Efficient large-scale synthesis of picolinic acid-derived nickel(II) complexes of glycine

Article abstract of DOI:10.1002/ejoc.200200688

An efficient, large-scale method for the preparation of 2-[N-(α-picolyl)amino]acetophenone (PAAP) and 2-[N-(α-picolyl)-amino] benzophenone (PABP), the hitherto unknown 4-methyl-2-[N-(α-picolyl)amino] benzophenone (4-Me-PABP) and 4-nitro-2-[N-(α-picolyl)am

Full text of DOI:10.1002/ejoc.200200688

FULL PAPER
Efficient Large-Scale Synthesis of Picolinic Acid-Derived Nickel(II) Complexes
of Glycine
[a]
[a]
[a]
[a]
Hisanori Ueki, Trevor K. Ellis, Collin H. Martin, and Vadim A. Soloshonok*
Keywords: Amides / Amino acids / Anhydrides
An efficient, large-scale method for the preparation of 2-[N-
α-picolyl)amino]acetophenone (PAAP) and 2-[N-(α-picolyl)-
amino]benzophenone (PABP), the hitherto unknown 4-
is described. The key step of the method is the formation of
the mixed anhydrides derived from o-picolinic acid and ethyl
chloroformate or p-toluenesulfonyl chloride.
(
methyl-2-[N-(α-picolyl)amino]benzophenone (4-Me-PABP)
and 4-nitro-2-[N-(α-picolyl)amino]benzophenone (4-NO
PABP), and their corresponding Ni complexes with glycine
2
-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
II
Picolinic acid-derived (PA-derived) NiII complexes 1a the ligand for complex 1a, starting from PA and 2-ami-
and 1b (Scheme 1) have emerged as a new type of highly noacetophenone and with the use of BOP (benzotriazol-1-
efficient achiral nucleophilic glycine equivalents.[
1Ϫ3]
Their yloxy-tris(dimethylamino)phosphonium hexafluorophos-
[
4]
superior qualities in relation to conventional N-(phenyl- phate) as condensing reagent. On the other hand, 2-[N-
methylene)glycine derivatives 2 include chemical stability (α-picolyl)amino]benzophenone (PABP, 3b), the ligand for
and predictable formation of the corresponding (Z) geo- complex 1b, was prepared in 85% yield from 2-aminobenzo-
metrically homogeneous enolates,[ a feature of paramount phenone and thionyl chloride through the in situ formation
importance for highly enantioselective homologation of the of the corresponding chloroanhydride of PA. For system-
glycine moieties in 1a and 1b. Thus, we and others have atic studies of complexes 1a and 1b, and in particular their
demonstrated an efficient application of complexes 1a and application as nucleophilic glycine equivalents for asymmet-
4]
[
2]
1
b as glycine equivalents in asymmetric Michael addition ric synthesis of amino acids, our group needed an ex-
[
1]
reactions and catalytic alkylations under phase-transfer peditious and reliable method for large-scale preparation of
conditions. Moreover, we recently reported an efficient 1a and 1b. We found that the literature methods,
[
2]
[2,4]
though
synthesis of symmetrically bis-substituted amino acids by successful, are unattractive for this purpose. For instance,
use of complex 1b as a stable yet highly reactive glycine the synthesis of 3a and 3b by application of peptide coup-
[
3]
equivalent under the strongly basic reaction conditions.
ling reagents such as BOP is a very simple and convenient
approach and could be effectively used for relatively small-
scale preparations. For large-scale synthesis, however, the
high molecular weights and cost of these reagents render
this method economically unattractive. On the other hand,
application of cheap thionyl chloride has serious synthetic
disadvantages, such as substantial formation of by-prod-
ucts, necessitating laborious purification of ligands 3a and
3b. In this paper we describe a simple and efficient method
for the large-scale preparation of ligands 3a and 3b, as well
as their hitherto unknown derivatives 4-methyl-2-[N-(α-pic-
olyl)amino]benzophenone (4-Me-PABP) 3c, 4-nitro-2-[N-
Scheme 1
(
α-picolyl)amino]benzophenone (4-NO -PABP) 3d, and
2
II
their corresponding Ni complexes with glycine 1aϪd.
