Synthesis of bis(N-acylamidines) from amidines and N-acylbenzotriazoles

Article abstract of DOI:10.1055/s-0029-1218685

Bis(N-acylamidines) 7, linked by a spacer connected to the carboxyl groups, were synthesized in moderate to good yields from bis(N-acylbenzotriazoles) 6 and amidines 2. In contrast, the corresponding bis(carboxylic acid) chlorides were not well suited for

Full text of DOI:10.1055/s-0029-1218685

PAPER
1485
Synthesis of Bis(N-acylamidines) from Amidines and N-Acylbenzotriazoles
B
is(
N
-acy
u
lamidines) fr
l
om
A
m
i
idines
a
a
nd
N
-Acy
n
lbenzotriazol
a
es Isabel Clodt, Verena Dorothea Hack, Roland Fröhlich, Ernst-Ulrich Würthwein*
Organisch-Chemisches Institut, Universität Münster, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8339772; E-mail: wurthwe@uni-muenster.de
Received 4 December 2009; revised 21 January 2010
appropriate acylating agent 3 (e.g., carboxylic acids,
Abstract: Bis(N-acylamidines) 7, linked by a spacer connected to
the carboxyl groups, were synthesized in moderate to good yields
from bis(N-acylbenzotriazoles) 6 and amidines 2. In contrast, the
corresponding bis(carboxylic acid) chlorides were not well suited
structure not shown). The preparation of some N-acyl-
amidines has been described by Pinner already in 1889,
for example, from benzamidine hydrochloride and benzo-
for the synthesis of the compounds 7. 2-Aminothiazole gave the bis- ic acid anhydride.5 In the past, several synthetic routes for
amide 8, where the amidine moieties are part of heterocyclic ring
systems. Furthermore, the reaction of a bis-amidine 9 with two
equivalents of N-benzoylbenzotriazole (10) gave the bifunctional
N-acylamidine 11, linked to the spacer at the amidine carbon atoms.
All substances were thoroughly characterized including nine X-ray
diffraction studies.
the synthesis of primary, secondary, and tertiary N-acyl-
amidines have been studied in our group.1,6 One general
pathway includes the reaction of carboxylic acid chlorides
4 with amidines7 2 according to Katritzky and co-
workers8 (Scheme 1), where R1 is a proton in the case of
the primary N-acylamidines.
Key words: acylation, amidines, ligands, N-acylbenztriazoles, su-
pramolecular chemistry
H
O
N
NH2
N
N
O
R1
Et3N
R1
R3
+
CH2Cl2
–15 °C to r.t.
R2
R2
R3
Cl
N-Acylamidines 1 are useful nitrogen and oxygen con-
taining monodentate or bidentate ligands for metal com-
plexation.1,2 Their coordination sphere resembles that of
the well-known b-iminoketones (b-ketoiminates).3 How-
ever, the nitrogen atom in 3-position strongly alters the
electronic structure and allows conjugation over all five
atoms even in the neutral form of the ligand. Furthermore,
these ligands have been shown to amplify the catalytic ef-
fects of transition metals in cross-coupling reactions.1b,1c,4
Primary (R1 = H) and secondary N-acylamidines 1 are
subject to tautomerism, where the proton can be located at
one of the nitrogen atoms or – less favored – at the oxygen
atom (Figure 1) offering possibilities for various con-
formers and inter- and intramolecular hydrogen bonding.
2
4
1
Scheme 1 Synthesis of N-acylamidines according to Katritzky and
co-workers8
In our work focusing on the synthesis of bi- and polyden-
tate ligands for supramolecular architectures, we investi-
gated the synthesis of bis(N-acylamidines) linked via the
carboxyl moieties of sterically constrained spacers like
adamantyl-, cyclohexyl- or biphenyl dicarboxylic acid de-
rivatives. Unfortunately, experiments starting from bi-
functional carboxylic acid chlorides and amidines only
led to low yields of crude products difficult to purify.9
Due to the failure of the acid chloride experiments we en-
visaged to utilize other well-studied synthetic pathways
for the preparation of our ligands starting from amidines 2
and other carboxylic acid derivatives. However, acylation
experiments of amidines with carboxylic acids 3, using
carbodiimides as coupling reagents and hydroxybenzotri-
azoles as additives, as known from peptide coupling, did
not lead to satisfactory results.10
H
R1
R2
H
N
N
O
N
O
R1
R2
R3
N
R3
1a
1a'
H
N
N
O
N
N
OH
R1
R1
Further studies using N-acylbenzotriazoles as active es-
ters for our syntheses seemed to be more promising. N-
Acylbenzotriazoles are useful neutral acylation agents for
N-, C-, S-, and O-acylation in cases where the correspond-
ing acid chlorides are unstable or difficult to prepare.11
Since they are easily accessible in one step from the cor-
responding carboxylic acids, we decided to investigate
these compounds as precursors for the desired ligands.
R2
R3
R2
R3
1b
1c
Figure 1 Tautomeric forms of N-acylamidines 1
A look at the tautomers 1a and 1b reveals that N-acyl-
amidines may be regarded as amide derivatives, which
may be synthesized by acylation of amidines 2 using an
For the preparation of the new bis(N-acylbenzotriazole)
derivatives 6 we used a procedure developed by Katritzky
et al.,12 according to which one equivalent of a dicarbox-
ylic acid 5, eight equivalents of 1H-1,2,3-benzotriazole,
SYNTHESIS 2010, No. 9, pp 1485–1492
Advanced online publication: 24.02.2010
DOI: 10.1055/s-0029-1218685; Art ID: T23309SS
x
x
.
x
x
.2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

1486
J. I. Clodt et al.
PAPER
and two equivalents of thionyl chloride in dichlo-
romethane at room temperature were reacted to give the
hitherto unknown bis(N-acylbenzotriazoles) 6 with ali-
phatic, aromatic, and olefinic spacers in moderate to good
yields (Scheme 2, Table 1).
