Synthesis of highly hindered polyanionic chelating ligands

Article abstract of DOI:10.1016/j.tet.2005.02.064

Practical and efficient protocols to obtain highly hindered polyanionic chelating ligands based on bis-(3,5-di-tert-butyl-2-hydroxybenzamido) compounds are reported here. N-3,5-di-tert-Butylsalicyloyloxysuccinimide was treated with aliphatic diamines to form aliphatic hydrocarbon-linked bis-amides 4a-4g. Aromatic diamines required more powerful electrophile, thus the corresponding benzylated acid chloride was used to form aromatic hydrocarbon-linked bis-amides 8a-8d. The yields ranged from good to very good and showed that choosing the right acylating agent is a key point in this synthesis. All the compounds were characterized by elemental analysis, IR, MS and NMR.

Full text of DOI:10.1016/j.tet.2005.02.064

Tetrahedron 61 (2005) 3933–3938
Synthesis of highly hindered polyanionic chelating ligands
*
´
Claudio A. Jimenez and Julio B. Belmar
´
´
Department of Organic Chemistry, Faculty of Chemical Sciences, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile
Received 14 December 2004; revised 21 February 2005; accepted 24 February 2005
Available online 16 March 2005
Abstract—Practical and efficient protocols to obtain highly hindered polyanionic chelating ligands based on bis-(3,5-di-tert-butyl-2-
hydroxybenzamido) compounds are reported here. N-3,5-di-tert-Butylsalicyloyloxysuccinimide was treated with aliphatic diamines to form
aliphatic hydrocarbon-linked bis-amides 4a–4g. Aromatic diamines required more powerful electrophile, thus the corresponding benzylated
acid chloride was used to form aromatic hydrocarbon-linked bis-amides 8a–8d. The yields ranged from good to very good and showed that
choosing the right acylating agent is a key point in this synthesis. All the compounds were characterized by elemental analysis, IR, MS and
NMR.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
it was tried with either aliphatic or aromatic diamines. The
reaction between salicyloyl chloride and diamines, the
obvious method, has been described and a few bis-amides
have already been reported.1h,6 However, substitution in the
aromatic moiety of the acid was different from the one
reported here. To our knowledge, bis-3,5-di-tert-butyl-2-
hydroxybenzamides have never been described by other
authors. N-hydroxysuccinimide esters have been used to
obtain tris-amides.7 These esters are acylating agents which
can be used under very mild conditions, usually providing
good yields. It was decided to explore this approach to
obtain bis-(3,5-di-tert-butyl-2-hydroxybenzamides) using
several diamines.
During the last few years, chelating agents have reached
incredible levels of importance due to the remarkable
applications that they have found in metal complexes
catalysis.1 Carboxamido ligands are interesting because it
has been shown that they are highly resistant to oxidative
degradation.2 The success of metal complexes in enantio-
selective catalysis depends, among other characteristics, on
the ability of the systems to tolerate very oxidative
environments.2d Amides work much better than other
ligands such as imines or phosphines, as reactions can be
followed from their turnover frequencies (TOF). TOF over
100 have been described for bis-amides while for Schiff
bases they reach only 30 in the best cases. However, amide-
based ligands are less known than imines or phosphines.
Polyanionic chelating ligands have been used in the
synthesis of chromium, manganese, iron, cobalt, nickel
and copper complexes with unusual geometries, oxidation
states and spin states.2,3 These characteristics are a
consequence of their strong ability to donate electron
density.2c Ligands containing voluminous groups have
become central in catalytic asymmetric synthesis since
they allow discrimination between different substrates and
even between faces of a substrate that is approaching the
active site.4 Our goal is to obtain ligands that combine
these two characteristics. We described the synthesis of
N,N-disubstituted-3,5-di-tert-butyl-2-hydroxybenzamides
using the corresponding acid chloride, some years ago.5
This procedure, however did not afford any bis-amide when
2. Results and discussion
The synthetic route that was followed in the first trials8 is
shown in Scheme 1. The yields were rather low, however,
we report here some modifications in the procedure, that
improved the yields up to 75%. Dimethylformamide was
used instead of acetone as solvent.
The starting ester 1 can be obtained in an almost quantitative
yield.5 The succinimide ester 3 is also easily obtained and
readily crystallized. Since 3 is a fairly stable compound, it
can be stored and used whenever needed. Furthermore, the
bis-amides 4 are also readily purified by crystallization. The
physical characteristics and the analytical data that confirm
the compounds are presented in the Section 4. The infrared
spectra show two characteristic absortions over 3000 cmK1
for NH and OH stretching. The C]O absortion is shifted to
lower wavenumber compared to the succinimide ester 3.
The 1H NMR spectra show two important low field signals,
Keywords: Amide ligands; Acylating agents; Ligands design.
