Synthesis of 3-amino(alkoxy)-2,4-dioxo-1,3-oxazolidine-5-carboxylates from tartronic esters

Article abstract of DOI:10.1515/znb-1999-0516

The reaction of tartronic esters (1a-d) with 1,1′-carbonyl-di-(1,2,4-triazole), hydrazines or hydroxylamines produces 3-amino/3-alkoxy(aralkoxy)-2,4-dioxo-1,3-oxazolidine-5-carboxylic esters (5,6) which are structurally related to the fungicides Famoxadone (I) and Chlozolinate (II). Under suitable conditions the carboxylic ester of 6 can be converted to a carboxamide (7), carbohydrazide (8) or carbohydroxamic acid (9).

Full text of DOI:10.1515/znb-1999-0516

Synthesis of 3-Amino(alkoxy)-2,4-dioxo-l,3-oxazolidine-5-carboxylates from
Tartronic Esters
Thomas Kurz, Detlef Geffken*
Institut für Pharmazie, Abteilung für Pharmazeutische Chemie, Universität Hamburg,
Bundesstrasse 45, D-20146 Hamburg, Germany
Z. Naturforsch. 54b, 667-673 (1999); eingegangen am 30. Dezember 1998
Tartronic Esters, l,l'-Carbonyl-di-(l,2,4-triazole), 3-Amino-2,4-dioxo-l,3-oxazolidine-5-
carboxylates, 3-Alkoxy-2,4-dioxo-l,3-oxazolidine-5-carboxylates
The reaction of tartronic esters (la-d) with l,l'-carbonyl-di-(l,2,4-triazole), hydrazines or
hydroxylamines produces 3-amino/3-alkoxy(aralkoxy)-2,4-dioxo-l,3-oxazolidine-5-carboxylic
esters (5,6) which are structurally related to the fungicides Famoxadone (I) and Chlozolinate
(II). Under suitable conditions the carboxylic ester of 6 can be converted to a carboxamide
(7), carbohydrazide (8) or carbohydroxamic acid (9).
Introduction
Chemistry
3-Amino-oxazolidin-2,4-diones, which were de-
scribed by Geffken [1] in 1981 have attracted con-
siderable interest in agricultural chemistry due to
their potent activity against phytopathogenic
fungi. Recently, Famoxadone (Famoxate®) (I) [2],
a member of this class of compounds was intro-
duced to the market as a broad spectrum fungicide
for control of infectious diseases of cereals, grapes
and legumes.
In continuation of our studies directed to struc-
tural analogues of I we now became interested in
synthesizing 3-heterosubstituted 2,4-dioxooxazoli-
dine-5-carboxylic esters (5,6), which can be under-
stood as a formal compromise between I and the
small spectrum fungicide Chlozolinate (II) [3].
According to previous studies on atrolactic acid
esters [4] we envisioned the tartronic esters la-d
[5,6] as suitable starting materials, which upon suc-
cessive treatment with either l,l'-carbonyldiimi-
dazole or l,l'-carbonyl-di-(l,2,4-triazole), hydrox-
ylamines or hydrazines should give the desired
heterocycles 5,6 via the open-chain intermediates
3,4
After several nonsatisfactory attempts to get ac-
cess to 5,6 by means of l,l'-carbonyldiimidazole,
we found that l,l'-carbonyl-di-(l,2,4-triazole) [7]
reacted smoothly with la,c in anhydrous methy-
lene chloride at ambient temperature to give the
intermediate triazolides 2 [i.r.: 1755-1765 cm-1,
(C=0)] which in turn underwent the expected hy-
drazinolysis or hydroxylaminolysis to 3 and 4. Fi-
nally, subsequent treatment of 3,4 with triethyl-
amine furnished the heterocycles 5,6 in overall
yields of 30-63% .
It should be noted, that in contrast to the
smooth reaction of la,c with CDT to give the in-
termediates 2 , the corresponding reaction of lb,d
required the presence of a base (e.g. triethyl-
amine), reflecting the lower reactivity of the terti-
ary alcoholic group. In all cases the cyclization step
could be clearly monitored by running i.r. spectra
from the reaction mixture, demonstrating the
gradual emergence of a (C=0)-band at 1820-1840
cm- 1 besides a strong (C=0)-absorption at 1750-
1780 cm-1, typical for 2,4-dioxooxazolidines [8 ].
Famoxadone (I)
Chlozolinate (II)
Scheme 1.
* Reprint requests to Prof. Dr. Detlef Geffken.
Fax: 040/428386573
e-mail: geffken@chemie.uni-hamburg.de
0932-0776/99/0500-0667 $06.00 © 1999 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
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668
Th. Kurz-D. Geffken • Tartronic Esters
H, R ! = Me
Me, R 2= Et
5a was converted by hydrogenolysis to the cyclic
N-hydroxy imide (5h), which is characterized by a
red colored reaction with ferric chloride.
