Heterocycles sulfur containing, thiophene

The Maillard reaction has received much attention since the 1950 s as the source of flavor chemicals in cooked foods. Numerous compounds produced by this reaction have been reported in the last two decades. The major flavor chemicals are nitrogen- and sulfur-containing heterocyclic compounds. For example, nitrogen-containing pyrazines contribute a characteristic roasted or toasted flavor to cooked foods. Sulfur-containing thiophenes and thiazoles give a characteristic cooked meat flavor. A striking property of these compounds is their extremely low odor thresholds. 

A heterocyclic sulfur-containing compound, 2-methyl-thiophene, was identified in boiled crayfish tail meat and pasteurized crabmeat. Thiazole and 3-methylthiopropanal were identified in the crayfish hepatopancreas. Heterocyclic sulfur-containing compounds play important roles in generating meaty aromas in a variety of meat products and are considered important volatile aroma components of marine crustaceans (12— 14). The 2-methylthiophene could be an important flavor cemponent in boiled crayfish tail meat. Both thiazole find 3-methylthiopropanal were important contributors to the desirable meaty aroma associated with crayfish hepatopancreas. The 3-methyl-thiopropanal, identified in boiled crayfish hepatopancreas, is derived from Strecker degradation of methionine (15), and has been considered to be an important cemponent in basic meat flavor (16). Pyridine was detected in the headspace of the hepatopancreas from freshly boiled crayfish. Pyridine and 2-ethylpyridine have been previously reported as components in the atmospheric distillate from a sample of crayfish hepatopancreas frozen for three months (2). 

Of particular interest is the identification of five different types of heterocyclic sulfur-containing flavor components, the preponderance of which were furans and thiophenes substituted with sulfur in the 2- and 3-position. The bulk of these flavor compounds had not been identified in meat and had not been reported in the literature so far. These sulfur-substituted heterocyclic flavor components will be further discussed below. 

Sulfur Heterocyclics. Sulfur containing compounds (thiols, thiophenes, thiazoles,. .. etc.) play a major role in the flavor of raw and processed foods. These compounds have characteristic flavor notes and the flavor thresholds are mostly low. Several reviews (ill, 112, 113) demonstrate the important role of sulfur compounds in food flavors. Organoleptic properties of these compounds may be pleasant, strong nut-like odor of U-methyl-5-vinylthiazole which is present in cocoa (llU) objectionable pyridine-like odor of thiazole (115) quinoline-like odor of benzothia-zole (ll6) strong tomato leaf-like odor of isobutylthiazole (117) and bread crust flavor of acetyl-2-thiazoline (ll8). A mixture of oxazoles, thiazoles, thiazolines, imidazoles, trithiolanes and... 

Numerous different types of heterocyclic compounds containing sulfur are produced via the Maillard reaction [61,62], These include thiophenes, dithioles, dithianes, dithiins, trithiolanes, trithanes, tetrathianes, thiazoles, thiazolines, and thiazolidines. The major heterocyclic sulfur-containing compounds produced via the Maillard reaction are thiazoles and thiophenes (Figure 5.6d and Figure 5.6e, respectively). 

Competitive metallation experiments with IV-methylpyrrole and thiophene and with IV-methylindole and benzo[6]thiophene indicate that the sulfur-containing heterocycles react more rapidly with H-butyllithium in ether. The comparative reactivity of thiophene and furan with butyllithium depends on the metallation conditions. In hexane, furan reacts more rapidly than thiophene but in ether, in the presence of tetramethylethylenediamine (TMEDA), the order of reactivity is reversed (77JCS(P1)887). Competitive metallation experiments have established that dibenzofuran is more easily lithiated than dibenzothiophene, which in turn is more easily lithiated than A-ethylcarbazole. These compounds lose the proton bound to carbon 4 in dibenzofuran and dibenzothiophene and the equivalent proton (bound to carbon 1) in the carbazole (64JOM(2)304). 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

Thiophene, a sulfur-containing heterocycle, undergoes typical aromatic substitution reactions rather than addition reactions. Why is thiophene aromatic ... 

