Display omitted
•Reduction of tetrachlorothiadiazine afforded unexpected new heterocycles.•1,2,6-Thiadiazine was converted via thiophilic agents in two-steps to pyrimidine.•A practical route towards ...4,5,6-trichloropyrimidine-2-carbonitrile was developed.
Tin reduction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine afforded perchloro-9-thia-1,5,8,10-tetraazaspiro5.5undeca-1,4,7,10-tetraene (10%) and 3,5-dichloro-4H-1,2,6-thiadiazine-4-thione (27%), the structures of which were supported by single crystal X-ray crystallography. Treating the tetrachlorothiadiazine with Ph3P (1equiv.) afforded the corresponding spirocycle in a useful 66% yield, the degradation of which with BnEt3NCl (0.5equiv.) afforded densely functionalized 4,5,6-trichloropyrimidine-2-carbonitrile in 81% yield. Rational mechanisms for the formation of products are proposed.
Display omitted
•3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine reacts with cat. BnEt3NCl to give a mixture of mono- and polycyclic heterocycles.•Single crystal X-ray studies support the structures of four ...minor products.•Independent synthesis for 8-bromo-4-chloropyrrolo2′,1′:2,3imidazo4,5-c1,2,6thiadiazine-6,7-dicarbonitrile.
3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine was reacted with BnEt3NCl (10 mol%) to give perchloro-9-thia-1,5,8,10-tetraazaspiro5.5undeca-1,4,7,10-tetraene (up to 18% yield), 4,5,6-trichloropyrimidine-2-carbonitrile (up to 44% yield) and four minor side products: 2,7-dichlorothiazolo5,4-dpyrimidine-5-carbonitrile, 2-(4-chloro-6H-thiazolo5,4-c1,2,6thia-diazin-6-ylidene)malononitrile, 4,8-dichloropyrrolo2′,1′:2,3imidazo4,5-c1,2,6thiadiazine-6,7-dicarbonitrile and 4,7-dichloro-1,2,6thiadiazino3,4-bthiazolo5,4-e1,4diazepin-9(10H)-one. Single crystal X-ray studies support the structures of the minor products. Tentative rationale for the formation of these minor products and the synthesis of 8-bromo-4-chloropyrrolo2′,1′:2,3imidazo4,5-c1,2,6thiadiazine-6,7-dicarbonitrile are presented.
A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano3,4-bindole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of ...3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.
3H-1,2-Dithiole-3-thiones are among the best studied classes of polysulfur-containing heterocycles due to the almost explosive recent interest in these compounds as sources of hydrogen sulfide as an ...endogenously produced gaseous signaling molecule. This review covers the recent developments in the synthesis of these heterocycles, including both well-known procedures and important novel transformations for building the 1,2-dithiole-3-thione ring. Diverse ring transformations of 3H-1,2-dithiole-3-thiones into various heterocyclic systems through 1,3-dipolar cycloaddition, replacement of one or two sulfur atoms to form carbon- and carbon-nitrogen containing moieties, and other unexpected reactions are considered.
The reactions of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)-6-ethoxy-4-phenylpyridine-3,5-dicarbonitrile (14) with a range of primary and secondary amines are investigated. Treatment with n-BuNH2 ...and BnNH2 gave 1,3-di-n-butyl- and 1,3-dibenzyl-2-(3,5-dicyano-6-ethoxy-4-phenylpyrid-2-yl)guanidines 15a (32%) and 15b (82%), respectively. While treatment with Et2NH, n-Pr2NH or Bn2NH gave the analogous 4-dialkylaminopyrido2,3-dpyrimidines 16c–e in high yields. Treatment of the dithiazole 14 with pyrrolidine, piperidine or morpholine gave the analogous 4-dialkylaminopyrido2,3-dpyrimidines 16f–h, the 2-aminopyridine 13 and 2-(diamino-1-ylmethyleneamino)-6-ethoxy-4-phenylpyridine-3,5-dicarbonitriles 15f–h. The 4-dialkylaminopyrido2,3-dpyrimidines 16f–h are converted to the 2-(dialkylamino-1-ylmethyleneamino)-6-ethoxy-4-phenylpyridine-3,5-dicarbonitriles 15f–h upon further reaction with excess dialkylamines. The structure and origins of the two side products 17 and 18 are also discussed. Tentative mechanisms for these transformations are proposed.
