Toluene refluxing

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Recently, Koitai et al. (17) have shown that 5,5-diphenyl-2,4-thiazolidinedithione (15) with aluminum chloride in refluxing toluene gives 4,5-diphenyl-A-4-thia2oline-2-thione (16) (Scheme 7). 3-Methyl-4,5-diphenyl (17) and 4,5-diphenyl-A-4-thia2oline-2-thiones (16) are obtained in very low yields (1 to 5%) as by-products of the reaction between deoxybenzoin. benzoin. l,2-diphenyl-1.2-ethanediol. 1.2-diphenylethanol, or benzil, and Sg in hexamethylphosphoamide (18), The transformation of A-4-thiazoline-2-ones to the corresponding thiones by P2S5 (19) is of little synthetic value since the latter are more easily prepared. 

For analysis, white phosphoms is typically extracted through a fritted thimble with refluxed toluene. Any trace amounts of water are captured in a cahbrated sidearm to the apparatus. The soflds on the frit are weighed, the water measured, and the phosphoms calculated by difference. For impure samples of phosphoms, the toluene extract may be analy2ed with a gas chromatograph (gc) equipped with a phosphoms—nitrogen detector. 

Anhydro-3-hydroxy-2-phenylthiazolo[2,3-6]thiazolylium hydroxide (407) underwent ready thermal reaction with alkynic and alkenic dipolarophiles in refluxing toluene. With the former dipolarophile sulfur was lost from the intermediate 1 1 cycloadduct (408) to give the substituted 5H-thiazolo[3,2- i]pyridin-5-ones (409). With the latter, the intermediate (410) lost H2S, also forming (409). 

Aldehydes react with a-nitroacetophenone in refluxing toluene to generate a 3-acetyl-2-isoxazoline (78USP4092327), while a-nitroacetophenone oxides react with alkenes to provide 2-isoxazolines (Scheme 121) (79ZOR735, 79ZOR2408, 80CPB479>. 

Diphenylisobenzofuran has been reported to react with azirine (75) in refluxing toluene to give cycloadduct (81), the primary product of a [4 + 2] cycloaddition (72JOC2508, 74JOC2031). ... 

The conjugated enone (177) is treated withp-toluenesulfonic acid in refluxing toluene to form the more stable product (178). The A -17-keto-system is formed by acid catalyzed cleavage of the A -17-ketal (see page 304), but the conditions are not drastic enough to cause equihbration to the more stable A " -compound. (The latter may be ketalized to form the A -17-ketal.) ... 

A similar sequence of reactions takes place with the enamlnes of cyclic ketones (55-57) the initially formed unstable cyclobutene rearranges with insertion of two carbon atoms into the ring. A wide variety of cyclic ketones have been allowed to react in this way. For instance, the enamine (75) gave 76 on reaction with dimethyl acetylenedicarboxylate in refluxing toluene (55) and the heterocyclic enamine (77) obtained from dihydro-3-(2H)-... 

A recent report demonstrates that trisubstituted furans can be prepared on a solid support using the Paal-Knorr condensation. Raghavan synthesized a variety of triaryl and alkyl diary] furans, one of which is highlighted below. Dione 50 was cyclized using p-toluenesulfonic acid in refluxing toluene followed by cleavage from the solid support to yield furan 51. ... 

Both 2,5-dialkyl-3-furoates and 2,5-dialkyl-3-phosphonofurans can be produced using the Paal-Knorr reaction. Methyl 2,5-diisopropyl-3-furoate (62) is available upon treatment of dione 61 with sulfuric acid. Phosphonodiones 63 can be efficiently converted into 2-substituted-3-diethylphosphono-5-methylfurans 64 by exposure to Amberlyst in refluxing toluene. ... 

Meguro and co-workers described the synthesis and hypoglycemic activity of 4-oxazoleacetic acid derivatives." For example, cyclization of 18 was performed by using phosphorus oxychloride in refluxing toluene to provide 5-methyI-2-(l-methylcyclohexyl)-4-oxazoleacetate in 73% yield and the subsequent hydrolysis gave 19. 

Oxidations of pyridopyrimidines are rare, but the covalent hydrates of the parent compounds undergo oxidation with hydrogen peroxide to yield the corresponding pyridopyrimidin-4(3 T)-ones. Dehydrogenation of dihydropyrido[2,3-(i]pyrimidines by means of palladized charcoal, rhodium on alumina, or 2,3-diehloro-5,6-dicyano-p-benzo-quinone (DDQ) to yield the aromatic derivatives have been reported. Thus, 7-amino-5,6-dihydro-1,3-diethylpyrido[2,3-d]-pyri-midine-2,4(lif,3f/)-dione (177) is aromatized (178) when treated with palladized charcoal in refluxing toluene for 24 hours. 

Oxidation of the dithiete 175 with MCPBA (1 equiv.) yielded the dithiete 1-oxide 202 which, when heated in refluxing toluene, formed a mixture of the ring-opened product sulflne 203 (blue, A ax 576 nm) and 202 in the ratio 7 1 (95TL8583). Further oxidation of 202 or oxidation of 175 with... 