R' = H, R* =
R1= Me, R ! =
"°y W
c
0
A
N-OCHjPh
H
/ p d. C
o - V c
THF
0
CH
Ö
CH
5a
5h
Scheme 3.
As exemplified by the reactions of 6 h with ben-
zylamine, N,N'-dimethylhydrazine or hydroxyl-
amine, the exocyclic ester group is attacked selec-
tively providing 2,4-dioxooxazolidine derivatives
with a carboxamide (7), carbohydrazide (8 ) or car-
bohydroxamic acid (9) group at C-5.
V h_c
<°
In contrast to 7, 8 , and 9 which are stable com-
pounds, the 5-carboxylated 2,4-dioxooxazolidine
derivative 10 could not be isolated: The alkaline
hydrolysis of 6 h (i) with potassium hydroxide in
ethanol followed by acidification as well as the hy-
drogenolysis of the benzylic ester 6 i (ii) only pro-
duced the 2,4-oxazolidindione 11, that obviously
arose from the spontaneous decarboxylation of 10.
A.
A.
' R
Mr’ o
5»-g
Reagents: CDT: l,l'-carbonyl-di-(l,2,4-triazole), Et3N: triethylamine
Alkyl(aralkyl) 3-amino-2,4-dioxo-l,3-oxazolidine-5-car-
boxylates (6)
Experimental
Melting points (uncorrected) were determined
on a Mettler FP 62. Elemental analysis were per-
formed on a Fleraeus CHN-O-Rapid. The IR
spectra were recorded on a Perkin Elmer 1600
FTIR spectrophotometer. The 1 H-NMR (400
MHz) and 1 3 C-NMR (100,62 MHz) spectra were
recorded on a Bruker AMX 400 spectrometer
using tetramethylsilane as an internal standard
and DMSO-d6 and CDC13 as solvents.
R1
6
R2
R3
H
R4
Ph
a
b
c
d
e
f
S
h
i
H
H
H
H
H
H
H
c h 3
CH,
CH,
c h 3
CH,
CH2Ph
CH->Ph
CH2Ph
CH^Ph
C2H5
CH2Ph
*(CH2)5-
-(CH2)5-
CH,
H
CH,
Ph
CH,
H
Ph
Ph
CH,
H
H
Dimethyl tartronate (la) and diethyl methyl-
tartronate (lb) were prepared according to litera-
ture [5,6].
H
Alkyl(aralkyl) 3-alkoxy-2,4-
boxylates (5)
•1,3-oxazolidine-5-car-
-dioxo-
The tartronates lc,d were prepared as follows
5
R1
R2
R5
To a stirred solution of tartronic or methyl-
tartronic acid (10 mmol) and N-ethyl-diisopropyl-
amine ( 2 2 mmol) in dimethyl acetamide ( 1 0 ml)
benzyl bromide ( 2 2 mmol) was added dropwise at
ambient temperature. After 24h the reaction mix-
ture was diluted with 1 0 0 ml water and the precipi-
tate dissolved in CH2C12, dried over Mg S 0 4, and
the solvent evaporated. The residue was purified
by column chromatography on silica gel with
CH2C12 as eluent.
a
b
c
d
e
f
H
H
H
H
CH,
CH,
CH,
CH,
CH, Ph
CH, Ph
CH, OCH,
CH,
CH, Ph
CH, -2,4-Cl-Ph
CH, -2,4-Cl-Ph
CH->Ph
CH.Ph
CH-.Ph
c2H5
C2H5
CH.Ph
g
Scheme 2.
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Th. Kurz-D. Geffken • Tartronic Esters
669
o
Pfv
°\ / JfPh
/
HN-
r
H
i t Or H
CH,
°
O
CH,
0
Ä
^
■ ° > t ^
O
C H,
6h
_JLN—N^.Ph
0
Ö
CH3
9
Reagents: i: benzylamine, ii: N,N'-dimethylhydrazine, iii: H2NOH • HCl/NaOEt
Scheme 4.
^Ph
N—N
-A .
m
^Ph
O
O
N—N
-co,
Har H H
o
c h 3 °
CH,
10
6hR2= Et
6i R2= Bz
Reagents, i: EtOH/KOH, HCl, ii: H2/Pd-C
Scheme 5.
Dibenzyl tartronate (lc): Colourless crystals
(80%); m.p. 73 °C (Et2 0/hexane); IR (KBr): v =
3423 (OH), 1739, 1733 (C=0) cm -1; 'H-NM R
(DMSO-d6): (5 (ppm) 4.88 (d, J = 7.6 Hz, 1H, CH),
6.63 (d, J = 7.6 Hz, 1H, OH), 5.15 (d, J = 12.6 Hz,
1H, O C //2Ph), 5.19 (d, J = 12.6 Hz, 1H, O C //2Ph),
7.30-7.38 (m, 10H, ArH); 1 3 C-NMR (DMSO-
d6):<5 (ppm) 66.4 (O C //2Ph), 71.4 (CH), 127.8,
128.1, 128.3 (C tert., ArC), 135.4 (C quart., ArC),
168.2 (C=0).