*
Corresponding author. Tel.: C56 41 204258; fax: C56 41 245974;
e-mail: jbelmar@udec.cl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.064

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C. A. Jimenez, J. B. Belmar / Tetrahedron 61 (2005) 3933–3938
3934
yields of amides were only moderate to good, the procedure
is still easy to be carried out. Besides benzylation,
acetylation and methylation were also tried without success.
Authors that used methylation to protect the phenolic
hydroxyl of other salicylic acid derivatives, failed in the
deprotection step.1h The IR spectra of the bis-amides 9 show
the same characteristic absortion bands above mentioned.
1
The H NMR spectra of compounds 9, show signals at
8.5 ppm for the aromatic amides NH.
Amides (4 and 9) were dried at room temperature in a
vacuum oven after crystallization and filtration. The
samples were then analyzed by thermogravimetry. Only
one mass loss of 97% was observed at 250 8C. Below that
temperature no mass loss regions were observed, showing
the absence of water. This result accounts for the sharp
coincidence between calculated and experimental values of
elemental analysis. This behavior has been reported by other
authors.11
Scheme 1.
the first, between 12 and 12.5 ppm for OH (2H), the second,
below 7 ppm for NH (2H). The NH signal is broad and the
multiplicity is not well resolved. The melting points, as
expected for amides, are high.
From the results, it can be seen that choosing the right
acylating system depends on the reactivity of the nucleo-
phile. When the extremely reactive chloride of acid 2 reacts
with aliphatic diamines, unwanted secondary reactions are
favored12 and the final product becomes very difficult to
isolate from the reacting mixture. A ‘milder’ electrophile
such as 3, affords the products without difficulties, provided
that ‘good’ nucleophiles are used. In fact, compound 3 does
not react with aromatic diamines, owing to their lower
reactivity. A stronger acylating agent is required in that
case, even stronger than the chloride of acid 2, as it is the
case with the benzylated chloride 7. The reactivity of this
compound that does not have acidic protons remains
unchanged in alkaline medium.
Unfortunately, the procedure has a serious drawback that
precludes its generality. It does not work with aromatic
diamines. Since the reaction proceeds in alkaline medium,
the actual reagent is a phenoxyde ion. Therefore, electro-
philicity at the carboxylic carbon diminishes. The com-
pound would become less reactive towards weaker
nucleophiles such as aromatic diamines. These statements
were confirmed by calculating the local electrophilicity
index at the reacting atom. This local philicity contains
information about the global electrophilicity, Fukui’s func-
tion and provides additional knowledge of electronegativity
as well as the local and global softness.9 Scheme 2 shows
the modification that was made to overcome the difficulty.
Co(III) complexes are currently being obtained in our
laboratory and we are working to characterize them. In order
to obtain the tetraanion, the ligands are deprotonated by
treatment with n-butyllithium. Anhydrous CoCl2 is added
and then oxygen is bubbled trough the solution during 2 h.
The characteristic bands associated with NH and OH
stretching are not observed in the IR spectra of the
complexes. Besides, the stretching band corresponding to
the amide carbonyl is shifted to higher frequencies with
respect to the free ligand. Far IR spectra show a signal
around 550 cmK1 corresponding to the Co–N stretching.
3. Conclusion
In summary, we have described convenient procedures to
obtain both aliphatic and aromatic bis-amides derived from
3,5-di-tert-butyl-2-hydroxybenzoic acid. The procedures
are easily carried out in good yields. Some of the
synthesized chelating molecules here described have a
very hindered coordinating center. These ligands are
promising species to be used in asymmetric catalysis.4,13,14
Thesepolyanionicchelatingmoleculeshavetwocarboxamido
and two phenolic groups, both of them strong electron donors,
therefore it is quite likely that they will be able to stabilize
high valence complexes with transition metals.2,3 Both, chiral
and nonchiral molecule can find many applications.15 Our
Scheme 2.
In the first trials to enhance the electrophilicity at the
carboxylic carbon, compound 3 was benzylated. The
product is obtained in good yield, however, it did not
react with aromatic diamines, being isolated unchanged.
Finally, the benzylated acid chloride 7 did react with
aromatic diamines. The bis-amides 8 were debenzylated by
hydrogenolysis using Pd/C with a continuous stream of
hydrogen and good stirring at 40 8C.10 Even though the

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C. A. Jimenez, J. B. Belmar / Tetrahedron 61 (2005) 3933–3938
3935
final goal is to try them in enantioselectively catalyzed
reactions.
(12C, arom.), 40.7 (2C, CH2N), 35.2, 34.3 (4C, CMe3),
31.4, 29.4 (12C, CMe3). MS: MC 524.35 (524.78). FT-IR:
3335 (OH), 2958 (C–H), 1541 (C]O).