Amidation of carboxylic acids in general and formation
of a peptide bond in particular has been an area of intense
Previously, we had reported the synthesis (95% yield) of
2-[N-(α-picolyl)amino]acetophenone (PAAP, 3a; Scheme 2),
[
5]
research and is well documented. The reagents most com-
[
a]
Department of Chemistry and Biochemistry, University of monly used to increase the electrophilicity of the carboxylic
Oklahoma,
[6]
function are carbodiimides, 1,1Ј-(carbonyldioxy)dibenzo-
Norman, OK 73019, USA
Fax: (internat.) ϩ 1-405/325-6111
E-mail: vadim@ou.edu
[
7]
[8]
triazole, sulfuryl chloride fluoride, arylsulfonyl chlo-
[
9]
[10]
[11]
rides, alkyl chloroformates,
and others.
Unfortu-
1954
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200200688
Eur. J. Org. Chem. 2003, 1954Ϫ1957

Picolinic Acid-Derived Nickel(II) Complexes of Glycine
FULL PAPER
triethylamine (TEA) to form the intermediate anhydride 4
(X ϭ COOEt) (Scheme 2). Unfortunately, the reaction pro-
ceeded sluggishly, giving rise to a mixture of the target
product 3a and the starting amine 5a in a ratio of 66/34
(Table 1, Entry 1). Under the same reaction conditions, we
treated PA with p- and m-aminoacetophenones, and this af-
forded the corresponding products in high chemical yields
(Entries 2 and 3). These results clearly suggested that elec-
tron-withdrawing and shielding effects (more pronounced)
of the acyl group in 5a do indeed have detrimental conse-
quences on its reactivity. We next decided to use p-tolu-
enesulfonyl chloride instead of ethyl chloroformate, since
the p-tosyloxy group generally exhibits superior leaving
ability. The result was fairly satisfactory, as we observed up
to 89% conversion of the starting amine 5a (Entry 4). Com-
plete conversion was achieved when we used 1.2 equiv. of
the intermediate anhydride (Entry 5). Without any ad-
ditional purification, compound 3a was used to prepare the
II
corresponding Ni complex 1a under reaction conditions
described previously. To demonstrate the reliability and
[
2]
Scheme 2
efficiency of this procedure, the preparation of ligand 3a
II
and its Ni complex 1a was repeated on Ͼ 100 g scale with
Ͼ 93% overall yield.
nately, in all these publications the synthetic power and gen-
erality of the methods is demonstrated by the use of an
With these results in hand we turned our attention to
admittedly wide range of amines, but only of conventional the amidation of PA with o-aminobenzophenone derivatives
ones, rarely including examples possessing a sterically hin- 5bϪd. We first conducted a reaction between PA and amine
dered or weakly nucleophilic amino function. Therefore, 5b under the conditions that we had found to give the best
amidation of acids with o-aminoaceto- and -benzophenone result for the amidation with 5a. The reaction proceeded at
derivatives 5aϪd is a rather challenging task, as these com- a substantially faster rate, affording the target compound
pounds possess the undesirable features both of steric con- 3d in quantitative chemical yield (Entry 6). Taking advan-
straint and of low amino group nucleophilicity. Of the tage of the higher reactivity of o-aminobenzophenone 5b,
methods cited above, activation of the carboxylic function we performed the amidation with ethyl chloroformate in-
by in situ formation of the corresponding mixed carboxylic- stead of p-toluenesulfonyl chloride. The reaction proceeded
sulfonic or -carbonic anhydrides was shown to be the most smoothly, affording virtually complete chemical conversion,
effective for reactions with sterically hindered or weakly nu- as was also observed with the more reactive p-toluenesul-
[
9,10]
cleophilic amines.
We first tried the amidation of PA fonyl chloride (Entry 6 vs. 7). This procedure, using ethyl
with acetophenone 5a by use of ethyl chloroformate and chloroformate, was also successfully reproduced on a
Table 1. Amidation of Picolinic Acid with Amines 5aϪd via Intermediate Mixed Anhydrides 4
Entry[a]
Amine 5aϪd
X in 4
Ratio 5aϪd/3aϪd[b]
Yield[c] of 3aϪd (%)
1
2
3
4
5
a [
COOEt
COOEt
COOEt
Ts
34/66
4/96
N.D.
