Pyrazines methoxypyrazines

Closely related compounds, even enantiomers, may not show similar binding affinities. OBP1 specifically bound 2- H-3 -isobutyl-3-methoxypyrazine, whereas OBP2 did not a derivative compound (2-isobutyl-3-methoxy-pyrazine) was unable to displace ligands from OBP-2 (Lobel et al., 1998). 

Minuscule quantities of naturally-occurring pyrazines have been found in some foodstuffs and are largely responsible for their flavor and aroma. For example, 3-isopropyl-2-methoxypyrazine is isolated from green peas and wine and a seasoned wine connoisseur can identify a ppt quantity. In addition, 2-methyl-6-vinylpyrazine exists in coffee. 

Figure 8. Intervalence spectrum of Creutz-Taube ion (------) and of the corresponding ion with 1-methoxypyrazine (-----) instead of pyrazine (DtO solution,...

Aposematic species from two different families produce pungent pyrazines, presumably as an additional warning to potential predators of their toxicity. These include Oncopeltus fasciatus (Lygaeidae, seed bug family) that secretes 2-isobutyl-3-methoxypyrazine [28], and the stink bug Murgantia histrionica (Pentatomidae), that oozes froth containing 2-isobutyl- and 2-sec-butyl-3-methoxypyrazine when molested [39]. 

Upstream migrating glass eels also swim toward compounds with earthy and green (vegetable) odors. These are pyrazines, thiazoles, and alcohols of the cyclohexanol type (Sola, 1995). One of these compounds, 2-isobutyl-3-methoxypyrazine, is common in rivers and lakes (Hwang eta/., 1984). 

Methoxypyrazine-2-one Af-oxides 341 were prepared from oxime derivatives 340 by one-pot cyclization in the presence of DCC/DME with subsequent interaction with Me2S04/K2C03 and NaOH (equation 148) . Similar intramolecular cyclizatiou of ester and oxime O-ethers groups iu the presence of lithium arylthiolate also leads to pyrazin-2-one ring formation . ... 

Examples of the 3-lithiation of both 2- and 2,6-disubstituted chloro- and methoxypyrazines, as well as 2-thiomethylpyrazine are known (88S881 90JOC3410 91JHC765, 91JOM(412)301] (Scheme 117). As with pyridazine, LiTMP has so far been the only base employed, and this same base system has also recently been used for the directed metalation of pyrazine... 

Three 3-alkyl-2-methoxypyrazines (24b, 24c, and 24d) are detected as odor components in the monarch butterfly, Danaus plexippus (Table III). The wide variability in pyrazine content observed with this insect is correlated with similar variability in the larval food plants, Asclepias sp. It seems possible that the pyrazines may be one of the factors implicated in the food choice mechanism (69). 

Alkyl-2-methoxypyrazines exhibit a base peak at miz 124 in the mass spectrum. The peak corresponds to a molecular ion in 2-methoxy-3-methylpyrazine (24a) and to a fragment ion, resulting from a McLafferty rearrangement of an alkyl group, in 3-isopropyl-2-methoxypyrazine (24b) and 3-5cc-butyl-2-methoxy pyrazine (24d) (97). 

Raw potato possesses little aroma. Approximately 50 compounds have been reported to contribute to raw potato aroma. Raw potatoes have a high content of LOX, which catalyses the oxidation of unsaturated fatty acids into volatile degradation products (Scheme 7.2) [187]. These reactions occur as the cells are disrupted, e.g. during peeling or cutting. Freshly cut, raw potatoes contain ( ,Z)-2,4-decadienal, ( ,Z)-2,6-nonadienal, ( )-2-octenal and hexanal, which are all products of LOX-initiated reactions of unsaturated fatty acids [188,189]. It is reported that two compounds represent typical potato aroma in raw potato methional and ( ,Z)-2,6-nonadienal [189]. Other important volatiles in raw potatoes produced via the LOX pathway are l-penten-3-one, heptanal, 2-pen-tyl furan, 1-pentanol and ( , )-2,4-heptadienal [189]. Pyrazines such as 3-iso-propyl-2-methoxypyrazine could be responsible for the earthy aroma of potato [35]. Some of the most important character-impact compounds of raw potatoes are summarised in Table 7.8. Aroma compounds from cooked, fried and baked potatoes have previously been reviewed [35]. 

Methoxypyrazines 3-isobutyl-2-methoxy-pyrazine, 3-isopropyl-2-methoxypyrazine Strong X No ... 

Azine oxides are versatile starting materials for heterocyclic synthesis and are frequently used for regioselective ring substitution reactions, most of which proceed with loss of the oxide substituent. Occasionally some unusual selectivities are observed. For example, treatment of 3-methoxypyrazine A-oxide with equimolar amounts of diethylcarbamoyl chloride and 4-methoxytoluene-a-thiol in refluxing acetonitrile gave 2-methoxy-6-(4-methoxybenzylthio)-pyrazine as the sole product in 60% yield. 

The presence of an N-oxide function in pyrazine is not sufficient in itself to promote electrophilic halogenation, and even the presence of other weak donor groups may fail to promote reaction unless they can act in concert. Although 2-methoxypyrazine 1-oxide could not be bromi-nated, the 3-methoxy isomer [and 3-aminopyrazine 1-oxide (54)] was bro-minated in the 2- and 6-positions (ortho to oxide and ortho or para to the amino group cf. Scheme 47). Similarly, 2-aminopyrazine was brominated more readily than its Af-oxide (55 R = H) where the two groups are in opposition [83JOC1064 84H(22) 1195]. 