4. Experimental
4.2.2. 1,2-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
propane (4b). Yield: 77%, mp: 223–2258. Anal. Elem.
C33H50N2O4: Calcd C, 73.56, H, 9.37, N, 5.20. Found. C,
The compounds synthesized were characterized using FTIR
(Nicolet, Magna 550, KBr discs). 13C and 1H NMR (Bruker
AC 250P; 62.9 and 250 MHz, respectively, TMS as internal
standard). The solvent was CDCl3, except when otherwise
stated. 1H–13C correlation spectra and DEPT were also used
for signal assignment. High resolution mass spectra were
obtained (VG Autospec Micromass with magnetic sector)
using the electronic impact technique (70 eV, 230 8C).
Melting points (in Celsius degrees) were obtained in a
Kofler Microscope and are uncorrected. Elemental analyses
were obtained in a Fison EA 1108 Analyzer. Infrared
values (n) are quoted in reciprocal centimeters (cmK1),
NMR chemical shifts (d) are quoted in ppm. Racemic
1,2-propanediamine was used. Racemic trans-1,2-cyclo-
hexanediamine16 and racemic 2,20-diamine-1,10-binaph-
thyl17 were resolved as reported.
1
73.59, H, 9.37, N, 5.16. H NMR: 12.75, 12.60 (s, s, 2H,
OH), 7.45 (s, broad 3H, 2H arom. and NH a to CH2), 7.35
(d, JZ6.55 Hz, 1H, NH a to CH), 7.24 (d, JZ2.48 Hz, 2H,
arom.), 4.37, 3.72, 3.52 (m, m, m, 3H, CH and CH2), 1.39 (s,
18H, CMe3), 1.35 (d, JZ6.66 Hz, 3H, CH3 b to N), 1.30 (s,
18H, CMe3). 13C NMR: 172.8, 172.2 (2C, C]O), 158.9,
158.8, 140.1, 138.2, 138.1, 129.9, 129.2, 119.5, 112.5 (12C,
arom.), 47.3 (1C, CH a to N), 46.2 (1C, CH2 a to N), 35.2,
34.3 (4C, CMe3), 31.4, 29.3 (12C, CMe3), 18.3, (1C, Me b
to N). MS: MC 538.38 (538.81). FT-IR: 3410 (NH), 3370
(OH), 2957 (CH), 1536 (C]O).
4.2.3. 1,3-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
propane (4c). Yield: 76%, mp: 218–2208. Anal. Elem.
C33H50N2O4: Calcd C, 73.56, H, 9.37, N, 5.20. Found. C,
1
73.60, H, 9.38, N, 5.25. H NMR: 12.73 (s, 2H, OH), 7.49
4.1. Synthesis of aliphatic bis-amides
(d, JZ2.18 Hz, 2H, arom.), 7.40 (t, not well resolved, 2H,
NH), 7.38 (d, JZ2.18 Hz, 2H, arom), 3.57 (m, 4H, CH2N),
1.83 (broad signal, 2H, CH2 b to N), 1.44, 1.34 (s, s, 36H,
CMe3). 13C NMR: 172.0 (2C, C]O), 158.8, 140.1, 138.2,
129.5, 113.0, (12C, arom.), 35.5 (2C, CH2N), 35.2, 34.3
(4C, CMe3), 31.4 (6C, CMe3), 29.5 (1C, CH2 b to N), 29.4
(6C, CMe3). MS: MC 538.26 (538.81). FT-IR: 3410 (NH),
3369 (OH), 2957 (CH), 1535 (C]O).
4.1.1. N-3,5-di-tert-Butylsalicyloyloxysuccinimide (3).
3,5-di-tert-Butylsalicylic acid 2 (20 g, 0.083 mol) and
N-hydroxysuccinimide (8.9 g, 0.088 mol) were dissolved
in 300 ml of dioxane. The solution was cooled to 10 8C and
dicyclohexylcarbodiimide (19.5 g, 0.094 mol) dissolved in
300 ml of the same solvent, was slowly dropped. The
reaction mixture was stirred for 24 h at room temperature.
The urea was separated by filtration and the filtrate
evaporated to dryness. The white solid was recrystallized
from ethanol. Yield: 74%, mp: 168–1708. Anal. Elem.
C19H25NO5: Calcd C, 65.69, H, 7.25, N, 4.03. Found. C,
65.67, H, 7.23, N, 4.05. 1H NMR: 10.12 (s, 1H, OH), 7.83,
7.76 (d, d, JZ2.45 Hz, 2H, CH arom.), 2.93 (s, 4H, CH2–
C]O), 1.42, 1.31 (s, s, 18H, CMe3). 13C NMR: 169.1 (2C,
C]O, imide), 166.3 (1C, C]O, ester), 159.7, 141.5, 137.8,
133.3, 123.4, 107.1 (6C, arom.). MS: MC 347.16 (347.40).
