Trithiolanes, formation

Tile behavior of /3-moiiooxo derivatives of 4-chlomaiioiies (27) toward morpholine was rather complex (98JOC9840). Tlius, the proposed thio-ketoiie 5-sulhde intermediates 28 would dimerize into either 1,2,4,5-tetrathianes 29 in a two-step manner or to 1,3,4,5,6-oxatetrathiocins 30 by a [5 + 3] cycloaddition. Meanwhile, the formation of oxadithiins 31 and 1,2,4-trithiolanes 32 is suggestive of the disproportionation of 28 into the thioke-tones 33 and the thioketone 5 -disulhdes 34. Tlie oxadithiins 31 correspond to a Diels-Alder dimer of 33, and the 1,2,4-trithiolanes 32 correspond to cycloadducts of 33 and 34. 

It has been suggested that the oligomers and polymers formed in the ozonolysis reactions of some alkenes arise from the reactive 1,2,3-trioxolane intermediates or their fragmentation products (cf. Section 4.15.4.1) , though relatively little is known about the mode of formation of many of these polymeric species. The tendency of simple 1,2,3-trithiolanes to polymerize has... 

Reaction of norbornane trithiolane (24) with both dichloro- and dibromocarbene afforded the trithiocarbonate (94), which upon further reaction with the dihalocarbene yielded the corresponding dithiocarbonate <90JOC1146>. The mechanism of formation of (94) from (24) is postulated to proceed by addition of the carbene to S-2 of the trithiolane, followed by a ring-expansion reduction sequence as outlined in Scheme 22. 

Reaction of various aldehydes with hydrogen sulfide leads to substituted thiophenes, dihydrothiophenes, dithiolanes and trithiolane, as well as to six-membered ring thiopyran derivatives and dithiins. Ledl (33) obtained 2,4-dimethylthiophene (1, R Me) as a product of the reaction of propionaldehyde with hydrogen sulfide in the presence of ammonia. Sultan (29) reported the formation of 2,4-diethylthiophene (1, R - Et), 2,4-dibutyl-thiophene (1, R - Bu), and their dehydro derivatives from the reaction of ammonium sulfide with butyraldehyde and caproaldehyde (hexanal), respectively. The mechanism suggested for their formation is depicted in Scheme 1. Space limitations do not allow us to discuss the mechanism here in detail (for additional information, see ref. 29). 

Scheme 13.17 Formation of 3,5-diethyl-l,2,4-trithiolane from acetaldehyde...

Wilson, el al. (41) also confirmed the presence of polysulfur heterocyclics in meat including thialdine (5,6-dihydro-2,4,6-tri-methyl-l,3,5-dithiazine) and trithioacetone (2,2,4,4,6,6-hexame-thyl-1,3,5-trithiane). Wilson (42) later discussed the possible routes of formation of some of these compounds from cysteine. Thialdine was found by Brinkman, et el. (43) in the headspace volatiles of beef broth. These workers also identified 3,5-di-methyl-1,2,4 - trithiolane from the same source. Both cis and trans isomers of this compound had previously been identified as flavor components of boiled beef by Chang, jit aL. (44) and Herz (45). 

The formation of 5,6-dihydro-2,4,6-trimethyl-l,3,5-dithiazine, 2,4,6-trimethyl-1,3,5-trithiane, and 3,5-d ime thy1-1,2,4-trithiolane by heating of acetaldehyde, hydrogen sulfide, and ammonia was outlined by Takken and coworkers (36) and is summarized in Figure 4. Under oxidative conditions, dialkyltrithiolanes are formed at low pH there is conversion to trialkyltrithianes at elevated temperature isomerization into trisulfides occurs, which compounds disproportionate into di and tetrasulfides and in the presence of ammonia, dithiazines are formed. These compounds and the conditions for their formation are of extreme importance for the production of desirable meat flavors. 

This important flavor compound was identified in the head-space volatiles of beef broth by Brinkman, et al. (43) and although it has the odor of fresh onions, it is believed to contribute to the flavor of meat. This compound can be formed quite easily from Strecker degradation products. Schutte and Koenders (49) concluded that the most probable precursors for its formation were etha-nal, methanethiol and hydrogen sulfide. As shown in Figure 5, these immediate precursors are generated from alanine, methionine and cysteine in the presence of a Strecker degradation dicarbonyl compound such as pyruvaldehyde. These same precursors could also interact under similar conditions to give dimethyl disulfide and 3,5-dimethyl-l,2,4-trithiolane previously discussed. 