92
98
Ͼ85
Ͼ94
99
99
99
91
97
d]
Ϫ
[
e]
Ϫ
a
a
b
b
c
Ͼ1/99
11/89
Ͼ1/99
Ͼ1/99
Ͼ1/99
Ͼ1/99
7/93
Ͼ1/99
46/54
49/51
20/80
Ͼ1/99
Ts[
f]
Ts[
f] [g]
6
[
f]
7
COOEt
Ts[
f]
8
9
0
1
2
3
4
c
c
d
d
d
d
COOEt
f]
1
1
1
1
1
COOEt[
Ts
N.D.
N.D.
78
COOEt
Ts[
h]
Ts[
h] [i]
99
[
a]
[b]
All reactions were run in commercial grade DCM overnight in the presence of TEA (PA/5 ϭ 1.1/1). Determined by NMR (300 MHz)
[c]
[d]
analysis of the crude reaction mixtures. Isolated yield of pure products based on 5. p-Aminoacetophenone was used in place of 5a.
[
e]
[f]
[g]
[h]
m-Aminoacetophenone was used in place of 5a. PA/5 ϭ 1.2/1. Reaction time was 4 h. Reaction was conducted in the presence
[
i]
of DMAP. Reaction was conducted in dichloroethane.
Eur. J. Org. Chem. 2003, 1954Ϫ1957
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1955

H. Ueki, T. K. Ellis, C. H. Martin, V. A. Soloshonok
FULL PAPER
Ͼ100 g scale, thus proving its efficiency and practicality. Large-Scale Preparation of Ligand 3b by the Use of ClCOOEt;
Typical Procedure: Ethyl chloroformate (87.48 g, 0.81 mol) was ad-
Under the same reaction conditions, 4-methyl-substituted
ded at 0 °C under N
.81 mol), triethylamine (81.91 g, 0.81 mol), and CH
After the mixture had been stirred at room temperature for 20 min,
b (134.02 g, 0.68 mol) was added and the mixture was kept stirring
2
to a flask containing picolinic acid (99.65 g,
amine 5c was used to prepare the new ligand 3c with a
virtually complete chemical conversion both with p-tolu-
enesulfonyl chloride (Entry 8) and with ethyl chloroformate
0
2
2
Cl (1.36 L).
5
(Entry 9, 10). In contrast, application of our standard con-
at 40Ϫ50 °C overnight. Water was then added to quench the reac-
tion, and the organic phase was washed three times with water.
After evaporation of the CH Cl , washing of the crude precipitate
2 2
ditions for preparation of ligand 3d starting from the NO2-
containing amine 5d gave unsatisfactory results (Entries 11,
1
2). To improve these results we decided to use 4-(dimeth- with ether afforded the target product 3b (200.73 g, 97.61%), which
II
ylamino)pyridine (DMAP) as a catalyst, as it has a known were used for preparing the corresponding Ni complex 1b without
powerful effect on many reactions, including acylations on further purification.
[
12]
nitrogen. After several attempts we found that the appli-
cation of DMAP in stoichiometric amounts could have a
noticeable effect on the chemical outcome (Entry 13). To
This procedure was successfully reproduced for the preparation of
ligand 3c.
improve the results further we conducted the amidation in Large-Scale Preparation of Ligand 3a by Use of TsCl: TsCl (45.60 g,
0
0
.24 mol) and 5a (27.02 g, 0.20 mol) were added, in that order, at
°C under N to a flask containing picolinic acid (29.53 g, 0.24
Cl (200 mL), and
dichloroethane, allowing us to run the reaction at a higher
temperature and to obtain the target compound in quanti-
tative chemical yield (Entry 14).
2
mol), triethylamine (40.45 g, 0.40 mol), and CH
2
2
the mixture was stirred at 40Ϫ50 °C overnight. AcOH (5% aq.)
was then added to quench the reaction, and the organic phase was
washed three times with water. After evaporation of the CH Cl ,
2 2
washing of the crude precipitate with ether furnished the desired
II
The corresponding Ni complexes 1aϪd were prepared
from ligands 3aϪd in high chemical yields under previously
reported conditions.[ In the H NMR spectra of com-
2]
1
plexes 1bϪd, the protons of the glycine methylene moiety
were found to be sensitive to the effect of the substituent. cation for preparation of the corresponding Ni complex 1a.
ligand 3a (46.51 g, 96.84%), which was used without further purifi-
II
Thus, the chemical shift of the glycine methylene group pro-
This procedure was successfully reproduced for the preparation of
tons in 1d was found to be shifted downfield (δ ϭ 3.88 ppm)
ligand 3c.
and in 1c shifted upfield (δ ϭ 3.79 ppm), relative to that of
the unsubstituted complex 1b (δ ϭ 3.83 ppm). This data Preparation of Ligand 3d: Triethylamine (5.41 mL, 38.50 mmol),
suggested that the glycine methylene moiety in 1d is more, DMAP (4.28 g, 35.06 mmol), ClCH
2
CH
2-amino-5-nitrobenzophenone
5.03 mmol) were added in that order at 0 °C under N
2
Cl (100 mL), TsCl (7.34 g,
3
3
8.63 mmol),
and
(8.48 g,
and in 1c less, CH acidic than the known complex 1b. This
observation provides grounds for a rational design of this
type of complexes with controlled reactivity of the glycine
methylene group.
In summary, an efficient, large-scale method for the prep-
aration of PAAP and PABP, the hitherto unknown ligands
2
to a flask
containing picolinic acid (4.74 g, 38.53 mmol). The mixture was
then heated at 60Ϫ70 °C and stirred overnight. The reaction was
quenched by addition of aq. AcOH (5%) and the organic phase
was washed three times with water. After evaporation of the
2 2
CH Cl , washing of the crude precipitate with EtOAc afforded the
4
-Me-PABP and 4-NO -PABP, and their corresponding
2
desired product 3d (12.43 g, 98.95% yield), which was used without
II
II
Ni complexes with glycine has been developed. The key further purification for preparation of the corresponding Ni com-
step of the method is the formation of the mixed anhydrides plex 1d.
derived from o-picolinic acid and ethyl chloroformate or p-
1
2
-(Picolinoylamino)acetophenone (PAAP, 3a):[4] M.p. 112.4 °C. H
toluenesulfonyl chloride. The synthetic efficiency and prac-
ticality of the methods were demonstrated by the prep-
NMR (CDCl
(
7
8
3
): δ ϭ 2.73 (s, 3 H), 7.16Ϫ7.21 (m, 1 H), 7.47Ϫ7.51
m, 1 H), 7.60Ϫ7.66 (m, 1 H), 7.90 (dt, J ϭ 8.7 Hz, 1.7 Hz, 1 H),
.97 (dd, J ϭ 7.8 Hz, 1.5 Hz, 1 H), 8.29 (d, J ϭ 8.1 Hz, 1 H),
.80Ϫ8.82 (m, 1 H), 9.03 (dd, J ϭ 8.5 Hz, 1.0 Hz, 1 H), 13.5 (br.
II
aration of the target Ni complexes on Ͼ100 g scales.
s, 1 H) ppm.
1
3
-(Picolinoylamino)acetophenone: M.p. 78.5 °C. H NMR (CDCl ):
3
Experimental Section
δ ϭ 2.64 (s, 3 H), 7.48 (t, J ϭ 7.69 Hz, 1 H), 7.50 (ddd, J ϭ 7.57,
.76, 1.22 Hz, 1 H), 7.73 (ddd, J ϭ 7.82, 1.71, 1.10 Hz, 1 H), 7.92
td, J ϭ 7.82, 1.71 Hz, 1 H), 8.08 (ddd, J ϭ 7.05, 2.19, 1.10 Hz, 1
H), 8.28 (ddd, J ϭ 7.81, 1.10, 0.98 Hz, 1 H), 8.32 (dd, J ϭ 2.07,
4
(
General: H and 13C NMR (299.94 MHz) were recorded with TMS,
1
3 3
CDCl , and CCl F as internal standards. High-resolution mass
spectra (HRMS) were recorded on facilities at the Department of
Chemistry, University of Oklahoma. Melting points (m.p.) are un-
corrected and were obtained in open capillaries. All reagents and
solvents, unless otherwise stated, are commercially available and
were used as received. Unless otherwise stated, yields refer to iso-
lated yields of products of greater than 95% purity as estimated by
1
1
1
.71 Hz, 1 H), 8.61 (ddd, J ϭ 4.76, 1.71, 0.85 Hz, 1 H), 10.2 (br. s,
13
H) ppm. C NMR (CDCl
3
): δ ϭ 26.8, 119.1, 122.2, 123.8, 123.9,
26.5, 129.2, 137.5, 137.6, 138.0, 147.8, 149.1, 162.0, 197.5 ppm.
