Réarrangement de thiénobenzothiépinones en thiénoisothiazolinone et benzoisothiazolinone

Under the conditions of the Schmidt reaction the thienobenzothiepinones 1 , 2 and 13 involve a rearrangement respectively in N-benzythieno[2,3-d]isothiazolin-3-one ( 5 ) and benzoisthiazolin-3-one ( 6 ). A mechanism for this rearrangement is proposed.     

The Synthesis of Bicyclic N4-Amino-2′-deoxycytidine Derivatives

Nucleosides which have ambivalent tautomeric properties have value in a variety of nucleic acid hybridization applications, and as mutagenic agents. We describe here synthetic studies directed to stable derivatives of this kind of nucleoside based on N⁴-aminocytosine. Treatment of the 4-(1H-1,2,4-triazol-1-yl)-5-(chloroethyl)pyrimidinone nucleoside derivative 5 with hydrazine leads to formation of the 6,6-bicyclic pyrimido-pyridazin-7-one 3 , and with methylhydrazine to the corresponding fixed tautomeric 1-methyl derivative 7 (Scheme 1). If these cyclization reactions are carried out in the presence of a base, the 6-ring bicyclic derivatives undergo rearrangement to their corresponding 5-ring pyrrolo-pyrimidin-2-one analogues 8 (Scheme 2). In the reaction of the triazolyl derivative 5 with 1-[(benzyloxy)carbonyl]-1-methylhydrazine, spontaneous cyclization gives the 5-ring derivative 13 related to 8 rather than the open-chain product 12 (Scheme 4). Reaction of an acetylated analogue of triazolyl derivative 5 with 1,1-dimethylhydrazine gives rise to some of the open-chain product 9 , but it too cyclizes to a product that we have assigned the structure of the 6,6-ring quaternary ammonium salt 11 (Scheme 3).     

Specifically (π → π*)-Induced Cyclohexenone Reactions 4a-(Z-1-Propenyl)-bicyclo[4.4.0]dec-1 (8a)-en-2-one and 4a-Z-1-Propenyl-bicyclo[4.4.0]deca-1(8a), 7-dien-2-one

4a-(Z-1-Propenyl)-bicyclo[4.4.0]dec-1(8a)-en-2-one ( 6 ) and 4a-(Z-1-propenyl)-bicyclo[4.4.0]deca-1(8a), 7-dien-2-one ( 17 ) undergo an intramolecular hydrogen transfer from the methyl group of the propenyl substitutent to the α-carbon atom of the enone group, and cyclization to the [4.4.3]propellane derivatives 9 and 30 , respectively, when excited in the π → π* wavelength region. The quantum yield for (Z)- 6 → 9 under optimum conditions is 0.29 at 254 nm. These reactions occur specifically from the S₂ (π,π*) state, competing with the S₂ → T decay. The triplet reactions of 6 are E–Z double-bond isomerization, double-bond shift to (E,Z)- 8 , and rearrangement to (E)- 10 . Further investigations concern some structural limitations in the scope of the reaction type 6 → 9 and enone S₂ reactivity in general.     

Nitro derivatives of 1,3-dihydrobenzimidazol-2-one: II. Rearrangement of <Emphasis Type="Italic">N</Emphasis>-nitrobenzimidazol-2-ones

N-Nitrobenzimidazol-2-ones readily undergo rearrangement to C-nitro derivatives on heating in various solvents (ethyl acetate, butyl acetate, acetonitrile, acetone, dioxane, o-dichlorobenzene, anisole, acetic acid). This rearrangement was used to develop a procedure for the synthesis of 4,5,6,7-tetranitro-1,3-dihydrobenzimidazol-2-one in high yield (90–96%) by nitration of 1,3-dihydrobenzimidazol-2-one, as well as of 5,6-dinitro- and 4,5,6-trinitro-1,3-dihydrobenzimidazol-2-ones, with a small excess of concentrated nitric acid in a mixture with acetic anhydride and acetic acid at 50–60°C.     

