1516 J. Agric. Food Chem., Vol. 44, No. 6, 1996
De Kimpe and Keppens
EXPERIMENTAL PROCEDURES
and GC analysis, the residue obtained after acidic and basic
workup with two equiv of (COOH)2‚2H2O was a mixture of
2-acetyl-1-pyrroline (6) (81%), its isomer 12 (8%), and some
unidentified, slightly higher boiling compounds (11%). The
yield of 6 in the reaction mixture was 43%. Distillation of this
residue did not result in any further purification (bp 22-24
°C/0.25 mmHg). 2-Acetyl-1-pyrroline (6) was isolated from this
mixture via preparative gas chromatography. All spectral data
(1H and 13C NMR, IR, MS) were identical to data reported in
the literature (De Kimpe et al., 1993a). As mentioned above,
no traces of the enamino form of 1-pyrroline 6 could be detected
(1H and 13C NMR).
Syn th esis of 2-(1,1-Dieth oxyeth yl)-1-p yr r olin e (18).
The procedure used to prepare 18 from R,R-diethoxyimine 17
(De Kimpe and Stevens, 1995) and stabase derivative 10b is
essentially the same as described above for the synthesis of
piperideine 2 from diimine 9a . For the preparation of 18, 1.2
equiv of LDA was used, and only 1 equiv of (COOH)2‚2H2O
was used for the acidic and basic workup. Starting from 35
mmol of imine 17, 4.12 g (64%) of pure 1-pyrroline 18 was
obtained after flash chromatography (pentane:Et2O 3:7, Rf )
0.27; purity g99%; GC-MS, 1H and 13C NMR). Spectral data
of 18: 1H NMR (CDCl3) δ 1.22 (6H, t, J ) 6.92 Hz, 2 ×
OCH2CH3), 1.50 [3H, s, MeC(OEt)2], 1.89 (2H, ∼pent., J )
∼7.92 Hz, CH2CH2N), 2.60 (2H, txt, J 1 ) 8.58 Hz, J 2 ) 1.98
Hz, CH2CdN), 3.45 (2H, dxq, J 1 ) 9.23 Hz, J 2 ) 6.92 Hz,
OCH2), 3.55 (2H, dxq, J 1 ) 9.23 Hz, J 2 ) 6.92 Hz, OCH2), 3.94
(2H, txt, J 1 ) 7.26 Hz, J 2 ) 1.98 Hz, CH2N); 13C NMR (CDCl3)
δ 15.40 (2 × OCH2CH3), 22.44 [MeC(OEt)2], 22.53 (CH2), 34.88
(CH2CdN), 57.11 (2 × OCH2), 61.35 (NCH2), 100.07 (Cq),
178.45 (CdN); IR (NaCl) 1648 cm-1 (CdN); mass spectrum,
m/ z (%) 185 (M+, <1), 141 (13), 140 (38), 117 (47), 112 (84),
96 (10), 95 (11), 94 (9), 89 (40), 70 (33), 68 (14), 61 (100), 45
(13), 44 (13), 43 (94), 42 (19), 41 (52). Anal. Calcd for
C10H19O2N: N, 7.56. Found: N, 7.70.
Syn th esis of 6-Acetyl-1,2,3,4-tetr a h yd r op yr id in e (2). A
solution of 5.04 g (30 mmol) of R-diimine 9a (Armesto et al.,
1987; De Kimpe et al., 1991) in dry THF (10 mL) was added
dropwise at 0 °C under nitrogen to an in situ prepared stirred
solution of 30.6 mmol of lithium diisopropylamide (LDA) in
dry THF (from diisopropylamine and n-butyllithium). After
6 h of stirring at 0 °C, a solution of 9.24 g (33 mmol) of stabase
derivative 10a (Djuric et al., 1981) in dry THF (10 mL) was
added. The stirred reaction mixture was allowed to reach
room temperature during 15 h, after which time it was poured
into 100 mL of an aqueous NaOH solution (0.5 N), extracted
with ether (3 × 50 mL), and dried (K2CO3). After filtration of
the drying agent and evaporation in vacuo, the residue was
dissolved in 100 mL of MeOH, and after addition of 12.42 g
(90 mmol) of K2CO3, the resulting suspension was stirred
under gentle reflux for a period of 3 h. The reaction mixture
was then poured into 150 mL of water, extracted with CH2Cl2
(3 × 100 mL), and dried (K2CO3). After filtration and evapora-
tion of the solvent, the residue was dissolved in 100 mL of
ether, after which a solution of 7.56 g (60 mmol) of (COOH)2‚-
2H2O in 100 mL of water was added. This two-layer system
was shaken thoroughly, and the aqueous phase was isolated.
After further extraction of the latter phase with ether (2 ×
100 mL), it was basified with solid NaOH and extracted with
CH2Cl2 (3 × 100 mL), after which the combined CH2Cl2 layers
were dried (K2CO3). After filtration and evaporation of the
solvent, the residue (2.45 g, 65% yield) consisted of a 1:4
mixture of 6-acetyl-1,2,3,4-tetrahydropyridine (2) and its imino
tautomer 3, respectively (purity g95%; GC-MS, 1H NMR, 13
C
NMR). The ratio of 2 to 3 gradually changed upon standing
until the tautomeric equilibrium was reached, at which point
this ratio amounted to approximately 3:1, respectively. The
reaction mixture may be distilled (bp 23-29 °C/0.01 mmHg),
but the yield dropped dramatically (0.83 g, 22%); distillation
did not result in any significant further purification (purity
96%; GC). All spectral data (1H and 13C NMR, IR, MS) of
compounds 2 and 3 were consistent with an earlier literature
report (De Kimpe and Stevens, 1993).