Analysis for C18H 180 5
Calcd C 68.78 H 5.77%,
Found C 68.51 H5.77%.
Alkyl(aralkyl) 3-alkoxy(aralkoxy)-2,4-dioxo-l,3-
oxazolidine-5-carboxylates (5a-5 g) and alkyl(aral-
kyl) 3-amino-2,4-dioxo-l,3-oxazolidine-5-carboxyl-
ates (6 a-i). General procedure.
l,l'-Carbonyl-di-(l,2,4-triazole) (10 mmol) was
added portionwise to a stirred solution of la-d
(5 mmol) in anhydrous CH2 C12 (10 ml). In the case
of lb,d one drop of triethylamine was added to the
reaction mixture. After lh the precipitated 1,2,4-
triazole was filtered off and the appropriate
Analysis for C17 H 16 0 5
Calcd C 67.99 H5.37%,
Found C 67.59 H5.38%.
Dibenzyl methyltartronate (Id): Colourless oil
(65%); IR (KBr): v = 3488 (OH), 1740 (C=0) cm -1; alkoxyamine or hydrazine (5 mmol) added to the
'H-NMR (DMSO-d6): (3 (ppm) 1,50 (s, 3H, CH3), filtrate. Stirring of the reaction mixture was con-
5.15 (s, 2H, O C //2Ph) 6.59 (s, 1H, OH), 7.28-7.37 tinued and in the case of la,c one drop of triethyl-
(m, 10H, ArH); 1 3 C-NMR (DMSO-d6): d (ppm)
amine was added after 2 h. After 40 h the reaction
22.8 (CH3), 66.4 (OCH9), 75.9 (C quart.), 127.7, mixture was washed with brine (5 ml), the organic
layer dried over M gS04 and concentrated. The
oily residues were chromatographed on silica gel
128.0, 128.3 (C tert., ArC), 135.5 (C quart., ArC),
170.4 (C=0).
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670
Th. Kurz-D. Geffken • Tartronic Esters
with CH2 C12 (5a-g) or CH2C12/Et20 (9:1) (6 a-i)
as eluents.
(s, 1H, CH), 7.34-7.43 (m, 5H, ArH); 1 3 C-NMR
(DMSO-d6):
d
(ppm) 64.9 (OCH3), 67.5
(OC7/2Ph), 74.9 (CH), 128.0 128.3, 128.4, (C tert.,
Methyl 3-benzyloxy-2,4-dioxo-l ,3-oxazolidine-5-
carboxylate (5a): Colourless crystals (41%); m.p. ArC), 134.8 (C quart., ArC), 150.2 (C-2, C=0),
54 °C (Et2 0/hexane); IR (KBr): v = 1837, 1777,
1761 (C =0) cm "1; 'H-NMR (CDC13): (3 (ppm)
3.86 (s, 3H, OCH,), 5.15 (s, 1H, CH), 5.17 (s, 2H,
NOCH?), 7.38-7.48 (m, 5H, ArH); 1 3 C-NMR
160.5, 161.6 (C=0).
Analysis for C1 2 H n N 0 6
Calcd
C 54.34 H 4.18 N5.28%,
Found C 53.88 H4.17 N5.22%.
(CDC13):
6
(ppm) 54.1 (OCH3), 74.6 (CH), 79.8
(NOCH,), 128.8, 130.0, 130.3 (C tert., ArC), 132.1
(C quart., ArC), 149.8 (C-2, C=0), 160.2, 161.9
(C=0).
Ethyl 3-benzyloxy-5-methyl-2,4-dioxo-l,3-oxa-
Zolidine-5-carboxylate (5e): Colourless crystals
(45%); m.p. 60 °C (Et2 0/hexane); IR (KBr): v =
1839, 1776, 1740 (C =0) cm "1; 'H-NMR (CDC13):
(3 (ppm) 1.27 (t, J = 7.1 Hz, 3H, CH2CH3), 1.68 (s,
3H, CH3), 4.25 (q, 4H, J = 7.1 Hz, C //2 CH3 ), 5.19
(s, 2H, NOCH2), 7.38-7.49 (m, 5H, ArH); 1 3 C-
NMR (CDC13): (3 (ppm) 13.9 (CH3), 18.9 (C-5,
CH3 ), 63.7 (OCH2), 79.5 (NOCH2), 82.3 (C-5),
128.7, 129.9, 130.3 (C tert., ArC), 132.3 (C quart.,
ArC), 149.9 (C-2, C =0), 163.8, 164.3 (0=0).
Analysis for Ci2H n N 0 6
Calcd
C 54.34 H 4.18 N5.28%,
Found C 54.84 H 4.36 N5.35%.
Benzyl 3-benzyloxy-2,4-dioxo-l,3-oxazolidine-5-
carboxylate (5b): Colourless crystals (45%); m.p.