Table 2 Bis(N-acylamidine) Derivatives Prepared
Product Structure
Yield
(%)
7a
7b
71
92
benzotriazole (BtH)
SOCl2
H
H
N
N
N
N
Ph
Ph
CH2Cl2
O
O
O
O
r.t., 2 h
Ph
O
O
Ph
N
spacer
spacer
Bt
Bt
HO
OH
6
5
H
N
H
N
N
Scheme 2 Synthesis of bifunctional N-acylbenzotriazoles 6 in ana-
logy to the work of Katritzky et al.12
Ph
O
O
Ph
OMe
OMe
Table 1 Bis(N-acylbenzotriazole) Derivatives Prepared
Product
Structure
Yield (%)
7c
39
N
NH
HN
N
6a
70
O
Ph
N
Ph
O
N
Bt
Bt
O
O
7d
7e
46 (86)a
H
H
N
Bt
Bt
O
64
N
6b
6c
(cis/trans mixture)
Ph
O
O
Ph
O
O
47
74
Bt
Bt
62
Ph
Ph
N
N
Ph
O
S
S
NH2
O
O
NH2
NH2
O
O
O
6d
N
7f
50
47
Bt
Bt
N
Ph
O2N
NO2
NH2
O
Ph NH
Ph
N
O
O
All compounds 6 are stable at room temperature; they are
crystalline and could be characterized by single crystal X-
ray diffraction. While the trans isomer of 6b is already
known12b we obtained cis/trans-6b from a commercially
available mixture of the corresponding dicarboxylic acids.
cis-6b could be characterized by X-ray crystal structure
analysis, which crystallized preferentially from the mix-
ture of diastereomers.
7g
Ph
N
HN Ph
NH2
H2N
O
Ph
Ph
O
N
7h
62
N
NO2
S
O2N
S
In the second step of the N-acylamidine synthesis, one
equivalent of the bis(N-acylbenzotriazoles) 6 was reacted
a After 18 h in refluxing CH2Cl2.
H
O
O
N
NH
+
R
spacer
2
CH2Cl2
with two or more equivalents of amidines 2 at room tem-
perature in dichloromethane for 16 hours to give the
bis(N-acylamidine) derivatives 7a–h in moderate to ex-
cellent yields (Scheme 3 and Table 2). These compounds
could be easily purified and may be stored at room tem-
perature in the presence of air.
r.t., 16 h
Bt
Bt
Ph
6a–d
2a–d
2a: R = Ph; 2b: R = 4-MeC6H4; 2c: R = 4-MeOC6H4; 2d: R = i-Pr
O
N
O
N
spacer
R
NH
Ph
HN
Ph
R
All compounds 7 are crystalline solids; the structures of
7e, 7f, and 7g were confirmed by single crystal X-ray
analysis. Thus, this method offers valuable advantages
concerning the variability of spacers separating the N-
7a–h
Scheme 3 Synthesis of bis(N-acylamidines) 7 from bis(N-acylben-
zotriazoles) 6 and amidines 2
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Bis(N-acylamidines) from Amidines and N-Acylbenzotriazoles
1487
acylamidine functionalities compared to the other meth-
ods, especially in comparison to the use of the rather reac-
tive and often unstable acid chlorides.
H
H
N
N
N
N
N
S
6a
+
2
NH2
The crystal structures of the bis(N-acylamidines) 7e and
7f are both characterized by inter- and intramolecular hy-
drogen bonding corresponding to tautomer type 1a¢.
Figure 2 displays the molecular structure of 7e·CHCl3.
The molecules are interconnected by hydrogen bonding
formed by an amino proton of one molecule and the oxy-
gen atom of the next molecule resulting in a molecular
chain. The intramolecular hydrogen bonds have O–N dis-
tances of 2.64 Å, whereas we find 2.62 and 2.87 Å for the
intermolecular hydrogen bonds (the sum of the van der
Waals radii of N and O amounts to 3.02 Å).13
S
S
O
O
8 (87%)
Scheme 4 Synthesis of bis-amide 8
One bis(N-acylamidine) 11, linked via the amidine moi-
ety, was synthesized under similar reaction conditions us-
ing bis-amidine 9 and N-benzoylbenzotriazole (10) as
precursors (Scheme 5). Because of the low solubility of
amidine 9 1,2-dichloroethane was used as solvent and the
reaction mixture was heated to 84 °C for six hours.
Ph
Ph
O
Bt
N
N
+
2
DCE
84 °C, 6 h
Ph
H2N
NH2
9
10
Ph
N
Ph
N
O
O
NH
HN
Ph
Ph
11
85%
Scheme 5 Synthesis of a bis(N-acylamidine) 11 linked via the car-
bon atoms of the amidine groups
In summary, we have shown that the reaction of N-acyl-
benzotriazoles with amidines is a facile method to synthe-
size bis(N-acylamidines) linked by different spacers
between the two functionalities. The new ligands are stud-
ied now to build up supramolecular architectures, for ex-
ample, networks or cavities interconnected by hydrogen
bonding and metal coordination.
Figure 2 Molecular structure of 7e in the solid state, single mole-
cule (top), hydrogen-bridged ensemble of three molecules (bottom)
[X-ray; solvent molecules (CHCl3) were omitted for clarity]
Figure 3 displays a single molecule of bis(N-acylamidine)
7f in the crystal showing intramolecular hydrogen bond-
ing similar to the structure of 7e. Additional intermolecu-
Melting Points: Büchi Melting Point B-540; melting points are un-
1
corrected. H, 13C, GCOSY, GHSQC and GHMBC spectroscopy:
lar aggregation leads to
a non-covalent organic
Varian INOVA, AMX 400, Bruker WM 300 spectrometer. TMS
(1H) (0.00 ppm), DMSO-d6 (1H) 2.50 ppm (13C) 39.5 ppm, pyri-
dine-d5 (1H) 8.74 ppm (13C) 150.5 ppm (13C), DMSO-d6, CDCl3
(13C) (77.0 ppm), were used as internal references; IR: Varian 3100
FT-IR (Excalibur Series). MS: mass spectra were recorded on a
Finnigan MAT 4200S, or Bruker Daltonics micrOTOF, or Waters-
Micromass Quatro LCZ (ESI) spectrometer. Elemental analysis:
automated Elementar Vario EL III CHNS analyzer. All solvents
(TBME: tert-butyl methyl ether; TFA: trifluoroacetic acid) and re-
agents were rigorously dried and purified by standard methods or
were used as received from Aldrich, Acros or Fluka. Column chro-
matography: silica gel Merck 60 (0.040–0.063 mm). TLC: Merck
silica gel plates (silica gel 60 F254), detection with UV light.
framework. The O–N distances of 2.60 Å for intramolec-
ular hydrogen bonding and 2.93 Å for intermolecular hy-
drogen bonding were measured.
Figure 3 Molecular structure of 7f in the solid state (X-ray)
N-2-Methylphenylbenzamidine (2b)
For the synthesis of a related derivative, in which the ami-
dine moiety is part of a heterocyclic ring system, we used
2-aminothiazole as a ‘hidden’ amidine. We obtained the
bis-amide 8 in 87% yield (Scheme 4).
