Trimethylaluminium-mediated reaction of primary carboxamides with amines and indoles: A convenient synthesis of amidines and indole-3-acylimines

Article abstract of DOI:10.1002/ejoc.201402386

A simple, convenient and general method, exhibiting good functional group tolerance, is described for the synthesis of N- and N,N-disubstituted amidines by the reaction of primary carboxamides with amines mediated by trimethylaluminium (AlMe₃).

Full text of DOI:10.1002/ejoc.201402386

FULL PAPER
DOI: 10.1002/ejoc.201402386
Trimethylaluminium-Mediated Reaction of Primary Carboxamides with
Amines and Indoles: A Convenient Synthesis of Amidines and
Indole-3-acylimines
A. Velavan,[a] S. Sumathi,*[a] and K. K. Balasubramanian*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Amines / Amides / Aluminium
A simple, convenient and general method, exhibiting good
functional group tolerance, is described for the synthesis of
N- and N,N-disubstituted amidines by the reaction of pri-
mary carboxamides with amines mediated by trimethylalu-
minium (AlMe3). Subsequent reaction of the indole systems
with primary carboxamides in the presence of AlMe3 gives
exclusively the C-3 substituted imine product.
related to the synthesis of amidines from secondary carbox-
amides, many research groups including Katritzky et al.,[28]
Thakur et al.,[29] Loughlin et al.,[30a] Shibasaki et al.,[30b]
and Bihel et al.,[30c] contributed significantly in this area.
Whereas these methodologies are suitable for secondary
carboxamides, they are strictly not applicable for primary
carboxamides. Indeed, activation of primary carboxamides
for the synthesis of amidines has not been successful in any
of the methods reported hitherto.
Introduction
Amidines, as a class of compounds, find wide applica-
tions as superbases[1] and in the fixation of CO2.[2,3] They
also find use in material science,[4,5] in the design of cata-
lysts,[6,7] in medicinal chemistry as biologically active mo-
lecules,[8–11] and as important intermediates for many chem-
ical transformations.[12–17] Amidines are usually synthesised
by reacting amines with common precursors such as ni-
triles,[18–26] secondary amides[27–30] or thioamides.[31] Often
in the functional group transformation of nitriles into amid-
ines, the nitrile functionality is activated by Lewis acid or
is converted into the corresponding imidate ester.[19–21] Shen
et al. reported the synthesis of amidines from nitriles cata-
lysed by Ytterbium amide[32,33] that involves a solvent-free
reaction. However, this reaction requires an extended time
and it is accompanied by the formation of the unwanted
side product triazine. Furthermore, 4-cyanopyridine, ali-
phatic nitriles, and aliphatic amines reacted sluggishly un-
der these conditions. The latter methodology requires the
use of excess amine (2.0 equiv.), and has been successfully
applied only for aromatic primary amines. Palladium-cata-
lysed amidine synthesis using cyanamide has been recently
reported by Larhed et al. but this approach has the limita-
tion of only employing aliphatic amines.[34]
Results and Discussion
During the course of our research work on trimethylalu-
minium (AlMe3) mediated organic transformations for the
synthesis of tetrasubstituted ureas,[35] we encountered dehy-
dration of the primary carboxamide (1) to nitrile (3), in-
stead of the expected urea (4) (Scheme 1). In the direct syn-
thesis of nitriles from esters or primary carboxamides using
methylchloroaluminium amide developed by Weinreb et al.,
there was no indication for the formation of any amidine
product.[36] Later, Gielen et al.[37] reported the preparation
of unsubstituted amidines directly from esters by employing
an excess of methylchloroaluminium amide. In this method-
ology, only ammonia (NH3) could be used, giving unsubsti-
tuted amidines. Reaction of primary/secondary amines with
esters in the presence of AlMe3 furnished only the amide
product.[38a] AlMe3-mediated amidine synthesis by acti-
vation of nitriles was first reported by Garigipati[23] and
later by many others.[24–26] Herein, we report the synthesis
of N- and N,N-disubstituted amidines by dual activation
of primary carboxamides and amines by AlMe3. A direct
synthesis of indole-3-acylimines is also described. Because
amidines were prepared from nitriles, we envisioned a one-
pot reaction whereby both the nucleophile (amine) and the
electrophile (primary carboxamide) could be activated to
form amidines.
Synthesis of amidines by electrophilic activation of ali-
phatic secondary or tertiary amides using triflic anhydride
was reported by Charette et al.,[27] but this approach is
found to be less effective in the case of both aliphatic and
aromatic primary carboxamides. Subsequent to this report
[a] Department of Chemistry, Hindustan University, Rajiv Gandhi
Salai,
Padur via Kelambakkam, Chennai, Tamilnadu 603103, India
E-mail: sumathi@hindustanuniv.ac.in
kkbalu@hotmail.com
http://hindustanuniv.ac.in/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402386.
