A-Mercaptoacetaldehyde

The condensation of a-mercaptoacetaldehyde with sulfones 8 affords 2-aminothiophenes 9 (Scheme 3) <2001BMC1123>. 2-Aminothiophene 10 <1998JHC933> and bis(2-amino-3-thienyl)sulfone 11 <1998JHC927> have been synthesized by use of this method. 

Analogues of a-mercaptoacetaldehyde were also used in this route to incorporate substituents at C-5. This approach to sulfolenes has been adapted by several other workers to provide useful diene precursors. In our laboratory we have recently developed a modification of the synthetic procedure to provide 3-carbomethoxy-3-sulfolene on a large scale, in one pot, and using cheaper reagents than the original method [74],... 

Scheme 6.76 (a) Piperidine/AcOH/benzene (b) a-mercaptoacetaldehyde/EtjN (c) mCPBA (d) 370°C (e) MeOH/H (f) DIBAL/THF (g) OMSO/TPAA/GHjCl ... 

A more recent method (31) is to prepare the Aj-thiazoline from the mercaptoacetaldehyde dimer, ammonia, and an aldehyde using Asinger s method (32). 

Craig and co-workers247 reported the synthesis of l-aza-2,4,10-trithiaada-mantane (227) as a by-product in the reaction of ammonium dithiocarbamate with an aqueous solution of chloroacetaldehyde. The same compound is reported to be obtained by the reaction of mercaptoacetaldehyde with ammonia248 and then by the reaction of tri(2,2-bis(ethoxy)ethyl]amine (228) with hydrogen sulfide in the presence of hydrobromic acid.249 The... 

While sulfur-free amino acids are broken down to amines via decarboxylation, the sulfur-containing amino acids such as cysteine can undergo more complex reactions. Fisher and Scott suggest that, because cysteine produces a powerful reducing aminoketone, hydrogen sulfide could be produced by reducing mercaptoacetaldehyde or cysteine.2... 

The symmetrical compounds (17, R = R = R ) are formed from an aldehyde and ammonium sulfide (2,29,35) or hydrogen sulfide and ammonia (33), Thialdine (17, R - R - R = Me) is an important aroma compound found in the volatiles of beef broth (48), pressure-cooked meat (49), and fried chicken (50), It is also obtained from acetaldehyde (2,29,37) or from B-mercaptoacetaldehyde and ammonium sulfide (37), In our experiments, it was synthesized as a white powder from a reaction of acetaldehyde with ammonium sulfide in 60% yield. 

Hydrogen sulphide is a key intermediate in the formation of many heterocyclic sulphur compounds. It is produced from cysteine by hydrolysis or by Strecker degradation ammonia, acetaldehyde and mercaptoacetaldehyde are also formed (Scheme 12.4). All of these are reactive compounds, providing an important source of reactants for a wide range of flavour compounds. Scheme 12.6 summarises the reactions between hydrogen sulphide and other simple intermediates formed in other parts of the Maillard reaction. 

It is precisely to the production of meatlike flavors that the great majority of patents based on the Maillard reaction have been directed. Mos of them indicate cysteine or cystine as the essential sulfur-containing compound. Other patents claim alternative sources for sulfur, e.g., derivatives of mercaptoacetaldehyde (36), mercaptoalkylamines (37), S-acetylmercaptosuccinic acid (38), 2-thienvltetrasulfide (39), "a sulfide" (40), and hydrogen sulfide (heated with aqueous xylose without any amino acid) (41). 

The mercaptoacetaldehyde diethylacetal (7 g) was mixed in 100 ml of toluene with 7 g of the above benzoyloxyacetaldehyde, a few crystals of p-toluenesulfonic acid added and the mixture place in an oil-bath at 120°C under N2. The formed ethanol was allowed to distill over, the mixture kept at 120°C for 30 min longer than cooled and washed with aqueous NaHC03, dried and evaporated in vacuo. The residue was distilled in vacuo to yield 9.8 g of 2-benzoyloxymethyl-5-ethoxy-l,3-oxathiolane as a mixture of cis- and transisomers, boiling point 140-143°C/0.1 mm. 

Most of the original patents referring to meat flavors utilizing Maillard technology vere claimed by Unilever (48-52 56,57). More recent patents are involved with the production of meat-like flavors. While a majority of patents are concerned vith cysteine, cystine, or methionine as the sulfur source, others claim alternatives such as mercaptoacetaldehyde, mercaptoalkamines, etc. Several patents (53,54), declare the contribution to meat-like flavors produced from thiamine in the Maillard reaction. Alternately, a technical report describes the volatile flavor compounds produced by the thermal degradation of thiamine alone (55). 

Heterocyclic compounds are dominant among the aroma compounds produced in the Maillard reaction, and sulfur-containing heterocyclics have been shown to be particularly important in meat-like flavors. In a recent review, MacLeod (6) listed 78 compounds which have been reported in the literature as possessing meaty aromas seven are aliphatic sulfur compounds, the other 71 are heterocyclic of which 65 contain sulfur. The Strecker degradation of cysteine by dicarbonyls is an extremely important route for the formation of many heterocyclic sulfur compounds hydrogen sulfide and mercaptoacetaldehyde are formed by the decarboxylation and deamination of cysteine and provide reactive intermediates for interaction with other Maillard products. 

Effenberger and coworkers reported a de novo approach to 5-thio-D-f/zreo-2-pentulofuranose (5-thio-D-xylulose, 20) (Figure 9.7) from 2-mercaptoacetaldehyde, employing rabbit muscle aldolase (RAMA EC 4.1.2.13) and yeast transketolase (EC 2.2.1.1) as the catalysts [32]. 

Hydrogen sulhde and 2-mercaptoacetaldehyde are obtained during the course of the Strecker degradation of cysteine (Fig. 5.17). In a similar way, methionine gives rise to methional, which releases methanethiol by P-ehmination (Fig. 5.18). Dimethylsulhde is obtained by methylation during heating of methionine in the presence of pectin ... 

In order to obtain thiophenes unsubstituted at C-4 and C-5, ethanal would be required as the aldehyde component, but there are only a few examples of this [63, 64], in one [64] of which zinc oxide was used instead of an organic base. In practice, l,4-dithiane-2,5-diol 24 is usually used (Scheme 35), and thus no sulfur needs to be introduced into the reaction mixture the reactant is a dimer of mercaptoacetaldehyde. Reaction is carried out in the presence of a base, which deprotonates an OH group and thus releases the aldehyde carbonyl from its hemithioacetal, ready for Knoevenagel condensation [56, 57]. 

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