73 °C (Et2 0/hexane); IR (KBr): v = 1835, 1772,
1750 (C=Ö) cm -1; 'H-NMR (CDC13): ö (ppm)
5.14 (s, 2H, NOCH2), 5.16 (s, 1H, CH), 5.26 (s, 2H,
O C //2Ph), 7.33-7.44 (m, 10H, ArH); 1 3 C-NMR
(CDC13): (3 (ppm) 69.1 (O C //2Ph), 74.6 (CH), 79.8
(NOCH2), 128.5, 128.7, 128.8, 129.0, 129.9, 130.3
(C tert., ArC), 132.1, 133.9 (C quart., ArC), 149.8
(C-2, C =0), 160.1, 161.4 (C=0).
Analysis for C14 H 15N 0 6
Calcd
C 57.34 H 5.16 N4.78%,
Found C 57.22 H 5.16 N4.84%.
Ethyl 3-(2,4-dichlorobenzyloxy)-5-methyl-2,4-di-
oxo-1,3-oxazolidine-5-carboxylate (5f): Colourless
crystals (48%); m.p. 83 °C (Et2 0/hexane); IR
(KBr): v = 1841,1764,1744 (C=0) c m '1; 'H-NMR
Analysis for C18 H 1 5 N 0 6
Calcd
C 63.34 H 4.43 N4.10%,
Found C 63.35 H 4.42 N4.17%.
(CDC13): (3 (ppm) 1.21 (t, J
= 7.1 Hz, 3H,
CH2 CH3), 1.75 (s, 3H, CH3), 4.28 (q, 2H, J = 7.1
Hz CH2CH 3 ), 5.28 (s, 2H, NOCH2), 7.29-7.50 (m,
3H, ArH); 1 3 C-NMR (CDC13): (3 (ppm) 13.9
(CH3), 18.9 (C-5, CH3), 63.9 (OCH2), 75.5
(NOCH2), 82.5 (C-5), 127.5, 129.7, 133.1(C tert.,
ArC), 129.3, 136.0, 136.6 (C quart., ArC), 149.7
(C-2, C =0), 163.7, 164.2 (C=0).
Benzyl 3-methoxymethoxy-2,4-dioxo-l,3-oxazol-
idine-5-carboxylate (5c): Colourless crystals (37%);
m.p. 76 °C (Et20/hexane); IR (KBr): v = 1836,
1780, 1750 (C =0) cm -1; 'H-NMR (DMSO-d6): (3
(ppm) 3.52 (s, 3H, OCH3), 5.06 (s, 2H, 0C H 2 0 ),
5.27 (d, J = 12.2 Hz, 1H, O C //2Ph), 5.31 (d, J =
12.2 Hz, 1H, O C //2Ph), 5.93 (s, 1H, CH), 7.34-
7.41 (m, 5H, ArH); 1 3 C-NMR (DMSO-d6): (3
(ppm) 57.1 (OCH3), 67.6 (O C //2Ph), 74.9 (CH),
101.0 (0C H 2 0 ), 127.9, 128.3, 128.4, (C tert., ArC),
134.8 (C quart., ArC), 150.6 (C-2, C=0), 161.0,
161.6 (C=0).
Analysis for C14 H 13 C12N 0 6
Calcd
C 46.43 H 3.62 N 3.87 CI 19.58%,
Found C 46.24 H 3.65 N 3.97 CI 19.63%.
Benzyl 3-(2,4-dichlorobenzyloxy)-5-methyl-2,4-
dioxo-l,3-oxazolidine-5-carboxylate (5 g): Col-
ourless crystals (52%); m.p. 99 °C (Et2 0/hexane);
IR (KBr): v = 1836, 1772, 1745 (C =0) cm -1; 'H-
NMR (DMSO-d6): d (ppm) 1.78 (s, 3H, CH3), 5.19
(s, 2H, NOCH2), 5.21 (d, J = 12.2 Hz, 1H,
OC/Z^Ph), 5.26 (d, J = 12.2 Hz. 1H, O C //2Ph),
Analysis for C1 3 H 1 3 N 0 7
Calcd
C 52.89 H 4.44 N4.74%,
Found C 52.81 H 4.47 N4.74%.
Benzyl 3-methoxy-2,4-dioxo-l ,3-oxazolidine-5-
carboxylate (5d): Colourless crystals (30%); m.p.
77 °C (Et20/hexane); IR (KBr): v = 1836, 1775, 7.20-7.40 (m. 8 H, ArH); 1 3 C-NMR (DMSO-d6):
<3 (ppm) 18.9 (C-5, CH3 ), 69.2 (O C //2 Ph), 75.6
1755 (C=0) cm "1; 'H-NMR (DMSO-d6): d (ppm)
(NOCH2), 82.5 (C-5), 127.5, 128.2, 128.9, 129.0
3.90 (s, 3H, OCH3), 5.25 (d, J = 12.3 Hz, 1H,
O C//,Ph), 5.29 (d. J = 12.3 Hz, 1H, O C //2Ph), 5.86 129.7, 133.0 (C tert., ArC), 134.0, 136.0, 136.6 (C
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Th. Kurz-D. Geffken • Tartronic Esters
671
quart., ArC), 149.5 (C-2, C=0), 163.6, 164.0
(C=0).
