Thiazolo[4,5-d]pyrimidines. Part I. synthesis and anti-human cytomegalovirus (HCMV) activity in vitro of certain alkyl derivatives

Alkyl derivatives of the thiazolo[4,5-d]pyrimidine congeners of guanine and uracil were prepared and assessed for in vitro activity against human cytomegalovirus (HCMV). The finding that the 3-pentyl 1b and 3-hexyl 1c derivatives of 5-aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (1e) had potent in vitro anti-HCMV activity prompted a broader study of alkyl derivatives in this ring system. A series of 3-alkyl derivatives of 1e , viz. 1f-w , were prepared by direct alkylation of the sodium salt of 1e and by subsequent modifications, 2a-d. For comparison with 1c , 5-amino-2-hexylaminothiazolo[4,5-d]pyrimidin-7(6H)-one (4) was prepared and studied. The 3-(2-alkenyl) derivatives of 1e were found to be the more active antiviral agents with the Z isomer of 5-amino-3-(2-penten-1-yl)thiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione (1f) having the better therapeutic index. Analogous 4-(2-alkenyl) derivatives of 2-aminothiazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione 6a and 6b were also prepared but were found to have poor therapeutic indices. Single crystal X-ray diffraction analysis was used to unequivocally establish the structure of 1f.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Five-membered 2,3-dioxoheterocycles: LXVII. Pyrroledione-pyrroledion recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates under the action of arylamines. Crystal and molecular structure of (z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)-methylene]pyrrolidine-2-carboxylate

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with aromatic amines involve a pyrroledione-pyrroledione recyclization to form isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(arylamino)methylene]pyrrolidine-2-carboxylates. The crystal and molecular structure of (Z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)methylene]pyrrolidine-2-carboxylate was proved by XRD analysis.     

C(2) symmetric chiral NHC ligand for asymmetric quaternary carbon constructing copper-catalyzed conjugate addition of grignard reagents to 3-substituted cyclohexenones

The asymmetric construction of quaternary carbon centers by conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones was realized in a maximum enantioselectivity of 80% by using a C 2 symmetric chiral N-heterocyclic carbene (NHC)-copper catalyst, generated from (4 S,5 S)-1,3-bis(2-methoxyphenyl)-4,5-diphenyl-4,5-dihydro-1 H-imidazol-3-ium tetrafluoroborate and copper(II) triflate. The stereostructures of the NHC-Au complexes were analyzed by X-ray crystallography, which rationalized the good stereocontrolling ability of N-aryl NHCs.     

Highly stereoselective iodolactonization of 4,5-allenoic acids--an efficient synthesis of 5-(1'-iodo-1'(Z)-alkenyl)-4,5-dihydro-2(3H)-furanones

In this paper, it is reported that the efficient iodolactonization of 4,5-allenoic acid with I2 in cyclohexane in the presence or absence of K2CO3 afforded 5-(1'-iodo-1'(Z)-alkenyl)-4,5-dihydro-2(3H)-furanones highly stereoselectively. However, the reaction of axially optically active 4,5-allenoic acids (R)-(-)-5 a and (R)-(-)-5 b with I2 afforded the corresponding products with a serious loss of chirality. This problem was solved by conducting the iodolactonization with N-iodosuccinimide in CH2Cl2 in the presence of Cs2CO3; however, the Z/E selectivity is somewhat lower. The pure optically active Z products were prepared by subsequent kinetic resolution with Sonogashira coupling. The reaction of the substrates with a substituent at the 3-position of the starting 4,5-allenoic acids afforded the trans-4,5-disubstituted gamma-butyrolactones as the only products. The reaction of the 4,5-allenoic acids (S)-(+)-1 l, (R)-(-)-1 l, and (S)-(+)-1 m with a center chirality at the 3-position afforded the trans products with very high enantiopurity and up to 98:2 Z/E selectivity regardless of the axial chirality of the allene moiety.     

Phosphinito- and phosphonito-oxazoline Pd(II) complexes as CO/ethylene insertion intermediates: synthesis and structural characterization

