The synthesis of substituted pyrazino[2,3-d]-1,2,4-triazolo[4,3-b]pyridazines

The synthesis of 1,2,4-triazolo[4,3-b]pyridazines and the unknown ring system, pyrazino[2,3-d]-1,2,4-triazolo[4,3-b]pyridazine, has been achieved. The preparation of the new tricyclic 1,2,4-triazole was accomplished first by ring closure of the triazole ring followed by formation of the pyrazine ring. Substitution of the pyrazino[2,3-d]-1,2,4-triazolo[4,3-b]pyridazine ring system was carried out in order to provide information of its reactivity and to provide a variety of interesting compounds for biological testing.     

The synthesis and chemical reactions of certain pyrazolo[1,5-a]-1,3,5-triazines

3-Aminopyrazole was utilized as a starting material for the preparation of certain pyrazolo-[1,5-a]-1,3,5-triazines. 4-Chloro-2-methylthiopyrazolo[1,5-a]-1,3,5-triazine was prepared and used for studies of nucleophilic displacement reactions, and it has been found that both the chloro and methylthio groups may be displaced by nucleophiles. By modifications of these procedures we have prepared the adenine, hypoxanthine, and xanthine analogs of the pyrazolo-[1,5-a]-1,3,5-triazine ring system. Electrophilic substitution occurs in the 8-position of this ring system. The methyl group was introduced into the 4-position by a novel ring opening and ring closing of the 1,3,5-triazine ring.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 7. [1]Benzothieno[2,3-c]naphtho[2,1-h]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-h][1,2,4]triazolo[4,3-a]quinoline

The synthesis of two novel polycyclic heterocyclic ring systems via photocyclization is described. These are [1]benzothieno[2,3-c]naphtho[2,1-h]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-h][1,2,4]triazolo[4,3-α]-quinoline. In the ¹H nmr spectrum the proton at position 6 is strongly deshielded in the first ring system while the proton at position 6 in the second ring system is shifted considerably upfield while the proton at position 8 in the second ring system is the most deshielded proton in that ring system. The bay regions in both ring systems are severely congested.     

The crystal and molecular structure of N-(17-methoxy-phenyl)-2-chloropyrrolo (2,3- b ) quinoline

N-(17-methoxy-phenyl)-2-chloropyrrolo (2,3-b) quinoline was solved by direct methods and refined to anR of 0.104 for 950 observed reflections. The intensity data were collected by the multiple film equi-inclination Weissenberg technique and estimated visually. The packing of the molecule is stabilised by van der Waals interaction. The pyrrolo (2,3-b) quinoline ring system is planar and the methoxy phenyl ring is approximately perpendicular to the plane of this ring system with a dihedral angle of 86.5°.     

Synthesis of some novel 2-phenylpyridazino[4,5-b][1,5]thiazepines

Synthesis of some derivatives of the pyridazino[4,5-b][1,5]thiazepine ring system is reported. Thus, 5-benzyl-8-methyl-2-phenyl-2,3.4,5-tetrahydro-5H-pyridazino[4,5-b][1,5]thiazepin-9(8H)-one ( 5 ) was prepared by an intramolecular S-alkylation reaction, whereas the thiazepine ring of sulfone analogue 21 , and that of the novel tricyclic pyrrolidino fused ring system 22 was elaborated by an intramolecular C-alkylation reaction. Unexpected formation of bicyclic pyrido- and thiazine fused pyridazine systems are also discussed.     

Studies on the benzo[1,2]cyclohepta[3,4,5-d,e]isoquinoline ring system

The syntheses of various oxidation states of the novel benzo[1, 2]cyclohepta[3, 4, 5-d, e]-isoquinoline ring system is described. The ring system was obtained by the Schmidt rearrangement, with exclusive alkyl migration, of 1, 6, 7, 11b-tetrahydro - 2H - dibenz-[cd,h]azulen-2-one and by a Bischler-Napieralski reaction of suitable derivatives of 10, 11-dihydro-5H-dibenzo[a, d]cycloheptene - 5 - methylamine. 4, 5, 10, 11 - Tetramethoxy derivatives of the new ring system were best prepared by a Pictet-Spengler reaction of the appropriate amine.     

Eight-membered heterocycles. 12H-dibenzo[d,g][1,3,2]dioxaphosphocin and 12H-dibenzo[d,g][1,3,2]dioxaborocin derivatives

The synthesis of phosphonite and thiophosphite derivatives of the 12H-dibenzo[d,g][1,3,2]dioxaphosphocin ring system is described. The 'H nmr shows evidence for long-range coupling of the C-12 methine proton to phosphorus. The ¹H nmr of the 12H-dibenzo[d,g][1,3,2]dioxaborocin ring system is compared to that of the phosphorus analog. The nmr spectral data suggest that the phosphorus and boron containing ring systems have similar ring conformations.     

