Roasty, Popcornlike Flavor Compound
J. Agric. Food Chem., Vol. 46, No. 6, 1998 2279
5-Acetyl-2,3-d ih yd r o-1,4-th ia zin e (1) (Meth od a , b). To
a solution of 0.91 g (8.8 mmol) of 2-mercaptoethylamine
hydrochloride in 20 mL of dimethylformamide (a) or acetoni-
trile (b) was added 1.68 g (8 mmol) of 1-bromo-3,3-dimethoxy-
2-butanone (6) and the mixture was refluxed for 2 h (a) (for 3
h (b)). After the reaction mixture was cooled to room temper-
ature, 10 mL of water were added to it, and stirring was
continued for 15 min. This mixture was poured in 50 mL of 1
N NaOH and extracted with ether (3 × 50 mL). The combined
extracts were dried (K2CO3) and filtered, and the solvent was
removed in vacuo. To remove residual DMF (a), the crude
mixture was evaporated at 0.01 mmHg (24 °C) to afford 0.55
g of pure 5-acetyl-2,3-dihydro-1,4-thiazine (1) (yield 48%,
purity > 97% (a); yield 56% (b)). This compound was addition-
ally purified (purity > 99%) by flash chromatography (silica
gel) (rfa ) 0.25) with CH2Cl2/hexane (9:1) giving a 27% yield.
The latter purification step is usually not necessary for further
experiments. 1H NMR (270 MHz, CDCl3) δ 2.28 (3 H, s, Me),
3.0 (2 H, m, CH2S), 3.5 (2 H, m, CH2N), 4.6 (1 H, br s, NH),
6.2 (1 H, s, S-CHd). 13C NMR (68 MHz, CDCl3) δ 23.3 (Me),
26.3 (CH2S), 40.5 (CH2N), 106.2 (S-CHd), 137.6 (N-Cd),
190.0 (CdO). IR (NaCl, cm-1) 3370 (NH), 1650 (CHdC-CdO).
Mass spectrum m/z (%) 143 (M+, 100), 128 (17), 100 (35), 73
(26), 72 (20), 43 (62). These spectrometric data proved to be
identical with those previously reported (Hofmann et al., 1995).
ter t-Bu tyl-N-(2-m er ca p toeth yl)ca r ba m a te (8). A solu-
tion of 0.187 g (1.65 mmol) of 2-mercaptoethylamine hydro-
chloride (9) in 8 mL of CH2Cl2 was treated with 0.33 g (3.3
mmol) of Et3N at room temperature. The mixture was stirred
for 30 min at room temperature and was then treated with
0.38 mL (1.65 mmol) of t-Boc2O and stirred for 2 h under a
nitrogen atmosphere. The reaction mixture was poured in
water (10 mL), extracted with ether (3 × 10 mL), dried
(MgSO4), and filtered, and the solvent was evaporated in vacuo
to give 0.25 g (yield 85%) of compound 8 with a purity of 95%
(GC). 1H NMR (270 MHz, CDCl3) δ 1.44 (9 H, s, t-Bu), 2.65 (2
H, m, CH2N), 3.30 (2 H, m, CH2S), 5.0 (1 H, br s, NH). 13C
NMR (68 MHz, CDCl3) δ 24.8 (CH2S), 28.3 (t-Bu), 43.6 (CH2N),
80.0 (OCMe3), 155.8 (NHCOO). IR (NaCl, cm-1): 3300 (NH),
1700 (CdO). Mass spectrum m/z (%) no M+, 121 (29), 104 (7),
74 (8), 62 (27), 61 (11), 60 (10), 59 (38), 58 (6), 57 (100), 56
(23), 55 (10), 44 (40), 43 (8), 42 (5), 41 (67), 40 (27).
ter t-Bu tyl N-[2-(3′,3′-Dim eth oxy-2′-oxobu tyl)m er ca p -
toeth yl]ca r ba m a te (7). A solution of 0.27 g (1.28 mmol) of
1-bromo-3,3-dimethoxy-2-butanone (6) in 5 mL of dry CH2Cl2
was treated with 0.25 g (1.4 mmol) of compound 8 and 0.14 g
(1.4 mmol) of Et3N at room temperature and then refluxed
for 2 h. The reaction mixture was poured in 50 mL of H2O
and extracted with ether (3 × 50 mL). The combined extracts
were dried (K2CO3) and evaporated in vacuo to afford 0.41 g
of a mixture of compound 8 and compound 7 (ratio 8/7, 17/83;
1H NMR) with a yield of 86% of compound 7. This mixture
was used in the following step without separation of the two
compounds. Spectroscopic data of compound 7: 1H NMR (270
MHz, CDCl3) δ 1.44 (12 H, s, Me + t-Bu, overlap), 2.6 (2 H, t,
CH2CH2S), 3.24 (6 H, s, (OMe)2), 3.35 (2 H, m, CH2N), 3.55 (2
H, s, COCH2S), 5.0 (1 H, br s, NH). 13C NMR (68 MHz, CDCl3)
δ 20.5 (Me), 28.1 (CH2CH2S), 28.4 (t-Bu), 32.4 (COCH2S), 36.8
(CH2N), 49.7 (C(OMe)2), 79.2 (OCMe3), 102.7 (C(OMe)2), 155.8
(NHCOO), 204.0 (CdO). IR (NaCl, cm-1) 3363 (NH), 2835
(OMe), 1713 (CdO), 1690 (NHCOO). Mass spectrum m/z (%)
no M+, 121 (4), 119 (4), 88 (10), 86 (61), 84 (100), 51 (5), 49
(22), 47 (22).