FT-IR: 3285 (OH), 2959 (CH), 1737 (C]O), 1598 (C]C).
4.2.4. 1,3-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
2,2-di-methylpropane (4d). Yield: 83%, mp: 251–2528.
Anal. Elem. C35H54N2O4: Calcd C, 74.15, H, 9.62, N, 4.94.
1
Found. C, 74.17, H, 9.60, N, 4.93. H NMR: 12.71 (s, 2H,
OH), 7.62 (t, JZ6.42 Hz, 2H, NH), 7.52, 7.44 (d, JZ
2.17 Hz, 4H, arom.), 3.29 (d, JZ6.70 Hz, 4H, CH2N), 1.45,
1.37 (s, s, 36H, CMe3), 1.04 (s, 6H, CH3). 13C NMR: 171.9
(2C, C]O), 158.8, 140.1, 138.1, 129.0, 119.4, 113.0 (12C,
arom.), 46.4 (2C, CH2N), 37.1 (1C, C(CH3)2), 35.2, 34.3
(4C, CMe3), 31.2, 29.3 (12C, CMe3), 23.8 (2C, CH3). MS:
MC 566.41 (566.87). FT-IR: 3317 (NH), 3270 (OH), 2958
(CH), 1553 (C]O).
4.2. bis-Amides (4a–4f). General method
To a solution of N-3,5-di-tert-butylsalicyloyloxysuccini-
mide (2.0 g, 5.6 mmol) and the corresponding diamine
(2.8 mmol) in 15 ml of DMF, 5 ml of Et3N and a catalytic
amount of DMPA were added. The reaction mixture was
stirred for 12 h at room temperature and then poured into
ice/10% HCl. The mixture was extracted with 50 ml of ethyl
acetate and the aqueous layer was extracted again. The
organic extracts were combined, washed with brine, dried
over Na2SO4 and rotovapped. The solid was recrystallized
from ethanol.
4.2.5. 1,4-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
butane (4e). Yield: 72%, mp: 248–2498. Anal. Elem.
C34H52N2O4: Calcd C, 73.86, H, 9.50, N, 5.07. Found. C,
73.90, H, 9.49, N, 5.07. 1H NMR: 12.64 (s, 2H, OH), 7.46,
7.19 (d, d, JZ2.3 Hz, 4H, arom.), 6.76 (t, broad, not well
resolved, 2H, NH), 3.53 (m, not well resolved, 4H, CH2N),
1.75 (broad signal, 4H, CH2 b to N), 1.42, 1.30 (s, s, 36H,
CMe3). 13C NMR: 171.6 (2C, C]O), 158.7, 139.1, 128.8,
119.1, 113.1 (12C, arom.), 39.4 (2C, CH2N), 35.2, 34.3 (4C,
CMe3), 31.4, 29.3 (12C, CMe3), 26.8 (2C, CH2 b to N). MS:
MC 552.29 (552.84). FT-IR: 3397 (NH, OH), 2956 (CH),
1542 (C]O).
4.2.1. 1,2-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
ethane (4a). Yield: 72%, mp: 235–2368. Anal. Elem.
C32H48N2O4: Calcd C, 73.23, H, 9.24, N, 5.34. Found. C,
73.22, H, 9.25, N, 5.35. 1H NMR: 12.67 (s, 2H, OH), 7.60 (s,
broad, 2H, NH), 7.46, 7.30 (d, d, JZ2.03 Hz, 4H, arom.),
3.71 (s, 4H, CH2N), 1.41, 1.31 (s, s, 36H, CMe3). 13C NMR:
172.8 (2C, C]O), 158.9, 140.2, 138.1, 129.2, 119.7, 112.5
4.2.6. 1,5-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
pentane (4f). Yield: 73%, mp: 215–2178. Anal. Elem.
C35H54N2O4: Calcd C, 74.15, H, 9.62, N, 4.94. Found. C,
74.19, H, 9.61, N, 4.93. 1H NMR: 12.69 (s, 2H, OH), 7.45,
7.12 (d, d, JZ2.28 Hz, 4H, arom.), 6.40 (t, not well

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C. A. Jimenez, J. B. Belmar / Tetrahedron 61 (2005) 3933–3938
3936
resolved, 2H, NH), 3.45 (m, 4H, CH2N), 1.71 (m, 4H, CH2 b
to N), 1.48 (m, 2H, CH2 g to N), 1.42, 1.30 (s, s, 36H,
CMe3). 13C NMR: 171.3 (2C, C]O), 158.7, 139.9, 138.2,
128.8, 118.9, 113.3 (12C, arom.), 39.6 (2C, CH2N), 35.2,
34.3 (4C, CMe3), 31.4, 29.3 (12C, CMe3), 29.3 (2C, CH2 b
to N), 24.4 (1C, CH2 g to N). MS: MC 566.39 (566.87).
FT-IR: 3403 (NH, OH), 2958 (CH), 1536 (C]O).
136.5, 129.8, 128.5, 128.1, 127.7, 127.5, 123.4 (12C,
arom.), 78.0 (1C, CH2-phenyl), 35.6, 34.7 (2C, CMe3),
31.3, 31.0 (6C, CMe3). MS: MC 340.16 (340.47). FT-IR:
3433 (OH), 2910 (CH), 1691 (C]O).
4.4. Benzylated bis-amides (8a–8d). General method
To a solution of 6 (2.5 g, 7.3 mmol) in CH2Cl2 and cooled to
0 8C, oxalyl chloride (1.3 ml, 0.015 mol, 1.9 g) and a
catalytic amount of DMF were added. The mixture was
stirred during 4 h at room temperature. When the reaction
was finished the solvent was removed under reduced
pressure in a rotary evaporator and the solid was treated
with some extra CH2Cl2 and again evaporated. This
treatment was repeated one more time. The residue was
redissolved in 30 ml of CH2Cl2 and cooled to 0 8C. To this
solution 5 ml of pyridine and a catalytic amount of DMPA
were added. The diamine was dissolved in 20 ml CH2Cl2
and dropped into the cooled solution. The mixture was
stirred during 12 h and then it was refluxed during 4 h. The
solution was finally poured into 500 ml of an ice–10%
NaOH mixture and filtered. The solid was recrystallized
from ethanol.
4.2.7. (R,R)-1,2-bis-(3,5-di-tert-Butyl-2-hydroxybenza-
mido) cyclohexane (4g). (R,R)-Cyclohexane-1,2-diammo-
nium mono-(C)-tartrate salt (0.70 g, 2.8 mmol), K2CO3
(0.81 g, 5.8 mmol) and 30 ml of EtOH/H2O (5:1) were
placed in a 100 ml one-necked round-bottomed flask
equipped with a reflux condenser. The mixture was stirred
and heated at 80 8C for 30 min. Then, it was cooled to room
temperature and compound 3 (2.0 g, 5.6 mmol) and DMPA
were added. Stirring was continued for 12 h. The work up
was the same described in the general method for bis-
amides. Yield: 62%, mp: 238–2428 (amorphous solid).
Anal. Elem C36H54N2O4: Calc. C, 74.69, H, 9.42, N, 4.84.
1
Found. C, 74.72, H, 9.42, N, 4.86. H NMR: 12.76 (s, 2H,
OH), 7.44, 7.20 (d, d, 4H, JZ2,0 Hz, arom.), 7.03 (t, not
well resolved, 2H, NH), 3.95 (broad signal, 2H, CHN), 2.22
(broad signal, 2H, CH2 b N), 1.92 (broad signal, 2H, CH2 b
N), 1.39, 1.31 (s, s, complex signal, 40H, CMe3 and CH2 g
N). 13C NMR: 171.8 (2C, C]O), 158.7, 139.9, 137.8,
128.9, 119.3, 112.3 (12C, arom.), 54.0 (2C, CHN), 34.9,
34.1 (4C, CMe3), 31.9 (2C, CH2 b to N), 31.2, 29.1 (12C,
CMe3), 24.4 (2C, CH2 g to N). MS: MC 578.39 (578.88).
FT-IR: 3348 (OH), 3296 (NH), 2955 (CH), 1550 (C]O).
4.4.1. 1,2-bis-(3,5-di-tert-Butyl-2-benzyloxybenzamido)
benzene (8a). Yield: 77%, mp: 196–1978. Anal. Elem.
C50H60N2O4: Calcd C, 79.74, H, 8.05, N, 3.72. Found. C,
1
80.02, H, 8.00, N, 3.69. H NMR: 8.97 (s, 2H, NH), 7.61,
7.48 (d, d, JZ2.57 Hz, arom.), 7.37–7.25, 7.02 (complex
signals, 12H, benzyl and phenyl groups), 4.97 (s, 4H, CH2-
phenyl), 1.43, 1.27 (s, s, 36H, CMe3). 13C NMR: 166.5 (2C,
C]O), 153.5, 146.5, 142.4, 136.6, 130.5, 128.7, 128.4,
127.7, 127.5, 126.8, 126.1, 125.9, 124.7 (26C, arom.), 77.2
(2C, CH2-phenyl), 35.4, 34.6 (4C, CMe3), 31.3, 30.9 (12C,
CMe3). MS: MC 752.39 (753.08). FT-IR: 3066 (NH), 2958
(CH), 1660 (C]O).
