One-pot synthesis of functionalized (4-oxo-1,3-thiazinan-5-yl)acetic acids from isothiocyanates, primary alkylamines, and ithaconic anhydride

Article abstract of DOI:10.1002/hlca.200900078

A one-pot synthesis of 2-(4-oxo-1,3-thiazinan-5-yl)acetic acids is described via a three-component reaction between primary alkylamines and ithaconic anhydride and phenyl isothiocyanate or benzoyl isothiocyanate.

Full text of DOI:10.1002/hlca.200900078

Helvetica Chimica Acta – Vol. 92 (2009)
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One-Pot Synthesis of Functionalized (4-Oxo-1,3-thiazinan-5-yl)acetic Acids
from Isothiocyanates, Primary Alkylamines, and Ithaconic Anhydride
by Issa Yavari*, Mohammad J. Bayat, Sanaz Souri, and Mehdi Sirouspour
Chemistry Department, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
(phone: þ 98-21-82883465; fax: þ 98-21-82883455; e-mail: yavarisa@modares.ac.ir)
A one-pot synthesis of 2-(4-oxo-1,3-thiazinan-5-yl)acetic acids is described via a three-component
reaction between primary alkylamines and ithaconic anhydride and phenyl isothiocyanate or benzoyl
isothiocyanate.
Introduction. – Polyfunctionalized heterocyclic compounds play important roles in
the drug discovery process. Analysis of drugs in late development or on the market
shows that 68% of them are heterocycles [1][2]. Therefore, it is not surprising that
research in the field of synthesis of heterocyclic compounds has received special
attention.
Multicomponent reactions (MCRs), because of their productivity, simple proce-
dures, convergence, and facile execution, are one of the best tools in combinatorial
chemistry [3]. Therefore, the design of novel MCRs has attracted great attention from
research groups working in various areas such as drug discovery, organic synthesis, and
material science. As a result, the number of new MCRs in recent years is growing
rapidly [4 – 7].
As part of our current studies on the development of new routes in heterocyclic
synthesis [8 – 12], we report a three-component synthesis to (4-oxo-1,3-thiazinan-5-
yl)acetic acids.
Results and Discussion. – The reaction of primary amines (1) with phenyl
isothiocyanate (2a) or benzoyl isothiocyanate (2b) in the presence of itaconic
anhydride (¼dihydro-3-methylidenefuran-2,5-dione, 3) proceeded smoothly in CH2Cl2
1
and was complete within 2 – 5 h. The H- and 13C-NMR spectra of the crude products
clearly indicated the formation of (4-oxo-1,3-thiazinan-5-yl)acetic acids (4a – 4l) in 56 –
85% yield (Scheme 1).
The structures of compounds 4a – 4l were deduced from their IR, 1H- and 13C-NMR
spectra. For example, the 1H-NMR spectrum of 4a in CDCl3 showed an AB system for
the CH2ꢀN group together with two AMX systems for CH2 H-atoms and a multiplet for
1
the CH H-atom. The H-decoupled 13C-NMR spectrum of 4a showed 15 distinct
resonances in agreement with the proposed structure. The IR spectrum of 4a displayed
1
characteristic C¼O (1724 and 1710 cmꢀ1) and C¼N (1689 cmꢀ1) bands. The H- and
13C-NMR spectra of 4b – 4l were similar to those for 4a, except for the substituents on
the N-atoms, which exhibited characteristic resonances in the appropriate regions of
the spectrum.
ꢀ 2009 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 92 (2009)
Scheme 1
Although the mechanistic details of the reaction are not known, a plausible
rationalization may be advanced to explain the product formation (Scheme 2).
Presumably, the initial event is the formation of thiourea 5 from the amine and
heterocumulene 2. Compound 5 subsequently attacks 3 to produce intermediate 6,
which undergoes cyclization to generate product 4.
Scheme 2
In summary, we report a three-component synthesis of new compounds from
primary alkylamines, ithaconic anhydride, and phenylisothiocyanate or benzoyliso-
thiocyanate. The present procedure has the advantage that the reactants can be mixed
without any prior activation or modification.
Experimental Part
General. Compounds 1, 2, and 3 were obtained from Merck and used without further purification.
M.p.: Electrothermal 9100 apparatus; uncorrected. IR Spectra: Shimadzu IR-460 spectrometer; in cmꢀ1
.
1H- and 13C-NMR Spectra: Bruker DRX-500 AVANCE instrument, in CDCl3 at 500.1 and 125.7 MHz,
resp.; d in ppm, J in Hz. MS: Finnigan-MAT-8430 mass spectrometer, at 70 eV; in m/z. Elemental
analyses (C, H, N): Heraeus CHN-O-Rapid analyzer.

Helvetica Chimica Acta – Vol. 92 (2009)
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General Procedure for the Preparation of Compounds 4. To the stirred soln. of 0.27 g of
phenylisothiocyanate (2a, 2 mmol) and 0.22 g of benzylamine (1a, 2 mmol) in 10 ml of CH2Cl2 was added
0.22 g of itaconic anhydride (3, 2 mmol) at r.t. After completion of the reaction (2 – 5 h), as indicated by
TLC (AcOEt/hexane, 2 :1), the solvent was removed under reduced pressure, and the residue was
purified by silica gel (SiO2; Merck 230 – 240 mesh) column chromatography (CC) using a 5 :1 hexane/
AcOEt mixture as eluent to afford the pure product.
2-[(2Z)-3-Benzyl-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4a). Yield: 0.58 g (82%).
Pale yellow oil. IR (KBr): 3385 (br.), 1724, 1710, 1689, 1610, 1588, 1428, 1379, 1272, 1161, 988, 899, 765,
730. 1H-NMR: 2.73 (dd, 3J ¼ 6.2, 2J ¼ 17.1, 1 H, CH); 2.85 (dd, 3J ¼ 3.6, 2J ¼ 12.5, 1 H, CH); 3.06 – 3.10 (m,
2
3
2 H, 2 CH); 3.38 – 3.43 (m, 1 H, CH); 5.46 (AB, DnAB ¼ 68.4, J ¼ 12.7, 2 H, CH2); 6.85 (d, J ¼ 7.8, 2 H,
CH); 7.17 (t, 3J ¼ 7.9, 1 H, CH); 7.33 (t, 3J ¼ 7.8, 1 H, CH); 7.38 – 3.40 (m, 4 H, CH); 7.47 (t, 3J ¼ 7.8, 2 H,
CH); 10.06 (br. s, 1 H, OH). 13C-NMR: 26.1 (CH2ꢀS); 34.6 (CH2); 40.8 (CH); 46.6 (CH2ꢀN); 120.3
(2 CH); 124.0 (CH); 127.0 (CH); 128.1 (2 CH); 128.2 (2 CH); 128.9 (2 CH); 137.3 (C); 147.6 (C); 150.1
(C¼N); 170.5 (CO); 176.4 (CO2). EI-MS: 154 (5), 77 (85), 59 (10), 45 (10). Anal. calc. for C19H18N2O3S
(354.42): C 64.39, H 5.12, N 7.90; found: C 64.17, H 5.06, N 8.02.
2-[(2Z)-3-(4-Methylbenzyl)-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4b). Yield:
0.62 g (85%). Yellow powder. M.p. 138 – 1398. IR (KBr): 3400 (br.), 1746, 1718, 1663, 1598, 1429,
1304, 1154, 996, 762. 1H-NMR: 2.36 (s, 3 H, CH); 2.70 (dd, 3J ¼ 6.5, 2J ¼ 17.5, 1 H, CH); 2.84 (dd, 3J ¼ 4.1,
2J ¼ 12.5, 1 H, CH); 3.04 – 3.07 (m, 2 H, CH); 3.35 – 3.38 (m, 1 H, CH); 5.35 (AB, DnAB ¼ 67.0, 2J ¼ 17.8,
2 H, CH2); 6.83 (d, 3J ¼ 8.0, 2 H, CH); 7.15 – 7.18 (m, 2 H, CH); 7.35 – 7.37 (m, 5 H, CH); 10.40 (br. s, 1 H,
OH). 13C-NMR: 20.6 (CH2ꢀS); 26.3 (Me); 34.9 (CH2); 41.1 (CH); 46.6 (CH2ꢀN); 120.6 (2 CH); 124.2
(CH); 128.6 (2 CH); 129.0 (2 CH); 129.2 (2 CH); 134.6 (C); 136.9 (C); 148.0 (C); 150.4 (C¼N); 170.7
(CO); 176.7 (CO2). EI-MS: 153 (5), 91 (50), 77 (85), 59 (5), 45 (10). Anal. calc. for C20H20N2O3S
(368.44): C 65.20, H 5.47, N 7.60; found: C 65.01, H 5.39, N 7.68.