(s, 1H, CH), 6.72-7.20 (m, 5H, ArH), 7.36-7.44
(m, 5H, ArH), 8.74 (s, 1H, NH); 13 C-NMR
(DMSO-d6): (3 (ppm) 1 3 C-NMR (DMSO-d6): (3
(ppm) 67.9 (O C //2Ph), 75.9 (CH), 112.3, 120.5,
128.1, 128.4, 128.5, 129.0 (C tert., ArC), 134.7,
145.1 (C quart., ArC), 153.1 (C-2, C=0), 162.3,
164.7 (C=0).
Analysis for C19H 15 C12N 0 6
Calcd
C 53.79 H 3.56 N 3.30 CI 16.71%,
Found C 53.71 H 3.55 N 3.42 CI 16.70%.
Methyl
2,4-dioxo-3-phenylamino-l,3-oxazoli-
Analysis for C17 H 14N20 5
dine-5-carboxylate (6 a): Colourless crystals (60%);
m.p. 138 °C (Et20/hexane); IR (KBr): v = 3316
(NH), 1836, 1766, 1751 (C=0) cm "1; 'H-NMR
(DMSO-d6): <3 (ppm) 3.84 (s, 3H, OCH3), 6.01 (s,
1H, CH), 6.77-7.22 (m, 5H, ArH), 8.73 (s, 1H,
NH); 1 3 C-NMR (DMSO-d6): (3 (ppm) 53.5
(OCH3), 75.8 (CH), 112.3, 120.5, 129.0 (C tert.,
ArC), 145.1 (C quart., ArC), 153.1 (C-2, C=0),
162.9, 164.8 (C=0).
Calcd
C 62.58 H 4.32 N8.59%,
Found C 62.43 H 4.34 N8.56%.
Benzyl 2,4-dioxo-3-(piperidinoamino)-l,3-oxa-
Zolidine-5-carboxylate (6 e): Colourless crystals
(57%); m.p. 91 °C (Et2 0/hexane); IR (KBr): v =
1825, 1761, 1734 (C=0) cm“1; 'H-NMR (CDC13):
<3 (ppm) 1.46 (dt, J = 6 .1/5.6 Hz, 2H, CH2), 1.73
(dt, J = 6 .1/5.6 Hz, 4H, 2 CH2), 3.19 (t, J = 5.6 Hz,
4H, CH2NCH7), 5.18 (s, 1H, CH), 5.26 (d, J = 12.2
Hz, 1H, O C //2Ph), 5.33 (d, J = 12.2 Hz, 1H,
O C //2Ph), 7.37 (s, 5H, ArH); 1 3 C-NMR (CDC13):
6 (ppm) 22.8, 25.8 (3 CH2), 52.6 (CH2NCH2), 68.9
(O C //2 Ph), 75.1 (CH), 128.4, 128.8, 129.0 (C tert.,
ArC), 134.0 (C quart.,ArC), 152.1 (C-2, C=0),
162.1, 164.1 (C=0).
Analysis for Cn H 10N2 O5
Calcd C 52.80 H 4.03 N 11.20%,
Found C 52.84 H 4.06 N 11.24%.
Methyl 2,4-dioxo-3-(piperidinoamino)-l,3-oxa-
Zolidine-5-carboxylate (6 b): Colourless crystals
(54%); m.p. 93 °C (Et2 0/hexane); IR (KBr): v =
1825, 1776, 1755 (C=0) c m '1; 'H-NMR (CDC13):
<3 (ppm) 1.47 (dt, J = 6.1/5.6 Hz, 2H, CH2), 1.74
(dt, J = 6 .1/5.6 Hz, 4H, 2 CH2), 3.23 (t, J = 5.6 Hz,
4H, CH2NCH2), 3.90 (s, 3H, OCH3) 5.18 (s, 1H,
CH); 1 3 C-NMR (CDC13): (3 (ppm) 22.8, 25.8 (3
CH2), 52.6 (CH2NCH2), 54.0 (OCH3), 75.0 (CH),
152.1 (C-2, C=0), 162.7, 164.2 (C=0).
Analysis for C16H 18N20 5
Calcd
C 60.37 H 5.70 N 8.80%,
Found C 60.10 H 5.68 N 8.77%.
