CHUPRUN et al.
1864
146 ppm. The positions of these signals, as well as of
the other signals in the NMR spectra of 2a–2g, unam-
biguously confirmed their structure as 1H-tetrazol-1-yl
derivatives.
spectrum (D2O), δ, ppm: 0.78–0.82 t (3H, CH3), 1.02–
1.06 t (3H, CH3), 1.28–1.34 m (2H, γ-H), 2.32–2.38 m
(1H, β-H), 5.44 d.d (1H, α-H, 3J = 11.2, 3.2 Hz), 9.32 s
(1H, 5-H). 13C NMR spectrum (D2O), δC, ppm: 10.38,
14.35, 24.76, 37.21, 66.86, 144.42 (C5), 170.89.
The stereoisomeric excess (ee and de) values of
2a–2g determined by chiral HPLC are given in table.
Only tetrazolyl analog of glutamic acid ester (2b) was
characterized by 100% ee. The other products had ee
values ranging from 20 to 96%. We have found no
relation between the enantiomeric purity and amino
acid nature or reaction conditions. Obviously, the
described reaction is inappropriate for the preparation
of optically pure compounds since the primary amino
group involved in heterocyclization is directly attached
to the asymmetric carbon atom. Factors responsible for
the observed partial racemization cannot be elucidated
on the basis of the heterocyclization mechanism
proposed in [10] and therefore further studies are
necessary.
2-(1H-Tetrazol-1-yl)-3-phenylpropanoic acid
(2d). Yield 3.08 g (63%), white crystals, [α]D21.5 = –5.3°
1
(c = 0.75, MeOH). H NMR spectrum (DMSO-d62), δ,
ppm: 3.32–3.40 m (1H, β-H), 3.60 d.d (1H, β-H, J =
3
3
14.5, J = 4.0 Hz), 5.26 d.d (1H, α-H, J = 11.4,
4.1 Hz), 7.05–7.20 m (5H, Harom), 9.29 s (1H, 5-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 38.57,
66.02, 126.78, 128.68, 129.09, 138.40, 144.12 (C5),
169.50. Mass spectrum (ESI): m/z 218.0811 [M + Na]+.
C10H10N4O2. Calculated: M + Na 218.0803.
3-(4-Hydroxyphenyl)-2-(1H-tetrazol-1-yl)pro-
panoic acids 2e and 2f. Acid 2e: yield 4.1 g (79%),
light yellow crystals, [α]D22.0 = +14.3° (c = 1.0, MeOH);
2f: yield 3.93 g (76%), light yellow crystals, [α]D22.0
=
–13.1 (c = 1.0, MeOH). 1H NMR spectrum
(DMSO-d6), δ, ppm: 3.17–3.29 m (1H, β-H), 3.45 d.d
Compounds 2a–2g (general procedure). A solution
of 22.4 mmol of amino acid in 40 mL of glacial acetic
acid was added to a suspension of 44.8 mmol of
sodium azide in 67.2 mmol of triethyl orthoformate.
The mixture was carefully heated to 55°C and was
stirred for 4 h at that temperature. It was then cooled,
and concentrated aqueous HCl was added until a solid
no longer separated. The precipitate was filtered off,
chloroform was added to the filtrate, and the mixture
was evaporated under reduced pressure. The product
was purified by column chromatography using chloro-
form–methanol (50:50) as eluent.
2
(1H, β-CH, J = 14.6, 3J = 3.6 Hz), 5.17 d.d (1H, α-H,
3
3J = 11.2, 4.1 Hz), 6.57 d (2H, Harom, J = 8.3 Hz),
3
6.83 d (2H, Harom, J = 8.3 Hz), 9.25 s (1H, 5-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 37.87,
66.54, 115.58, 128.05, 129.95, 144.09 (C5), 156.53,
169.93. Mass spectrum (ESI): m/z 257.0651 [M + Na]+.
C10H10N4O3. Calculated: M + Na 257.0645.
3-(1H-Indol-3-yl)-2-(1H-tetrazol-1-yl)propanoic
acid (2g). Yield 1.32 g (23%), yellow–orange crystals,
[α]D21.6 = +55° (c = 0.75, MeOH). H NMR spectrum
1
(DMSO-d6), δ, ppm: 3.58 d.d (1H, β-H, 2J = 15.2, 3J =
4-(Benzyloxy)-4-oxo-2-(1H-tetrazol-1-yl)-
butanoic acid (2a). Yield 4.02 g (65%), mp 188–
2
11.2 Hz), 3.75 d.d (1H, β-H, J = 15.2, 3.8 Hz),
190°C, [α]D23.5 = +35° (c = 1.0, H2O). H NMR spec-
1
3
5.54 d.d (1H, α-H, J = 11.2, 3.9 Hz), 6.91 d (1H,
3
trum (D2O), δ, ppm: 3.38–3.41 m (2H, β-H), 5.05–5.06 t
Harom, J = 2.2 Hz), 6.93–7.00 m (1H, Harom), 7.01–
3
3
(2H, PhCH2), 5.65 d.d (1H, α-H, J = 11.2, 4.8 Hz),
7.08 m (1H, Harom), 7.29 d (1H, Harom, J = 8.1 Hz),
7.21–7.36 m (5H, Harom), 9.11 s (1H, 5-H). 13C NMR
spectrum (D2O), δC, ppm: 36.53, 59.85, 66.13, 67.45,
128.29, 128.78, 135.15, 144.49 (C5), 171.50, 171.81.
3
7.51 d (1H, Harom, J = 7.9 Hz), 9.39 s (1H, 5-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 28.52,
64.58, 109.93, 111.90, 118.49, 118.90, 121.46, 123.96,
127.26, 136.49, 144.16 (C5), 170.38. Mass spectrum
(ESI), m/z: 257.0923 [M + Na]+. C12H11N5O2. Calcu-
lated: M + Na 257.0912.
(2S)-5-(Benzyloxy)-5-oxo-2-(1H-tetrazol-1-yl)-
pentanoic acid (2b). Yield 3.92 g (64%), white crys-
tals, mp 195–198°C, [α]D23.5 = +40° (c = 1.0, H2O).
1H NMR spectrum (D2O), δ, ppm: 2.22–2.25 m (2H,
γ-H), 3.21–3.24 m (2H, β-H), 5.11–5.13 t (2H, PhCH2),
1
The H and 13C NMR spectra were recorded on
Varian DPX-300 (300 and 75.5 MHz, respectively) and
Bruker Avance-III-400 (400 and 100 MHz) spectrom-
eters at 25°C; the chemical shifts were measured
relative to the residual proton and carbon signals of the
deuterated solvent. The high-resolution mass spectra
were obtained on Bruker MicroTOF and Bruker
Daltonik MaXis instruments. The melting points were
3
5.53 d.d (1H, α-H, J = 11.4, 3.8 Hz), 7.17–7.34 m
(5H, Harom), 9.13 s (1H, 5-H). 13C NMR spectrum
(D2O), δC, ppm: 28.80, 31.15, 53.95, 66.13, 67.45,
126.14, 126.64, 132.45, 144.85 (C5), 170.41, 171.22.
3-Methyl-2-(1H-tetrazol-1-yl)pentanoic acid
1
(2c). Yield 3.42 g (83%), yellow oily liquid. H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 12 2016