Jan-Feb 2006
Reactions of Cephalosporin Sulfones 3
185
MHz, deuteriodimethylsulfoxide): δ 1.99 (3H, s, 3-CH ), 3.78 (3H,
dichloromethane (10 mL). The organic phase was washed with
water, 10% sodium bicarbonate solution and water. After evapo-
ration the residue was chromatographed (silica gel,
toluene–EtOAc 3:1) yielding 62 mg of bright yellow microcrys-
talline product (2a), mp 166-168 °C (from isopropyl alcohol); ir
3
s, COOCH ), 4.23, 4.37 (2H, ABq, J = 18.20 Hz, 2-CH ), 5.33 (H, d,
3
2
J = 4.68 Hz, 6-H), 6.04 (H, dd, J = 4.68, 9.39 Hz, 7-H), 6.86-7.00
13
(5H, m, aromatic), 8.60 (H, d, J = 9.39 Hz, NH); C nmr (500 MHz,
deuteriodimethylsulfoxide): δ 19.40, 52.54, 55.36, 57.61, 66.81,
67.10, 114.70, 121.26, 121.99, 129.48, 130.43, 156.83, 161.18,
163.10, 168.27.
-1
(KBr): ν 1806, 1730, 1532, 1510, 1240 cm ; ms: m/z (70eV) 522
+
1
(M ), 365 (M-157); H nmr (200 MHz, deuteriochloroform) δ
1.93 (9H, s, C(CH ) ), 2.50 (3H, s, -COCH ), 3.84 (3H, s, -
Anal. Calcd for C
H N O S (MW 394.08) C, 51.77; H,
3 3
3
17 18 2 7
OCH ), 5.44, 5.80 (2H, ABq, J = 11.8 Hz, 3’-CH ), 6.25 (H, d, J
4.60; N, 7.10. Found: C, 51.99; H, 4.58; N: 7.23.
3
2
= 4.5 Hz, H-6), 6.44 (H, dd, J = 4.5 Hz, 8.8 Hz, H-7), 7.55-7.9
(5H, m, Ph), 8.26 (H, d, J = 8.8 Hz, 7-NH), 11.45 (H, s, NHPh);
C nmr (500 MHz, deuteriodimethylsulfoxide): δ 21.26, 28.59,
53.74, 58.12, 63.14, 70.68, 82.30, 115.14, 123.12, 123.25,
125.48, 126.58, 130.18, 141.78, 154.48, 161.59, 163.84, 171.05.
tert-Butyl 7β-(Methylsulfonylamino)-3-deacetoxycephalospora-
nate 1,1-dioxide (1e)
13
a) tert-Butyl 7β-Amino-3-deacetoxy-cephalosporanate was
prepared from 7-amino-3-deacetoxycephalosporanic acid and
.
tert-butylacetate by BF Et O catalysis according to the method
Anal. Calcd for C
H N O S (MW 522.53): C, 50.57; H,
3
2
22 26 4 9
of Grigan et al. [7].
b) The above ester was mesylated to tert-butyl 7β-(methylsul-
fonylamino)-3-deacetoxy-cephalosporanate using methanesul-
5.02; N, 10.72; S, 6.14. Found: C, 50.28; H, 5.09; N, 10.67; S,
6.59.
2b, c and d were similarly prepared as 2a:
1
fonyl chloride [8], mp 148-149 °C (ethyl acetate – hexane);
H
nmr (200 MHz, deuteriochloroform): δ 1.52 (9H, s, 4-
Methyl 7β-[(Phenoxyacetyl)amino-2-(phenylhydrazono)-3-
deacetoxycephalosporanate 1,1-dioxide (Methyl (6R,7R)-3-
Methyl-8-oxo-7-[(phenoxyacetyl)amino]-4-(phenylhydrazono)-5-
thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5,5-dioxide) (2b):
COOC(CH ) ), 2.11 (3H, s, 3-CH ), 3.14 (3H, s, 7-CH SO ),
3 3
3
3
2
3.24, 3.50 (2H, ABq, J = 19.5 Hz, 2-CH ), 4.99 (H, d, J = 4.8 Hz,
2
6-H), 5.25 (H, dd, J = 4.8, 10.4 Hz, 7-H), 5.61 (H, d, J = 10.4 Hz,
7-NH).
Mp 160-162 °C; ir (KBr): ν 1802, 1704, 1530, 1488,1264,
c) The above tert-butyl 7β-(methylsulfonylamino)-3-
deacetoxycephalosporanate (1.55 g) was dissolved in 30 ml of
ethyl acetate and 3ml of 30% hydrogen peroxide solution was
added followed by 0.1 g of sodium tungstate. The reaction mix-
ture was stirred at 50 °C for 24 hours. The product partly crystal-
lized out from the solution, it was filtered off and rinsed thor-
oughly with water. The organic solution was washed with water,
dried over magnesium sulfate and evaporated to yield another
crop of the product. The combined solid products were recrystal-
lized from isopropyl alcohol – acetone yielding 1.26 g of white
-1
1
1242, 1170 cm ; H nmr (200 MHz, deuteriodimethylsulfoxide):
δ 2.28 (3H, s, 3-CH ), 3.82 (3H. s, COOCH ), 4.62, 4.72 (2H,
3
3
ABq, 2H, J = 15.3, OCH CONH), 5.82 (H, d, J = 4.6 Hz, 6-H),
2
6.20 (H, dd, J = 4.6, 6.2 Hz, 7-H), 6.9-7.6 (10H, m, 10H, aro-
13
matic), 8.87 (H, d, J = 6.2 Hz, 7-NH), 11.52 (H, s, 2-NH-Ar);
C
nmr (500 MHz, deuteriochloroform): δ 14.37, 53.28, 59.29,
67.37, 70.61, 115.23, 115.31, 119.72, 122.80, 125.13, 125.29,
130.08, 130.20, 132.08, 142.00, 157.28, 162.38, 162.52, 168.91.