2-[(2Z)-3-(4-Methoxybenzyl)-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4c). Yield:
0.64 g (84%). Yellow oil. IR (KBr): 3382 (br.), 1733, 1703, 1606, 1582, 1508, 1378, 1293, 1266, 1177,
1
3
2
3
2
1107, 1029, 979. H-NMR: 2.69 (dd, J ¼ 6.5, J ¼ 17.1, 1 H, CH); 2.83 (dd, J ¼ 4.0, J ¼ 13.0, 1 H, CH);
3.03 – 3.06 (m, 2 H, 2 CH); 3.34 ꢀ 3.37 (m, 1 H, CH); 3.80 (s, 3 H, CH); 5.35 (AB, DnAB ¼ 71.0, 2J ¼ 17.9,
2 H, CH2); 6.82 (d, 3J ¼ 7.5, 2 H, CH); 6.89 (d, 3J ¼ 8.9, 2 H, CH); 7.14 (t, 3J ¼ 8.7, 1 H, CH); 7.35 (t, 2 H,
CH); 7.40 (d, 3J ¼ 8.5, 2 H, CH); 10.01 (br. s, 1 H, OH). 13C-NMR: 26.3 (CH2ꢀS); 34.9 (CH2); 41.0 (CH);
46.3 (CH2ꢀN); 55.3 (MeO); 113.7 (2 CH); 120.6 (2 CH); 124.2 (CH); 129.1 (2 CH); 129.8 (C); 130.3
(2 CH); 147.9 (C); 150.4 (C); 158.8 (C¼N); 170.7 (CO); 176.6 (CO2). EI-MS: 153 (5), 106 (55), 77 (80),
59 (5), 45 (10). Anal. calc. for C20H20N2O4S (384.45): C 62.48, H 5.24, N 7.29; found: C 62.40, H 5.15, N
7.31.
2-[(2Z)-3-(2-Chlorobenzyl)-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4d). Yield:
0.56 g (72%). Yellow oil. IR (KBr): 3391 (br.), 1766, 1708, 1604, 1481, 1378, 1289, 1161, 1038, 993,
902, 764, 733. 1H-NMR: 2.71 (dd, 3J ¼ 6.9, 2J ¼ 17.2, 1 H, CH); 2.91 (dd, 3J ¼ 3.8, 2J ¼ 12.9, 1 H, CH); 3.03
3
2
3
2
(dd, J ¼ 5.8, J ¼ 17.3, 1 H, CH); 3.15 (dd, J ¼ 12.3, J ¼ 12.5, 1 H, CH); 3.40 – 3.43 (m, 1 H, CH); 5.30
2
3
3
(AB, DnAB ¼ 71.9, J ¼ 15.5, 2 H, CH2); 6.71 (d, J ¼ 7.5, 2 H, CH); 7.11 (t, J ¼ 7.5, 1 H, CH); 7.23 – 7.26
(m, 3 H, CH), 7.29 (t, 3J ¼ 6.5, 2 H, CH); 7.35 (t, 3J ¼ 7.8, 1 H, CH); 10.16 (br. s, 1 H, OH). 13C-NMR: 26.4
(CH2ꢀS); 34.6 (CH2); 41.3 (CH); 46.6 (CH2ꢀN); 120.5 (2 CH); 124.2 (CH); 126.6 (CH); 128.2 (CH);
128.5 (CH); 129.1 (2 CH); 129.5 (CH); 133.1 (C); 134.5 (C); 147.6 (C); 150.0 (C¼N), 170.6 (CO); 176.4
(CO2). EI-MS: 153 (10), 112 (60), 77 (70), 59 (5), 45 (10). Anal. calc. for C19H17ClN2O3S (388.86): C
58.69, H 4.41, N 7.20; found: C 58.62, H 4.35, N 7.10.
