Fused systems

Pyrimidine-fused Systems.—Starting from the corresponding 2-amino-3-cyanothiophen, (194) has been prepared. Compounds such as (195) have been transformed into (196) and further derivatives of this system. 

Miscellaneous Fused Systems.—The reaction of 2-vinylthiophen with azodicar-boxylates gave a mixture of tetra- and dihydro-thienopyridazine diesters upon dicarbethoxylation with TFA followed by oxidation, these gave thieno[2,3-c]pyridazine. ° Thieno[2,3-6]pyrazine has been synthesized from 2-chloro-3-cyanopyrazine by reaction with ethyl thioglycollate and condensation with base 

Miscellaneous Fused Systems.— Ethyl 3-aminothieno[2,3- ]pyrazine-2-carboxyIate has been prepared from 2-chloro-3-cyanopyrazine and ethyl a-mercaptoacetate, and then converted into (269) by reaction with formamide. Other derivatives of (269) were subsequently prepared. Fused thieno[3,2-c/]-y/c-triazin-4-ones 

Studies of the chemistry of the thieno-borazaro-pyridines (271) and (272), prepared by the reaction of or/Ao-formyl- or or//ro-acetyl-thiophenboronic acids with hydrazines, have continued. Bromination of (271 R = Me) and (272  

Miscellaneous Fused Systems.-An elegant synthesis of thieno[2,3-c ]-pyridazine in 40% yield consists of heating thiophen-2-carbaldehyde azine with AlCla-triethylamine at 170-200°C. 2,3-Dimethylthieno[3,4-i ]-pyrazine has been prepared from 2,4-diaminothiophen. A derivative of the unusual thienopterine (303 R = OH) that was isolated from human urine in 1940, namely (303 R = H), has been synthesized from 2-amino-3,5-dicyano- 

6-chloropyrazine in nine steps. First a thiophen ring is fused by reaction with 

Watanabe, and N. Kawahara, Chem. Pharm. Bull., 1981, 29, 1039. 

Thieno[2,3-c]coumarins have been prepared. Reactions of 5-phenylthieno[3,2-Z ] pyran-7-one, 2-phenylbenzo[6] thieno[3,2- ] pyran-4-one, and the corresponding thiones with sodium ethylate, guanidines, hydrazines, and enamines have been investigated. Pyridino[3,2-Z ] thieno-[3,4-c] [1,4] diazepines that have potential CNS activity have been prepared from (23).  

Miscellaneous Fused Systems.— The oxidation of thieno[2,3-b]thiapyrylium perchlorate (490) with Mn02 gave, among other products, 2-thieno[2,3-b]-thiophenaldehyde and 2H-thieno[2,3-b]thiopyran-2-one/ Similar results were obtained with the isomeric thieno[3,2-b]thiopyrylium perchlorate. The l-benzothieno-[3,2-b]- and -[2,3-b]-selenopyrylium salts (491) and (492) 

Tadino, L. Christiaens, M. Renson, and P. Cagniant, Bull. Soc. chim. beiges, 1972,81,595. V. I. Dulenko, I. G. Katts, L. V. Dulenko, and G. N. Dorofeenko, Khim. geterotsikl. Soedinenii, 1970, 134. 

A convenient method for the synthesis of the borepino[3,2-b 6,7-b]di-thiophen system (498) has been worked out. By comparing its spectral properties with those of the corresponding dihydro-derivative and with the isoelectronic dithienotropylium ions, some evidence for aromatic stabilization was obtained. The chemistry of another boron-containing fused thiophen system (499) has been studied.  

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Eady fusing systems, such as that used in the Xerox 914, employed radiant heat produced by incandescent lamps. Black toner is an extremely good... 

Pyrimidines from purines and related fused systems... 

The cleavage of fused pyrazines represents an important method of synthesis of substituted pyrazines, particularly pyrazinecarboxylic acids. Pyrazine-2,3-dicarboxylic acid is usually prepared by the permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring resembles the pyridine ring in its stability rather than the other diazines, pyridazine and pyrimidine. Fused systems such as pteridines may easily be converted under either acidic or basic conditions into pyrazine derivatives (Scheme 75). 

All four possible pyridopyrimidine systems, pyrido[2,3-Chemical Abstracts nomenclature is used throughout this Chapter. For the reasons given above (Section 2.15.1), the pyrido[2,3-[Pg.201]

In the benzo fused systems only derivatives of the pyridazino[4,5-6]quinoline system appear to have been studied <72BSF1588). 

Similarly, no systematic study of the IR spectra of the pyridopyridazines has been recorded, but the spectra of the [2,3-d] derivatives have been discussed <68AJCl29l). The diones of this series have also been studied <69MI21501), and IR used to distinguish between the structure (303) and the possible isomeric formulation (304) <74JHC35l). The IR spectra of some of the azodicarboxylic ester adducts <79X2027) have been recorded, whilst in the benzo fused systems some problems with the structure of acyl derivatives in the pyridazino[4,5-6]quinoline series have been resolved with the help of IR spectroscopy <71BSF906, 72BSF1588). 

In the benzo fused systems, tautomerism in pyridazino[4,5-6]quinolinediones has been elucidated with the help of UV methods (80CPB3457). 

The only reactions of this type noted in the pyridopyridazine series are two classic Bischler-Napieralski type closures in benzo fused systems in which 3- or 4-benzamidopyridazines are cyclized to an adjacent phenyl group to give a 6-aryIpyridazino-[3,4-c]- (e.g. 361—> 362) or -[4,5-c]- isoquinoline respectively (59JCS1, 59JCS6). 

Both the possible non-bridgehead pyridopyrazines, pyrido[2,3-f ]pyrazine (386) and pyrido[3,4-f ]pyrazine (387), are well known, the numbering being as shown. In the older literature they may be known as pyridino-2, 3 -2,3- and -3, 4 -2,3-pyrazines, as 1,4,5- and 1,4,6-triazanaphthalenes, or as 5- and 6-azaquinoxalines respectively. Some derivatives may also be referred to and numbered as deazapteridines, or as deaza derivatives of various natural products (see Section 2.15.16.3). Of the benzo fused systems, representatives of one angular (388) and two linear (389) and (390) derivatives of the [2,3-f ] system are known, but only the linear benzo fused [3,4-6] system (391). 

The major internal comparisons to be made within this chapter are between (13) pyrrole (1), furan (2), thiophene (3), selenophene (4) and tellurophene (5) b) pyrrole (1) and indole (6) (c) indole (6), benzo[6 Jfuran (7) and benzo[6]thiophene (8) d) indole (6), isoindole (9) and indolizine (10) and (e) benzo[6] and benzo[c] fused systems. The names of relevant heterocyclic radicals are given with the structures of the parent heterocycle. 

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

The benzo[Z)] fused systems participate in a number of [2 + 2] cycloaddition reactions (81JOC3939, 81TL521). The photocycloaddition products of benzo[Z)]thiophenes and DMAD are dependent on the irradiation wavelength (Scheme 56). 

Ring-fused systems Syntheses Using 1,2-Bielectrophiles... 

Variations of these approaches to [5,5] ring-fused systems are found in Chapter 4.36. 

Other C—C fused systems are also available by utilization of 1,4-dicarbonyl-type systems. The substituted pyrimidinethione (59) on treatment with polyphosphoric acid readily formed the thiazolo[5,4-d]pyrimidine system (60) without any of the alternative ring closure product (65JOC1916). 

Scheme 3 illustrates two general annulation procedures, one with the a-halogenoketone moiety incorporated in a cyclic system leading to C—C fused systems. The other, with the heteroatoms already incorporated in a heterocycle, results in a product with a heteroatom at a fusion point. 

The latter approach is illustrated by the conversion of the 2-thiazolethione (90) into the thiazolo[2,3-6]thiazolylium salt (92) by reaction with the a-halogenoketone. The intermediate (91) may be isolated, and strong acid was required to effect the final cyclization (77HC(30-1)1). A wide variety of [5,5] fused systems are prepared in this way, and variations of this approach are discussed in Chapter 4.36. 

In contrast to the above, the reaction of a heterocyclic thione with an a-halogenoketone (Scheme 3) has been widely exploited as a route to [5,6] ring-fused systems with a heteroatom at a ring fusion point. 

The syntheses of ring-fused systems with both C—C and C—-N fusion points are particularly suited for cyclocondensations of this type. Treatment of the 4,5-diaminopyrazole... 

This method of ring closure is the most convenient for the synthesis of ring-fused 1,2,4-triazoles with this arrangement of nitrogen atoms. It has been used extensively to form the analogous [5,6] ring-fused systems, and structural ambiguity is only encountered... 

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