Prepared partially in analogy to a literature procedure.7Benzonitrile
(6.20 g, 60 mmol) and AlCl3 (8.00 g, 60 mmol) were mixed togeth-
er in a dry flask and cooled to 0 °C. o-Toluidene (6.43 g, 60 mmol)
was added dropwise. The mixture was heated to 160 °C until homo-
Synthesis 2010, No. 9, 1485–1492 © Thieme Stuttgart · New York

1488
J. I. Clodt et al.
PAPER
geneity was achieved. The melt was poured into an ice-cold solution
of concd HCl (2.5 mL) and H2O (200 mL) and stirred for 20 min.
The aqueous mixture was filtered and added to a cold solution of
NaOH (20 g) in H2O (150 mL). The aqueous phase was extracted
with CH2Cl2 (3 × 50 mL). The combined organic layers were dried
(MgSO4) and evaporated; yield: 10.25 g (82%); light yellow solid;
mp 108.4 °C.
Anal. Calcd for C24H22N6O2;C, 67.62; H, 5.22; N, 19.68. Found: C,
67.59; H, 5.20; N, 19.71.
X-ray Crystal Structure Analysis for 6a14–20
C24H22N6O2, M = 426.48, colorless crystal 0.60 × 0.10 × 0.07 mm,
a = 21.0320(1), b = 14.2679(1), c = 6.9020(1) Å, b = 99.840(1)°,
V = 2040.70(3) Å3, rcalc = 1.388 g cm–3, m = 0.748 mm–1, empirical
absorption correction (0.662 £ T £ 0.950), Z = 4, monoclinic, space
group C2/c (No. 15), l = 1.54178 Å, T = 223(2) K, w and j scans,
7575 reflections collected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 1766
independent (Rint = 0.065) and 1405 observed reflections [I ≥ 2
s(I)], 146 refined parameters, R = 0.050, wR2 = 0.132, max. (min.)
residual electron density 0.17 (–0.22) e Å–3, hydrogen atoms calcu-
lated and refined as riding atoms.
IR (KBr): 3439 (m), 3150 (m), 3059 (m), 2967 (m), 2914 (m), 1630
(s), 1595 (s), 1564 (s), 1499 (m), 1479 (s), 1447 (m), 1385 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 2.17 (s, 3 H, CH3), 6.84–6.86 (m,
1 Harom), 6.95–6.99 (m, 1 Harom), 7.14–7.23 (m, 2 Harom), 7.39–7.48
(m, 3 Harom), 7.85–7.87 (m, 2 Harom).
13C NMR (100 MHz, CDCl3): d = 17.6 (CH3), 121.0, 123.0, 126.7,
126.8, 128.4 (CHarom), 129.4 (Cipso), 130.4, 130.7 (CHarom), 135.6,
148.0 (Cipso), 153.8 (C=N).
[4-(Benzotriazol-1-carbonyl)cyclohexyl]benzotriazol-1-ylmeth-
anone (6b)
Prepared from a cis/trans mixture of 1,4-cyclohexanedicarboxylic
acid (1.72 g, 10.0 mmol). Crystallization from THF gave 2.41 g
(64%) of cis/trans mixture of 6b as colorless needles; mp 193 °C.
HRMS (ESI): m/z calcd for C14H14N2: 211.1230; found: 211.1232.
Anal. Calcd for C14H14N2: C, 79.97; H, 6.71; N, 13.32. Found: C,
79.67; H, 6.67; N, 13.18.
IR (KBr): 3045 (vw), 3024 (vw), 2955 (m), 2868 (w), 1728 (vs),
1595 (m), 1485 (s), 1450 (s), 1391 (s), 1350 (s), 1286 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 1.90–2.20 (m, 4 H, CH2), 2.30–
2.45 (m, 4 H, CH2), 4.04 (m, 0.6 H), 4.18 (1.4 H, CH), 7.47–7.53
(m, 2 Harom), 7.61–7.69 (m, 2 Harom), 8.09–8.13 (m, 2 Harom), 8.29–
8.31 (m, 2 Harom).
N-Isopropylbenzamidine (2d)
Prepared from benzonitrile (6.20 g, 60 mmol), AlCl3 (8.00 g,
60 mmol) and i-PrNH2 (3.55 g, 60 mmol) as described for 2b. Vac-
uum distillation gave 4.21 g (43%) of a colorless oil, which solidi-
fied slowly to a colorless solid; bp 90 °C/0.83 mbar; mp 63.0 °C
(Lit.7 mp 63–64 °C).
13C NMR (100 MHz, CDCl3): d = 26.0, 28.0 (CH2), 40.2, 42.5
(CH), 114.5, 114.5, 120.1, 120.1, 126.1, 126.2, 130.4, 130.4
(CHarom), 131.1, 131.2, 146.0, 146.1 (Cipso), 174.5, 174.6 (C=O).
1H NMR (300 MHz, CDCl3): d = 1.25 [d, 3J = 6.5 Hz, 6 H,
CH(CH3)2], 4.05 [sept, 3J = 6.4 Hz, 1 H, CH(CH3)2], 7.30–7.50 (m,
5 Harom).
13C NMR (75 MHz, CDCl3): d = 22.5 [CH(CH3)3], 42.7
[CH(CH3)3], 125.8 (p-CHarom), 128.4, 131.9 (o/m-CHarom), 138.3
(Cipso), 163.3 (C=N).
HRMS (ESI): m/z calcd for C20H18N6O2 + Na: 397.1383; found:
397.1382.
Anal. Calcd for C20H18N6O2: C, 64.16; H, 4.85; N, 22.45. Found: C,
63.81; H, 4.82; N, 22.15.
Bis(N-acylbenzotriazoles) 6a–d; General Procedure
These compounds were synthesized according to a general proce-
dure by Katritzky et al.12a
X-ray Crystal Structure Analysis for 6b14–20
C20H18N6O2, M = 374.40, colorless crystal 0.15 × 0.10 × 0.05 mm,
a = 6.7907(1), b = 34.0197(6), c = 7.6258(2) Å, b = 90.883(1)°,
V = 1761.48(6) Å3, rcalc = 1.412 g cm–3, m = 0.785 mm–1, empirical
absorption correction (0.891 £ T £ 0.962), Z = 4, monoclinic, space
group P21/c (No. 14), l = 1.54178 Å, T = 223(2) K, w and j scans,
9846 reflections collected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 2770
independent (Rint = 0.069) and 2050 observed reflections [I ≥ 2
s(I)], 253 refined parameters, R = 0.060, wR2 = 0.168, max. (min.)
residual electron density 0.20 (–0.18) e Å–3, hydrogen atoms calcu-
lated and refined as riding atoms.
To a solution of benzotriazole (8 equiv) dissolved in CH2Cl2
(100 mL) were added SOCl2 (2 equiv) at 25 °C with stirring. After
30 min, the appropriate dicarboxylic acid (1 equiv) was added in
one portion and the stirring was continued overnight. The white pre-
cipitate was filtered off and dissolved in CH2Cl2 (2 × 50 mL). The
combined organic layers were washed with aq 2 N NaOH (3 ×
60 mL), dried (MgSO4), and concentrated under reduced pressure.