Anal. Calcd for C
H N O S (MW 498.52) C, 55.42; H,
23 22 4 7
1
4.45; N, 11.24. Found: C, 55.02; H, 4.35; N: 11.29.
product (77%), mp 197-201 °C; H nmr (200 MHz, deuteriochlo-
roform): δ 1.53 (9H, s, 4-COOC(CH ) ), 2.13 (3H, s, 3-CH ),
3 3
3
Methyl 7β-[(Phenoxyacetyl)amino-2-[(4-bromophenyl)hydra-
zono]-3-deacetoxycephalosporanate 1,1-dioxide (Methyl
(6R,7R)-3-Methyl-8-oxo-7-[(phenoxyacetyl)amino]-4-[(4-bro-
mophenyl)phenylhydrazono]-5-thia-1-azabicyclo[4.2.0]oct-2-
ene-2-carboxylate 5,5-dioxide) (2c):
3.15 (3H, s, 7-CH SO ), 3.63, 3.88 (2H, ABq, J = 18.0 Hz, 2-
3
2
CH ), 4.83 (H, d, J = 4.7 Hz, 6-H), 5.47 (H, dd, J = 4.7, 11.6 Hz,
2
13
7-H), 5.95 (H, d, J = 11.6 Hz, 7-NH) ; C nmr (500 MHz, deu-
teriochloroform): δ 18.96, 27.40, 41.54, 55.05, 61.54, 67.15,
83.05, 122.50, 127.62, 159.40, 162.34.
1
Mp 193-195 °C; H nmr (200 MHz, deuteriodimethylsulfox-
Standard diazotation procedure.
ide): δ 2.26 (3H, s, 3-CH ), 3.82 (3H, s, COOCH ), 4.63, 4.74
3
3
(2H, ABq, J = 14.9 Hz, OCH CONH), 5.82 (H, d, J = 4.7 Hz, 6-
Aniline (1.9 g, 0.02 mole, or the equivalent amount of 4-
chloro- or 4-nitroaniline) was dissolved in 10 ml of 1:1 mixture
of cc. HCl – water. The mixture was cooled to 0-5 °C and a solu-
2
H), 6.23 (H, dd, J = 4.7, 6.3 Hz, 7-H), 6.9-7.9 (9H, m, aromatic),
13
8.84 (H, d, J = 6.3 Hz, 7-NH), 11.55 (2-NH-Ar); C nmr (500
MHz, deuteriodimethylsulfoxide): δ 14.86, 53.62, 59.63, 67.01,
70.49, 115.47, 116.58, 118.09, 120.29, 122.14, 127.69, 130.40,
132.98, 139.60, 142.88, 158.33, 162.82, 163.26, 169.02.
tion of of 1.4 g NaNO in 7 mL of water was added dropwise
while the temperature was maintained at this temperature. This
solution was used for the subsequent coupling reactions.
2
Anal. Calcd for C
3.67; N, 9.70; Br: 13.84. Found: C, 47.64; H, 3.77; N: 9.66; Br,
13.51.
H BrN O S (MW 577.41) C, 47.84; H,
23 21 4 7
Methyl 7-tert-Butoxycarbonylamino-2-phenylhydrazono-
cephalosporanate 1,1-dioxide (Methyl (6R,7R)-3-[(Acetyloxy)-
methyl]-7-[(tert-butoxycarbonyl)amino]-8-oxo-4-(phenyl-
hydrazono)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
5,5-dioxide) (2a).
Methyl 7β-[(Phenoxyacetyl)amino-2-[(4-nitrophenyl)hydra-
zono]-3-deacetoxycephalosporanate 1,1-dioxide (Methyl
(6R,7R)-3-Methyl-8-oxo-7-[(phenoxyacetyl)amino]- 4-[(4-nitro-
phenyl)phenylhydrazono]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-
2-carboxylate 5,5-dioxide) (2d):
To an ice-cold solution of 200 mg of 1a [9] in 20 ml of
methanol a hydrochloric acid solution of diazoted aniline was
added in several portions (prepared from 1.9 ml of aniline as
described above) until no starting material could be detected by
thin layer chromatography. After 1 hour in the cold the reaction
mixture was diluted with 30 mL of water, extracted twice with
1
Mp 226-227 °C; H nmr (200 MHz, deuteriodimethylsulfox-
ide): δ 2.27 (3H, s, 3-CH ), 3.85 (3H, s, COOCH ), 4.63, 4.74
(2H, ABq, J = 15.4, OCH CONH), 5.90 (H, d, H, J = 5.0 Hz, 6-
3
3
2