Polycyclic N‐Heterocyclic Compounds. Part 78: Synthesis of N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclohepten‐1‐yl]formamide Oximes and Their Evaluation as Inhibitors of Platelet Aggregation

N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclohepten‐1‐yl]formamide oximes were synthesized by fusion of (6,7,8,9‐tetrahydro‐5H‐cyclohepta[1,2‐d]pyrimidin‐4‐yl)amidines with hydroxylamine hydrochloride through a subsequent rearrangement reaction. Effects of the products as well as the structurally related N‐[4‐([1,2,4]oxadiazol‐5‐yl)‐2,3‐dihydro[1]benzoxepin‐5‐yl]formamide oximes and N‐[4‐([1,2,4]oxadiazol‐5‐yl)‐2,3‐dihydro[1]benzothiepin‐5‐yl]formamide oximes on platelet aggregation were evaluated.     

Herstellung der 1H-Indazole durch Photolyse von 2-Aminophenylketon-O-(äthoxycarbonyl)oximen und von 3,1,4-Benzoxadiazepin-2 (1H)-onen

1H-Indazoles Obtained by Photolysis of 2-Aminophenylketon-O-(ethoxycarbonyl)oximes and of 3, 1, 4-Benzoxadiazepine-2(1 H)-ones Irradiation of (E)- and (Z)-O-(ethoxycarbonyl)oximes 1 of 2-aminophenyl ketones in solution with UV, and/or visible light gives 1 H-indazole derivatives 2 in high yields (Scheme 1). For this reaction the amino group must be un- or mono substituted. With the N, N-disubstituted (E)- 1d (Scheme 2) no 1 H-indazole formation is observed, because the radicals formed by its photolysis react in an unspecific manner with each other and with the solvent. From the behaviour of (E)- 1d and from the lack of any E/Z-isomerization of 1 we conclude that the photoreaction starts with a splitting of the N, O-bond in two separate radicals, whereas the radical pair produced by the also studied photolysis of 3,1,4-benzoxadiazepine-2(1 H)-one derivatives 3 is fixed in the parent molecule, and therefore tends to recombine. This makes a prolonged irradiation necessary to convert the benzoxadiazepinones 3 into the 1 H-indazoles 2 . The different reaction rates of the (E) and (Z)-isomers of 1 (provided R⁴ = H) are understood by means of different intramolecular H-bridges.     

Chiral exo-Alkylidenecyclopentanes from (1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one

(1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one oxime in the system (CF₃CO)₂O-CF₃COOH and (1S,4R)-1-(1,2-dibromoethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one in the system MeONa-MeOH undergo fragmentation to give exo-alkylidenecyclopentane derivatives, (4R)-4-cyanomethyl-5,5-dimethyl-1-[(1E)-trifluoroacetoxyethylidene]cyclopentane and isomeric (4R)-4-carboxymethyl-1-[(1ZE)-2-methoxyethylidene]-5,5-dimethylcyclopentanes, respectively. The trifluoroacetate derivative undergoes unusual rearrangement, yielding an equilibrium mixture of two isomers with endo- and exocyclic double bond.     

Studies on quinones. Part 25. Synthetic approaches to 6,9-dioxygenated-benzazepinones

The Schmidt and Beckmann rearrangement of 3,4-dihydro-4,4-dimethyl-1(2H)-naphthalenones bearing oxygenated groups at the 5,8-positions, and some of their oximes are reported. Depending upon the structure of the substrates and the reaction conditions 4,5-dihydro-3H-naphth[1,8-cd]isoxazol, benzazepin-2-one and 5,6-dihydro-7H-tetrazolo[1,5-a][2]benzazepine derivatives were generated.     