The crude products were purified as stated below.
[3-(Benzotriazol-1-carbonyl)tricyclo[4.3.1.13,8]undec-1-yl]ben-
zotriazol-1-ylmethanone (6a)
Prepared from 1,3-adamantanedicarboxylic acid (5.33 g,
25.3 mmol), benzotriazole (24.02 g 202.4 mmol), and SOCl2
(5.98 g, 50.6 mmol). Crystallization from THF gave 7.70 g (70%)
of 6a as colorless needles; mp 193 °C.
(E)-1,6-Di(benzotriazol-1-yl)hex-3-ene-1,6-dione (6c)
Prepared from trans-hex-3-enedicarboxylic acid (1.44 g, 10 mmol),
benzotriazole (9.53 g 80 mmol), and SOCl2 (2.36 g, 20.0 mmol).
Crystallization from THF gave 1.64 g (47%) of 6c as light yellow
needles; mp 189.6 °C.
IR (ATR): 3088 (m), 3030 (m), 2949 (m), 2897 (m), 1736 (s), 1605
IR (KBr): 3103 (vw), 2976 (m), 2887 (s), 1717 (vs), 1595 (s), 1485
(s), 1448 (s), 1360 (vs), 1325 (s), 1310 (s), 1283 (vs), 1240 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 1.90 (s, 2 H, CH2), 2.33–2.56 (m,
10 H, CH2, CH), 2.97 (s, 2 H, CH2), 7.38–7.44 (m, 2 Harom), 7.53–
7.60 (m, 2 Harom), 8.01–8.05 (m, 2 Harom), 8.20–8.24 (m, 2 Harom).
13C NMR (100 MHz, CDCl3): d = 28.2 (CH), 35.3(CH2), 37.8
(CH2), 39.4 (CH2), 45.5 (Cq), 115.1 (m-CHarom), 119.9 (p-CHarom),
126.0 (m-CHarom), 130.4 (o-CHarom), 132.2 (Cipso), 144.7 (Cipso),
175.4 (C=O).
(m), 1597 (m), 1485 (m), 1452 (m), 1387 (vs), 1348 (s), 1288 cm–1
(s).
1H NMR (300 MHz, CDCl3): d = 4.27–4.30 (m, 4 H, CH2), 6.10–
6.20 (m, 2 H, CH=CH), 7.50–7.55 (m, 2 Harom), 7.64–7.70 (m, 2
Harom), 8.11–8.14 (m, 2 Harom), 8.26–8.30 (m, 2 Harom).
13C NMR (300 MHz, CDCl3): d = 39.0 (CH2), 114.3 (m-CHarom),
120.2 (p-CHarom), 126.3 (m-CHarom), 126.3 (CH=CH), 130.5 (o-
CHarom), 131.0 (Cipso), 146.2 (Cipso), 170.0 (C=O).
HRMS (ESI): m/z calcd for C18H14N6O2 + Na: 369.1055; found:
369.1070.
HRMS (ESI): m/z calcd for C24H22N6O2 + Na: 449.1687; found:
449.1696.
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Bis(N-acylamidines) from Amidines and N-Acylbenzotriazoles
1489
Anal. Calcd for C18H14N6O2: C, 62.42; H, 4.07; N, 24.27. Found: C,
62.24; H, 3.85; N, 23.92.
1H NMR (400 MHz, CDCl3–TFA, 1:1): d = 1.85 (br s, 2 H, CH2ad),
2.09–2.20 (m, 8 H, CH2ad), 2.41, 2.46 (br s, 4 H, CHad, CH2ad), 7.09
(d, 3J = 6.9 Hz, 4 Harom), 7.30–7.56 (m, 14 Harom), 7.67–7.70 (m, 2
Harom), 10.07, 13.48 (br s, 4 H, NH).
X-ray Crystal Structure Analysis for 6c14–20
C18H14N6O2, M = 346.35, light yellow crystal 0.40 × 0.25 × 0.10
13C NMR (100 MHz, CDCl3–TFA, 1:1): d = 29.7 (CHad), 36.2,
38.7, 39.5 (CH2ad), 46.5 (Cq), 127.2 (o/m-CHarom), 127.3 (Cipso),
131.3, 132.3, 132.7 (o/m-CHarom), 132.8 (p-CHarom), 135.7 (Cipso),
137.7 (p-CHarom), 168.8 (C=O), 184.2 (C=N).
mm,
a = 7.5662(2),
b = 10.0801(3),
c = 10.6640(3)
Å,
b = 102.475(2)°, V = 794.12(4) Å3, rcalc = 1.448 g cm–3, = 0.824
mm–1, empirical absorption correction (0.734 £ T £ 0.922), Z = 2,
monoclinic, space group P21/c (No. 14), l = 1.54178 Å, T = 223(2)
K, w and j scans, 4834 reflections collected ( h, k, l), [(sin q)/
l] = 0.60 Å–1, 1394 independent (Rint = 0.037) and 1266 observed
reflections [I ≥ 2 s(I)], 118 refined parameters, R = 0.038,
wR2 = 0.102, max. (min.) residual electron density 0.15 (–0.11) e Å–3,
hydrogen atoms calculated and refined as riding atoms.
HRMS (ESI): m/z calcd for C38H36N4O2 + H: 581.2911; found:
581.2914.
Anal. Calcd for C38H36N4O2: C, 78.59; H, 6.25; N, 9.65. Found: C,
78.20; H, 6.26; N, 9.42.
Adamantane-1,3-dicarboxylic Acid Bis(1-phenyl-1-o-tolylami-
nomethylideneamide) (7b)
Prepared from N-2-methylphenylbenzamidine (2b; 1.05 g,
5.0 mmol) and bis(N-acylbenzotriazole) 6a (0.85 g, 2.0 mmol) ac-
cording to the general procedure at r.t. The residue was purified by
flash chromatography (pentane–acetone; 5:1, 5% Et3N, Rf = 0.44)
to give 1.13 g (92%) of 7b as a colorless solid; mp 159 °C.
{5-[3-(Benzotriazole-1-carbonyl)-4-nitrophenyldisulfanyl]-2-
nitrophenyl}benzotriazol-1-ylmethanone (6d)
Prepared from 5,5¢-dithiobis(2-nitrobenzoic acid) (1.00 g,
2.5 mmol), benzotriazole (2.38 g, 20 mmol), SOCl2 (60 g,
5.0 mmol). Crystallization from THF gave 1.11 g (74%) of 6d as
colorless needles; mp 235.5 °C.
IR (ATR): 3107 (m), 3026 (m), 1726 (s), 1599 (m), 1566 (s), 1518
IR (ATR): 3071 (vw), 3030 (vw), 2980 (vw), 2936 (vw), 2899 (vw),
1655 (s), 1587 (m), 1562 (w), 1510 (vw), 1449 (vw), 1404 (vw),
1393 (vw), 1325 cm–1 (vw).
(vs), 1485 (s), 1450 (s), 1395 (vs), 1371 (s), 1337 (vs), 1219 cm–1
(s).
1H NMR (300 MHz, CDCl3): d = 7.57 (ddd, 2 H, 4J = 1.0 Hz,
1H NMR (400 MHz, pyridine-d5): d = 1.40–2.54 (m, 20 H, CH3,
4
3
3J = 7.2, 8.2 Hz, CHbt), 7.75 (ddd, 2 H, J = 1.0, J = 7.2, 8.2 Hz,
CHbt), 7.79–7.88 (m, 4 Harom), 8.10 (m, 2 H, CHbt), 8.28–8.28 (m, 2
Harom), 8.38–8.42 (m, 2 H, CHbt).
CH2, CH), 7.03–7.56, 8.21–8.33 (m, 18 Harom).
13C NMR (100 MHz, pyridine-d5): d = 18.6 (CH3), 29.0 (CH),
35.9, 38.7, 40.6 (CH2), 42.8 (Cq), 119.8, 125.1, 126.9, 129.2, 129.2
(CHarom), 131.1 (Cipso), 131.2, 131.7 (CHarom), 137.7, 148.8 (Cipso),
152.9 (C=N), 177.1 (C=O).
13C NMR (300 MHz, CDCl3): d = 114.2, 120.5 (CHbt), 125.6,
126.4, 126.9, 128.6 (CHarom, CHbt), 130.8, 131.0 (Cipso, Cipso,bt),
131.0 (CHbt), 144.1, 145.2, 146.2 (Cipso, Cipso,bt), 164.0 (C=O).
HRMS (ESI): m/z calcd for C40H40N4O2 + H: 609.3224; found:
609.3222.
HRMS (ESI): m/z calcd for C26H14N8O6S2 + Na: 621.0369; found:
621.0370.
Anal. Calcd for C40H40N4O2: C, 78.92; H, 6.62; N, 9.20. Found: C,
78.68; H, 6.57; N, 9.18.
Anal. Calcd for C26H14N8O6S2: C, 52.17; H, 2.36; N, 18.72. Found:
C, 52.40; H, 2.22; N, 18.73.
Adamantane-1,3-dicarboxylic Acid Bis[1-(4-methoxyphenyl-
amino)-1-phenylmethylideneamide] (7c)
X-ray Crystal Structure Analysis for 6d14–20
Prepared from N-methoxyphenylbenzamidine (2c;21 0.45 g,
2.2 mmol) and bis(N-acylbenzotriazole) 6a (0.43 g, 1.0 mmol) ac-
cording to the general procedure at r.t. The precipitate was collected
by filtration and washed with CH2Cl2 and Et2O to give 0.25 g (39%)
of a yellow solid; mp 217.9 °C.
C26H14N8O6S2, M = 598.57, colorless crystal 0.30 × 0.20 × 0.10
mm, a = 14.8146(2), b = 11.2958(2), c = 15.6873(2) Å,
b = 104.184(1)°, V = 2545.12(7) Å3, rcalc = 1.562 g cm–3, m = 2.435
mm–1, empirical absorption correction (0.529 £ T £ 0.793), Z = 4,
monoclinic, space group P21/n (No. 14), l = 1.54178 Å, T = 223(2)
K, w and j scans, 18775 reflections collected ( h, k, l), [(sin q)/
l] = 0.60 Å–1, 4485 independent (Rint = 0.044) and 4152 observed
reflections [I ≥ 2 s(I)], 379 refined parameters, R = 0.041,
wR2 = 0.110, max. (min.) residual electron density 0.29 (–0.20) e Å–3,
hydrogen atoms calculated and refined as riding atoms.
IR (ATR): 3237 (m), 3003 (w), 2932 (m), 2837 (w), 1655 (s), 1576
(m), 1501 (s), 1462 (m), 1296 (m), 1246 (s), 1209 cm–1 (m).
1H NMR (300 MHz, CDCl3–TFA, 1:1): d = 1.84 (s, 2 H, CH2ad),
2.07–2.18 (m, 8 H, CH2ad), 2.39, 2.45 (s, 4 H, CH2ad, CHad), 3.87 (s,
3
3
6 H, OCH3), 6.93 (d, J = 9.0 Hz, 4 Harom), 7.04 (d, J = 9.0 Hz, 4
H
arom), 7.43–7.57 (m, 8 Harom), 7.70 (t, 3J = 7.2 Hz, 2 Harom), 10.01,
Bis(N-acylamidines) 7a–i; General Procedure
13.41 (s, 4 H, NH).
Bis(N-acylbenzotriazole) (1 equiv) was added in small portions to a
solution of a primary or secondary amidine (at least 2 equiv) in
CH2Cl2 (20 mL). The reaction mixture was stirred for 16 h at r. t.
and then concentrated in vacuo. The crude product was purified as
stated below.
13C NMR (75 MHz, CDCl3–TFA, 1:1): d = 27.7 (CHad), 34.2, 36.7,
37.4 (CH2ad), 44.5 (Cq), 56.1 (OCH3), 116.0 (CHarom), 125.5 (Cipso),
126.7 (CHarom), 126.9 (Cipso), 129.3, 130.4, 135.7 (CHarom), 160.6
(Cipso), 166.2 (C=O), 182.2 (C=N).
HRMS (ESI): m/z calcd for C40H40N4O4 + H: 641.3122; found:
641.3126.
Adamantane-1,3-dicarboxylic Acid Bis(1-phenyl-1-phenylami-
nomethylideneamide) (7a)
Prepared from N-phenylbenzamidine (2a;7 0.88 g, 4.5 mmol) and
bis(N-acylbenzotriazole) 6a (0.85 g, 2.0 mmol) according to the
general procedure at r.t. The precipitate was collected by filtration
and washed with CH2Cl2 (5 mL) and Et2O (5 mL) to give 0.83 g
(71%) of 7a as a white solid; mp 244.9 °C.
Anal. Calcd for C40H40N4O4: C, 74.98; H, 6.29; N, 8.74. Found: C,
74.86; H, 6.02; N, 8.44.