4.3. Synthesis of aromatic bis-amides
4.3.1. Methyl 3,5-di-tert-butyl-2-benzyloxybenzoate (5).
In a 100 ml one-necked round-bottomed flask methyl 3,5-di-
tert-butylsalicylate (10 g, 0.038 mol), benzyl bromide
(5.0 ml, 0.042 mol, 7.1 g) and K2CO3 (5.2 g, 0.038 mol) in
40 ml of DMF were stirred during 48 h at room temperature.
The mixture was then poured into 500 ml of ice, stirred
some minutes and filtered. The white solid was recrysta-
lizated from ethanol. Yield: 90%, mp: 81–838. Anal. Elem.
C23H30O3: Calcd C, 77.95, H, 8.54. Found. C, 78.01, H,
4.4.2. 2,6-bis-(3,5-di-tert-Butyl-2-benzyloxybenzamido)
pyridine (8b). Yield: 65%, mp: 209–2118. Anal. Elem.
C49H59N3O4: Calcd C, 78.04, H, 7.90, N, 5.57. Found. C,
78.91, H, 7.95, N, 5.41. 1H NMR: 9.06 (s, 2H, NH), 8.03 (d,
JZ8.0 Hz, 2H, CH py), 7.84 (d, JZ2.35 Hz, 2H, arom.),
7.71 (t, JZ8.55 Hz, 1H, CH py), 7.59 (d, JZ2.37 Hz, 2H,
arom.), 7.37 (d, JZ7.48 Hz, 4H, benzyl group), 7.18 (t, JZ
7.41 Hz, 4H, benzyl group), 7.03 (t, JZ7.28 Hz, 2H, benzyl
group), 4.82 (s, 4H, CH2-phenyl), 1.37, 1.15 (s, s, 32H,
CMe3). 13C NMR: 165.7 (2C, C]O), 153.6, 149.5, 146.9,
143.0, 140.9, 136.1, 128.6, 128.2, 127.9, 127.8, 127.6,
126.5, 110.0 (29C, arom.), 77.8 (2C, CH2-phenyl), 35.6,
34.7 (4C, CMe3), 31.4, 31.1 (12C, CMe3). MS: MC 753.41
(754.07). FT-IR: 3375 (NH), 2959 (CH), 1675 (C]O).
1
8.59. H NMR: 7.62, 7.54 (d, d, JZ2.54 Hz, 2H, arom.),
7.49–7.33 (complex signal, 5H, benzyl group), 4.91 (s, 2H,
CH2-phenyl), 3.80 (s, 3H, OCH3), 1.41, 1.33 (s, s, 18H,
CMe3). 13C NMR: 168.7 (1C, C]O), 155.6, 145.2, 142.8,
137.5, 128.3, 128.1, 127.6, 127.0, 126.1, 124.7 (12C,
arom.), 76.5 (1C, CH2-phenyl), 52.2 (1C, OCH3), 35.4,
34.5 (2C, CMe3), 31.3, 30.7 (6C, CMe3). MS: MC 354.11
(354.50). FT-IR: 2956 (CH), 1728 (C]O), 1226 (C–O).
4.3.2. 3,5-di-tert-Butyl-2-benzyloxybenzoic acid (6). To a
solution of 5 (10.1 g, 0.030 mol) in 150 ml of methanol,
KOH (6.7 g, 0.11 mol) dissolved in 50 ml of water was
added. The resulting mixture was refluxed with stirring
during 4 h and then poured into 500 ml of an ice-10% NaOH
mixture, stirred and filtered. The white solid was recrys-
tallized from ethanol. Yield: 75%, mp: 173–1758. Anal.
Elem. C212H28O3: Calcd C, 77.67, H, 8.31. Found. C, 76.79,
H, 8.19. H NMR: 11.31 (s, 1H, OH), 7.91, 7.63 (d, d, JZ
2.41 Hz, 2H, arom.), 7.49–7.36 (complex signal, 5H, benzyl
group), 4.97 (s, 2H, CH2-phenyl), 1.46, 1.34 (s, s, 18H,
CMe3). 13C NMR: 170.6 (1C, C]O), 156.1, 146.3, 143.1,
4.4.3. 1,8-bis-(3,5-di-tert-Butyl-2-benzyloxybenzamido)
naphthalene (8c). Yield: 51%, mp: 204–2068. Anal.
Elem. C54H62N2O4: Calcd C, 80.75, H, 7.80, N, 3.49.