Hyd r olysis of 1-P yr r olin e 18. A mixture of 1.85 g (10
mmol) of 18 and 50 mL (100 mmol) of 2N HCl aqueous solution
was stirred at room temperature for 2 days, after which time
it was cooled to -5 °C. Under vigorous stirring at this
temperature, a 1 N aqueous solution of NaOH was added
dropwise very slowly (caution!) until the solution was alkaline.
This aqueous solution was extracted with CH2Cl2 (3 × 30 mL)
and dried (MgSO4). After filtration and evaporation of the
solvent, the residue (1.02 g, 92% yield) was analyzed im-
Syn t h esis of 6-P r op ion yl-1,2,3,4-t et r a h yd r op yr id in e
(4). The procedure used to prepare 4 starting from diimine
9b is essentially the same as described above for the synthesis
of 6-acetyl-1,2,3,4-tetrahydropyridine (2). For the preparation
of 4, 1.05 equiv of LDA and 1.2 equiv of 10a were used.
Starting from 5.46 g (30 mmol) of 9b, 2.81 g (67%) of nearly
pure 4+5 was obtained (purity g98%; 1H and 13C NMR, GC-
MS). The reaction mixture was distilled (bp 71-76 °C/7
mmHg) but resulted again in a poor yield (1.50 g, 36%). IR
(NaCl) 1645-1695 cm-1 (CdO and CdN). Other spectral data
of 4 and 5 were deduced from a sample containing a tautomeric
mixture of 4 and 5. The mass spectral data of tautomers 4
and 5 were consistent with an earlier literature report (Ledl
and Schleicher, 1990).
Spectral data of 4: 1H NMR (CDCl3) δ 1.11 (3H, t, J ) 7.59
Hz, Me), 1.8-1.9 (2H, m, CH2CH2N), 2.2-2.3 (2H, m, CH2CdC),
2.67 (2H, q, J ) 7.59 Hz, CH2CdO), 3.16 (2H, ∼t, CH2N), 5.64
(1H, t, J ) 4.46 Hz, CHd), NH invisible; 13C NMR (CDCl3) δ
8.99 (Me), 21.89 and 22.66 (each CH2), 28.95 (CH2CdO), 40.99
(CH2N), 108.01 (CHd), 141.40 (dCN), 197.41 (CdO); mass
spectrum, m/ z (%) 139 (M+, 81), 124 (57), 97 (42), 96 (100), 82
(43), 79 (16), 69 (85), 68 (43), 55 (41), 54 (24), 44 (43), 43 (87),
42 (54), 41 (60).
Spectral data of 5: 1H NMR (CDCl3) δ 1.07 (3H, t, J ) 7.26
Hz, Me), 1.6-1.8 [4H, m, (CH2)2CH2CdN], 2.3-2.4 (2H, m,
CH2CdN), 2.84 (2H, q, J ) 7.26 Hz, CH2CdO), 3.7-3.8 (2H,
m, NCH2); 13C NMR (CDCl3) δ 7.85 (Me), 18.81 and 21.70 (each
CH2), 23.97 (CH2CdN), 29.54 (CH2CdO), 50.13 (CH2N), 166.84
(CdN), 202.67 (CdO); mass spectrum, m/ z (%) 139 (M+, 81),
138 (21), 124 (34), 111 (30), 110 (24), 96 (16), 84 (23), 83 (92),
82 (85), 80 (15), 68 (11), 67 (12), 57 (80), 56 (19), 55 (84), 54
(100), 53 (19), 52 (11), 44 (16), 42 (17), 41 (34).
Syn th esis of 2-Acetyl-1-p yr r olin e (6). 2-Acetyl-1-pyrro-
line (6) was prepared from R-diimine 9a (30 mmol) and stabase
derivative 10b in essentially the same way as described above
for the synthesis of 2. According to 1H and 13C NMR data
1
mediately (GC, H and 13C NMR) and consisted of 2-acetyl-1-
pyrroline (6) and its structural isomer 12 in a ratio of 47:53,
respectively. Both compounds 6 and 12 were isolated via
preparative gas chromatography. All spectral data (1H and
13C NMR, IR, MS) of 2-acetyl-1-pyrroline (6) were consistent
with literature data (De Kimpe et al., 1993). Spectral data of
12: 1H NMR (CDCl3) δ 2.08-2.12 (2H, m, CH2CH2N), 2.12
(3H, s, Me), 2.52 (2H, ∼t, J ) 6.93 Hz, CH2CdO), 3.81-3.86
(2H, m, NCH2); 13C NMR (CDCl3) δ 18.60 (Me), 22.70 (CH2),
35.33 (CH2), 48.65 (NCH2), 163.00 (CdN), 189.90 (CdO); IR
(NaCl) 1695 (CdO), 1630 cm-1 (CdN); mass spectrum, m/ z
(%) 111 (M+, 35), 83 (27), 55 (81), 54 (8), 44 (54), 43 (22), 42
(100), 41 (43).
RESULTS AND DISCUSSION
For the syntheses of the bread flavor compounds 2
and 4, the principal rice flavor component 6 and its
protected form 18, a recently developed strategy for the
synthesis of cyclic imines was used (De Kimpe et al.,
1993). This procedure involved R-deprotonation with
LDA and R-alkylation of a suitable imine with a stabase-
protected ω-bromoalkylamine 10, which led to an amino-
protected functionalized imine (such as 11) as the key
intermediate (Scheme 3). Deprotection of the primary
amine function resulted in spontaneous cyclization via
transimination and formation of the desired azahetero-
cycle. To synthesize the flavor components 2, 4, and 6
in this way, the diimines 9 were prepared from the
corresponding R-diones 8 (Armesto et al., 1987; De