2-[(2Z)-3-(4-Chlorobenzyl)-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4e). Yield:
0.59 g (76%). Pale yellow oil. IR (KBr): 3389 (br.), 1765, 1708, 1601, 1487, 1431, 1377, 1274, 1159,
1
3
2
3
2
1102, 1012, 900, 798. H-NMR: 2.73 (dd, J ¼ 6.5, J ¼ 17.2, 1 H, CH); 2.84 (dd, J ¼ 4.0, J ¼ 12.9, 1 H,
3
2
3
2
CH); 2.99 (dd, J ¼ 5.8, J ¼ 17.3, 1 H, CH); 3.08 (dd, J ¼ 12.3, J ¼ 12.5, 1 H, CH); 3.35 – 3.57 (m, 1 H,
CH); 5.37 (AB, DnAB ¼ 74.5, 2J ¼ 14.2, 2 H, CH2); 6.79 (d, 3J ¼ 7.5, 2 H, CH); 7.14 (t, 3J ¼ 7.5, 1 H, CH);
7.30 (d, 3J ¼ 8.0, 2 H, CH); 7.34 (t, 3J ¼ 7.5, 2 H, CH); 7.40 (d, 3J ¼ 8.4, 2 H, CH); 10.35 (br. s, 1 H, OH).
13C-NMR: 26.3 (CH2ꢀS); 34.9 (CH2); 41.0 (CH); 46.2 (CH2ꢀN); 120.5 (2 CH); 124.4 (CH); 128.5
(2 CH); 129.2 (2 CH); 130.2 (2 CH); 133.1 (C); 136.1 (C); 147.7 (C); 150.2 (C¼N); 170.7 (CO); 176.8

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Helvetica Chimica Acta – Vol. 92 (2009)
(CO2). EI-MS: 153 (8), 112 (45), 77 (80), 59 (5), 45 (10). Anal. calc. for C19H17ClN2O3S (388.86): C
58.69, H 4.41, N 7.20; found: C 58.59, H 4.33, N 7.13.
2-[(2Z)-3-Butyl-4-oxo-2-(phenylimino)-1,3-thiazinan-5-yl]acetic Acid (4f). Yield: 0.54 g (84%).
White powder. M.p. 108 – 1108. IR (KBr): 3385 (br.), 1705, 1700, 1668, 1584, 1435, 1390, 1304, 1181, 1121,
1
3
953, 767. H-NMR: 0.95 (t, J ¼ 7.5, 3 H, Me); 1.37 – 1.40 (m, 2 H, CH2); 1.67 – 1.70 (m, 2 H, CH2); 2.66
3
2
3
2
3
2
(dd, J ¼ 6.7, J ¼ 17.1, 1 H, CH); 2.84 (dd, J ¼ 3.8, J ¼ 12.8, 1 H, CH); 2.99 (dd, J ¼ 6.0, J ¼ 16.9, 1 H,
CH); 3.10 (dd, 3J ¼ 12.5, 2J ¼ 12.8, 1 H, CH); 3.30 – 3.33 (m, 1 H, CH); 4.16 – 4.19 (m, 2 H, CH2); 6.85 (d,
3J ¼ 8.0, 2 H, CH); 7.12 (t, 3J ¼ 7.4, 1 H, CH); 7.34 (t, 3J ¼ 7.8, 2 H, CH); 10.70 (br. s, 1 H, OH). 13C-NMR:
13.8 (Me); 20.1 (CH2); 26.5 (CH2); 29.8 (CH2ꢀS); 35.0 (CH2); 41.0 (CH); 44.3 (CH2ꢀN); 120.6 (2 CH);
124.2 (CH); 129.1 (2 CH); 148.1 (C); 150.4 (C¼N); 170.6 (CO); 176.9 (CO2). EI-MS: 153 (8), 134 (45),
77 (80), 59 (10), 45 (5). Anal. calc. for C16H20N2O3S (320.40): C 59.98, H 6.29, N 8.74; found: C 59.88, H
6.20, N 8.63.
