B. Dziuk, J. B. Kyzioł, J. Zaleski, K. Ejsmont, and B. Zarychta
Vol 000
3
Scheme 3. The resonance effect in 1.
2H and 1.20, t J = 7.0 Hz, 3H (ethyl group), 2.36, s, 3H
(4-methyl group).
Ethyl (2-amino-4-thiazolyl)acetate (2).
The aqueous
mother liquors from filtration of crude precipitate of 1
were extracted (3 × 70 mL) with chloroform. The
extract was dried, concentrated to a small volume,
and cooled. The crude product (mp 84–115°C)
collected by filtration and crystallized from methanol.
Recrystallization from toluene gave light yellow prisms
of ethyl (2-amino-4-thiazolyl)acetate (3, 2.76 g, 5%),
suitable for X-ray diffraction studies; mp 90–92°C. MS,
m/z (int.): 186 (M+, 59), 141 (5), 113 (100), 86 (8), 71
(3), 69 (14). IR (KBr): 3419, 3350, 1626 (stretching and
deformation of the primary amino group); 1716, 1263
(ester group). 13C-NMR (DMSO-d6): 170.1 (carbonyl
group); 168.2 (C-2, thiazole ring); 144.4 (C-4); 103.0
(C-5); 60.1 and 14.0 (ethyl group); 36.9 (4-methyl
group). 1H-NMR (DMSO-d6): 6.86, s, 2H (amine
protons); 6.30, s, 1H (H-5), aromatic proton; 4.07, q, 2H
Conjugation between complementary (donor–acceptor)
substituents across the thiazole ring causes its
deformation. The N(3)–C(4) bond in 1 is shorter [1.366
(2) Å vs 1.4092 (19) Å and 1.4010 (19) Å in 2], while
the C(4)–C(5) bond is, for ~0.010 (2) Å, longer in 1 than
in 2. The mesomeric effect is not reflected in the 13C-
NMR spectra; the chemical shifts of the ring carbons are
in a good agreement with the values calculated from the
spectrum of parent compound, namely, 2-amino-4-
methylthiazole and the substituents effects.
An interesting feature of 1 molecule is its planar O,S-anti
conformation. Aromatic ring, ester, and amino groups are
situated in the same plane. The torsion angles along the
C(2)–N(21) and C(5)–C(6) bonds are ~1° only. The
methylene group, insulating thiazole ring and ester group
in molecule 2, makes it more flexible and makes the ester
group nearly perpendicular to the thiazole ring. The
dihedral angles between the ring and the OCO plane
amount to 88.7° and 76.4° in two independent molecules
2 (Fig. 4).
3
and 1.18, t J = 7.0 Hz, 3H (ethyl group); 3.45, s, 2H
(4-methylene group).
Crystallographic measurements.
The measurements
were performed on an Xcalibur CCD diffractometer with
graphite monochromated MoKα (λ 0.71073 Å)
=
radiation. An Oxford Cryosystems (Oxford, United
Kingdom) cooler was used for the measurement at 85.0
(1) K. The reflections were measured using the ω-scan
EXPERIMENTAL
Table 1
2-Amino-5-ethoxycarbonyl-4-methylthiazole (1). Bromine
(15.4 mL, 0.3 mol), dissolved in carbon tetrachloride
(250 mL), was slowly dropped with stirring into the
solution ethyl acetoacetate (38.0 mL, 0.3 mol) in carbon
tetrachloride (250 mL). The solvent was evaporated under
reduced pressure, the aqueous (600 mL) solution of
thiourea (45.70 g, 0.6 mol) was added, and the mixture was
stirred for an hour at 70°C and left for 12 h at room
temperature. It was cooled to 5–10°C and neutralized with
concentrated aqueous solution of potassium hydroxide
(~17 g). A voluminous precipitate was collected by
filtration, washed with water, and dried in vacuum to the
constant weight. The crude product was crystallized from
toluene (800 mL) boiling with charcoal. 2-Amino-5-
ethoxycarbonyl-4-methylthiazole (24.65 g, 44%) was
obtained as light yellow needles melting at 176–178°C.
MS, m/z (int.): 186 (M+, 99), 158 (30), 141 (100), 130 (7),
114 (58), 112 (19), 71 (17). IR (KBr): 3373, 3301 (free and
hydrogen-bonded amino group); 1674 (carbonyl band);
1651 (deformations of the primary amino group); 1280
(ester CO–O band). 13C-NMR (DMSO-d6): 170.3 (carbonyl
group); 162.6, 159.4, and 107.5 (ring carbons); 59.8
and 14.4 (ethyl group); 17.2 (4-methyl group). 1H-
NMR (DMSO-d6): 7.67, s, 2H (amine protons); 4.12, q,
Experimental details.
1
2
Crystal data
Chemical formula
Mr
Crystal system,
space group
a, b, c (Å)
C7H10N2O2S
186.82
Trigonal, P3–
C7H10N2O2S
186.23
Monoclinic, P21/n
18.9515 (11),
18.9515 (11),
4.4865 (4)
90, 90, 120
1395.5 (2)
6
14.9317 (13),
8.3611 (5),
15.7225 (14)
90, 110.696 (8), 90
1836.2 (3)
α, β, γ (°)
V (Å3)
Z
8
0.32
μ (mmÀ1
)
0.31
0.4 × 0.3 × 0.3
Crystal size (mm)
Data collection
No. of measured,
independent and
observed [I > 2σ(I)]
reflections
0.30 × 0.25 × 0.21
9298, 1823,
1416
11708, 3584, 2907
Rint
0.029
0.617
0.016
0.617
(sin θ/λ)max (ÅÀ1
Refinement
)
R[F2 > 2σ (F2)],
0.033, 0.089,
1.05
1823
114
0.31, À0.22
0.031, 0.086, 1.09
wR(F2), S
No. of reflections
3584
221
0.39, À0.25
No. of parameters
ρ
max, ρmin (e ÅÀ3
)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet