Synthesis of a new heterocyclic ring system 2,3,5,6,7,9,10,11-octahydro-lH-cyclopenta[9,H)]benzo[i,j] quinolizine-1,9-dione

Reaction of 1,2,3,4-tetrahydroquinoline (1) with different α,β-unsaturated acids in the presence of PPA has been investigated. With acrylic acid, 1 affords two compounds identified as 1-keto-benzo[i,j]quinolizine (III) and 2,3,5,6,7,9,10,1 1-octahy dro-1H-cy el open ta [9,10] benzo [i,j]-quinolizine-1,9-dione (IV). A similar reaction of 1 with a-methyl acrylic and crotonie acids gives compounds V and VI whose structures are analogous to that of IV. These were deduced from their spectral and analytical data.     

Studies in spiroheterocycles. Part XIII. Synthesis of a novel spiro system: Spiro[9H-acridine-9,3′-[3h]indol]-2′(1′H)-one and related compounds from new fluorinated spiro[3H-indole-3,9′-[9H]xanthen]-2(1H)-ones

A new spiroheterocyclic system spiro[9H-acridine-9,3′-[3H]indol]-2′(1′H)-one and related compounds have been prepared by the reaction of spiro[3H-indole-3,9′-[9H]xanthen]-2(1H)-ones with aromatic amine or ammonium acetate. The latter were prepared by heating fluorinated indole-2,3-diones with m-/p-cresols or α-naphthol in the presence of sulphuric acid at 230-240°. The synthesized compounds have been characterized on the basis of their elemental analyses, ir, nmr (1_H, 13_C, 19_F) and mass spectral data.     

A simple synthesis of 8-(trifluoromethyl)-2,3,5,6,11,12,14,15-octahydro-1H,4H,10H, 13H-diquinolizino[9,9a,1-bc:9′,9a',1-hi] xanthylium perchlorate,an efficient dye

A one-step procedure is described for the preparation of the title compound I, an efficient laser dye operating in the red region.     

The addition of benzocyclobutenylidene to benzene : The facile rearrangement of spiro[benzocyclobutene-1,7'-cyclohepta-1',3',5'-triene] to 9a,10-dihydrobenz[α]azulene

Thermal decomposition of the sodium salts of benzocyclobutenone tosylhydrazone and 2-methylbenzocyclobutenone tosylhydrazone in benzene affords 9a,10-dihydrobenz[α]azulene 4 and trans-10-methyl-9a, 10-dihydrobenz[α]azulene 3, respectively. A mechanism involving initially the addition of the carbene benzocyclobutenylidene, or its 2-Me derivative, to the benzene ring is postulated. A proposed intermediate in the reaction, spiro [benzocyclobutene 1,7' cyclohepta-1',3',5'-triene] 12 has been synthesised, and shown to give rise to 4 under the reaction conditions. The rate of rearrangement of 12 → 4 has been measured, and the activation energy determined: E_a = 125.9 ± O.8 KJmol^?1 and A = 1.38 × lO¹⁴sec^?1. The mechanism for the rearrangement must involve ring opening of the benzocyclobutene moiety of 12 to give an o- xylylene intermediate which is postulated to possess considerable diradical character. At 71.8 °, this ring opening is 2.7 × 10⁶ times faster than the ring opening of the parent benzocyclobutene molecule. The decomposition of the sodium salt of 2-(7' -cyclohepta-1',3',5' trienyl)benzaldehyde tosylhydrazone has also been investigated and is shown to yield 4a,10-dihydrobenz[α]azulene, 9,10-dihydrobenz[α]azulene and 8,9-benzotricyclo [5.3.0.0^2.10]deca-3,5,8-triene. A mechanism involving intramolecular 1,3-dipolar addition of a diazo grouping to a cycloheptatriene Π-bond, followed by decomposition of the resulting pyrazoline intermediate, is proposed.     