2-{(2Z)-3-(4-Methylbenzyl)-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid (4g).
Yield: 0.49 g (62%). Pale yellow powder. M.p. 129 – 1318. IR (KBr): 3395 (br.), 1732, 1712, 1696,
1636, 1584, 1433, 1409, 1302, 1266, 1215, 1181, 1058. 1H-NMR: 2.25 (s, 3 H, Me); 2.84 (dd, 3J ¼ 6.0, 2J ¼
17.1, 1 H, CH); 2.99 (dd, 3J ¼ 5.0, 2J ¼ 17.3, 1 H, CH); 3.15 (dd, 3J ¼ 3.5, 2J ¼ 12.5, 1 H, CH); 3.43 (dd, 3J ¼
2
2
13, J ¼ 13.3, 1 H, CH); 3.48 – 3.51 (m, 1 H, CH); 5.40 (AB, DnAB ¼ 82.4, J ¼ 14.5, 2 H, CH2); 7.12 (d,
3J ¼ 8.0, 2 H, CH); 7.25 (d, 3J ¼ 8.0, 2 H, CH); 7.39 (t, 3J ¼ 7.5, 2 H, CH); 7.54 (t, 3J ¼ 7.1, 1 H, CH); 7.84 (d,
3J ¼ 7.1, 2 H, CH), 10.06 (br. s, 1 H, OH). 13C-NMR: 26.8 (CH2ꢀS); 35.1 (CH2); 37.7 (Me); 41.7 (CH);
47.9 (CH2ꢀN); 128.2 (2 CH); 129.1 (2 CH); 129.8 (2 CH); 130.4 (2 CH); 133.6 (CH); 135.6 (C); 135.9
(C); 137.2 (C); 161.2 (C¼N); 172.0 (C¼O); 172.5 (CO2); 176.3 (C¼O). EI-MS: 153 (10), 150 (45), 136
(85), 77 (80), 59 (10), 45 (5). Anal. calc. for C21H20N2O4S (396.46): C 63.62, H 5.08, N 7.07; found: C
63.50, H 5.11, N 7.14.
2-{(2Z)-3-(4-Methoxybenzyl)-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid (4h).
Yield: 0.57 g (70%). Pale yellow powder. M.p. 116 – 1198. IR (KBr): 3390 (br.), 1740, 1702, 1695, 1611,
1
3
2
1509, 1434, 1309, 1269, 1248, 1159, 902, 812. H-NMR: 2.80 (dd, J ¼ 6.4, J ¼ 17.2, 1 H, CH); 2.90 (dd,
3J ¼ 3.5, 2J ¼ 12.8, 1 H, CH); 2.99 (dd, 3J ¼ 4.9, 2J ¼ 17.3, 1 H, CH); 3.22 (dd, 3J ¼ 12.7, 2J ¼ 12.9, 1 H, CH);
3.40 – 3.43 (m, 1 H, CH), 3.77 (s, 3 H, MeO); 5.40 (AB, DnAB ¼ 46.9, 2J ¼ 14.1, 2 H, CH2); 6.83 (d, 3J ¼ 8.0,
2 H, CH); 7.33 (d, 3J ¼ 8.0, 2 H, CH); 7.39 (t, 3J ¼ 7.4, 2 H, CH); 7.53 (t, 3J ¼ 7.1, 1 H, CH); 7.95 (t, 3J ¼ 7.6,
2 H, CH); 10.49 (br. s, 1 H, OH). 13C-NMR: 26.5 (CH2ꢀS); 34.7 (CH2); 40.6 (CH); 47.4 (CH2ꢀN); 55.3
(MeO); 113.9 (2 CH); 128.4 (2 CH); 129.1 (C); 129.6 (2 CH); 129.9 (2 CH); 133.1 (CH); 134.5 (C); 159.0
(C¼N); 160.3 (CꢀO); 171.2 (CO); 176.0 (CO2); 176.4 (CO). EI-MS: 153 (5), 136 (80), 105 (50), 77 (85),
59 (5), 45 (10). Anal. calc. for C21H20N2O6S (412.46): C 61.15, H 4.89, N 6.79; found: C 61.02, H 4.85, N
6.85.