When methyl 2-(indol-2-yl)acrylate derivative (22a) reacted with A-methoxy-carbonyl-l,2-dihydropyridine (8a) in refluxing toluene, in addition to the dimer of 22a (25%), a mixture of the expected isoquinculidine 23a and the product 24a (two isomers) was obtained in 7% and 45% yields, respectively (81CC37). The formation of 24a indicates the involvement of the 3,4-double bond of dihydropyridine. Similarly, Diels-Alder reaction of methyl l-methyl-2-(indol-2-yl)acrylate (22b) with 8a gave, in addition to dimer of 22b, a mixture of adducts 23b and 24b. However, in this case, product 23b was obtained as a major product in a 3 2 mixture of two isomers (with a- and (3-COOMe). The major isomer shows an a-conhguration. The yields of the dimer, 23b, and 24b were 25%, 30%, and 6%, respectively. Thus, a substituent on the nitrogen atom or at the 3-position of indole favors the formation of the isoquinuclidine adduct 23. 

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

The synthesis of monocyclic thiepins from thiophene and dimethyl acetylenedicarboxylate is often accompanied by the loss of sulfur. In particular, in cases where room temperature is required for efficient rates of cycloaddition and rearrangement76 (see Section 2.1.3.3.), the desulfurization reaction proceeds rather quickly with the consequence that thiepin formation can be monitored by low temperature HNMR spectroscopy, but the products cannot be isolated.76 - 78 However, in the case of thiepin 1 where R1 = R2 = C02Me and R3 = H, refluxing toluene is necessary for the extrusion of sulfur.78... 

Thiepins synthesized via thiopyrylium salts (see Section 2.1.3.4.) normally cannot be isolated due to their rapid loss of sulfur, especially when 2,7-diisopropyl substituents are present, e.g. 3.79 In contrast, when substituted with tm-butyl groups, which stabilize thiepins, extrusion of sulfur only occurs in refluxing toluene.80 81... 

Recently reported289 is an analogous reaction involving the acid-catalyzed cyclization of (lZ,3 ,5Z)-l,6-diphenylhexa-l,3.5-triene-l,6-diamine (14) in refluxing toluene to 2,7-diphenyl-3//-azepine (15). The l,6-bis(4-tolyl) and 1,6-dibenzyl derivatives behave similarly, but give substantially lower yields (14-18%). 

The first cyclopent[A]azepine 19 was obtained as dark-green crystals by the acid-catalyzed condensation of 4-hydroxy-2,3,4-triphenylcyclopent-2-en-l-one (18) with pyrrolidine in refluxing toluene.106... 

Subsequently, it was shown that cyclopentadienones are very efficient in trapping 2//-azirines formed transiently during the thermolysis of vinyl azides,109 and that 3//-azepines may be formed by heating the vinyl azide directly in the presence of the cyclopentadienone rather than with the often foul-smelling 2//-azirine.31,109 An example of this procedure is the preparation of the dihydro-3/f-naphth[2,l-fe]azepine 29 by thermolysis of 4-azido-l,2-dihydronaph-thalene (28) with 2,5-dimethyl-3,4-diphenylcyclopentadienone in refluxing toluene. 

Tetraphenyl-3//-azepine (2) is formed by the action of sodium hydride on 1-benzyl-2,4,6-triphenylpyridinium tetrafluoroborate (1) in refluxing toluene.37 The 3//-azepine. which arises by attack of the carbanion, generated at the benzylic carbon, at the 2-position of the pyridine ring, is also formed, unexpectedly, in the reaction of the pyridinium tetrafluoroborate with the enolate of ethyl 2-methyl-3-oxobutanoate. 

In contrast, the diphenyl derivative 44 (R1 = R2 = Ph) fails to ring expand, whereas the methyl derivative 44 (R1 = Me R2 = H) yields the a.xo-methylene compound 45 (63 %), which undergoes quantitative acid-catalyzed isomerization to 10-methyl-5/7-dibenz[6,/]azepine (46) in refluxing toluene. The mechanistic implications of these reactions have been discussed. 

Ar-Alkylations of 5//-dibenz[6,/]azcpines, e.g. 5 > 8 can be readily achieved via their nitranions, which are generated from the NH compounds by standard methodology, e.g. with sodium hydride, or sodamide, in refluxing toluene or xylene.30-J1-bt, 7° 124,1 s2 Occasionally, dioxane,187 or a mixture of tetrahydrofuran and hexamethylphosphoric triamide is used as solvent.137... 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

The thiadiazepinone 1 loses sulfur in refluxing toluene to give a pyrimidone.327... 

The only heterocyclic seven-membered ring system with maximum unsaturation containing six heteroatoms is 1,3A4,5,2,4,6-trithiatriazepine (1). The methoxycarbonyl derivative 2 is a minor product (14%) of the complex reaction of tetrasulfur tetranitride with dimethyl acetylenedicarboxylatc in refluxing toluene, which gives mainly dimethyl l,2,5-thiadiazole-3,4-dicarboxylate (3, 67%) (see Houben-Wcyl, Vol. E8d, pl54ff which includes an experimental procedure). Two other products are the trithiadiazepine 4 (5%, see Section 4.4.1.1.1.) and the 1,2,4-thiadiazole derivative 5 (3%).385... 

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