1
Found. C, 81.01, H, 7.91, N, 3.42. H NMR: 9.46 (s, 2H,
NH), 7.59–7.47, 7.17–7.11 (complex signals, 16H, benzyl
and phenyl groups), 7.53, 7.39 (d, d, JZ2.32 Hz, 4H,
arom.), 4.79 (s, 4H, CH2–phenyl), 1.30, 1.18 (s, s, 32H,
CMe3). 13C NMR: 166.8 (2C, C]O), 153.0, 146.5, 142.2,
136.3, 135.4, 132.3, 129.0, 128.3, 127.7, 126.6, 126.3,
125.9, 125.2, 121.7 (34C, arom.), 76.9 (2C, CH2–phenyl),
35.4, 34.6 (4C, CMe3), 31.4, 30.9 (12C, CMe3). MS: MC

´
C. A. Jimenez, J. B. Belmar / Tetrahedron 61 (2005) 3933–3938
3937
802.67 (803.14). FT-IR: 3338, 3342 (NH), 2957 (CH), 1662
(C]O).
4.5.4. (R)-2,20-bis-(3,5-di-tert-Butyl-2-hydroxybenza-
mido)-1,10-binaphthyle (9d). Yield: 51%. mp: 136–1488
(amorphous solid). Anal. Elem. C50H56N2O4: Calcd C,
80.17, H, 7.55, N, 3.74. Found. C, 80.15, H, 7.45, N, 4.01.
1H NMR: 12.24 (s, 2H, OH), 8.85 (d, JZ9.09 Hz, 2H,
arom.), 8.16 (d, JZ9.09 Hz, 2H, arom.), 8.08 (d, JZ
8.10 Hz, 2H, binaph.), 7.93 (s, 2H, NH), 7.53–7.22
(complex signal, 6H, binaph.), 6.18 (d, JZ1.53 Hz, 2H,
binaph.), 1.36, 0.97 (s, s, 18H, CMe3). 13C NMR: 169.5 (2C,
C]O), 159.0 (2C, C–NH, binaph.), 140.1, 138.1, 134.8,
132.1, 131.3, 130.5, 129.2, 128.6, 128.0, 126.0, 124.6,
120.8, 119.9, 119.0, 113.1 (30C, arom.), 35.1, 33.8 (4C,
CMe3), 31.1, 29.2 (12C, CMe3). MS: MC 748.40 (749.04).
FT-IR: 3415 (NH, OH), 2956 (CH), 1592 (C]O).
4.4.4. (R)-2,20-bis-(3,5-di-tert-Butyl-benzyloxybenza-
mido)-1,10-binaphthyle (8d). Yield: 54%. mp: 194–
196 8C. Anal. Elem. C64H68N2O4: Calcd C, 82.71,H, 7.39,
1
N, 3.02. Found. C, 83.01, H, 7.83, N, 2.98. H NMR: 8.35
(d, JZ8.97 Hz, 2H, arom.), 7.97 (s, 2H, NH), 7.89 (d, JZ
9.0 Hz, 2H, binaph.), 7.76 (d, JZ8.2 Hz, 2H, arom.), 7.26–
6.91 (complex signal, 10H, benzyl and binaph.) 4.61, 4.59
(s, s, 4H, CH2–phenyl), 1.08, 1.05 (s, s, 36H, CMe3). 13C
NMR: 166.9 (2C, C]O), 153.4, 145,6, 142.3, 136.7, 135.2,
132.3, 131.3, 129.7, 128.9, 128.1, 127.8, 127.7, 127.2,
126.9, 125.4, 125.0, 124.5, 122.2, 122.0 (22C, arom.), 76.7
(2C, CH2–Phenyl), 35.2, 34.3 (4C, CMe3), 31.2, 30.6 (12C,
CMe3). MS: MC 928.70 (929.30). FT-IR: 3391, 3353 (NH),
2959 (CH), 1676 (C]O).
Acknowledgements
4.5. Hydrogenolysis. General procedure
´
This work was supported by University of Concepcion
(PDI 201.023.026-1.0 and 203.023.032-1.0). CONICYT
provided a doctoral scholarship for Mr. C.A.J. The authors
´
are grateful to Dr. Catalina Ruiz Perez and Mr. Fernando
Delgado, Laboratorio de Rayos X y Materiales Moleculares,
A solution of the corresponding bis-amide (1–1.5 mmol) in
5 ml of toluene was diluted with 100 ml of absolute ethanol
and debenzylated at 40 8C over a 10% Pd/C catalyst. A
continuous stream of H2 was passed trough the suspension
until no O-benzylated material was detected by TLC. The
reaction mixture was filtered through Celite and evaporated
under reduced pressure. The solid was recrystallized from
ethanol.
´
´
Departamento de Fısica Fundamental II, Facultad de Fısica.
Universidad de La Laguna, Tenerife, Espan˜a, for recording
the mass spectra.
4.5.1. 1,2-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
benzene (9a). Yield: 79%, mp: 251–2538. Anal. Elem.