Sigmatropische Umlagerungen von Aryl-propargyläthern; Synthese von 1, 5-Dimethyl-6-methylen-tricyclo[3, 2, 1, 02,7]-oct-3-en-8-on-Derivaten. Vorläufige Mitteilung

2, 6-Dimethylphenyl propargyl ether ( 10 ) and its derivatives 12–15 rearrange thermally to 1, 5-dimethyl-6-methylene-tricyclo [3.2.1.0^2,7]oct-3-en-8-one ( 9 ) and related compounds 16–19 . The ethers undergo first an aromatic [3, 3]-sigmatropic rearrangement to ortho-allenyldienones 11 , which then undergo ring closure to the tricyclic products by an electrocyclic reaction. Only in the case of the γ-methylpropargyl ether 13 , the ortho-dienone 11 is further rearranged in low yield to the para-butynylphenol 20 , but the tricyclic ketone 17 is again the main product. New data show that the known thermal cyclisation of aryl propargyl ethers to chromenes (e. g. 4 → 8 ) involves a preliminary [3, 3]-sigmatropic rearrangement.     

3-Nitro-1,2,4-triazol-5-one derivatives

3-Nitro-1,2,4-triazol-5-one and its monomethyl derivatives react with methyl vinyl ketone to give products of addition to the ring N₁ and N₄ atoms. The reaction with formaldehyde and N-methylolacetamide proceeds only at the N₁ atom. The keto derivatives of 3-nitro-1,2,4-triazol-5-one undergo the Schmidt reaction to give the corresponding acetamides. A number of compounds that include functional groups in the N₁-alkyl substituent of the 3-nitro ring were obtained by treatment of the bases of N₁-substituted 3,5-dinitro-1,2,4-triazoles in aprotic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 552–558, April, 1981.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

Ring contraction in reactions of 3-benzoylquinoxalin-2-ones with 1,2-phenylenediamines. Quinoxaline-benzoimidazole rearrangement

The reactions of 3-benzoylquinoxalin-2-one and its N(1)-alkyl derivatives with 1,2-phenylenediamines were accompanied by ring contraction as a result of the quinoxaline-benzoimidazole rearrangement giving rise to 2-benzoimidazolyl-substituted quinoxalines. The possible pathways of these reaction are discussed.     

Platinum‐Catalyzed Multi‐Step Reaction of Propargyl Alcohols with N‐Heteroaromatics

N‐Methyl indole reacts with but‐2‐yn‐1‐ol in the presence of PtCl₂ in MeOH giving indole derivatives having a substituted 3‐oxobutyl group at the 3‐position in good yield. Under the reaction conditions, various substituted indoles and substituted propargyl alcohols are successfully involved in the reaction giving the corresponding addition products in good to moderate yields. The catalytic reaction can be further extended to N‐phenyl pyrrole. In the present multi‐step reaction, PtCl₂ likely plays dual roles: as the catalyst for the rearrangement of propargyl alcohols to the corresponding alkenyl ketones and as the catalyst for the addition of indoles to the alkenyl ketones. Experimental evidence is provided to support the proposed mechanism.     

Novel chemical modifications at the 4-position of chromones. Synthesis and reactivity of 4H-chromene-4-spiro-5′-isoxazolines and related compounds

Reactions of chromones with dilithiooximes proceed via nucleophilic 1,2-addition to give, on acidification, 4H-chromene-4-spiro-5′-isoxazoline derivatives in high yields. On treatment with concentrated H₂SO₄ the isoxazoline ring of this novel spiroannulated heterocyclic system opens to give α,β-unsaturated oximes, which undergo nitrosation, bromination, and the Beckmann rearrangement to the corresponding spiroisoxazolines and α,β-unsaturated amides, respectively. The latter can be obtained directly by the Beckmann rearrangement of 4H-chromene-4-spiro-5′-isoxazolines.     

Some transformations of 3-amino-4-alkoxycarbonyl-6-hydroxy-2H-1-benzopyran-2-ones. The synthesis of [1] benzopyrano[3,4-d]-[1,3]oxazine and [1] benzopyrano[3,4-d]pyrimidine derivatives

Acylation of 4-alkoxycarbonyl-3-amino-6-hydroxy-2H-1-benzopyran-2-one derivatives 3 and 4 gave under mild conditions the O-substituted derivatives 5–10, N,O -disubstituted derivative 11 and N,N-disubstituted derivative 12 . The compound 4 was transformed with benzoyl chloride under more drastic conditions into 13 , a derivative of a new heterocyclic system 2-benzopyrano[3,4-d][1,3]oxazine. The derivatives of 1-benzopyrano-[3,4-d]pyrimidine 19 and 20 were prepared either from 3 and 4 through the corresponding N-heteroarylformamidines 14 and 15 and N-heteroarylformamide oximes 17 and 18 or by cyclization of thiourea derivative 20 .     