2-{(2Z)-3-(2-Chlorobenzyl)-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid (4i).
Yield: 0.47 g (56%). Pale yellow powder. M.p. 125 – 1278. IR (KBr): 3432 (br.), 1722, 1708, 1694,
1631, 1470, 1434, 1405, 1303, 1269, 1216, 1167, 1083. 1H-NMR: 2.87 (dd, 3J ¼ 6.0, 2J ¼ 17.3, 1 H, CH); 3.02
(dd, 3J ¼ 4.9, 2J ¼ 17.3, 1 H, CH); 3.22 (dd, 3J ¼ 3.5, 2J ¼ 12.5, 1 H, CH); 3.55 (dd, 3J ¼ 15.1, 2J ¼ 15.2, 1 H,
CH); 3.63 – 3.65 (m, 1 H, CH); 5.50 (s, 2 H, CH2); 7.23 – 7.28 (m, 3 H, CH); 7.3 (t, 3J ¼ 7.4, 2 H, CH); 7.40
(t, 3J ¼ 7.2, 1 H, CH); 7.51 (d, 3J ¼ 7.1, 1 H, CH); 7.78 (d, 3J ¼ 7.6, 2 H, CH); 10.35 (br. s, 1 H, OH).
13C-NMR: 26.9 (CH2ꢀS); 35.0 (CH2); 41.7 (CH); 46.4 (CH2ꢀN); 127.9 (CH); 128.0 (CH); 129.1 (CH);
129.3 (2 CH); 130.1 (CH); 130.5 (2 CH); 133.7 (CH); 135.5 (C); 135.8 (C); 161.9 (C); 168 (C¼N); 172.5
(CO); 172.8 (CO2); 176.2 (CO). EI-MS: 171 (55), 153 (8), 136 (80), 77 (90), 59 (3), 45 (5). Anal. calc.
for C20H17ClN2O4S (416.88): C 57.62, H 4.11, N 6.72; found: C 57.51, H 4.01, N 6.82.
2-{(2Z)-3-(4-Chlorobenzyl)-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid (4j).
Yield: 0.60 g (72%). Yellow powder. M.p. 136 – 1388. IR (KBr): 3389 (br.), 1728, 1700, 1693, 1634,
1489, 1459, 1401, 1302, 1271, 1215, 1141, 1083. 1H-NMR: 2.83 (dd, 3J ¼ 6.7, 2J ¼ 17.4, 1 H, CH); 2.94 (dd,
3J ¼ 4.0, 2J ¼ 13.0, 1 H, CH); 2.99 (dd, 3J ¼ 5.1, 2J ¼ 17.3, 1 H, CH); 3.27 (dd, 3J ¼ 12.7, 2J ¼ 12.9, 1 H, CH);
3.40 – 3.42 (m, 1 H, CH); 5.41 (AB, DnAB ¼ 52.3, 2J ¼ 14.5, 2 H, CH2); 7.26 ( d, 3J ¼ 7.8, 2 H, CH); 7.36 (d,
3
3
3
3J ¼ 7.8, 2 H, CH); 7.41 (t, J ¼ 7.5, 2 H, CH); 7.50 (t, J ¼ 7.1, 1 H, CH); 7.88 (t, J ¼ 7.6, 2 H, CH); 10.51
(br. s, 1 H, OH). 13C-NMR: 29.6 (CH2ꢀS); 34.5 (CH2); 40.7 (CH); 47.3 (CH2ꢀN); 127.3 (CH); 128.4
(2 CH); 128.7 (2 CH); 129.4 (2 CH); 129.8 (2 CH); 133.1 (C); 134.4 (C); 135.5 (C); 160.5 (C¼N); 171.2

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(CO); 174.2 (CO2); 176.3 (CO). EI-MS: 171 (50), 153 (10), 136 (75), 77 (80), 59 (5), 45 (5). Anal. calc.
for C20H17ClN2O4S (416.88): C 57.62, H 4.11, N 6.72; found: C 57.51, H 4.02, N 6.81.
