Thieno quinoline

Other Pyridine-fused Thiophen-containing Systems.—A number of thieno-quinolines such as (557) and (558) have been prepared by applying the... 

Thieno[3,4-h]quinoline, 1,3-diphenyl-synthesis, 4, 1026 Thienoquinolines, 4, 1025 Thieno[2,3-h]quinolines, 4, 1025 Thieno[3,2-c]quinolines synthesis, 4, 785, 788 Thieno[3,4-h]quinolines, 4, 1026 Thieno[3,4-h]quinoxaline, 1,3-diphenyl-synthesis, 4, 1027 Thienoquinoxalines, 4, 1026 Thieno[2,3-h]quinoxalines synthesis, 4, 1026... 

Variable results have been reported for the halogenation of thieno[2,3-6]quinoline (123). Initial attack was mainly at the 3-position, but it was difficult to avoid the formation of 2,3-dihalogenated products, even when only 1 mol of halogen was used (predictions are for 2- and 3-substitution [77ZN(B)1331]). Bromine buffered in chloroform gave the 3-monobromo derivative, but analogous chlorination gave a mixture that included some... 

Thieno[4,5-c]isoquinoline formed the 2,3-dibromo product in 60% yield, whereas the [3,4-c] isomer decomposed under the same conditions (89CS309). Thieno[3,2-/]quinoline was brominated in 57% yield at C-2 [70JCS(C)2334]. 

INAC reactions have also led to enantioselective syntheses of key intermediates in the synthesis of antibiotic l 3-Methylcarbapenem (724), to optically pure derivatives of tetrahydropyrano[2,3] cyclohexane (725a) to novel terahydro-isoxazolo-fused pyrano 2,3-/ quinolines (725b) and to a novel heterocyclic system, isoxazolo[3,4-d]thieno[2,3-b]pyridine (Scheme 2.229) (221). 

Thieno[2,3-/]quinolines (153) were reacted with EMME at 130-140°C to afford 6-thienoquinolinylmethylenemalonates (154) in 66-89% yields (88AP241). 

Thieno[2,3-/]quinolin-6-yl)methylenemalonates (746) were cyclized by heating in polyphosphate at 110-130°C for 4-7 hr to give benzo-thieno[5,6,7- ylquinolizine-6-carboxylates (747) in 53-68% yields (88AP241). 

The thermal cyclization of A/-(2,3-dihydrobenzo[ ]thien-6-yl)amino-methylenemalonates (847, n = 0,2) by heating in boiling Dowtherm A for 35 min and 4 hr gave a roughly 1 1 mixture of thieno[3,2-g]quinoline-... 

Thienyl sulfides with the 2-position of the thiophene ring blocked, e.g., allyl 2-methyl-3-thienyl sulfide (51), also undergo sigmatropic rearrangement when heated in quinoline [Eq. (23)]. 2,6-Dimethyl-2,3-dihydro-thieno[3,4-Z ]thiophene (52) is formed, together with other products. 

Thienothiophenes undergo the indophenine reaction with isatin (see Section III,I). Oster reported that thieno[2,3-6]thiophene (1) gave a green product with a ratio of isatin to thienothiophene 1 1, and a blue substance with the ratio of the initial substances 2 1. Steinkopf and HempeP could not obtain this blue substance instead they isolated a brown material with the isatin to thienothiophene 1 ratio 2 3 at +50° they isolated a substance with the ratio 1 1 and at +70°, with ratio 1 2. Steinkopf and PetersdorP found that a reaction of 2-acetylthieno[2,3-6]thiophene with isatin produces 2- or 3-(2-thieno[2,3-6]thienyl) cinchoninic acid. The acid was decarboxylated to 2- or 3 2-thieno[2,3-6]thienyl)quinoline (the site of quinoline group in thienothiophene 1 molecule was not established). 

Castle and co-workers <1996JHC119, 1996JHC185, 1997JHC1597, 1998JHC1441> used 3-chlorothieno [2,3-3]thiophene-2-carbonyl chloride 280 in the synthesis of the appropriate amides, which by oxidative photo-cyclization gave novel polycyclic heterocyclic ring systems thieno[3, 2 4,5]thieno[2,3-f][l,10]phenanthroline 281, thieno[3, 2 4,5]thieno[2,3-f]naphtho[2,iy ]quinoline 282 and thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-g]qui-noline 283, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2y ]quinoline 284, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2 7]-[l,2,4]triazolo[3,4- ]quinoline 286, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-/]tetrazolo[l,5- ]quinoline 288, benzo[ ]thieno[3, 2 4,5]thieno[2,3-f]quinoline 285, benzo /]thieno[3, 2 4,5]thieno[2,3-f]quinoline 287, benzol/] thieno[3, 2 4,5]thieno[2,3-f]tetrazolo[l,5- ]quinoline 289, and benzo[/jthieno[3, 2 4,5]thieno[2.3-f][l,2,4]triazolo[4,3- ]-quinoline 290. 

