Synthesis and Herbicidal Activity of 5‐Alkyl(aryl)‐3‐[(3‐trifluoromethyl)anilino]‐4,5‐dihydro‐1H‐pyrazolo[4,3‐d]pyrimidin‐4‐imines

A series of novel 5‐alkyl(aryl)‐3‐[(3‐trifluoromethyl)anilino]‐4,5‐dihydro‐1H‐pyrazolo[4,3‐d]pyrimidin‐4‐imines were designed and synthesized by the multistep reactions. 1 reacted with 3‐(trifluoromethyl)aniline to obtain N,S‐acetals 2 in the presence of 10 mol% DBU. 2 reacted with hydrazine to form 5‐amino‐3‐[(3‐trifluoromethyl)anilino]‐1H‐pyrazol‐4‐ nitrile 3 , the target compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m were obtained by the reaction of 3 with triethyl orthoformate followed by the cyclization of 4 with various amines. Their structures were confirmed by IR, ¹H NMR, EI‐MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L at the concentration of 100 mg/L. For example, compounds 5f , 5g , 5h , and 5j possessed 60.1%, 63.4%, 67.1%, and 61.3% inhibition against Brassica campestris L at the concentration of 100 mg/L.     

Design,Synthesis, and Herbicidal Activities of 3‐Aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. N‐(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3‐aryl‐4‐substituted‐4H‐[1,2,4]triazol‐5‐thiols 1 , which reacted with methyl sulfate in the presence of K₂CO₃ to give 3‐aryl‐5‐methylsulfanyl‐4‐substituted‐4H‐[1,2,4]triazoles 2 . The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3‐(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus‐galli at the concentration of 100 and 10 µg/mL.     

Synthesis and Herbicidal Activities of 3‐Trifluoromethyl‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐Triazol‐4‐Schiff Bases

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐(trifluoromethyl)‐4‐(arylimino)‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. Their structures were confirmed by IR, ¹H NMR, EI‐MS and elemental analyses. The preliminary bioassay indicated that compounds 4b , 4f , and 4h possessed 69.4%, 72.6%, and 88.5% inhibition against Brassica campestris L at the concentration of 100 mg/L. Generally speaking, this type of compounds exhibited weak herbicidal activity and might be not suitable as herbicide lead compound for further optimization.     

New Pyrazolyl‐Nicotinic Acids,Methyl Esters,and 1,3,4‐Oxadiazolyl‐pyrazolyl‐pyridine Tricyclic Scaffold Derivatives from 6‐Hydrazinylnicotinic Acid Hydrazide Hydrate

This paper describes an efficient approach for the synthesis of a new series of 6‐[3‐alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl]nicotinic acids (where alkyl = CH₃; aryl = Ph, 4‐OCH₃Ph, 4,4′‐BiPh; and heteroaryl = 2‐Furyl) from the hydrolysis reaction of alkyl(aryl/heteroaryl)substituted 2‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐5‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐1‐carbonylpyrazol‐1‐yl)pyridines, under basic conditions and at 70–95% yields. In a subsequent step, the esterification reaction of pyrazolyl‐nicotinic acids done in thionyl chloride and methanol led to the isolation of a series of methyl 6‐[alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl] nicotinates as stable hydrochloride salts at 64–84% yields, which could be easily converted to hydrazides to give new oxadiazolyl‐pyrazolyl‐pyridine tricyclic scaffolds at good yields from a [4 + 1] cyclocondensation reaction with 1,1,1‐triethoxyethane and 1‐(triethoxymethyl)benzene as the reagent/solvent.     