Zur Lokalisierung funktioneller Gruppen in Steroiden mit Hilfe der Massenspektrometrie: XIII—Massenspektren von 3,7,17-Trihydroxyandrostanen und 7,17-Dihydroxyandrostan-3-onen

Androstanes with a trans connected A/B ring system and hydroxy groups in positions 3, 7 and 17 show in their mass spectra key ions of mass 99 and 178. The ion of mass 99 contains the carbon atoms of ring D, and the ion of mass 178 those of the A/B ring system and C-11. If the rings A and B are cis connected, the ion of mass 178 is produced with much lower abundance and the ion of mass 99 is almost absent. The α or β position of a hydroxy group in position 7 can be deduced from the spectra of corresponding trimethylsilyl derivatives: a fragment of [M ? 131] dominated by presence of a 7α-trimethylsilyl ether group and trans connection of the A/B ring system. Determination of the configuration of the hydroxy group in position 3 is very difficult. Analogous fragments are observed in the spectra of the corresponding 7, 17-dihydroxyandrostan-3-ones.     

Linearly fused isoquinolines. Part II. The synthesis of the s-triazolo[4,3-b]isoquinoline system

3-Hydrazinoisoquinoline ( 2 ) was synthesized via its N-oxide derivative by removal of the N-oxide funçtion with titanium trichloride. Acylation of the hydrazino compound ( 2 ) led to suitable starting materials ( 4 and 6 ) for cyclization to the novel, linearly fused ring system: tri-azolo[4,3-b]isoquinoline, which was more stable in the form of its perchlorate salt. The structure of the first representatives of the new ring system was proved by ir, nmr and ms spectroscopy.     

The synthesis of substituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidines

A convenient synthesis of derivatives of the pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidine ring system from readily available 2-amino-3-cyano-5,7-diphenylpyrazolo[1,5-a]pyridine I and carbon disulfide, aryl isothiocyanates or nitriles is described. Derivatives of compound I undergo cyclization to the titled ring system by action of dimethylformamide dimethylacetal or hydrogen sulfide followed by treatment with triethylamine.     

Eight-membered organosulfur heterocycles. Synthesis of dibenzo[d,g][1,3,6,2]dioxathiaphosphocin and dibenzo[d,g][1,3,6,2]dioxathiasilocin ring systems

The reaction of 2,2′-thiobisphenols with either phenylphosphonous dichloride or phosphorus trichloride followed by an alcohol gave derivatives of the dibenzo[d,g][1,3,6,2]dioxathiaphosphocin ring system. The analogous reaction of 2,2′-thiobisphenols with alkyl and aryl dichlorosilanes gave the heretofore unreported dibenzo[d,g][1,3,6,2]dioxathiasilocin ring system. The analytical and spectral data are reported.     

Cinnamoyl shikonin

The title compound, 1-(5,8-di­hydro-1,4-di­hydroxy-5,8-dioxo-2-naphthyl)-4-methyl­pent-3-en-1-yl cinnamate, C₂₅H₂₂O₆, crystallizes in space group P2₁. The phenyl ring of the cinnamate is anti to the carbonyl group of the same moiety [C—C—C—C = −175.6 (2)°] and is nearly parallel to the naphthyl ring system. Two six-membered rings formed by intramolecular hydrogen bonds, with O—H⃛O distances of 2.587 (2) and 2.589 (2) Å, occur on either side of the fused ring system, creating a tetracyclic pyrene-shaped system. The phenyl ring forms an intermolecular stack with the benzo­quinone ring, as a result of aromatic π–π interactions.     

The synthesis of 4H-imidazo[5,1-c][1,4]benzothiazine derivatives

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.     

6H-indeno[1,2-b]pyrido[3,2-e]pyrazines. A new heterocyclic ring system

Condensation of 1,2-indanedione and 1,2,3-indanetrione hydrate (ninhydrin) with 2,3-diamino-pyridines gave a number of compounds belonging to the hitherto unknown 6H-indeno[1,2-b]-pyrido[3,2-e]pyrazine ring system. The unsymmetrical nature of the reactants can theoretically result in isomeric ring closure products. Assignment of the 6H- ring system was based upon the identity of 6H-indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one obtained from 2,3-diaminopyridine and ninhydrin with material prepared by unequivocal synthesis. The direction of cyclization of ninhydrin and 1,2-indanedione with the diamines was shown to be the same by reduction of the indenopyridopyrazinones to the corresponding indenopyridopyrazines. Some physical, chemical, and tumor growth-inhibitory properties of the products are reported.     