α-Oximierung von gesättigten Ketonen durch das photochemisch angeregte Nitrit-Ion

The photochemical behaviour of the nitrite ion must be considered as being similar to that of the carbonyl group. Like the carbonyl group, the nitrite ion in n, π* excitation is capable of abstracting hydrogen atoms from various compounds. During this reaction the nitrite ion is reduced to NO. The radicals obtained by abstracting α-H atoms from saturated ketones then react with the NO to give nitroso derivatives which undergo a rearrangement to the corresponding oximes - provided that the same carbon bears further hydrogen atoms. Dimethylformamide and probably also acetylacetone act as quenchers in this photoreaction, whereas aromatic aldehydes and excess NO do not.     

Nitrosation of methyl and phenyl styryl ketoximes under oxygen. Formation of 4-nitro-1-hydroxypyrazole 2-oxides and 3,5-diphenyl-4-nitrato-4,5-dihydroisoxazole

The nitrosation of the oximes of 4-phenyl-3-buten-2-one and 1,3-diphenyl-2-propen-1-one under oxygen has been reinvestigated. In addition to 4-oxo- and 4-oximino-4H-pyrazole 1,2-dioxides previously reported, the reactions give 4-nitro-1-hydroxypyrazole 2-oxides. In the case of 1,3-diphenyl-2-propen-1-one oxime the nitrosation reaction also gives 3,5-diphenyl-4-nitrato-4,5-dihydroisoxazole. Evidence is presented suggesting that the nitrate ester is formed through the rearrangement of a peroxynitrite intermediate.     

Polycyclic N‐heterocyclic compounds. Part 66: Synthesis of N‐[2‐([1,2,4]oxadiazol‐5‐yl)cyclopenten‐1‐yl]formamide oximes and their evaluation as inhibitors of platelet aggregation

N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclopenten‐1‐yl]formamide oximes were synthesized by fusion of (6,7‐dihydro‐5H‐cyclopenta[1,2‐d]pyrimidin‐4‐yl)amidines and/or their amide oximes with hydroxylamine hydrochloride through a subsequent rearrangement reaction. Assay of the products for anti‐platelet aggregation activity revealed that certain of them showed promising inhibitory effect on arachidonic acid‐induced platelet aggregation. J. Heterocyclic Chem., (2011).     

Synthesis of new carbamate derivatives of indole and their modification

Oximation of indoles having a methoxycarbonylamino group on C⁵ and an acyl group on C³ with hydroxylamine hydrochloride in the presence of pyridine gave the corresponding oximes. The reduction of the 3-C=O group with sodium tetrahydridoborate in the presence of sodium hydroxide was accompanied by removal of the methoxycarbonyl group at the pyrrole nitrogen atom with formation of racemic alcohols. 1,4-Addition of 1-(pyridin-3-yl)butane-1,3-dione to dimethyl 1,4-benzoquinone diimine N,N′-dicarboxylate in dioxane in the presence of sodium methoxide, followed by heating in boiling 22% hydrochloric acid, afforded methyl 2-methyl-5-(methoxycarbonylamino)-3-(pyridin-3-ylcarbonyl)-1H-indole-1-carboxylate. 3-(Dimethylamino)-1-(4-methyl-1,2,5-oxadiazol-3-yl)prop-2-en-1-one reacted with N,N′-bis(methoxycarbonyl)- and N,N′-bis(phenylsulfonyl)-1,4-benzoquinone diimines in methylene chloride and acetic acid, respectively, in the presence of BF₃ · Et₂O to produce indoles having a 1,2,5-oxadiazolylcarbonyl group on C₃.