The phosphinito-oxazoline ligand 4,4-dimethyl-2-[methoxy(diphenylphosphine)]-4,5-dihydrooxazole (2a) and the phosphonite-oxazoline ligand 4,4-dimethyl-2-[methoxy(6H-dibenz[c,e][1,2]oxaphosphorin)]-4,5-dihydrooxazole (8a) were prepared by deprotonation of (4,5-dihydro-4,4-dimethyloxazol-2-yl)methanol (1a) and reaction with the corresponding P-Cl function, similar to the ligands 2b (4,4-dimethyl-2-[1-oxy(diphenylphosphine)-1-methylethyl]-4,5-dihydrooxazole) and 8b (4,4-dimethyl-2-[1-oxy(6H-dibenz[c,e][1,2]oxaphosphorin)-1-methylethyl]-4,5-dihydrooxazole) reported previously. These ligands react with [PdClX(COD)] to give complexes of the type [PdClX(P,N)] (3a P,N = 2a, X = Cl; 4a P,N = 2a, X = Me; 4b P,N = 2b , X = Me; 9a P,N = 8a, X = Cl; 9b P,N = 8b, X = Cl; 10a P,N = 8a, X = Me; 10b P,N = 8b, X = Me). Complexes 4a,b and 10a,b reacted with AgCF(3)SO(3) to yield [PdMe(P,N)OSO(2)CF(3)] 5a,b and 11a,b, respectively. From the stepwise insertion reaction of CO and ethylene into the Pd-C bond of 5a and 11a,b, the alkyl ketone chelate complexes [Pd{CH(2)CH(2)C(O)Me}(P,N)]CF(3)SO(3) 7a and 14a,b respectively, have been isolated and spectroscopically characterized. Complexes 3a.CH(2)Cl(2), 5a, 9b, 10a,b, [PdMe(H(2)O)(P,N)]CF(3)SO(3) 12b, (P,N = 8b) and 14a,b have also been characterized by X-ray crystallography and the structures of 14a,b represent still rare examples of structurally characterized CO/ethylene coupling products.     

Syntheses and structures of azol-1-yl derivatives of nitronyl and imino nitroxides

2-(Pyrazol-1-yl)-, 2-(imidazol-1-yl)-, 2-([1,2,4]triazol-1-yl)-, and 2-(benzotriazol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl were prepared by reactions of 2-bromo-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NIT-Br) with the corresponding sodium azolides. In prepared 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyls, the NIT-N_Het bond is readily hydrolyzed. Reduction of imidazole-3-oxide-1-oxyls leads to corresponding 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyls, which are much more stable against hydrolysis. The structures of spin-labeled imidazoles, [1,2,4]triazoles and benzotriazoles are confirmed by X-ray analysis, showing that the paramagnetic molecules form packings with motifs from centrosymmetric dimers to topologically linear chains.     

Heterocyclizations of functionalized heterocumulenes with C,N-, C,O-, and C,S-binucleophiles: XIII. Synthesis of dialkyl 2-oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates and their reaction with arylhydroxymoyl chlorides

Dialkyl 2-oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates obtained by condensation of 1-chlorobenzyl isocyanates with N-allylfumarates reacted regioselectively with arylhydroxymoyl chlorides with the formation of dialkyl 6-aryl-3-[(3-aryl-4,5-dihydro-5-isoxazolyl)methyl]-2-oxo-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

XPS spectra of free nitroxyl radicals and their electronic structure

The N(1s) and O(1s) XPS spectra of stable nitroxyl radicals and molecules with a related heterocycle structure: 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxyphenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxy-3-nitrophenyl)-4,5-dihydro-1Himidazole-3-oxide-1-oxyl, and 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide were studied. The possibility to apply X-ray electron spectra for investigation of the charge electron and spin density distribution on free radical atoms and at their coordination by a metal is considered.     

Preparation of aminotriazole-thione derivatives from n-aryl-n-carboxyethyl-β-alanines

Depending on the substituents in the aryl moiety, the fusion of N-aryl-N-ethoxycarbonyl-β-alanines with thiocarbohydrazide gives di- or monotriazole derivatives, namely, 4-amino-(2-{[2-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones, 1-[2-(4-amino- 5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]-2,3-dihydroquinolin-4(1H)-ones, 4-amino-3-[2-(4-methylanilino))ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione and 4-amino-3-[2-(4-ethoxyanilino)-ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione. A ditriazolethione derivative was also obtained from the diethyl ester of N-ethoxycarbonyl-N-(4-ethoxyphenyl)- β-alanine.     

Synthesis of Azaheterocyclic Cymantrene Derivatives

The reduction of acetylcymantrene with sodium tetrahydridoborate gave cymantrenylethanol which was acylated with 4,5-dichloroisothiazole- and 5-(4-methylphenyl)isoxazole-3-carbonyl chlorides to obtain esters containing a 1,2-thia(oxa)zole fragment. The condensation of acetylcymantrene with 5-arylisoxazole-3- carbaldehydes, (5-arylisoxazol-3-yl)methoxybenzaldehydes (Ar = Ph, 4-Tol), and 4,5-dichloroisothiazole-3- carbaldehyde afforded the corresponding (E)-3-(azol-3-yl)-1-cymantrenylprop-2-en-1-ones. The resulting α,β- unsaturated ketones reacted with semicarbazide hydrochloride and thiosemicarbazide to produce substituted 4,5-dihydro-1H-pyrazole-1-carboxamides and -1-carbothioamides, and their reaction with hydroxylamine hydrochloride led to the formation of 4,5-dihydroisoxazoles containing cymantrene and 1,2-azole fragments. Heterocyclization of azolylcymantrenylpropenones with guanidine gave 2-aminopyrimidine derivatives, and dihydropyrimidine-2-thiones were obtained by their reaction with thiourea.     