Synthesis of enantiopure ethyl (1S,9aS)- and (1S,9aR)-1-phenyl-4,9-dioxohexahydropyrrolo[1,2-d][1,4]oxazepine-9a(7H)-carboxylate by carbenoid/ylide/Stevens-[1,2]-shift with ring enlargement

Enantiomerically pure ethyl (1S,9aS)- and (1S,9aR)-1-phenyl-4,9-dioxohexahydropyrrolo[1,2-d][1,4]oxazepine-9a(7H)-carboxylate were obtained by Cu(II)-catalyzed decomposition of an α-diazo carbonyl tethered to a chiral morpholinone. The reaction occurred with moderate diastereoselectivity but with complete enantioselectivity through the carbenoid/spiro-[5,6]-ammonium ylide/Stevens-[1,2]-shift with ring enlargement sequence.     

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors V. A series of new derivatives containing a spiro[imidazo[1,2-a]pyrazine-2(3H),4'-piperidin]-5(1H)-one scaffold

We have already reported unique compounds containing a N,O-spiro acetal structure as an orally active factor Xa (FXa) inhibitor. This time, we described a N,N-spiro acetal structure as an analogue of the N,O-spiro acetal structure for an orally active FXa inhibitor. The synthesis of these analogues could be achieved in a similar fashion to the N,O-spiro acetal synthesis. Consequently, FXa inhibitory activity was increased and more active compounds could be found (M58163: IC50 = 0.61 nM, M58169: IC50 = 0.58 nM). Additionally, the absolute configuration could be determined by X-ray crystallography analysis (M58169: (R)-config.).     

Synthesis of nitrogen‐containing heterocycles 9. Preparation and carbon‐carbon bond cleavage of spiro[cycloalkane[1′,2′,4′]‐triazolo[1′,5′‐a][1′,3′,5′]triazine] derivatives and related compounds

Diaminomethylenehydrazones of cyclic ketones 1–5 reacted with ethyl N‐cyanoimidate (I) at room temperature or with bis(methylthio)methylenecyanamide (II) under brief heating to give directly the corresponding spiro[cycloalkane[1′,2′,4′]triazolo[1′,5′,‐a][1′,3′‐5′]triazine] derivatives 7–12 in moderate to high yields. Ring‐opening reaction of the spiro[cycloalkanetriazolotriazine] derivatives occurred at the cycloalkane moiety upon heating in solution to give 2‐alkyl‐5‐amino[1,2,4]triazolotriazines 13–16. Diaminomethylenehydrazones 17–19, of hindered acyclic ketones, gave 2‐methyl‐7‐methylthio[1,2,4]‐triazolo[1,5‐a][1,3,5]triazines 21–23 by the reaction with II as the main products with apparent loss of 2‐methylpropane from the potential precursor, 2‐tert‐butyl‐2‐methyl‐7‐methylthio[1,2,4]triazolo[1,5‐a]‐[1,3,5]triazines 20, in good yields. In general, bis(methylthio)methylenecyanamide II was found to be a favorable reagent to the one‐step synthesis of the spiro[cycloalkanetriazolotriazine] derivatives from the diaminomethylenehydrazones. The spectral data and structural assignments of the fused triazine products are discussed.     

Heterocyclic Spiro-naphthalenones. Part VI. Some reactions with spiro [naphthalene-2 (1H), 2′-pyrrolidine]-1,5′-dione leading to various 6-, 7-, 8-, 9-, 10- and 11-membered azacycloalkanes

The spirolactam 5 was reduced to the spiro[naphthalene, pyrrolidine] 7 which was N-aralkylated to give 9 and 17 . Cyclization of 9 gave the phenanthridines 10 and 11 ; similarly, 17 afforded the 7- and 8-membered heterocycles 18 and 19 . Compounds 10, 18 and 19 when subjected to an intramolecular Hofmann elimination yielded the 9-, 10- and 11-membered ring systems, respectively 16, 22 and 23 .