Benzyl 3-dimethylamino-2,4-dioxo-l,3-oxazoli-
dine-5-carboxylate (6 f): Colourless crystals (48%);
m.p. 93 °C (Et20/hexane); IR (KBr): v = 1825,
1782, 1753 (C=0) c m '1; 'H-NMR (DMSO-d6): (3
(ppm) 2.77 (s, 6 H, (CH3 )2N), 5.28 (s, 2H,
O C //2Ph), 5.72 (s, 1H, CH), 7.34-7.41 (m, 5H,
Analysis for Ci0H 14N2 O5
Calcd C 49.59“ H 5.83 N 11.57%,
Found C 49.16 H 5.78 N 11.50%.
ArH); 13 C-NMR (DMSO-d6):
ö
(ppm) 43.1
(N(CH3)2), 67.5 (O C //2Ph), 75.1 (CH), 127.9,
128.3, 128.4 (C tert., ArC), 134.9 (C quart., ArC),
152.2 (C-2, C=0), 162.2, 164.1 (C=0).
Methyl 3-dimethylamino-2,4-dioxo-l,3-oxazoli-
dine-5-carboxylate (6 c): Colourless crystals (45%);
m.p. 92 °C (Et2 0/hexane); IR (KBr): v = 1819,
1777, 1750 (C=0) cm"1; 'H-NMR (DMSO-d6): (3
(ppm) 2.77 (s, 6 H, (CH3 )2N), 3.78 (s, 3H, OCH3),
5.64 (s, 1H, CH); 1 3 C-NMR (DMSO-d6): (3 (ppm)
43.1 (N(CH3)2), 53.2 (OCH3), 75.0 (CH), 152.2 (C-
2, C=0), 162.8, 164.1 (C=0).
Analysis for C13 H 14N20 5
Calcd
C 56.11 H 5.07 N 10.07%,
Found C 55.90 H 5.04 N 10.02%.
Benzyl 3-amino-2,4-dioxo-l,3-oxazolidine-5-car-
boxylate ( 6 g): Colourless crystals (58%); m.p.
103 °C (Et2 0/hexane); IR (KBr): v = 3348, 3263
(NH2), 1820, 1739 (C=0) cm“1; 'H-NMR
(DMSO-d6): (3 (ppm) 5.17 (s, 2H, NH2), 5.25 (d,
J = 12.2 Hz, 1H, O C //2Ph), 5.30 (d, J = 12.2 Hz,
1H, O C //2Ph), 5.87 (s, 1H, CH), 7.34-7.41 (m, 5H,
ArH); 1 3 C-NMR (DMSO-d6): 67.6 (O C //2Ph),
75.3 (CH), 127.9, 128.3, 128.4 (C tert., ArC), 134.8
(C quart., ArC), 154.3 (C-2, C=0), 162.5, 165.1
(C=0).
Analysis for C7H 10N2 O5
Calcd C 41.59 H4.99 N 13.86%,
Found C 41.37 H 4.91 N 14.01%.
Benzyl
2,4-dioxo-3-phenylamino-l,3-oxazoli-
dine-5-carboxylate (6 d): Colourless crystals (61%);
m.p. 126 °C (EtzO/hexane); IR (KBr): v = 3327
(NH), 1836, 1771, 1754 (C =0) cm’ 1; 'H-NMR
(DMSO-d6): (3 (ppm) 5.34 (s, 2H, OC//^Ph), 6.07
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Th. Kurz-D. Geffken • Tartronic Esters
672
Analysis for C1 iH ,0N2OS;
Analysis for C7 H9N 0 6
Calcd C 41.39 H 4.47 N 6.89%,
Calcd
C 52.80 H 4.03 N 11.20%,
Found C 52.49 H 4.02 N 11.27%.
Found C 41.38 H 4.48 N6.89%.
N- Benzyl-5-methyl-2,4-dioxo-3-phenylamino-1,3-
oxazolidine-5-carboxamide (7):
Ethyl 5-methyl-2,4-dioxo-3-phenylamino-l,3-ox-
azolidine-5-carboxylate (6h): Colourless crystals
(61%); m.p. 99 °C (Et20/hexane); IR (KBr): v =
3306 (NH), 1836, 1767, 1739 (C=0) cm "1; 'H-
NMR (DMSO-d6): (3 (ppm) 1.26 (t, 7 = 7.1 Hz, 3H,
CH2 CH3), 1.86 (s, 3H, CH,), 4.26-4.38 (m, 2H,
C //2CH3), 6.75-7.26 (m, 5H, ArH), 8.77 (s, 1H,
NH); 13 C-NMR (DMSO-d6): (3 (ppm) 13.6 (CH,),
18.1 (C-5, CH3 ), 63.5 (OCH2), 82.8 (C-5), 112.2,
120.7, 129.1 (C tert., ArC), 145.2 (C quart., ArC),
152.6 (C-2, C=0), 164.4, 168.2 (C=0).
A solution of 6h (5 mmol) and benzylamine
(5 mmol) in CH2 C12 (5 ml) was allowed to stand
for 20 h at ambient temperature. After removal of
the solvent the residue was chromatographed with
Et2 0/C H 2 C12 (3:7) as eluent.