Adamantane-1,3-dicarboxylic Acid Bis(1-isopropylamino-1-
phenylmethylideneamide) (7d)
Prepared from amidine 2d (0.41 g, 2.0 mmol) and bis(N-acylbenzo-
triazole) 6a (0.43 g, 1.0 mmol) according to the general procedure
IR (ATR): 3254 (vw), 3059 (vw), 2928 (vw), 2853 (vw), 1657 (vs),
1622 (m), 1593 (m), 1580 (vw), 1479 (vs), 1449 (m), 1250 (m),
1213 cm–1 (s).
Synthesis 2010, No. 9, 1485–1492 © Thieme Stuttgart · New York

1490
J. I. Clodt et al.
PAPER
at r.t. Purified by column chromatography (EtOAc + 5% Et3N) to
give 0.18 g (46%) of a white solid; mp 189.4 °C, Rf = 0.47.
IR (KBr): 3312 (m), 3177 (m), 2916 (vw), 2893 (vw), 1599 (vs),
1574 (s), 1506 (s), 1472 (s), 1443 (s), 1325 (m), 1312 (s), 1300 cm–
1 (s).
1H NMR (300 MHz, DMSO-d6): d = 3.18 (m, 4 H, CH2), 5.74 (br s,
2 H, CH=CH), 7.44–7.57 (m, 6 Harom), 7.99 (br s, 4 Harom), 9.15,
10.08 (br s, NH).
13C NMR (75 MHz, DMSO-d6): d = 44.7 (br, CH2), 126.8, 127.7
(br), 128.3 (CH=CH, CHarom), 131.9 (Cipso), 134.3, 165.2 (C=N),
186.3 (C=O).
IR (ATR): 3250 (s), 3101 (w), 2968 (w), 2930 (m), 1611 (s), 1585
(m), 1522 (vs), 1456 (m), 1447 (m), 1346 (m), 1327 (m), 1279
cm–1 (m).
1H NMR (500 MHz, CDCl3, 348 K): d = 1.21 [d, 3J = 6.5 Hz, 12 H,
CH(CH3)2], 1.60 (br s, 2 H, CH2ad), 1.73 (br s, 8 H, CH2ad), 1.88 (br
s, 2 H, CH2ad), 2.06 (br s, 2 H, CHad), 4.04 [br s, 2 H, CH(CH3)2],
7.33–7.50 (m, 10 Harom).
13C NMR (500 MHz, CDCl3, 348 K): d = 21.3 [CH(CH3)2], 27.9
(CHad), 35.4 (CH2ad), 38.6 (CH2ad), 41.5 (CH2ad), 42.5 [CH(CH3)2],
43.0 (Cq), 127.0, 127.4, 129.2 (CHarom), 135.1 (Cipso), 160.1 (C=N),
186.8 (C=O).
HRMS (ESI): m/z calcd for C20H20N4O2 + H: 349.1659; found:
349.1653.
X-ray Crystal Structure Analysis for 7f14–20
C20H20N4O2, M = 348.40, colorless crystal 0.40 × 0.20 × 0.07 mm,
a = 8.2780(2), b = 9.7590(2), c = 11.6178(3) Å, b = 105.713(1)°,
V = 903.47(4) Å3, rcalc = 1.281 g cm–3, m = 0.689 mm–1, empirical
absorption correction (0.770 £ T £ 0.953), Z = 2, monoclinic, space
group P21/c (No. 14), l = 1.54178 Å, T = 223(2) K, w and j scans,
6118 reflections collected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 1589
independent (Rint = 0.039) and 1500 observed reflections [I ≥ 2
s(I)], 124 refined parameters, R = 0.041, wR2 = 0.109, max. (min.)
residual electron density 0.15 (–0.16) e Å–3, hydrogen atom at N1
from difference Fourier maps, others calculated and refined as
riding atoms.
HRMS (ESI): m/z calcd for C32H40N4O2 + H: 513.3217; found:
513.3224.
Anal. Calcd for C32H40N4O2: C, 74.97; H, 7.86; N, 10.93. Found: C,
74.70; H, 7.47; N, 10.92.
Adamantane-1,3-dicarboxylic Acid Bis(1-amino-1-phenylmeth-
ylideneamide) (7e)
Prepared from benzamidine (0.36 g, 3.10 mmol) and bis(N-acyl-
benzotriazole) 6a (0.66 g, 1.55 mmol) according to the general pro-
cedure. The solution was washed with aq 2 N NaOH (2 × 20 mL),
dried (MgSO4), and evaporated. In order to obtain single crystals,
the solid was recrystallized from CHCl3–pentane mixtures; yield:
0.41 g (62%); colorless solid; mp 130–140 °C.
Cyclohexane-1,4-dicarboxylic Acid Bis(1-phenyl-1-phenylami-
nomethylideneamide) (7g)
Prepared from amidine 2a (1.37 g, 7 mmol) and bis(N-acylbenzo-
triazole) 6b (1.12 g, 3 mmol) according to the general procedure.
The solution was washed twice with aq 2 N NaOH (2 × 20 mL),
dried (MgSO4), and evaporated. Crystallization from DMF gave
0.75 g (47%) of 7g as a colorless solid; mp 216.4 °C.
IR (ATR): 3327 (w), 3069 (w), 2934 (vw), 2851 (vw), 1661 (vw),
1597 (s), 1570 (s), 1520 (s), 1506 (s), 1470 (m), 1443 (m), 1304 (m),
1275 cm–1 (m).
1H NMR (400 MHz, DMSO-d6): d = 1.65 (s, 2 H, CH2ad), 1.87 (br
s, 8 H, CH2ad), 2.06 (s, 2 H, CH2ad), 2.13 (s, 2 H, CHad), 7.47–7.60
(m, 6 Harom) 8.04–8.08 (m, 4 Harom), 9.02 (br s, 2 H, NH2), 10.05 (br
s, 2 H, NH2).
IR (KBr): 3238 (m), 3036 (m), 2951 (m), 2866 (m), 1684 (m), 1659
(s), 1624 (s), 1595 (m), 1483 (s), 1447 (s), 1315 (m), 1294 cm–1 (m).
1H NMR (400 MHz, pyridine-d5): d = 1.41–1.81 (m, 4 H, CH2),
13C NMR (400 MHz, DMSO-d6): d = 28.1 (CHad), 35.7 (CH2ad),
38.6 (CH2ad), 41.1 (CH2ad), 43.8 (Cq) 127.7 (m-Carom), 128.3 (o-
Carom), 131.8 (p-Carom), 134.8 (Cipso), 164.9 (C=N), 192.3 (C=O).
1.97–2.36 (m, 4 H, CH2), 2.45–2.66 (m, 2 H, CH), 6.84–8.07 (m, 18
Harom), 8.19–8.37 (m, 2 Harom), 10.91 (NH).