ϩ
HRMS [M Na ] found m/z 263.0713, calcd. for
C
ϩ
14
H
12
N
2
NaO 263.0796.
2
1
13
4-(Picolinoylamino)acetophenone: M.p. 173.2 °C. 1H NMR
(CDCl ): δ ϭ 2.60 (s, 3 H), 7.51 (ddd, J ϭ 6.556, 4.76, 1.22 Hz, 1
H), 7.76Ϫ8.04 (m, 5 H), 8.30 (ddd, J ϭ 7.81, 1.22, 0.98 Hz, 1 H),
H and C NMR spectrometry. All new compounds were charac-
1
13
terized by H and C NMR and HRMS. Abbreviations used in
3
the paper: PA: picolinic acid, BOP: benzotriazol-1-yloxy(dimethyl-
amino)phosphonium hexafluorophosphate, TEA: triethylamine, 8.62 (ddd, J ϭ 4.76, 1.71, 0.97 Hz, 1 H), 10.2 (br. s, 1 H) ppm.
1
3
C
DCM: dichloromethane, DMAP: 4-(dimethylamino)pyridine.
NMR (CDCl
3
): δ ϭ 26.6, 118.8, 122.4, 126.7, 129.7, 132.7, 137.6,
1956
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 1954Ϫ1957

Picolinic Acid-Derived Nickel(II) Complexes of Glycine
FULL PAPER
41.8, 147.8, 149.0, 162.0, 196.6 ppm. HRMS [M ϩ Na ] found NiII Complex of Glycine Schiff Base with 5-NO
ϩ
-PABP (1d): Yield
95.43%. M.p. Ͼ 300 °C (dec.). H NMR (CDCl ): δ ϭ 3.88 (s, 2
H), 7.00Ϫ7.38 (m, 4 H), 7.54 (m, 1 H), 7.62 (m, 1 H), 7.85 (d, J ϭ
1
2
1
m/z 263.0981, calcd. for C14
H
12
N
2
NaO
2
263.0796.
3
-(Picolinoylamino)benzophenone (PABP) (3b):[2] M.p. 154.9 °C. H
NMR (CDCl ): δ ϭ 7.07 (m, 1 H), 7.35Ϫ7.43 (m, 3 H), 7.43Ϫ7.60
m, 3 H), 7.65Ϫ7.71 (m, 2 H), 7.81 (td, J ϭ 7.69, 1.71 Hz, 1 H),
1
2
2
7
4
.44 Hz, 1 H), 7.95 (d, J ϭ 7.81 Hz, 1 H), 8.06 (dd, J ϭ 7.69,
.57 Hz, 1 H), 8.16 (dd, J ϭ 9.28, 2.20 Hz, 1 H), 8.34 (d, J ϭ
.89 Hz, 1 H), 9.13 (d, J ϭ 9.64 Hz, 1 H) ppm. HRMS [M ϩ
3
(
8
1
.21 (br. d, J ϭ 7.82 Hz, 1 H), 8.68 (ddd, J ϭ 4.76, 1.71, 0.85 Hz,
H), 8.82 (d, J ϭ 8.30 Hz, 1 H), 12.6 (br. s, 1 H) ppm.
ϩ
ϩ
H Na ] found m/z 485.0386, calcd. for
C
21
H
15
N
4
NaNiO
461.05, C, 54.71, H 3.06, N
2.15; found C 54.88, H 3.16, N 12.11.
5
4
1
14 4 5
85.0509. calcd. for C21H N NiO
4
1
0
-Methyl-2-(picolinoylamino)benzophenone (4-Me-PABP) (3c): M.p.
1
82.9 °C. H NMR (CDCl
3
): δ ϭ 2.47 (s, 3 H), 6.94 (dq, J ϭ 4.88,
Acknowledgments
.86 Hz, 1 H), 7.40Ϫ7.60 (m, 5 H), 7.70Ϫ7.80 (m, 2 H), 7.88 (td,
The work was supported by the start-up fund provided by the De-
partment of Chemistry and Biochemistry, University of Oklahoma,
and by the Undergraduate Research Opportunities Program,
Honors College, University of Oklahoma.