supernatant organic layer was decanted and the salt was
washed with dry ether and dried in vacuo to afford a 0.39 g
(yield 86%) of a light-yellow solid. Mp 171-172 °C. 1H NMR
(270 MHz, CDCl3) δ 2.4 (3 H, s, Me), 3.31 (2 H, m, CH2S), 3.61
(2 H, m, CH2N), 7.95 (1 H, s, S-CHd). 13C NMR (68 MHz,
CDCl3) δ 23.68 (Me), 24.1 (CH2S), 41.23 (CH2N), 126.5 (dCquat),
134.4 (S-CHd), 190 (CdO). IR (KBr, cm-1): 3550-3400/
2850-2400 (+NH2), 1650 (CHdC-CdO).
RESULTS AND DISCUSSION
To synthesize the new Maillard compound 1, 1-bromo-
3,3-dimethoxy-2-butanone (6) was reacted with a small
excess of 2-mercaptoethylamine hydrochloride in dimeth-
ylformamide or acetonitrile at reflux. The reaction
mechanism proceeds via nucleophilic substitution, fol-
lowed by intramolecular transimination and successive
hydrolysis of the acetal function. This process is final-
ized during the aqueous treatment, to give, after basic
workup, 5-acetyl-2,3-dihydro-1,4-thiazine (1), free of side
products and in good overall yields (48% in DMF; 56%
in CH3CN) (Scheme 1). The transimination reaction is
most probably assisted by the basicity of the solvent,
necessary for trapping the proton from the nucleophilic
displacement and to liberate the primary amino function
to allow the nitrogen atom to attack the carbonyl group.
This reaction is best explained through an equilibrium
between the protonated form of the solvent, the primary
amino group of the mercaptoamine, and the oxygen of
the carbonyl group (Scheme 2). During the aqueous
treatment at room temperature the acetal function was
completely hydrolyzed, after which the basic workup
afforded the final products. Initially the imino form (13)
of thiazine derivative 1 was probably formed but rapidly
tautomerized to its free enamino form 1. A similar
tautomerism has been observed for the most important
bread flavor compound 6-acetyl-1,2,3,4-tetrahydropyri-
dine (De Kimpe and Stevens, 1995), which was detected
(NMR) together with its imino form, 6-acetyl-2,3,4,5-
tetrahydropyridine. In contrast to the analogous tet-
rahydropyridine, the imino tautomer (13) of the thiazine
was never detected. This different behavior could be
explained by a more extended conjugation of thiazine 1
compared to 6-acetyl-1,2,3,4-tetrahydropyridine, due to
the sulfur atom.
The same reaction mixture from the reaction of
1-bromo-3,3-dimethoxy-2-butanone (6) with 2-mercap-
toethylamine hydrochloride (9) in dimethylformamide
was directly worked up with 1 N NaOH, affording a
mixture, which mainly consisted of 5-acetyl-2,3-dihydro-
1,4-thiazine (1), as well as some unidentified com-
pounds. An acetal group could be distinguished in this
mixture by 1H NMR, perhaps the carbonyl-protected
form of 1 (see 14) and its imino tautomer (12).
The reaction mechanism was further unraveled by 1H
NMR experiments. 5-Acetyl-2,3-dihydro-1,4-thiazine (1)
was found in the reaction mixture from the reaction of
1-bromo-3,3-dimethoxy-2-butanone (6) with 2-mercap-
toethylamine hydrochloride (9) in acetonitrile, before
(salt) as well as after the aqueous, and then basic,
treatment. It proved that the cyclization reaction and
the successive hydrolysis of the acetal function already
occurred before the workup and came to completion
during the workup. Moreover, the reaction of 1-bromo-
3,3-dimethoxy-2-butanone (6) with 2-mercaptoethyl-
amine hydrochloride was tried in other solvents, e.g.,
ether or dichloromethane, without any good result
(probably because of the poor basicity/polarity of the
solvent). In similar way, when a mixture of water/
5-Acetyl-2,3-d ih yd r o-1,4-th ia zin e (1) (Meth od c).
A
solution of 0.36 g (1.18 mmol) of compound 7 in 10 mL of dry
CH2Cl2 was treated with 0.9 mL (12.8 mmol) of trifluoroacetic
acid (TFA) at 0 °C and was stirred at room temperature for 3
h. The mixture was neutralized with a saturated solution of
NaHCO3 (30 mL) at 0 °C and then extracted with CH2Cl2 (3
× 50 mL). The combined extracts were dried (K2CO3) and
filtered and the solvent was evaporated in vacuo to give 160
mg (yield 88%) of compound 1 (purity > 97%).
5-Acetyl-2,3-dih ydr o-1,4-th iazin e Hydr och lor ide (1‚HCl).
A solution of 0.36 g (2.5 mmol) of compound 1 in 20 mL of dry
ether was treated with saturated dry HCl in ether (6 mL). The