Synthesis and determination of pKa values of some new 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous solvents

3-Alkyl(Aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) reacted with 2-furoyl chloride and thiophene-2-carbonyl chloride to afford the corresponding 3- alkyl(aryl)-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3) and 3-alkyl(aryl)- 4-(2-thienylcarbonylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4), respectively. The new compounds synthesized were characterized by using IR, 1H-NMR, 13C-NMR and UV spectral data together with elemental analysis. In addition, to investigate the effects of solvents and molecular structure upon acidity, compounds 3 and 4 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, N,N-dimethylformamide and acetonitrile). The half-neutralization potential values and the corresponding pKa values were determined for all cases.     

1,4-shifts in a dinuclear Ni(I) biarylyl complex: a mechanistic study of C-H bond activation by monovalent nickel

The known aryne complex (PEt3)2Ni(eta2-C6H2-4,5-F2) (1a) reacts with a catalytic amount of Br2Ni(PEt3)2 over 1% Na/Hg to afford the dinuclear Ni(I) biarylyl complex [(PEt3)2Ni]2(mu-eta1:eta1-3,4-F2C6H2-3',4'-F2C6H2) (2a), which results from a combination of C-C bond formation and C-H bond rearrangement. The dinuclear benzyne [(PEt3)2Ni]2(mu-eta2:eta2-C6H2-4,5-F2) (3) was obtained by the reaction of 1a with a stoichiometric amount of Br2Ni(PEt3)2 over excess 1% Na/Hg, and 3 was found to catalyze the conversion of 1a to 2a. The reaction of 1a with B(C6F5)3 produced the trinuclear complex (PEt3)3Ni3(mu3:eta1:eta1:eta2-4,5-F2C6H2)(mu3:eta1:eta1:eta2-4,5-F2C6H2-4',5'-F2C6H2) (6). The addition of PEt3 to 6 produced 1 equiv of 1a and 1 equiv of [(PEt3)2Ni]2(mu-eta1:eta1-4,5-F2C6H2-4',5'-F2C6H2) (7a). Both 6 and 7a were identified as intermediates in the conversion of 1a to 2a. The analogue [(PEt3)(PMe3)Ni]2(mu-eta1:eta1-4,5-F2C6H2-4',5'-F2C6H2) (7b) was prepared by the addition of PMe3 to 6 and was structurally characterized. NMR spectroscopic evidence identified the additional asymmetric biarylyl [(PEt3)2Ni]2(mu-eta1:eta1-4,5-F2C6H2-3',4'-F2C6H2) (8a) during the conversion of 1a to 2a. The initial observation of 2 equiv of 8a for every equivalent of 2a produced from solutions of 7a suggests that 8a and 2a are formed from a common intermediate. A crossover labeling experiment shows that the C-H bond rearrangement steps in the conversion of 1a to 2a occur with the intermolecular scrambling of hydrogen and deuterium labels. The evidence collected suggests that Ni(I) complexes are capable of activating aromatic C-H bonds.     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita

Abstract

A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0?mg L^?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0?mg L^?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.     

Syntheses, structures, and electrochemical properties of platinum(II) complexes containing di-tert-butylbipyridine and crown ether annelated dithiolate ligands