J ϭ 7.82, 1.71 Hz, 1 H), 8.28 (d, J ϭ 7.81 Hz, 1 H), 8.72Ϫ8.86 (m,
H), 12.9 (br. s, 1 H) ppm. 1 C NMR (CDCl
3
2
1
1
3
): δ ϭ 22.3, 121.8,
21.9, 122.4, 123.1, 126.2, 128.0, 129.7, 131.9, 133.7, 137.2, 138.9,
ϩ
39.9, 145.1, 148.5, 150.0, 163.4, 198.6 ppm. HRMS [M ϩ Na ]
16 2 2
found m/s 339.1007, calcd. for C20H N NaO 339.1010.
[
[
1]
2]
V. A. Soloshonok, C. Cai, V. J. Hruby, Org. Lett. 2000, 2, 747.
Y. N. Belokon’, K. A. Kochetkov, T. D. Churkina, N. S. Ikonni-
kov, O. V. Larionov, S. R. Harutyunyan, S. Vyskocil, M. North,
H. B. Kagan, Angew. Chem. Int. Ed. 2001, 40, 1948.
T. K. Ellis, C. H. Martin, H. Ueki, V. A. Soloshonok, Tetra-
hedron Lett. 2002, 4, issue #5, in press.
5
2
-Nitro-2-(picolinoylamino)benzophenone (5-NO
2
-PABP) (3d): M.p.
1
36.4 °C. H NMR (CDCl
3
): δ ϭ 7.48 (m, 3 H), 7.62Ϫ7.70 (m, 1
H), 7.76Ϫ7.86 (m, 2 H), 7.93 (td, J ϭ 7.81, 1.71 Hz, 1 H), 8.30
ddd, J ϭ 7.81, 1.22, 0.86 Hz, 1 H), 8.45Ϫ8.52 (m, 2 H), 8.78 (dd,
J ϭ 0.86, 1.59 Hz, 1 H), 9.17 (d, J ϭ 9.28 Hz, 1 H), 13.0 (br. s, 1
H) ppm. 13C NMR (CDCl
): δ ϭ 121.2, 122.7, 123.8, 126.8, 128.3,
28.4, 128.5, 129.7, 137.1, 137.1, 137.3, 141.2, 144.8, 148.5, 148.8,
[
[
3]
4]
(
V. A. Soloshonok, C. Cai, V. J. Hruby, L. V. Meervelt, T. Yama-
zaki, J. Org. Chem. 2000, 65, 6688.
3
1
1
[5] [5a]
M. A. Ogliaruso, J. F. Wolfe, in The Chemistry of Acid De-
ϩ
63.5, 196.7 ppm. HRMS [M ϩ Na ] found m/s 370.0924, calcd.
rivatives; (Ed.: S. Patai), John Wiley & Sons, New York, 1979,
part I. [ G. Benz, In Comprehensive Organic Synthesis (Ed.:
B. M. Trost) Pergamon Press, Oxford, 1991, vol. 6, 381Ϫ417.
Y. N. Belokon’, A. G. Bulychev, S. V. Vitt, Y. T. Struchkov, A.
S. Batsanov, T. V. Timofeeva, V. A. Tsyryapkin, M. G. Ryzhov,
L. A. Lysova, V. I. Bakhmutov, V. M. Belikov, J. Am. Chem.
Soc. 1985, 107, 4252.
5b]
for C19
H
13
N
3
NaO
4
370.0804.
II
[6]
For preparation of the Ni complexes 1aϪd described previously,
[
4]
the general procedure was followed.
NiII Complex of Glycine Schiff Base with PAAP (1a): Yield
[4]
[
[
7]
8]
1
M. Ueda, H. Oikawa, T. Teshirogi, Synthesis 1983, 908.
G. A. Olah, S. C. Narang, A. Garcia-Luna, Synthesis 1980,
9
7.35%. M.p. Ͼ 290 °C (dec.). H NMR (CDCl
3
): δ ϭ 2.43 (s, 3
H), 4.20 (s, 2 H), 7.01 (m, 1 H), 7.32Ϫ7.43 (m, 2 H), 7.63 (d, J ϭ
.55 Hz, 1 H), 7.81 (d, J ϭ 7.33 Hz, 1 H), 7.95 (t, J ϭ 7.57 Hz, 1
6
61.