Synthesis of Novel Bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes,Bis(2‐S‐alkylpyridines), and Bis(3‐aminothieno[2,3‐b]pyridines) Incorporating 2,6‐Dibromophenoxy Moiety

The synthetic precursors pyridine‐2(1H)‐thiones 2a , b and bis(pyridine‐2(1H)‐thione) derivative 4 , using aldehydes 1a , b incorporating 2,6‐dibromophenoxy moiety, were prepared and used to synthesize the novel target materials bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes 5a , b , bis(2‐S‐alkylpyridines) 8a , b , and bis(3‐aminothieno[2,3‐b]pyridines) 13a–c through facile procedures. Characterization of the newly prepared compounds via elemental analyses and spectral data is established.     

Syntheses of Some 3—[1′（1′H）—Substituent—pyrazol—5′—yl] benzo [5,6] coumarins

3-[1′(1′H)-Substituent-pyrazol-5′-yl]benzo[5,6]coumarins and 3-(1′,2′-oxazol-5′-yl)benzo[5,6]coumarin were prepared via condensation of 3-(2′-formyl-1′-chlorovinyl)benzo[5,6] coumarin with hydrazine derivatives or hydroxylamine.Reaction of 3-[1′(1′H)-pyrazol-5′-yl]benzo[5,6]coumarin with alkyl halides,olefinic compunds or acid chlorides are described.     

Synthesis of dihydrothieno[2,3‐b]pyridines based on titanium(IV) chloride‐mediated michael reactions of 2‐amino‐4,5‐dihydro‐3‐thiophenecarbonitriles with α,β‐unsaturated ketones

2‐Arnino‐4,5‐dihydro‐3‐thiophenecarbonitriles 1a‐c reacted with α,β‐unsaturated ketones (e.g. methyl vinyl ketone 2 and benzalacetone 3 ) in the presence of titanium(IV) chloride to give the corresponding Michael adducts 4a‐c and 5a‐c. Thermal treatment of compounds 4a‐c and 5a‐c with titanium(IV) chloride caused intramolecular cyclocondensation to yield the corresponding tetrahydrothieno[2,3‐b]pyridines 6a‐c and 7a‐c. Aromatization of 6a‐c and 7a‐c with potassium tert‐butoxide in refluxing tert‐butyl alcohol pro ceeded smoothly to afford the corresponding dihydrothieno[2,3‐b]pyridines 8a‐c and 9a‐c.     

Synthesis and Herbicidal Activity of Novel N‐(2‐Fluoro‐5(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydro‐pyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxyacetamide Derivatives

Thirteen novel N‐(2‐fluoro‐5‐(3‐methyl‐2,6‐dioxo‐4‐(trifluoromethyl)‐2,3‐dihydropyrimidin‐1(6H)‐yl)phenyl)‐2‐phenoxy)acetamides were designed and synthesized utilizing 4‐fluoro‐aniline and ethyl 3‐amino‐4,4,4‐trifluoro‐but‐2‐enoate as starting materials. The chemical structures of all compounds were confirmed by ¹H NMR, IR, mass spectrum and elemental analyses. Subsequently, the herbicidal activities of the as‐prepared compounds were evaluated in the greenhouse. Bioassay results indicated that most of compounds had better herbicidal activities against dicotyledonous weeds. Among all the tested compounds, compounds 4a – 4i showed good herbicidal activities at both pre‐emergence and post‐emergence treatment against two or three kinds of dicotyledonous weeds, such as Abutilon theophrasti Medic, Amaranthus ascendens L, and Chenopodium album L at the dosage of 75 g ai/ha.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Synthesis of dihydrofuro[2,3‐b]pyridines by the reaction of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles with α,β‐unsaturated carbonyl compounds

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles 1a‐d with α,β‐unsaturated carbonyl compounds in the presence of sodium ethoxide (0.1 equivalent) gave the corresponding Michael adducts 2a‐d , 3a‐d and 4a‐d. Compounds 2a‐d and 3a‐c reacted with sodium alkoxide (1 equivalent) to yield the corresponding 7a‐alkoxyhexahydrofuro[2,3‐b]pyridines 5a‐d, 6a‐d, 7a‐c and 8a‐c . Treatment of 5a‐d, 6a‐d, 7a‐c and 8a‐c with potassium tert‐butoxide produced the corresponding dihydrofuro[2,3‐b]pyridines 9a‐d and 10a‐c . The reaction of 4a‐c with sodium ethoxide (1 equivalent) afforded the corresponding dihydro‐furo[2,3‐b]pyridines 11a‐c .     

Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

Microwave‐Assisted Synthesis of Novel 2,4‐Dihydro‐5‐[4‐(trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones and Potentiometric Determination of Their pKa in Nonaqueous Solvents

The novel 4‐amino‐ or 4‐aryl‐substituted 2,4‐dihydro‐5‐[(4‐trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones 3a – 3g were synthesized by reaction of N‐(ethoxycarbonyl)‐4‐(trifluoromethyl)benzenehydrazonic acid ethyl ester ( 2 ) and primary amines or hydrazine by microwave irradiation. Compounds 3a – 3g were potentiometrically titrated with tetrabutylammonium hydroxide (Bu₄NOH) in four nonaqueous solvents, i.e., ⁱPrOH, ^tBuOH, MeCN, and N,N‐dimethylformamide (DMF). Also half‐neutralization potential values and the corresponding pK_a values were determined in all cases.     

Reactions of hydrazonoyl halides 43 : Synthesis of some new 2,3‐dihydro‐1,3,4‐thiadiazoles,pyrazoles, pyrazolo[3,4‐d]‐pyridazines,thieno[2,3‐b]pyridines,pyrimidino[4′,5′:4,5]thieno[2,3‐b]‐pyridines and pyrrolo[3,4‐d]pyrazoles

2,3‐Dihydro‐1,3,4‐thiadiazoles, pyrazoles, pyrazolo[3,4‐d]pyridazines, thieno[2,3‐b]pyridines, pyrim‐idino[4′,5′:4,5]thieno[2,3‐b]pyridines and pyrrolo[3,4‐d]pyrazoles were obtained in a good yields by treatment of hydrazonoyl halides with each of alkyl carbodithioates, 3‐(dimethylamino)‐1‐naphtho[1,2‐d]furan‐2‐ylprop‐2‐en‐1‐one and N‐arylmalemides.     

Design,Synthesis, and Characterization of (2‐Alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone

The important therapeutic properties of imidazole‐related drugs have encouraged the medicinal chemists to synthesize and test a large number of novel molecules. In this investigation, it was of interest to synthesize (2‐alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone by short reaction times of N‐triazol‐3‐yl imidate with phenacyl bromides under basic conditions. All compounds were elucidated by spectroscopic methods including IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectral analysis.     

Synthesis of Potential Bioactive Novel 7‐[2‐Hydroxy‐3‐(1,2,3‐triazol‐1‐yl)propyloxy]‐3‐alkyl‐4‐methylcoumarins

A series of 50 novel 7‐[2‐hydroxy‐3‐(1,2,3‐triazol‐1‐yl)propyloxy]‐3‐alkyl‐4‐methylcoumarins had been designed and synthesized in good to excellent yields via Cu(I)‐catalyzed 1,3‐dipolar cycloaddition reaction “click chemistry” of 7‐(3‐azido‐2‐hydroxypropyloxy)‐3‐alkyl‐4‐methylcoumarins with variety of acetylene derivatives. In turn, the precursor compound, that is, 7‐(3‐azido‐2‐hydroxypropyloxy)‐3‐alkyl‐4‐methylcoumarin, was synthesized by condensation of epichlorohydrin with 7‐hydroxy‐3‐alkyl‐4‐methylcoumarins followed by opening of the epoxide ring in the resulted 7‐epoxymethoxy‐3‐alkyl‐4‐methylcoumarins with sodium azide. All the synthesized compounds were unambiguously identified on the basis of their spectral data analyses (IR, ¹H‐NMR, ¹³C‐NMR spectra, and HRMS).     