Ethyl-3-methoxypyrazine (3-Ethyl-2-methoxy pyrazine) C2H5 och3... 

Isopropyl-5-methoxy pyrazine (5-Isopropyl-2-methoxypyrazine) i-C3H7 OCH3... 

The odor threshold of the pyrazines range from 0.006 ppb in water for 2—propyl—3-methoxypyrazine (29) to 43 ppm in water for 2,5—dimethyl—3-ethyl pyrazine (30). A excellent review of the pyrazines found in food products has been prepared by Maga (31). 

Pyrazines were eluted from the Sep-Pak with 2 x 1 ml. aliquots of methanol. Recoveries of wine spiked with methoxypyrazines in the ppb ranged from 10 to 63%. While recoveries appear low, they were reproducible and quite suitable to address the problem being investigated. 

Pyrazines are the major volatile flavor chemicals produced in Maillard reactions. The discovery of this role of pyrazines was one of the most significant advances in flavor chemistry and two comprehensive reviews of pyrazines have appeared (25, 26). In the 1970 s, pyrazines were well-characterized as the compounds which directly contribute to roasted or smoky flavors. Some pyrazines possess an extremely low odor threshold (25, 29). For example, odor threshold of 2-isobutyl-3-methoxypyrazine in water is 0.002 ppb. 

A new set of Mannich bases of 10//-indolo[3,2-6]quinoxaline was prepared <02IJH157>. A versatile synthetic route to /V-protected L-amino acid (3-benzylquinoxalin-2-yl)hydrazides was developed <02LPS49>. The properly substituted bis(indole) pyrazine 165 from the marine alkaloid dragmacidin D was prepared from 2,5-dibromo-3-methoxypyrazine (164) <02JOC9392>. 

Methoxypyrazine (142) gave 2-(a-cyanobenzyl)pyrazine (143) (PhCH2CN, NaH, THF, reflux, 30 min then substrate j, reflux, N2, TLC monitored 46%).309 other carbanions seem to have been less successful.309... 

Diethoxy-3-(l-hydroxy-l-methylethyl)pyrazine (155) gave 2,5-diethoxy-3-isopropenylpyrazine (156) (TsOH, PhH, molecular sieves, reflux 80%) 6 2-(l-hydroxy-2-methylpropyl)-6-iodo-3-methoxypyrazine gave 2-iodo-5-methoxy-6-(2-methylprop-l-enyl)pyrazine (157) (TsOH, PhMe, reflux with H20 removal, 6 h 65%).1588... 

Isobutyl-3-methoxy-5-[3-(tetrahydropyran-2-yloxy)propyl]pyrazine (132) gave 2-(3-hydroxypropyl)-5-isobutyl-6-methoxypyrazine (133) (TsOH, MeOH, 20°C, ultrasonication, 2 h > 95%) 295 analogues likewise.298... 

Hydroxypropyl)-5-isobutyl-6-methoxypyrazine (157, R = Hu ) gave 2-isobutyl-3-methoxy-5-(3-phthalimidopropyl)pyrazine (158, R = Hu ) (phthal-imide, Et02CN=NC02Et, Ph3P, A, 20°C, 12 h 93%), and thence 2-(3-amino-propyl)-5-isobutyl-6-methoxypyrazine (159, R = Hu ) (H2NNH2.H20, EtOH, reflux, 4 h 83%) 295 2-(3-aminopropyl)-5-isopropyl-6-methoxypyrazine (159, R = Pfl)298 and other homologues295,298 were made similarly. 

Pyrazine A-oxides have continued to attract much attention in recent years, perhaps because the presence of an A-oxide entity can substantially modify the properties of the whole system, especially in respect of activities at other positions on the ring. For example, the aromaticity index for 2-methoxypyrazine is decreased by 23% on formation of its 4-oxide 383 and formation of an A-oxide activates adjacent positions toward direct bromination,782deuteration,1457 and other electrophilic attack.1078... 

Methoxy-3,6-dimethylpyrazine 4-oxide (283) gave only 2-acetoxymethyl-3-methoxy-5-methylpyrazine (284) (neat AC2O, reflux, 1 h 88%) 324 in contrast, the homologous substrate, 2,5-dibenzyl-3-methoxypyrazine 1-oxide (285), gave a separable mixture of 2-(a-acetoxybenzyl)-5-benzyl-3-methoxy-pyrazine (286) and 2-acetoxy-3,6-dibenzyl-5-methoxypyrazine (287) (neat Ac20, reflux, 90 min 55 and 20%, respectively).312... 

The major and recently used preparative routes to azidopyrazines have been covered already by azidolysis of halogenopyrazines (Sections 4.2.6 and 4.4) and by treatment of hydrazinopyrazines with nitrous acid (Section 7.4). In addition, direct C-azidation of pyrazines has been used for example, the lithio intermediate (225), generated in THF by treatment of 2-methoxypyrazine (224) with lithium 2,2,6,6-tetramethylpiperidine, gave 2-azido-3-methoxypyrazine (226) (87%) on subsequent treatment with p-toluenesulfonyl azide.232... 

Acetamidoethyl)pyrazine 2-Acetamido-5-ethylpyrazine 2- Acetamido-6- ethylpyrazine 2-Acetamido-3-guanidinocarbonyl-5-isopropylaminopyrazine 2-Acetamido-3-guanidinocarbonyl-5-methoxyaminopyrazine 2-Acetamido-3-guanidinocarbonyl-5-methoxypyrazine... 

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