1453
K[ Kowalski and J[ Zakrzewski
M¦H!1CO[ Elemental analysis ] Found ] C 50[97 ^ H
2[61 ^ N 7[71[ Calc[ for C21H11N3O6Fe ] C 59[86 ^ H
2[41 ^ N 7[78[
Reaction of 1 with Na!ethosuximide
A solution of 1 "091 mg\ 9[19 mmol# and etho!
suximide "29 mg\ 9[10 mmol# in 9[94 M NaOMe in
MeOH "3 ml# was incubated at 49>C for 1 d\ cooled
to r[t[\ poured to water "19 ml# and extracted with
dichloromethane "2×4 ml#[ The combined extracts
were dried with sodium sulphate and evaporated to
dryness to give yellow oil[ The oil was dissolved in
ether "½19 ml#\ diluted with hexanes and slowly con!
centrated in vacuo to give an yellow solid "42 mg\
40)#[ IR "cm−0# ] 1934\ 0889\ "FeÐCO# ^ 0664\ 0619
"amide and succinimide CO# ^ 0534 "phthalimide
CO# ^ 0H!NMR ] 7[21 bs\ 0H\ NH ^ 6[61\ d "J ꢂ 7 Hz#\
0H and 6[43\ d "J ꢂ 7 Hz#\ 0H\ H!4 and H!5 ^ 6[56\ s\
0H\ H!2 ^ 4[01\ s\ 4H\ Cp ^ 3[27\ s\ 1H\ COCH1 ^ 1[66\
d "J ꢂ 07 Hz# 0H and 1[43\ d "J ꢂ 07 Hz#\ 0H\ suc!
cinimide ring CH1\ 0[71 m\ 1H CH1 "in Et# ^ 0[27\ s\
2H\ Me ^ 9[83\ t "J ꢂ 6 Hz#\ 2H\ CH2 "in Et# ^ FAB
MS ðpositive ions\ m:e "intensity#Ł ] 419 "15)#\
M¦H ^ 353 "40)#\ M¦H!1CO[ Elemental analysis ]
Found ] C 44[57 ^ H 3[01 ^ N\ 7[21[ Calc[ for C13H10
N2O6Fe ] C 44[40 ^ H 3[97 ^ N\ 7[98[
Experimental
All reactions were carried out under argon[ Dichlo!
romethane was distilled from CaH1[ CpFe"CO#1ðh0!
N"0#!3!aminophthalimidatoŁ "0# was prepared
according to the earlier published procedure ð00Ł[ All
reagents and other solvents "reagent grade# were used
as received from Aldrich or Fluka[ Column chro!
matographies were carried out using Kieselgel 59
"129Ð399 mesh ASTM# purchased by Merck[ Instru!
mentation ] IR!Specord 64 IR ^ 0H NMR ] Varian
Gemini 199BB "199 MHz# ^ FAB MS ] Finnigan MAT
0
84[ IR spectra were recorded in CHCl2\ H!NMR in
CDCl2 and referenced to internal TMS\ FAB spectra
in m!nitrobenzyl alcohol matrices[
CpFe"CO#1"h0!N"0#!3!iodoacetamidophthalimidato#
"1#
To a solution of 0 "209 mg\ 9[81 mmol# in CH1Cl1
"4 ml# DCC "195 mg\ 0[9 mmol# and iodoacetic acid
"075 mg\ 0[9 mmol# were added[ After 0 h stirring at
r[t[ the solid formed was _ltered o} and the _ltrate
evaporated to dryness[ Column chromatography
"eluent CHCl2# and crystallization "CH1Cl1!ether#
gave 1 as yellow solid[ Yield 275 mg "72)#[ IR
"cm−0# ] 1949 and 0884 cm−0 "FeÐCO#\ 0589 cm−0
"COÐamide#\ 0544 "COÐphthalimide#\ 0424 "amide!
II#[ 0H NMR "CHCl2# ] 7[09\ b\ 0H\ NH ^ 6[65\ d
"J ꢂ 7[9 Hz#\ 0H and 6[47\ d "J ꢂ 7[9 Hz#\ 0H\ H!4
and H!5 ^ 6[58\ s\ 0H\ H!2 ^ 4[01\ s\ 4H\ Cp ^ 2[89\ s\
1H\ CH1[ Residual ether "9[1 molecule# shows signals
at 2[38\ q and 0[11\ t[
RESULTS AND DISCUSSION
Our results are summarized in Scheme 0[
We have found that readily accessible 3!ami!
nophthalimidato complex 0 ð00Ł readily reacts with
iodoacetic acid and N\N?!dicyclohexylcarbodiimide
"DCC# in dichloromethane at room temperature to
give the 3!iodoacetamido derivative 1 in high yield[
Its structure was con_rmed by spectroscopic as well
as elemental analyses data[ The amino group in 0 can
be therefore acylated under mild conditions and 0 is a
potential labeling reagent for biomolecules containing
carboxylic functions[ This possibility\ however\ will
be a subject of further studies[
The iodoacetamido complex 1 readily reacts with
sodium salts of phenytoin and ethosuximide "pre!
pared by dissolving of the corresponding NH acids in
methanol containing the equimolar amount of sodium
methoxide# to a}ord conjugates 2 and 3\ respectively[
The structures of these complexes were con_rmed by
Analysis ] Found ] C\ 39[50\ H\ 1[26 ^ N\ 4[72\ I\
13[64[ Calc[ for C06H00N1O4IFe×9[1 C3H09O ] C\
39[24 ^ H\ 1[08 ^ N\ 4[43 ^ I\ 14[97[
Reaction of 1 with Na!phenytoin
A solution of 1 "091 mg\ 9[19 mmol# and phenytoin spectroscopic and elemental analysis data[ Their FAB
"40 mg\ 9[19 mmol# in 9[94 M NaOMe in MeOH "3 mass spectra "meta!nitrobenzyl alcohol as a matrix#
ml# was incubated at 49>C for 13 h\ cooled to r[t[ and display\ in the positive ions mode\ peaks cor!
poured to water "19 ml#[ The yellow precipitate was responding to M¦H and M¦H!1CO ions and in the
0
_ltered o}\ dried under vacuum and recrystallized negative ions mode to M!H and M!H!1CO ions[ H
−
from CH1Cl1 pentane[ Yield 096 mg "74)#[ IR NMR spectra of conjugates 2 and 3 show charac!
"cm−0# ] 1934\ 0889 "FeÐCO# ^ 0679\ 0614 "phenytoin teristic singlet of 0COCH1N0 protons "3[33 ppm
0
and amide CO# ^ 0534 "phthalimide CO# ^ H!NMR ] for 2 and 3[27 ppm for 3#\ shifted down_eld in com!
8[00\ bs\ 0H "NH# ^ 6[2Ð6[7\ m\ 02H "aromatic Hs# ^ parison to the signal of the 0COCH1I protons in 1
4[96\ s\ 4H "Cp# ^ 3[23\ s\ 1H "CH1# ^ FAB MS ðpositive "2[89 ppm#[ The complexes 2 and 3 are yellow air!
ions\ m:e "intensity#Ł ] 520 "13)#\ M¦H ^ 464 "45)#\ stable microcrystalline solids\ soluble in polar organic
Kowalski, Konrad