Synthesis and Characterization of New 3‐(3‐Hydroxyphenyl)‐4‐ alkyl‐3,4‐dihydrobenzo[e][1,3]oxazepine‐1,5‐dione Compounds

A series of 3‐(3‐hydroxyphenyl)‐4‐alkyl‐3,4‐dihydrobenzo[e][1,3]oxazepine‐1,5‐dione compounds with general formula C_nH_2n+1CNO(CO)₂C₆H₄(C₆H₄OH) in which n are even parity numbers from 2 to 18. The structure determinations on these compounds were performed by FT‐IR spectroscopy which indicated that the terminal alkyl chain attached to the oxazepine ring was fully extended. Conformational analysis in DMSO at ambient temperature was carried out for the first time via high resolution ¹H NMR and ¹³C NMR spectroscopy.     

Microwave Induced Synthesis of 3‐Aryl‐6‐(6‐/8‐substituted 4‐chloroquinoline‐3‐yl) ‐ s ‐triazolo [3,4‐b] −1,3,4‐thiadiazoles

The condensation of 4‐amino‐3‐aryl‐5‐mercapto‐1, 2, 4‐triazoles (1a‐f) with 6‐/8‐substituted 1,4‐dihydro‐4‐oxo‐quinoline‐3‐carboxylic adds (2a‐d) in the presence of phosphorus oxychloride on refluxng or under microwave irradiation gave twenty four novel 3‐aryl‐6‐ (6‐/8‐substituted 4‐chloroquinoline‐3‐yl)‐s‐triazolo[3,4‐b]‐1, 3,4‐thiadiazoles (4a‐x), Considerable increase in the reaction rate has been observed with improved yields under microwave irradiation. The structures of the compounds synthesized were determined by elemental analyses, IR, ¹H NMR and MS spectra. Their spectral properties and the reaction mechanism were also discussed. The preliminary biological test showed that some of compounds bad moderate antibacterial activities.     

Synthesis,Modification, and Anticonvulsant Activity of 3′‐R1‐Spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones Derivatives

Previously unknown 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazoline]‐2,2′‐(7′H)‐diones and their N‐substituted analogues were obtained via reaction of 6‐R¹‐3‐(2‐aminophenyl)‐1,2,4‐triazin‐5‐ones with isatin and its substituted derivatives. It was shown that alkylation of 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′‐(7′H)‐diones by N‐R³‐chloroacetamides or chloroacetonitrile in the presence of а base proceeds by N‐1 atom of isatin fragment. The spectral properties (¹H and ¹³C NMR spectra) of synthesized compounds were studied, and features of spectral patterns were discussed. The high‐effective anticonvulsant and radical scavenging agents among 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones and their N‐substituted derivatives were detected. It was shown that compounds 2.2 , 2.8 , and 3.1 exceed or compete the activity of the most widely used in modern neurology drug—lamotrigine on the pentylenetetrazole‐induced seizures model. The aforementioned fact may be considered as a reason for further profound study of synthesized compounds using other pathology models.     

Synthesis of Derivatives of Pyrido[4,3‐d]pyrimidin‐4(3H)‐one via an Iminophosphorane

A series of new, 2‐substituted 3‐aryl‐8,9,10,11‐tetrahydro‐5‐methyl[1]benzothieno[3′,2′ : 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones, compounds 5a – q , were designed and synthesized via the aza‐Wittig reaction as the key step. The iminophosphorane 1 reacted with phenyl isocyanate (or 4‐chlorophenyl isocyanate) to the carbodiimide 4 , which was cyclized to 5 upon addition of different amines, EtOH, or phenols in the presence of a catalytic amount of EtONa or K₂CO₃ (Schemes 1 and 2). The structures of compounds 5 were confirmed by IR, ¹H‐ and ¹³C‐NMR, EI‐MS, elemental analyses, and, in the case of 5l , by single‐crystal X‐ray diffraction (Figure).