A series of new platinum(II) complexes containing both 4,4'-di-tert-butyl-2,2'-bipyridine (dbbpy) and the extended tetrathiafulvalenedithiolate ligands have been prepared and characterized. These complexes include [Pt(dbbpy)(C8H4S8)] (1; C8H4S82- = 2-{(4,5-ethylenedithio)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate), [Pt(dbbpy)(ptdt)] (2; ptdt = 2-{(4,5-cyclopentodithio)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate), [Pt(dbbpy)(mtdt)] (3; mtdt = 2-{(4,5-methylethylenedithio)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate), [Pt(dbbpy)(btdt)] (4; btdt = benzotetrathiafulvalenedithiolate), [Pt(dbbpy)(C8H6S8)] (5; C8H6S82- = 2-{4,5-bis(methylthio)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate), [Pt(dbbpy)(3O-C6S8)] (6; 3O-C6S82- = 2-{4,5-dithia-(3',6',9'-trioxaundecyl)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate), and [Pt(dbbpy)(4O-C6S8)] (7; 4O-C6S82- = 2-{4,5-dithia-(3',6',9',12'-tetraoxatetradecyl)-1,3-dithiol-2-ylidene}-1,3-dithiol-4,5-dithiolate). The crystal structures of a new ligand precursor (2-[4,5-dithia-(3',6',9',12'-tetraoxatetradecyl)-1,3-dithiol-2-ylidene]-4,5-bis(2-cyanoethylsulfanyl)-1,3-dithiole, IIIc) and complexes 5-7 have been determined by X-ray crystallography. Complexes 1-7 show intense electronic absorption bands in the UV-vis region due to the intramolecular mixed metal/ligand-to-ligand charge-transfer transition, and they display significant solvatochromic behavior. Redox properties of these compounds have been investigated by cyclic voltammetry, and complex 7 shows a significant response for Na+ ions with a large positive shift of ca. 45 mV.     

Five-membered 2,3-dioxo heterocycles: LXXII. Recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates by the action of aliphatic amines

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with alkylamines involve pyrroledione-pyrroledione recyclization with formation of isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(alkylamino)methylidene]pyrrolidine-2-carboxylates.     

Synthesis of novel acyclonucleosides. Reactions of 1-(1-bromo or 3-bromo-2-oxopropyl)pyridazin-6-ones

Reaction of 1-(3-bromo-2-oxopropyl)pyridazin-6-ones 1 and 2 with sodium azide at room temperature gave the corresponding 1-(3-azido-2-oxopropyl)pyridazin-6-ones 3 and 4 , whereas reaction of 1-(1-bromo-2-oxo-propyl)pyridazin-6-ones 5 and 6 with excess sodium azide afforded 4-azido-5-chloropyridazin-6-one 7 and 4,5-diazido-3-nitropyridazin-6-one 8 by dealkylation. Some 1-(2-hydroxypropyl)pyridazin-6-ones 9, 10, 11 were synthesized from the corresponding 1-(2-oxopropyl) derivatives 1, 2, 3 . 4,5-Dichloro-1-(2,3-dihydroxypropyl)-pyridazin-6-one 13 was also prepared from compound 9 via the corresponding 2,3-epoxypropyl derivative 12 . Treatment of compound 5 with thiourea gave 4,5-dichloro-1-(2-amino-4-methylthiazol-5-yl)pyridazin-6-one 14 . Reaction of compounds 1 and 2 with thiourea at 20° afforded the corresponding 3-formamidinylthio-2-oxo-propyl derivatives 15 and 16 , whereas treatment of compound 1 with thiourea at 45° gave 4,5-dichloro-1-[(2-aminothiazol-5-yl)methyl]pyridazin-6-one 17 . Compound 17 was also prepared from compound 15 by refluxing in ethanol.     

Two-step α-ureidoalkylation of ureas with 4,5-dihydroxyimidazolidin-2-ones

Two-step α-ureidoalkylation of ureas with various 4,5-dihydroxyimidazolidin-2-ones gave novel 1,3-dialkyl-4,5-bis(3-alkylureido)-, 1,3-dialkyl-4,5-bis[3-(2-pyrimidyl)ureido]-, or 1,3-dialkyl-4,5-bis(3,3-dialkylureido)imidazolidin-2-ones and ensembles of three imidazolidine rings. The structure of 4,5-bis(2-oxoimidazolidin-1-yl)imidazolidin-2-one was confirmed by X-ray diffraction data. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 140–145, January, 2007.     

The Preparation of 4,5-Dihydro-5-Phenyl-5-(2-Phenylethenyl)Isoxazoles, 4,5-Dihydro-5-Methyl-5-(2-Phenylethenyl)Isoxazoles,or 4,5-Dihydro-5,5-DI-(2-Phenylethenyl)Isoxazoles from Dilithiated C(α),O-Oximes and Select α,β–-Unsaturated Ketones

C(α),O-oximes were dilithiated with lithium diisopropylamide and condensed with three α,β-unsaturated ketones: (2E)-1,3-diphenyl-2-propen-1-one, or (1E, 4E)-1,5-diphenyl-1,4-pentadien-3-one, or (3E)-4-phenyl-3-buten-2-one, followed by immediate acid cyclization to variously substituted 4,5-dihydroisoxazoles: 4,5-dihydro-5-phenyl-5-(2-phenylethenyl)isoxazoles, 4,5-dihydro-5-methyl-5-(2-phenylethenyl)isoxazoles, or 4,5-dihydro-5,5-di-(2-phenylethenyl)-isoxazoles.