Sometimes, hydrogen sulfide converts an oxygen-containing heterocycle into a sulfur-containing one, and as furans and polycyclic furans are very common in nature such reactions may be the origin of the polycyclic thiophenes mentioned above. A typical example is the formation of the isothiazolin-3-thione (6) from the isoxazolin-3-thione (7) on treatment with hydrogen sulfide and hydrogen bromide.8... 

Photodimerizations have been observed in a variety of sulfur-containing heterocycles notable examples include the photodimerization of 2- and 3-ary lbenzo[b]thiophens,287 benzo[h]thiophen 1-oxide,288 benzo[h]thiophen 1,1-dioxide,289 and its 2-bromo289 and 2-methyl derivatives.290 All four possible dimers were obtained on irradiation of thio-chromone in aromatic solvents,291 and 1-thiauracil (345) is converted into... 

Catalytic hydrodesulfurization (HDS) is a very important industrial process that involves removal of sulfur from crude oils by high-temperature ( 400°C) treatment with hydrogen over Co- or Ni-promoted Mo or W catalysts supported on alumina. In an attempt to determine the mechanism of this process, many transition metal complexes of thiophene, a sulfur-containing heterocycle that is particularly difficult to desulfurize, have been prepared and their reactivities studied in order to compare their behavior with those of the free thiophenes that give H2S and C4 hydrocarbons under HDS conditions (88ACR387). Thiophene can conceivably bind to the catalyst surface by either cr-donation via a sulfur electron pair or through a variety of -coordination modes involving the aromatic system... 

The resonance energy per electron for the sulfur-containing heterocycles (13)-(15) (X = Y = S) have been determined. The values are —0.005/1, —0.008/1, and — 0.012/S, respectively. These values, when compared with thiophene (0.032/1), indicate these isomers (13)-(15) are not aromatic (73JA3907). 

Many sulfur-containing heterocycles have potential as materials for inducing electrical conductivity, for example materials based on polymeric thiophenes have been examined for possibilities in electrical conductivity <90SM327>, and cyclopenta- and benzobis-1,3-dithioles and benzothiadiazoles... 

The thioacylated products are frequently useful intermediates and they have been transformed into sulfur-containing heterocyclic compounds. Reflux of acyclic 1,1-enediamines 176 with phenacyl bromide or chloroacetone in ethanol gives the tetra-substituted thiophenes 178142. The reaction includes 5-alkylation and cyclization steps (equation 70). 

Juzo Nakayama is a professor of the department of chemistry at Saitama University and the vice president for research work of the same University. He received an award from the Society of Synthetic Organic Chemistry, Japan and the International Council on Main Group Chemistry for Excellence in Main Group Chemistry (ICMGC Award). His research interests include the chemistry of a range of sulfur-containing heterocycles (dithiiranes, thiirenes, dithietes, thiophenes, etc.), and sulfur-containing inner salts. 

The reaction of sulfur-containing heterocyclic compounds such as thiophenes and thiazoles (Eq. 68) is specifically enhanced by addition of Cul, while the role is not yet definitive [135]. The use of a bulky phosphine ligand such as P(f-Bu)3 also promotes the arylation [141]. 2-Iodothiophenes are polymerized to produce polythiophenes (Eq. 69) [142]. 

In our view, it is this circumstance which accounts for the chemical and physical similarities between thiophene and benzene, as well as between pyrazine and 1,2,5-thiadiazole, which have frequently been pointed out in this review and in the chemical literature. In a formal sense the sulfur atom having two pd orbitals is like an ethylenic fragment with two p orbitals. We therefore propose that a sulfur-containing heterocycle be termed quasiethylenic with its cyclic counterpart in which the sulfur atom is replaced by two doubly bonded carbon atoms. 

Since sulfur is the most effective of all catalyst poisons, the hydrogenation of sulfur containing heterocycles is not easily accomplished unless there are no unshared electron pairs on the sulfur atom or the catalyst used is not affected by the poison. The hydrogenation of the cyelie sulfone, 58, takes palace over an excess of palladium in acetic acid at room temperature and atmospheric pressure (Eqn. 17.57). Thiophene, itself, can be hydrogenated to tetrahydrothiophene over rhenium heptasulfide at 250°C and 300 atmospheres of hydrogen or over a large excess of palladium in methanolic sulfuric acid at room temperature and 3-4 atmospheres. No hydrogenolysis of the carbon-sulfiir bond was observed in these reactions. 

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