7: Colourless crystals (28%); m.p. 149 °C
(CH2 Cl2/hexane); IR (KBr): v = 3306, 3221 (NH),
1819, 1741, 1697 (C=0) cm"1; 'H-NMR (DMSO-
d6): Ö (ppm) 1.84 (s, 3H, CH3), 4.63 (d, J = 15.8 Hz,
1H, N C //2 Ph), 4.69 (d, J = 15.8 Hz, 1H, N C //2Ph),
6.62-7.13 (m, 5H, ArH), 7.24-7.37 (m, 5H, ArH),
7.93 (s, 1H, NNH), 10.46 (s, 1H, NH); 1 3 C-NMR
(DMSO-d6): (3 (ppm) 18.8 (C-5, CH,), 43.2
(NC//,Ph), 84.4 (C-5), 112.0, 112.2, 118.9, 127.0,
127.2, 127.7, 128.2, 128.5, 128.6, 129.0 (C tert.,
ArC), 134.8, 148.4 (C quart., ArC), 153.9 (C-2,
C =0), 163.8, 170.3 (C=0).
Analysis for C1 3 H 14N20 5
Calcd
C 56.11 H 5.07 N 10.07%,
Found C 56.02 H 5.10 N 10.03%.
Benzyl 5-methyl-2,4-dioxo-3-phenylamino-l,3-
oxazolidine-5-carboxylate (6i): Colourless crystals
(63%); m.p. 109 °C (Et20/hexane); IR (KBr): v =
3295 (NH), 1836, 1768, 1739 (C=0) cm"1; 'H-
NMR (DMSO-d6): (5 (ppm) 1.89 (s, 3H, CH,), 5.33
(d, J = 12.2 Hz, 1H, O C //2Ph), 5.36 (d, J = 12.2
Hz, 1H, O C //2Ph), 6.65-7.11 (m, 5H, ArH), 7.36-
7.44 (m, 5H, ArH), 8.71 (s, 1H, NH); 1 3 C-NMR
(DMSO-d6): (3 (ppm) 18.3 (C-5, CH3), 68.5
(O C //2 Ph), 82.8 (C quart.), 112.2, 120.5, 128.3,
128.6, 129.0 (C tert., ArC) 134.5, 145.1 (C quart.,
ArC), 152.5 (C-2, C=0), 164.3, 168.0 (C=0).
Analysis for C18H 17N ,0 4
Calcd
C 63.71 H 5.05 N 12.38%,
Found C 63.31 H 5.08 N 12.33%.
N2-Dimethyl-5-methyl-2,4-dioxo-3-phenylamino-
1,3-oxazolidine-5-carbohydrazide (8): From 6h
(5 mmol) and N,N-dimethylhydrazine (5 mmol)
according to the procedure for 7.
8 : Colourless crystals (24%); m.p. 179 °C
(CH2 Cl2/hexane); IR (KBr): v = 3370, 3177 (NH),
1830, 1755, 1681 (C=0) c irr1; 'H-NMR (DMSO-
d6): (3 (ppm) 1.80 (s, 3H, CH3), 2.81 (s, 6 H,
(CH3 )2N), 6.65-7.20 (m, 5H, ArH), 7.93 (s, 1H,
NNH), 10.44 (s, 1H, CONH); 1 3 C-NMR (DMSO-
d6): (3 (ppm) 18.6 (C-5, C H ,), 43.3 (N(CH,)2), 82.6
(C-5), 112.1, 118.9, 128.6 (C tert., ArC), 148.5 (C
quart., ArC), 151.6 (C-2, C=0), 163.7, 168.6
(C=0).
Analysis for Ci8H 16N20 5
Calcd
C 63.52 H 4.74 N8.23%,
Found C 63.55 H 4.79 N8.23%.
Ethyl
3-hydroxy-5-methyl-2,4-dioxo-l,3-oxazoli-
dine-5-carboxylate (5h):
5a (1,5 mmol) was hydrogenated in THF using
catalytic amounts of 10% Pd/C. The reaction mix-
ture was stirred at ambient temperature for lh,
filtrated and rotoevaporated. The oily residue was
crystallized from CH2Cl2/hexane (1:1).
5h: Colourless crystals (91%); m.p. 91 °C (Et?0/
hexane); IR (KBr): v = 3216 (OH), 1837, 1770,
1707 (C=0) cm“1; 'H-NMR (DMSO-d6): (3 (ppm)
Analysis for C1 3 H )6N40 4
Calcd
C 53.42 H 5.52 N 19.17%,
Found C 53.42 H 5.58 N 18.73%.