Nuclear magnetic resonace spectra of substituted oxazoles and oxazolidinones

During the synthesis of 2,5-disubstituted oxazoles and 4-oxazolidinones, NMR spectroscopy was utilized to obtain information on the structure, bonding and geometric isomerism in the various compounds. Long range couplings between substituents attached at C₂ and C₅ in both ring systems was of particular utility in this respect. The aromaticity of the oxazole ring is substantiated by the ability of the π system to transmit long range coupling through the ring and by the chemical shifts of the ring protons. Geometric isomers of the 4-oxazolidinones are identified by observing long-range cis and trans couplings of the order of 1·8 to 2·4 Hz.     

Polyaddition of bifunctional 1,3‐benzoxazine and 2‐methylresorcinol

A polyaddition system consisted of a bifunctional N‐n‐propyl benzoxazine and 2‐methylresorcinol ( MR ) that proceeds at ambient temperature has been developed. In this system, the aromatic ring of MR acted as a bifunctional monomer, reacting with a two equivalent amount of benzoxazine moieties via their ring‐opening reaction. The polyaddition gave the corresponding linear polymer bearing phenolic moieties bridged by Mannich‐type linkage in the main chain. The linear polymer had a high glass transition temperature, which was comparable to that of the linear polybenzoxazine synthesized by the ring‐opening polymerization of a monofunctional N‐n‐propyl benzoxazine. The employment of a bifunctional N‐allyl benzoxazine in the polyaddition system resulted in the formation of the corresponding polymer with allyl pendants, which exhibited improved heat resistance due to its thermally induced crosslinking reaction. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3867–3872     

Hetarylpyrazoles. II. Reactions of pyrazol-l'-ylpyridines

Pyrazol-l'-ylpyridines undergo electrophilic substitution reactions (bromination, chlorination, and nitration) preferentially in the pyrazole ring. There is some evidence of the mutual influence of the pyrazole and the pyridine ring on the reactivity of the system. Some modifications of the substituents were also carried out. A dihydro derivative of a new ring system, pyrazolo[1′,2′-a]pyrido[2,1-c][l,2,4]triazine was also obtained.     

Synthesis of N-methyl-3-aza[10] paracyclophane: A rigid analog of phenethylamine

The synthesis of N-methyl-3-aza[10]paracyclophane is reported which represents the first example of this ring system being formed via an acyloin reaction. This 3-aza[10]paraeyclophane ring system behaves physiochemically inbetween the normal [9]- and [10]paracyclophane ring systems. Reductive desulfurization of N-methyl-3-aza[10]paracyclophane-6-ethylene thioketal in ethanol provides a small amount of the title compound and an unexpected, ring-opened product, N-ethyl-N-methyl-p-heptylphenethylamine. A possible mechanism for the ring-opening process is suggested.     

Imdazole systems. I. Imidzo[2,1-b][1,3,5]benzothiadiazepine derivatives as potential antipsychotic agents

Imidazo[2,1-b][1,3,5]benzothiadiazepine 3 constitutes a novel ring system, and its analogs 3a-i were synthesized to investigate their potential antipsychotic activity. The synthesis of the ring system was achieved by reaction of 2-aminophenylthioimidazoles 7 with phosgene or thiophosgene and by ring closure of the 1-[2-(2-imidazolyl)thiophenyliminocarbonyl]-1-piperazines 13 . An efficient method for the conversion of thioureas 8, 12 to guanidine 3a via the corresponding cyanothioamidines 11, 14 was developed.     

(E)‐6‐Methoxy‐3‐(α‐methoxybenzyl­idene)benzo[b]furan‐2(3H)‐one at 173 K

The title compound, C₁₇H₁₄O₄, is an unprecedented new synthetic isoaurone‐type enol ether that has the E configuration. The planar furanone ring is fused to a methoxy­benzene ring system, with an interplanar angle of 175.7 (1)°. Due to this ring fusion, the six‐membered ring has a significant amount of ring strain, as shown by the internal ring angle range of 115.8 (1)–124.7 (1)°, whereas the vinylic phenyl ring has internal angles between 119.7 (1) and 120.2 (1)°. The mol­ecules form infinite hydrogen‐bonding layers along the b direction of the form C—H?O, where the keto O atom acts as a bifurcated acceptor. These layers are connected along the c direction by another hydrogen bond with a methoxy H atom as donor. In addition to this connection, the layers are stacked via centres of symmetry by a pair of symmetry‐related benzo­furan­one ring systems.