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

Reaction of the quaternized salts of 4-ethoxycarbonyl-3,5-dimethyl-f-phenylpyttolo(furo or thieno)[2,3-c]pyrazole 34 with the iodomethane quaternary salts of pyridine, quinoline, and isoquinoline in ethanol with catalytic piperidine gave 3-[4(f)]-monomethine cyanine dyes (e.g., 35). Additionally, 3-[2(4)]-trimethine cyanine dyes and 4-[2(4)]-di-3[2(4)]-tri-mixed methine cyanine dyes (e.g., 36 and 37, respectively) were similarly prepared from the intermediates derived by reaction of 34 with triethyl orthoformate in the presence of piperidine (Scheme 8) <2002CCS106f>. 

The photolysis of quinoline TV-imides (262) (which are in equilibrium with their dimers) (77JOC1856) gives IH- 1,2-benzodiazepines (263). Reactions of this type have also provided routes to pyrido-, thieno- and furo-l,2-diazepines (79CPB2183,79H( 12)471). 

As in the case of the furopyridines (Section 3.17.2.1.1), there are six thienopyridine systems (Scheme 59) those derived from benzo[Z> ]thiophene (258-261) and those that are analogs of benzo[c]thiophene (262-264). The chemistry of thienopyridines has previously been reviewed both as an overview (72IJS(B)(7)309) and in a detailed manner (77AHC(2l)65, 81H(15)1285). The latter article presents a correlation of the chemistries of thieno[2,3-/ ]pyridine and thieno[3,2-6]pyridine with those of benzo[6]thiophene and quinoline. 

The pKa values for the four readily available thienopyridines (258-261) have been determined (Table 9). As can be seen from these data, the isoquinoline analogs are stronger bases than the quinoline analogs the same is true for isoquinoline and quinoline. The UV data of the benzo[6]thiophene analogs (258-261) (Table 10) show a considerable similarity to that of quinoline (258, 261) and isoquinoline (259,260). As expected, the spectra of thieno-[3,4-6]- and -[3,4-c]-pyridine differ from the parent compounds the colors of (262) and (263) are probably due to their long-wavelength maxima. 

The chemistry of thienoquinolines has been explored to a limited degree. Two types (378,379) will be described in this subsection. The pharmacological interest in thieno[2,3-Z>]quinoline (378) and derivatives thereof stems from their isosteric and isoelectronic resemblance to acridine furthermore, (378) constitutes the sulfur analog of furoquinoline (Section 3.17.2.1.5), which is the parent system of a number of alkaloids. Thieno[3,4-6]quinoline (379) is an o-quinonoidal heterocycle which is of interest both for theoretical reasons compared with its isoconjugate analogues and as a synthon in Diels-Alder reactions for the preparation of other condensed heterocycles. 

A convenient synthesis of thieno[2,3-6]quinoline (Scheme 111) (76ZN(B)1297,76ZN(B)1685, 77JCS(P1)2024) utilizes the readily available methyl 2-oxo-3-vinyl-l//-quinoIin-4-carboxylate (380) as starting material. Treatment of (380) with phosphorus oxychloride yields the chloroquinoline which on addition of bromine gives a trihalo compound. The cyclization to (381) is effected with thiourea in boiling ethanol. Elimination of the methoxycarbonyl group yields thieno[2,3-6]quinoline as colorless needles with m.p. 107-108 °C, which can be characterized as the picrate with m.p. 213-214 °C. 

C(8a)—C(9) are elongated. The common bond C(3a)—C(9a) is also lengthened. A comparison of the 7r-electron densities reveals that all three procedures show almost the same trends. The calculated 7r-electron densities for thieno[2,3-6]quinoline (378) and thieno[3,4-6]quinoIine (379) do not differ significantly from the corresponding thienopyridines provided that the same set of parameters is used. Calculated reactivity indices indicate that electrophilic substitution reactions should occur predominantly in the thiophene unit. 

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