2-{(2Z)-3-(Naphthalen-1-ylmethyl)-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid
(4k). Yield: 0.69 g (80%). Brown powder. M.p. 130 – 1328. IR (KBr): 3371 (br.), 1725, 1700, 1690, 1634,
1490, 1432, 1411, 1303, 1269, 1215, 1165, 1084. 1H-NMR: 2.89 (dd, 3J ¼ 6.0, 2J ¼ 17.5, 1 H, CH); 3.04 (dd,
3J ¼ 5.2, 2J ¼ 17.5, 1 H, CH); 3.25 (dd, 3J ¼ 3.5, 2J ¼ 12.5, 1 H, CH); 3.58 (dd, 3J ¼ 10.7, 2J ¼ 11.1, 1 H, CH);
3.60 – 3.62 (m, 1 H, CH); 5.94 (AB, DnAB ¼ 82.3, 2J ¼ 17.8, 2 H, CH2); 7.17 (t, 3J ¼ 7.5, 2 H, CH); 7.33 (d,
3J ¼ 7.0, 1 H, CH); 7.40 – 7.43 (m, 3 H, CH); 7.58 – 7.61 (m, 2 H, CH); 7.82 (d, 3J ¼ 7.9, 1 H, CH); 7.95 (d,
3
3J ¼ 7.5, 2 H, CH); 8.22 (d, J ¼ 8.0, 1 H, CH); 10.49 (br. s, 1 H, OH). 13C-NMR: 26.8 (CH2ꢀS); 35.0
(CH2); 41.8 (CH); 45.9 (CH2ꢀN); 123.3 (CH); 123.7 (CH); 126.2 (CH); 126.5 (CH); 127.1 (CH); 128.0
(CH); 128.9 (2 CH); 129.6 (CH); 130.2 (2 CH); 132.4 (C); 133.4 (C); 133.5 (CH); 134.7 (C); 135.9 (C);
161.5 (C¼N); 167.7 (CO); 172.7 (CO2); 176.2 (CO). EI-MS: 153 (5), 136 (80), 77 (85), 59 (5), 45 (10).
Anal. calc. for C24H20N2O4S (432.49): C 66.65, H 4.66, N 6.48; found: C 66.52, H 4.51, N 6.52.
2-{(2Z)-3-Butyl-4-oxo-2-[(phenylcarbonyl)imino]-1,3-thiazinan-5-yl}acetic Acid (4l). Yield: 0.54 g
(78%). White powder. M.p. 120 – 1228. IR (KBr): 3375 (br.), 1725, 1705, 1668, 1584, 1435, 1390, 1340,
1
3
1181, 1121, 953, 767, 689. H-NMR: 0.95 (t, J ¼ 7.5, 3 H, Me); 1.40 – 1.42 (m, 2 H, CH2); 1.69 – 1.71 (m,
2 H, CH2); 2.76 (dd, 3J ¼ 6.1, 2J ¼ 17.2, 1 H, CH); 2.96 (dd, 3J ¼ 5.3, 2J ¼ 17.2, 1 H, CH); 3.08 (dd, 3J ¼ 3.5,
2J ¼ 12.4, 1 H, CH); 3.33 (dd, 3J ¼ 12.9, 2J ¼ 13.1, 1 H, CH); 3.34 – 3.37 (m, 1 H, CH); 4.20 – 4.22 (m, 2 H,
CH2); 7.51 (t, 3J ¼ 8.0, 2 H, CH); 7.60 (t, 3J ¼ 7.9, 1 H, CH); 8.12 – 8.14 (d, 3J ¼ 7.9, 2 H, CH); 10.72 (br. s,
1 H, OH). 13C-NMR: 20.8 (Me); 26.9 (CH2); 29.3 (CH2); 35.0 (CH2ꢀS); 37.6 (CH2); 41.5 (CH); 45.6
(CH2ꢀN); 128.2 (CH); 129.3 (2 CH); 130.3 (2 CH); 135.9 (C); 162.8 (C¼N); 172.0 (CO); 172.6 (CO2);
176.3 (CO). EI-MS: 193 (55), 156 (8), 136 (75), 77 (80), 59 (10), 45 (10). Anal. calc. for C17H20N2O4S
(348.41): C 58.60, H 5.79, N 8.04; found: C 58.54, H 5.71, N 8.11.
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Received March 8, 2009