13C NMR (100 MHz, pyridine-d5): d = 29.4 (CH2), 44.8 (CH),
121.7 (CHarom), 124.7 (p-CHarom), 129.2, 129.4, 129.7 (o/m-CHarom),
131.7 (p-CHarom), 137.6, 150.6 (Cipso), 153.3 (C=N), 175.8 (C=O).
HRMS (ESI): m/z calcd for C26H28N4O2 + H: 429.2275; found:
429.2285.
Anal. Calcd for C26H28N4O2: C, 72.87; H, 6.59; N, 13.07. Found: C,
73.16; H, 6.52; N, 12.77.
HRMS (ESI): m/z calcd for C34H32N4O2 + H: 529.2598; found:
529.2627.
X-ray Crystal Structure Analysis for 7e14–20
Anal. Calcd for C34H32N4O2: C, 77.25; H, 6.10; N, 10.60. Found: C,
76.92; H, 5.99; N, 10.18.
C26H28N4O2·CHCl3,
M = 547.89,
colorless
crystal
0.30 × 0.15 × 0.07
mm, a = 12.3543(5),
b = 9.9727(4),
c = 21.6838(9) Å, b = 92.895(2)°, V = 2668.16(19) Å3, rcalc = 1.364
g cm–3, m = 3.368 mm–1, empirical absorption correction (0.432 £ T
£ 0.798), Z = 4, monoclinic, space group P21/c (No. 14),
l = 1.54178 Å, T = 223(2) K, w and j scans, 16303 reflections col-
lected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 4682 independent
(Rint = 0.047) and 4081 observed reflections [I ≥ 2 s(I)], 337 refined
parameters, R = 0.056, wR2 = 0.161, max. (min.) residual electron
density 0.15 (–0.11) e Å–3, hydrogen atoms at N1 and N18 from dif-
ference Fourier maps, others calculated and refined as riding atoms.
X-ray Crystal Structure Analysis for 7g14–20
C34H32N4O2·2
C3H7NO,
M = 674.83,
colorless
crystal
0.20 × 0.20 × 0.07
mm,
a = 15.2107(6),
b = 13.3684(6),
c = 19.7555(9) Å, b = 112.288(3)°, V = 3717.0(3) Å3, rcalc = 1.206
g cm–3, m = 0.633 mm–1, empirical absorption correction (0.884 £ T
£
0.957), Z = 4, monoclinic, space group C2/c (No. 15),
l = 1.54178 Å, T = 223(2) K, w and j scans, 13024 reflections col-
lected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 3253 independent
(Rint = 0.041) and 2733 observed reflections [I ≥ 2 s(I)], 231 refined
parameters, R = 0.048, wR2 = 0.129, max. (min.) residual electron
density 0.23 (–0.17) e Å–3, hydrogen atom at N3 from difference
Fourier maps, others calculated and refined as riding atoms.
(E)-Hex-3-enedioic Acid Bis(1-amino-1-phenylmethylidene-
amide) (7f)
Prepared from benzamidine (1.20 g, 10 mmol) and bis(N-acylben-
zotriazole) 6c (1.71 g, 5 mmol) according to the general procedure.
The precipitate was collected by filtration and washed with CH2Cl2
(2 × 5 mL). In order to obtain single crystals, the solid was recrys-
tallized from CH2Cl2–DMF mixtures; yield: 0.86 g (50%); light-
orange solid; mp 162.4 °C.
5,5¢-Dithiobis(2-nitrobenzoic Acid) Bis(1-amino-1-phenylmeth-
ylideneamide) (7h)
Prepared from benzamidine (0.18 g, 0.7 mmol) and bis(N-acylben-
zotriazole) 6d (0.42 g, 0.7 mmol) according to the general proce-
dure. After removal of the solvents by evaporation, TBME (5 mL)
was added to the residue. Ultrasonication led to a yellow solid. The
Synthesis 2010, No. 9, 1485–1492 © Thieme Stuttgart · New York

PAPER
Bis(N-acylamidines) from Amidines and N-Acylbenzotriazoles
1491
solid was collected by filtration and washed with TBME (5 mL) to
give 0.26 g (62%) of 7h as a light-yellow solid; mp 101.3 °C (dec.).
13C NMR (100 MHz, CDCl3): d = 123.9, 126.1, 128.4, 129.4,
129.7, 129.8, 132.6 (CHarom), 137.0, 138.5, 147.7, 151.2 (Cipso),
164.0 (br, C=N), 165.6 (C=N), 179.5 (br, C=O).
IR (ATR): 3333 (m), 3308 (m), 3184 (w), 3088 (m), 1605 (s), 1562
(s), 1530 (s), 1477 (s), 1441 (s), 1369 (s), 1319 (vs), 1290 cm–1 (m).
HRMS (ESI): m/z calcd for C34H26N4O2 + H: 523.2129; found:
523.2116.
1H NMR (400 MHz, DMSO-d6): d = 7.47 (t, 3J = 7.6 Hz, 4 H,
CHarom), 7.56 (t, 3J = 7.3 Hz, 2 H, CHarom), 7.85 (dd, 4J = 2.2,
3J = 8.5 Hz, 2 H, CHarom), 7.98–7.90 (m, 6 Harom), 8.15 (d,
4J = 2.2 Hz, 2 Harom), 9.69 (s, 2 H, NH), 10.24 (s, 2 H, NH).
13C NMR (101 MHz, DMSO-d6): d = 121.1, 124.7, 126.8, 128.2,
128.5, 132.6 (CHarom), 133.5, 134.4, 140.1, 148.0 (Cipso), 167.0
(C=N), 175.4 (C=O).
Anal. Calcd for C34H26N4O2: C, 78.14; H, 5.01; N, 10.72. Found: C,
77.82; H, 5.12; N, 10.55.
X-ray Crystal Structure Analysis for 1114–20
C34H26N4O2·2
0.10 × 0.08 × 0.05
C2H6OS,
mm,
M = 678.84,
a = 5.4554(1),
colorless
crystal
b = 11.5381(2),
c = 13.3390(3) Å, a = 98.112(1), b = 92.331(1), g = 96.284(1)°,
V = 824.88(3) Å3, rcalc = 1.367 g cm–3, m = 1.853 mm–1, empirical
absorption correction (0.836 £ T £ 0.913), Z = 1, triclinic, space
group P1 (No. 2), l = 1.54178 Å, T = 223(2) K, w and j scans, 8843
reflections collected ( h, k, l), [(sin q)/l] = 0.60 Å–1, 2924 inde-
pendent (Rint = 0.050) and 2525 observed reflections [I ≥ 2 s(I)],
239 refined parameters, R = 0.043, wR2 = 0.107, max. (min.) resid-
ual electron density 0.20 (–0.27) e Å–3, hydrogen atom at N5 from
difference Fourier maps, others calculated and refined as riding at-
oms.