C36H48N2O4: Calcd C, 75.48, H, 8.46, N, 4.89. Found. C,
References and notes
1
75.70, H, 8.55, N, 4.78. H NMR (DMSO): 12.95 (s, 2H,
1. (a) Collins, T. J.; Ozaki, S.; Richmond, T. G. J. Chem. Soc.,
Chem. Commun. 1987, 803. (b) Ozaki, S.; Mimura, H.;
Yasuhara, N.; Masui, M.; Yamagata, Y.; Tomita, K. J. Chem.
Soc., Perkin Trans. 2 1990, 353. (c) Zhang, W.; Jacobsen,
E. N. J. Org. Chem. 1991, 56, 2296. (d) Hayashi, M.; Inoue, T.;
Miyamoto, Y.; Ogumi, N. Tetrahedron 1994, 50, 4385.
OH), 10.36 (s, 2H, NH), 7.78, 7.71, 7.49 (broad signals, 8H,
arom.), 1.45, 1.29 (s, s, 36H, CMe3). 13C NMR (DMSO):
171.6 (2C, C]O), 159.3, 140.0, 138.1, 135.1, 130.0, 129.1,
127.1, 125.9, 126.4, 119.5, 112.3 (22C, arom.), 35.2, 33.91
(4C, CMe3), 31.1, 29.4 (12C, CMe3). MS: MC 572.30
(572.82). FT-IR: 3302 (NH, OH), 2958 (CH), 1529 (C]O).
¨
(e) Moberg, C.; Adolfsson, H.; Warnmark, K. Acta Chem.
Scand. 1996, 50, 195. (f) Hwang, C.; Hwang, D.; Uang, B.
J. Org. Chem. 1998, 63, 6762. (g) Belekon, Y. N.; North, M.;
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R. C.; Plietker, B. J.; Backvall, J. J. Organomet. Chem. 2003,
687, 508.
4.5.2. 2,6-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)-
pyridine (9b). Yield: 45%. mp: 287–2898. Anal. Elem.
C35H47N3O4: Calcd C, 73.26, H, 8.27, N, 7.32. Found. C,
72.91, H, 8.18, N, 7.19. 1H NMR: 12.22 (s, 2H, OH), 8.34 (s,
broad, 2H, NH), 8.00 (d, JZ8.0 Hz, 2H, CH py), 7.78 (t, JZ
7.80 Hz, 1H, CH py), 7.48 (d, JZ2.07 Hz, 2H, arom.), 7.28
(d, JZ2.02 Hz, 2H, arom.), 1.38, 1.29 (s, s, 36H, CMe3).
13C NMR: 169.8 (2C, C]O), 159.4, 149.1, 141.0, 140.4,
138.6, 130.0, 119.2, 112.9, 110.7 (17C, arom.), 35.3, 34.4
(4C, CMe3), 31.5, 29.3 (12C, CMe3). MS: MC 573.35
(573.81). FT-IR: 3382 (NH), 2961 (CH), 1673 (C]O).
2. (a) Anson, F. C.; Christie, J. A.; Collins, T. J.; Coots, R. J.;
Furutani, T. T.; Gipson, S. L.; Keech, J. T.; Krafft, T. E.;
Santarsiero, B. D.; Spies, G. H. J. Am. Chem. Soc. 1984, 106,
4460. (b) Collins, T. C.; Richmond, T. G.; Santarsiero, B. D.;
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Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem. Rev. 2000,
100, 2159.
4.5.3. 1,8-bis-(3,5-di-tert-Butyl-2-hydroxybenzamido)
naphthalene (9c). Yield: 58%, mp: 291–2938. Anal.
Elem. C40H50N2O4: Calcd C, 77.13, H, 8.11, N, 4.50.
3. (a) Anson, F. C.; Collins, T. J.; Richmond, T. G.; Santarsiero,
B. D.; Toth, J. E.; Treco, B. G. R. T. J. Am. Chem. Soc. 1987,
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Slebodnick, C.; Uffelman, E. S. J. Am. Chem. Soc. 1990, 112,
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1
Found. C, 77.18, H, 8.10, N, 4.48. H NMR: 12.48 (s, 2H,
OH), 8.61 (s broad, 2H, NH), 7.93, 7.90 (d, d, JZ1.89 Hz,
2H, napht.), 7.52 (complex signal, 4H, naph.), 7.35, 6.99 (d,
d, JZ2.14 Hz, 4H, arom.), 1.39, 0.93 (s, s, 36H, CMe3). 13
C
NMR: 170.2 (2C, C]O), 158.2, 139.8, 136.6, 134.7, 128.5,
127.1, 126.7, 121.9, 113,5 (18C, arom.), 34.7, 34.0 (4C,
CMe3), 31.2, 29.2 (12C, CMe3). MS: MC 622.34 (622.88).
FT-IR: 3439, 3305 (NH, OH), 2958 (CH), 1590 (C]O).

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C. A. Jimenez, J. B. Belmar / Tetrahedron 61 (2005) 3933–3938
3938
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