5-MethyI-2,4-dioxo-3-phenylamino-l,3-
oxazolidine-5-carbohydroxamic acid (9):
5bh (2 mmol) and H2NOH HCl (2.2 mmol)
1.21 (t, J = 7.1 Hz, 3H, CH.CH,), 1.77 (s, 3H. were dissolved in anhydrous EtOH (10 ml) and
dropwise treated with a freshly prepared solution
of NaOEt (4 mmol Na in 10 ml EtOH). After 36
h the reaction mixture was adjusted to pH 3 with
HC1 and extracted with EtOAc. The combined or-
CH3), 4.24 (q, 2H, J = 7.1 Hz CH2CH3), 11.67 (s,
1H, OH); 13 C-NMR (DMSO-d6): (3 (ppm) 13.6
(CH3), 18.3 (C-5,CH3), 63.2 (OCH2), 81.9 (C-5),
151.4 (C-2, C=0), 164.5, 165.0 (C=0).
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673
Th. Kurz-D. Geffken • Tartronic Esters
reaction mixture was adjusted with HC1 (5%)
under ice cooling to pH 1 and extracted with
EtOAc (5 x 10 ml). The combined organic lay-
ers were dried over M gS04 and rotoevapor-
ated. The solid residue was recrystallized from
Et20/hexane (65%).
ganic layers were dried over M gS04, rotoevapor-
ated and the resulting oil crystallized from CH2C12.
9: Colourless crystals (38%); m.p. 161 °C
(CH2 C12); IR (KBr): v = 3324 (OH), 3262 (NH),
1836, 1754, 1699 (C=0) c m '1; 'H-NMR (DMSO-
d6): (3 (ppm) 1.84 (s, 3H, CH3), 6.66-7.17 (m, 5H,
ArH), 7.93 (s, 1H, NNH), 10.47 (s, 1H, NH), 11.60
(s, 1H, OH); 1 3 C-NMR (DMSO-d6): Ö (ppm) 18.8
(C-5, CH3), 82.5 (C-5), 112.1, 118.9, 128.7 (C tert.,
ArC), 148.4 (C quart., ArC), 151.4 (C-2, C=0),
163.6, 165,9 (C=0).
b) 6 i (1.5 mmol) was hydrogenated in THF using
catalytic amounts of 10% Pd/C. The reaction
mixture was stirred at ambient temerature for
lh, filtrated and the oily residue crystallized
from Et20/hexane (85%).
(11): Colourless crystals; m.p. 109 °C (EbO/hex-
ane); IR (KBr): v = 3305, (NH), 1825, 1752, (C=
O) cm "1; 1 H-NMR (DMSO-d6): Ö (ppm) 1.56 (d ,
J = 7.1 Hz, 3H, CH3), 5.34 (q, J = 7.1 Hz 1H, CH)
6.77-7.23 (m, 5H, ArH), 8.57 (s, 1H, NH); 1 3 C-
NMR (DMSO-d6): (3 (ppm) 16.0 (C-5, CH3), 75.1
(CH), 112.3, 120.2, 129.0 (C tert., ArC), 145.5 (C
quart., ArC), 153.8 (C-2, C=0), 172.1 (C-4, C=0).
Analysis for Cn H u N3 0 5
Calcd C 49.81 H 4.18 N 15.84%,
Found C 49.40 H 4.15 N 15.76%.
5-Methyl-3-phenylamino-l,3-oxazolidin-2,4-dione
(11):
Analysis for C10 H 10 N2 O3
a) KOH (3 mmol) in 10 ml EtOH was added
dropwise to a stirred solution of 6 h (3 mmol)
in EtOH (10 ml) within 60 min. After 24 h the
Calcd
C 58.25 H 4.89 N 13.59%,
Found C 58.13 H 5.01 N 13.43%.
[4] D. G effk en , J. B. A dam s, Jr., D. R. R aynor , PCT
Int. P atent A ppln. W O 90/ 12791, 1990.
[5] B. B ak, L iebigs A nn. C hem . 537, 286 (1939).
[6] S. E sk ola, S u om en K em istilehti 20B, 16 (1947); C.
A . 42, 122h (1948).
[7] H. A . Staab, A ngew . C hem ie 74, 407 (1962).
[8] B. M. Pianka, D. J. Polton, J. Chem . Soc. 1960, 983.
[1] D. G effk en , Synthesis 1981, 38; Z. N aturforsch. 38b,
1008 (1983).
[2] M. M. Joshi, J. A . Sternberg, Proc. Br. Crop. Prot.
Con.
-
Pests Dis. 1, 21 (1996); J. A . Sternberg, D.
G effk en , J. B. A dam s (Jr.), D. B. Jordan, R. Pöstges,
C. G. Sternberg, C. L. C am pbell, W. K. M oberg,
R. S. Livingston, Synthesis and C hem istry o f
A grochem icals V, A C S Sym p. Ser. 686, 216 (1998).
[3] The Pesticide M anual, C. D. S. Tom lin, E d., 11th ed i-
tion, The British Crop P rotection C ouncil, Farnham ,
Surrey, U K ., 2 4 4 -2 4 5 (1997); A . Fujinam i, K.
O zaki, T. N odera, K. Tanaka, A gric. B iol. C hem . 36,
318 (1972).
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