Tetraphenyl-l,2,4-trithiolane 221 precipitated with a yield of 84% from a solution of 3-methyl-2,2-diphenylthiirane 220 (R = Me) and thiobenzophenone in a twofold molar excess kept in ether at room temperature during 3 weeks. In the mother liquor, 1,1-diphenylpropene was present in 90% yield. It was concluded that the 1,2,4-trithiolane has a remarkable formation tendency (Scheme 73) <1997T939>. 

Assuming that the mechanism of this isomerization involves fragmentation and formation of a thiocarbonyl. S -sulfidc, refluxing in toluene in the presence of adamantane-2-thione 216 led to a mixed trithiolane 245 (Equation 19) <2000CC1535>. 

Asinger s studies demonstrated that product formation is sensitive to the ratio of sulfur to ketone (1), the structure of the ketone, the replacement of ammonia by amines, the temperature and the medium. Room temperature (20-25 °C) reactions in which the ratio of sulfur to ketones is 0.5 favors the formation of 3-thiazoline, 2, as shown in Figure 1. The formation of 5-alkylidene-3-thiazolines, 3, sometimes competes with the formation of 3-thiazolines such is the case when aryl ketones such as l-phenylpropan-2-one and l-phenylbutan-2-one are employed (4). Also the additional presence of hydrogen sulfide promotes the generation of 1,2,4-trithiolanes and 1,2,4,5-tetrathiolanes from ketones ana aldehydes at the expense of 3-thiazoline formation (11-12). Increasing the S/ketone ratio to 8 favors the formation of the 3-imidazoline-5-thione (5), a product which has a greater tendency to result from aryl methyl ketones (3). 

The volatile components identified from the reaction of cystine and DMHF in aqueous medium are shown in Table I. 2,4-Hexanedione, 3,5-dimethyl-l,2,4-trithiolanes and thiophenes are the major compounds. The mechanistic relationship of the three thiophenones produced has been postulated (23). The major groups of volatile components identified from the reaction in the glycerol medium are 1,3-dioxolanes and thiazoles (Table II). 1,3-Dioxolanes are formed by the reaction of glycerol and the degraded carbonyls by ketal or acetal formations. Comparison of the reaction of cystine and DMHF in water and in glycerol is outlined in Table III. 

The effect of reaction time on the major components of the reaction of cystine and DMHF in water is shown in Table IV. It is noteworthy that amounts of 2,4-hexanedione, 3,5-dimethyl-l,2,4-trithiolanes and thiophenones were found at a maximum after one hour. It was also found that the amount of 2-acetylthiazole increased with time and that acetol acetate decreased with time as expected. In the glycerol medium, the effect of reaction time on the major components is shown in Table V. Apparently, the 1,3-dioxo-lane, which is a ketal formed from glycerol and acetone, decreased over time. Also, long reaction time favors the formation of cyclic compounds, including 2,5-dimethyl-2-hydroxy-3(2H)-thiophene, cyclo-pentenones and 4,5-dimethyl-l,2-dithiolenone. 

The water content significantly affects the formation of some compounds. Figure 2 shows that the formation of thiazoles decreases as the water content increases. Figure 3 shows the relationship between water content and the formation of a 3,5-dimethyl-1,2,4-trithiolane, 3-hydroxy-pentanone and 2,4-hexanedione. The highest level of trithiolanes was obtained from the sample prepared with 75% water. Figure 4 shows that these three thiophenones were also produced at maximum at 75% water medium. 

Figure 3. The effect of water content on the formation of 3,5-dimethyl-l,2,4-trithiolane, 3-Hydroxy-2-pentanone and 2,4-Hexanedione from the reaction of cystine and DMHF.

C, no esters and furanones are found, but thiazoles, cyclopen-tenones and other heterocyclic compounds dominate. These data imply that esters and furanones are stable at mild temperatures while the formation of thiazoles, cyclopentenones and other heterocyclic compounds require a higher temperature. Also at 160°C, trithiolanes, thiophenones and 2,4-hexanedione predominate, indicating that formation of such compounds is favored by a medium temperature. Bread, crusty and caramel aromas were found in the 100°C sample, pot-roasted, roasted, meaty and clean aromas were found at 160°C, and roasted, roasted-meat, chemical and off-notes were produced at 200°C. 

The optimal conditions for generating the major products formed from cystine and DMHF are as follows 3,5-dimethyl-l,2,4-trithio-lane, thiophenones and 2,4-hexanedione are all found preferentially in an aqueous medium heated to 160°C. The trithiolane and thiophe-none are optimized at 75% H2O and pH 4.5, while 2,4-hexanedione formation is better at 100% H2O and lower pH. Thiazoles, on the other hand, require a higher temperature and a nonaqueous medium. 

