized compounds were charecterised by IR, 1H NMR and Massspectral studies. All the newly synthesized compounds have been evaluated for their antimicrobial activity against gram-positive and gram-negative bacteria and fungi The synthesized compounds were active against gram positive, gram negative bacterial and fungal species. Para nitro substituted derivatives are good antimicrobial agents among all the derivatives.

α,β-Unsaturated γ- and δ-lactones were selectivity reduced to the corresponding saturated lactones and oxospiro systems respectively using sodium borohydride in the presence of triethylamine in THF, in excellent yields.

A series of novel azetidinones 5a-i have been synthesized by cyclocondensation of various Schiff bases of coumarin with chloro acetyl chloride in presence of triethyl amine. The reaction of 4-hydroxy coumarin with POCl3 yielded 4-chloro coumarin 2 and 4-chloro-3, 4', 3', 4

Design, synthesis and biological evaluation of some novel isoniazid cyclocondensed azetidinones

N-(2-Pyridyl)-2-chloroacetamide reacted with 1-methylpiperazine and gave the expected compound III. Attempts at preparing the N-substituted N-(2-pyridyl)-2-chloroacetamides by reactions of N-substituted 2-aminopyridines with chloroacetyl chloride in benzene in the presence of N,N-dimethylacetamide were negative and took an unexpected course. 2-Anilinopyridine and 2-(cyclohexylamino)pyridine afforded compounds which were identified by 1H and 13C NMR spectra as the heterocyclic betaines IVa and IVb. 2-(1-Butylamino)pyridine, 2-(benzylamino)pyridine and 2-(2-phenylethylamino)pyridine gave similarly compounds IVc-IVe. The chloromethyl compounds IVa-IVe underwent normal substitution reactions with 1-methylpiperazine and gave the methylpiperazino compounds Va-Ve. Attempts to reduce the betaines with sodium borohydride in aqueous ethanol proceeded in one case as the hydrogenolytic displacement of the chlorine atom with hydrogen (product VIa), in another case as ethanolysis (product VIIb). Formation of VIb by treatment of IVb with hydrogen bromide in boiling acetic acid is probably the result of a disproportionation reaction. Compound III (dimaleate VÚFB-17 103) was practically equipotent with pirenzepine (I) as an anti-ulcer agent in the test of indomethacine-induced gastric lesions in rats but was much weaker in tests for antocholinergic and antisecretory activity.