8
[
9] [9a]
Z. M. J a´ szay, I. Petneh a´ zy, L. Töke, Synthesis 1989, 745.
H), 8.18 (d, J ϭ 4.88 Hz, 1 H), 8.69 (d, J ϭ 8.79 Hz, 1 H) ppm.
[9b]
J. C. Lee, Y. H. Cho, H. K. Lee, S. H. Cho, Synth. Commun.
1
995, 25, 2887.
NiII Complex of Glycine Schiff Base with PABP (1b):[2] Yield
[
[
10] [10a]
H. Y. Rhyoo, Y.-A. Yoon, H.-J. Park, Y. K. Chung, Tetra-
1
9
2
7
2
5
9.07%. M.p. Ͼ 270 °C (decomp). H NMR (CDCl
3
): δ ϭ 3.83 (s,
[10b]
hedron Lett. 2001, 42, 5054.
M. J. Alc o´ n, M. Iglesias, F.
H), 6.83 (br. t, J ϭ 7.57 Hz, 1 H), 6.91 (br. d, J ϭ 7.81 Hz, 1 H),
.11 (br. d, J ϭ 7.08 Hz, 2 H), 7.34Ϫ7.47 (m, 2 H), 7.50Ϫ7.60 (m,
H), 7.89 (br. d, J ϭ 6.83 Hz, 1 H), 7.99 (m, 1 H), 8.29 (br. d, J ϭ
.37 Hz, 1 H), 8.99 (d, J ϭ 8.06 Hz, 1 H) ppm.
S a´ nchez, I. Viani, J. Organomet. Chem. 2001, 634, 25.
11] [11a]
L. E. Barstow, V. J. Hruby, J. Org. Chem. 1971, 36, 1305.
11b]
[
A. G o´ recka, M. Leplawy, J. Zabrocki, A. Zwierzak, Syn-
thesis 1978, 474. [
11c]
H. Suzuki, J. Tsuji, Y. Hiroi, N. Sato,
Chem. Lett. 1983, 449. [
11d]
A. R. Katritzky, J.-J. V. Eynde, J.
NiII Complex of Glycine Schiff Base with 4-Me-PABP (1c): Yield
[11e]
Chem. Soc., Perkin Trans. 1 1989, 639.
J. Cossy, C. Pale-
[
11f]
1
Grosdemange, Tetrahedron Lett. 1989, 30, 2771.
Fürstner, D. N. Jumbam, Tetrahedron 1992, 48, 5991.
A.
B. S.
P.
9
2.78%. M.p. Ͼ 270 °C (dec.). H NMR (CDCl
3
): δ ϭ 2.33 (s, 3
[
11g]
H), 3.79 (s, 2 H), 6.61 (m, 1 H), 6.78 (d, J ϭ 8.31 Hz, 1 H), 7.09
[
11h]
Jursic, Z. Zdravkovski, Synth. Commun. 1993, 23, 2761.
(
(
m, 2 H), 7.43 (ddd, 1 H, J ϭ 7.08 Hz), 7.48Ϫ7.60 (m, 3 H), 7.87
m, 1 H), 7.98 (td, J ϭ 7.56, 1.22 Hz, 1 H), 8.26 (m, 1 H), 8.85 (br.
Frøyen, Synth. Commun. 1995, 25, 959. [ M. Curini, F. Espi-
11i]
fano, F. Maltese, O. Rosati, Tetrahedron Lett. 2002, 43, 4895.
13
s, 1 H) ppm. C NMR (CDCl
3
): δ ϭ 61.7, 122.7, 123.3, 123.8,
[12] [12a]
G. Höfle, W. Steglich, H. Vorbüggen, Angew. Chem. Int.
1
1
4
24.2, 125.9, 126.8, 129.4, 134.3, 134.6, 140.3, 142.8, 144.4, 146.7,
[12b]
Ed. Engl. 1978, 17, 569.
Chem. Res. 1998, 31, 494.
U. Ragnarsson, L. Grehn, Acc.
ϩ
53.2, 170.2, 172.4, 177.2 ppm. HRMS [M ϩ Na ] found m/z
52.0668, calcd. for C22 NaNiO 452.0521.
H
17
N
3
3
Received December 7, 2002
Eur. J. Org. Chem. 2003, 1954Ϫ1957
www.eurjoc.org
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1957