In some recent research on flavor formation during deep-fat frying at Rutgers University, a number of heterocyclic compounds with long-chain alkyl substituents were found the volatiles of fried chicken (15) and fried potato (16). These included pyridines, thiazoles, oxazoles, trithiolanes and a pyrazine. Only the involvement of lipids or lipid degradation products in the formation of... 

The synthesis of 4,5-dicyano-l,2,3-trithiole 2-oxide (172) starts from sodium cyanide and carbon disulfide which via (170) gave the disodium salt of 2,3-mercaptomaleonitrile (171 M = Na). Treatment of the corresponding silver salt (171 M = Ag) with thionyl chloride yielded (172) <66HC(2l-l)l). Phenylsulfine (174), prepared in situ by dehy-drohalogenation of phenylmethanesulfinyl chloride (173), slowly decomposed in ether solution at room temperature to give cis- and trans-stilbenes, mms-4,5-diphenyl-l,2,3-trithiolane 1,1-dioxide (36) and a 5,6-diphenyl-l,2,3,4-tetrathiane dioxide (68JCS(C)1612). The mechanisms of formation of these heterocycles are obscure. 

Symmetrical 3,5-dialkyl-l,2,4-trithiolanes (178) can be synthesized in reasonable yield by chlorination of dialkyl disulfides (175) to a-chiloroalkyl sulfenyl chlorides (176), which are then reacted with potassium iodide to give di-a-chloroalkyl disulfides (177). Subsequent cyclization with sodium sulfide gave (178) (72T3489). When (176) was treated with one molar equivalent of sodium sulfide, the reductive dimerization and cyclization was effected in one step (78HCA1404). Treatment of perfluoropropene with sodium hydrogen sulfide in THF resulted in the formation of 3,5-bis(2,2,2-trifluoroethyl)-l,2,4-trithiolane (179) (72IZV2517). 

These compounds, produced in the reaction of H2S and ethanal, have been detected in a synthetic solution and in a white wine by Rauhut and Dittrich (1993). These authors made H2S at concentrations from 1 to 5 mg/L react with ethanal at variables concentrations from 100 to 500 mg/L. This reaction produces cis-ltrans-3,6-dimethyl-1,2,4,5-tetrathiane, the cw-/fran -4,7-dimethyl-l,2,3,5,6-pentathiepane and the c -/fran -3,5-dimethyl-l,2,4-trithiolane and the precursor of these compounds, 1,1-ethanedithiol. However, the same reaction with copper does not prevent formation of these compounds. In contrast, the reaction reported by some authors between H2S and ethanal to form ethanethiol, does not take place. 

Two experiments were performed to try to determine which of these reactions was occurring. After macerating the red wine grapes for one day the coloured must obtained was seeded with yeasts (100 mg/L of LSA). Also, a commercial white must was seeded with the same dose of yeasts. When fermentation started, 5 mg/L of H2S were added and the analysis was carried out one week after finishing alcoholic fermentation. In both cases, the formation of cw-/fran.y-3,6-dimethyl-1,2,4,5-tetrathiane and of cA-//ran.y-3,5-dimethyl-1,2,4-trithiolane was detected. The mass spectra are shown in Figs. 10.9 and 10.10. By contrast, in this experimentdx-Z/rani-4,7-dimethyl-1,2,3,5,6, pentathiepane and 1,1-ethanedithiol did not appear. 

The formation of the 1,2,3-trithiolane (11) has also been observed when norbomene was heated with ben-zopentathiepin, 1,2-6611485, in DMF in the presence of triethylamine (yield 48%, at 100 °C) (equation 95). Ben-zopentathiepin, heated in the presence of R3N, apparently... 

A mechanism has been reported for the formation of trithlolane from the reaction of aldehydes with hydorgen sulfide (51). The identification of 3-methyl-5-butyl-l,2,4-trithiolane and 3-methyl-5-pentyl-1,2,4-trithiolane in food flavor suggests that pentanal and hexanal were Involved in the formation of these compounds (Figure 5). Pentanal and hexanal are major thermal and oxidative decomposition products of lipids. 

A very unusual intermolecular sulfur transfer from one thione to the sulfur atom of another occurs during the formation of the type 6 complex. According to Alper and Chan, it is likely that a trithiolane or similar species is involved in the formation of this complex (21). 

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