HRMS (ESI): m/z calcd for C28H20N6O6S2 + H: 601.0959; found:
601.0957.
Anal. Calcd for C28H20N6O6S2: C, 55.99; H, 3.36; N, 13.99. Found:
C, 55.88; H, 3.73; N, 14.21.
N,N¢-Di(1,3-thiazol-2-yl)-1,3-adamantanedicarboxamide (8)
Prepared from 2-aminothiazole (0.6 g, 6.0 mmol) and bis(N-acyl-
benzotriazole) 6a (1.28 g, 3.0 mmol) according to the general pro-
cedure at r.t. Crystallization from EtOH gave 1.02 g (87%) of 10 as
a light orange solid; mp 275.0–277.6 °C.
IR (ATR): 3186 (w), 3055 (vw), 2911 (m), 2853 (m), 1678 (vs),
1530 (vs), 1487 (s), 1458 (s), 1447 (s), 1435 (s), 1331 (s), 1269
cm–1 (vs).
1H NMR (300 MHz, DMSO-d6): d = 1.68 (br s, 2 H, CHad), 1.82–
2.02 (m, 8 H, CHad), 2.16 (br s, 4 H, CHad), 7.18–7.19 (d,
3J = 3.6 Hz, 2 Harom), 7.48–7.49 (d, 3J = 3.6 Hz, 2 Harom).
Acknowledgment
We thank Dr. Christof Wigbers for preliminary experiments in this
field. This work was supported by the International Research Trai-
ning Group 1444 Münster (DFG) and the Fonds der Chemischen In-
dustrie (Frankfurt).
13C NMR (300 MHz, DMSO-d6): d = 27.6 (CHad), 34.4, 36.6, 38.2
(CH2ad), 41.0 (Cq,ad), 113.4 (SCHthiazolyl), 137.5 (NCHthiazolyl), 158.5
(C=N), 175.3 (C=O).
References
(1) (a) Eberhardt, J. K.; Glaser, T.; Hoffmann, R. D.; Fröhlich,
R.; Würthwein, E.-U. Eur. J. Inorg. Chem. 2005, 1175.
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HRMS (ESI): m/z calcd for C18H20N4O2S2 + H: 398.1106; found:
398.1100.
Anal. Calcd for C18H20N4O2S2: C, 55.65; H, 5.19; N, 14.42. Found:
C, 55.48; H, 5.03; N, 14.38.
X-ray Crystal Structure Analysis for 814–20
C18H20N4O2S2, M = 388.50, colorless crystal 0.30 × 0.20 × 0.10
mm, a = 7.2609(4), b = 12.1746(7), c = 19.6542(10) Å,
V = 1737.4(2) Å3, rcalc = 1.485 g cm–3, m = 2.963 mm–1, empirical
absorption correction (0.470 £ T £ 0.756), Z = 4, orthorhombic,
space group Pna21 (No. 33), l = 1.54178 Å, T = 223(2) K, w and j
scans, 9365 reflections collected ( h, k, l), [(sin q)/l] = 0.60 Å–1,
2815 independent (Rint = 0.035) and 2801 observed reflections [I ≥
2 s(I)], 242 refined parameters, R = 0.032, wR2 = 0.087, max.
(min.) residual electron density 0.27 (–0.16) e Å–3, refined as race-
mic twin, hydrogen atoms at N3 and N21 from difference Fourier
maps, others calculated and refined as riding atoms.
(5) Pinner, A. Ber. Dtsch. Chem. Ges. 1889, 22, 1600.
(6) Wigbers, C.; Prigge, J.; Fröhlich, R.; Chi, L.; Mu, Z.;
Würthwein, E.-U. manuscript in preparation.
(7) In analogy to a procedure by Cooper et al.: Cooper, F. C.;
Partridge, M. W. Org. Synth. 1956, 36, 64.
(8) Chua, S.-O.; Cook, M. J.; Katritzky, A. R. J. Chem. Soc.,
Perkin Trans. 2 1974, 546.
(9) (a) Hack, V. unpublished results. (b)See: Hack, V. Diploma
Thesis; University of Münster: Germany, 2007, Carpino L.
A.; J. Am. Chem. Soc.; 1993, 115: 4397.
N-(1-Phenylamino-1-{4-[phenylamino(benzoylimino)meth-
yl]phenyl}methylidene)benzamide (11)
Diamidine 921,22(0.31 g, 1.0 mmol) and N-benzoylbenzotriazole
(10; 0.47 g, 2.1 mmol) were suspended in CH2Cl2 (20 mL) and re-
fluxed for 6 h. The solvent was removed under reduced pressure,
TBME (5 mL) was added to the residue and the white precipitate
was collected by filtration after sonication. The solid was dissolved
in CH2Cl2 (50 mL) and the CH2Cl2 layer was washed with aq 0.1 N
NaOH (20 mL). The organic layer was dried (MgSO4), filtered, and
evaporated to give 0.44 g (85%) of a colorless solid; mp 225.7 °C.
(10) Carpino, L. A. J. Am. Chem. Soc. 1993, 115, 4397.
(11) Katritzky, A. R.; Suzuki, K.; Wang, Z. Synlett 2005, 1656.
(12) (a) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003,
2795. (b) Katritzky, A. R.; Meher, N. K.; Cai, C. S.;
Sandeep, K. Rev. Soc. Quim. Mexico 2004, 4, 275; Chem.
Abstr. 2005, 143, 26540.
IR (ATR): 3267 (w), 3132 (w), 3034 (w), 2984 (w), 1601 (m), 1578
(s), 1522 (s), 1497 (s), 1443 (s), 1406 (m), 1369 (s), 1267 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 6.94–7.02 (m, 4 Harom), 7.10–7.22
(m, 6 Harom), 7.40–7.47 (m, 4 Harom), 7.52–7.54 (m, 2 Harom), 7.56 (s,
4 Harom,spacer), 8.30–8.31 (m, 4 Harom), 12.27 (s, 2 H, NH).
Synthesis 2010, No. 9, 1485–1492 © Thieme Stuttgart · New York

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J. I. Clodt et al.
PAPER
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(14) Data sets were collected with a Nonius KappaCCD
diffractometer. Programs used: data collection COLLECT;15
data reduction Denzo-SMN,16 absorption correction
Denzo,17 structure solution SHELXS-97,18 structure
refinement SHELXL-97,19 graphics SCHAKAL.20 CCDC
755612–755620 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44(1223)336033, E-mail:
deposit@ccdc.cam.ac.uk].
(21) Cooper, F. C.; Partridge, M. W. J. Chem. Soc. 1953, 255.
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Synthesis 2010, No. 9, 1485–1492 © Thieme Stuttgart · New York