Display omitted
The cyclisation reactions of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-amino)phenol (5a), 3-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)pyridin-2-ol (5b) and ...2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)pyridin-3-ol (5c) are investigated. Thermolysis in hot PhCl (132 °C) or under solvent free conditions at ca. 200 °C gave benzodoxazole-2-carbonitrile (4a), oxazolo5,4-bpyridine-2-carbonitrile (4b) and oxazolo4,5-bpyridine-2-carbonitrile (4c) in high yields, while treatment with either NaH in dry THF at 66 °C or with i-Pr2NEt in DCM at 20 °C gave benzob1,2,3dithiazolo5,4-e1,4oxazine (6a), 1,2,3dithiazolo5,4-epyrido2,3-b1,4oxazine (6b) and oxazolo4,5-bpyridine (4c), respectively. The transformation of benzoxazine 6a and the pyridoxazine 6b into the corresponding oxazoles 4a and 4b was also investigated, and tentative mechanistic pathways for these transformations are proposed.
Display omitted
Tetrafluoro-substituted aryne, 3,4,5,6-tetrafluoro-1,2-dehydrobenzene, has been generated in situ from 2-amino-3,4,5,6-tetrafluorobenzoic acid, and its reactivity in reactions with 1,2,4-triazines as ...dienes has been studied. In these reactions, the corresponding azine ring transformation products,
i.e.
, 1,2,3,4-tetrafluoro-10-(1
H
-1,2,3-triazol-1-yl)pyrido1,2-
a
indoles, have been obtained, in the case of triazines activated by the presence of electron-withdrawing groups, such as 6-aryl-3-(2-pyridyl)-5-cyano-1,2,4-triazines. The crystal structure of the obtained products was confirmed by X-ray diffraction analysis.
Although several methods of quantitative conformational characterization exist in the literature, all these methods use a spherical polar coordinate representation which is in contrast to the ...qualitative description based on the IUPAC nomenclature. To bridge this gap this paper introduces a method to characterize six-membered ring conformations as a linear combination of ideal basic conformations. The linear combination coefficients are derived by projection of the vector of torsion angles onto those of ideal basic conformations. As the IUPAC nomenclature uses subscripts and superscripts to indicate atoms below and above the reference plane, the linear combination coefficients combined with the IUPAC name provide an instant visual image of the conformation. The method introduced here is based on endocyclic dihedral angles and requires only three dihedral angles for a full characterization, which is often available by NMR measurements for rigid conformations. We provide a table of equations to determine the missing dihedral angles based on redundancy conditions. The relationship between linear combinations and spherical representation similar to the well-known Cremer–Pople parameters is presented. In deriving the spherical conformational parameters we solved an inconsistency of previous definitions for spherical representation, namely that none of previous definitions place the intermediate halfchair or twistboat conformations exactly halfway between the pole (chair) and the equator (boat and twistboat) of the sphere as expected based on intuitive stereochemistry. To make our method generally available we provide an interface on the Internet that carries out all calculations described in the paper and allows the user to visualize, rotate and manipulate the ring (http://www.nrc.ca/ibs/6ring.html). By simplifying both the concepts and the access to carry out the calculations more experimental chemists can benefit from the description of ring conformation.
The action of sulfur diethylaminotrifluoride on 19β,28-epoxyoleanan-3-ol (allobetulin) causes dehydration of the terpenoid and isomerization of the ring A via its contraction to isopropylcyclopentene ...ring resulting in 19β,28-epoxy-A-
neo
-18α-olean-3(5)-ene (α-allobetulin) in a high yield.
It was found that brief refluxing of
N
-hetarylcyclopentano
d
1,2,3triazolines in methanol resulted in the elimination of nitrogen, accompanied by cyclopentane ring opening with the formation of
N
...-hetarylvaleramidines. Amidines containing pyrimidine-2,4-dione ring were synthesized by a one-step procedure – the reaction of 5-azidopyrimidine-2,4-diones with endocyclic enamines containing a cyclopentene ring proceeded through an
N
-pyrimidyl-1,2,3-triazoline intermediate. Triazolines containing a 1,3,5-triazine ring at position 1 did not form valeramidines upon refluxing in methanol.
N
-(1,3,5-triazin-2-yl)cyclopenta
d
1,2,3triazoline containing a morpholine ring at position 6a underwent a different type of transformation upon dissolving in acetic acid, resulting in the formation of
N
-(1,3,5-triazin-2-yl)diaminoalkene. Mechanisms for these transformations are proposed.
PDF