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Convenient Synthesis of Amidines and Indole-3-acylimines
Table 2. Scope of the reaction with primary amines.[a]
Scheme 1. Primary carboxamide dehydration using AlMe3.
For this methodology, p-phenitidine (1a) and benzamide
(1b) were chosen for optimization of the reaction conditions
(Table 1). When a mixture of 1a (1.1 mmol) and 1b
(1.0 mmol) were heated in anhydrous toluene with AlMe3
(1.5 equiv.) under a nitrogen atmosphere for 4 h, only a very
low conversion of the reactant into amidine 1c (11–23%)
was observed.
Table 1. AlMe3-promoted direct coupling of p-phenitidine (1a) with
benzamide (1b).
Entry
AlMe3
[equiv.]
Conversion after 4 h [%][a]
80 °C
Reflux
1
2
3
1.5
2.2
2.8
11
59
89
23
72
99[b]
[a] Conversion based on 1b by HPLC analysis. [b] After 2.5 h.
[a] Reaction conditions: amine (1.1 mmol), primary carboxamide
(1.0 mmol). [b] Isolated yield. [c] Amine (2.0 equiv.) was used.
A better conversion was realised with an excess of AlMe3
(2.2 equiv.), however, a considerable amount of benzamide
1b remained unreacted. Although the stoichiometry of the
We then studied the reactivity difference between the ali-
reaction demands 2.0 equiv. AlMe3 for the dehydration of phatic and the aromatic primary carboxamides. 2,6-Dieth-
primary carboxamide, the amidine reaction proceeded to ylaniline (11a), a sterically hindered aromatic primary
completion with 2.8 equiv. of AlMe3 (Table 1, entry 3). By amine, was chosen as a standard and it was allowed to react
employing the optimised conditions, the reaction of benz- with a selection of carboxamides (Table 3, 1–5b). Aliphatic
amide 1b with a variety of amines (1–10a) of varying nu- carboxamides 2b and 4b were found to be less reactive com-
cleophilicity was studied (Table 2). Both aromatic primary pared with the aromatic primary carboxamide 1b. It is
amines (Table 2, entries 1–9) as well as aliphatic primary interesting to note that α,β-unsaturated carboxamide 3b
amine 10a, exhibited good reactivity under these condi- (entry 3) displayed a high reactivity and afforded amidine
tions. Functional groups such as OEt, OCHF2, and Cl (en- 13c in very good yield, unlike phenylacetamide 2b. The re-
tries 1, 4, 6 and 8) were found to be compatible with this action of 3b was clean and free from side products gener-
methodology. Even the less reactive 2,6-dichloroaniline (6a) ated due to isomerisation of the double bond or Michael
reacted to afford amidine 6c, although the maximum con- addition of the amine or methyl group.[39] The diminished
version was observed after 12 h reflux in toluene (entry 6). reactivity of the aliphatic amides may be due to the lower
Thus, the AlMe3-mediated reaction of benzamide 1b with acidity of the amide protons[40] compared with their aro-
primary amines proved to be a useful method for the prepa- matic counterparts, and consequent difficulty in forming
ration of N-substituted amidines.
the aluminium imidate (A, Scheme 4). The aliphatic carbox-
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A. Velavan, S. Sumathi, K. K. Balasubramanian
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amide 4b, derived from the anti-inflammatory drug, ibup- ine formation from secondary amides. There was no reac-
rofen, was less reactive than 2b (entry 4). Trimethylalumin- tion when secondary amide 10b was subjected to the reac-
ium-mediated amidine formation from (S)-(4-isobutyl- tion conditions outlined in Scheme 2.
phenyl)-2-methylpropionamide (4b) was observed with par-
Table 4. Reactivity of carboxamides with aromatic secondary
tial racemisation, and the product 14c was isolated in 81%
yield with 64% (ee) as revealed by chiral HPLC analysis.
Pivalamide 5b was found to be totally unreactive, and no
amidine product was observed in this case (entry 5), which
may be due to steric crowding around the amide function-
ality emanating from the amide 5b as well as from 2,6-di-
ethyaluminium amide.
amines in amidine synthesis.[a]
Table 3. Reactivity of various carboxamides with aromatic primary
amine 11a.[a]
[a] Reaction conditions: amine (1.1 mmol), primary carboxamide
(1.0 mmol). [b] 4-Chloro-N-methylaniline was used. [c] Diphenyl-
amine was used. [d] Isolated yield. [e] HPLC conversion of carbox-
amide in 2 h at 80 °C. [f] Not observed.
[a] Reaction conditions: amine (1.1 mmol), primary carboxamide
(1.0 mmol). [b] Isolated yield. [c] Not observed.
We then investigated the scope of this amidine synthesis
by employing secondary amines with diphenylamine (13a)
as a standard. Compound 13a was treated with a selection
of aromatic primary carboxamides 1b and 6–9b bearing dif-
ferent substituents (Table 4). All the amides reacted equally
well except p-nitrobenzamide (9b). The reaction was com-
plex in the case of 9b (entry 6). The synthesis of amidines
18c and 19c, bearing halogen substituents from the corre-
sponding halobenzoic acids, is more economical than from
the corresponding halogenated benzonitriles. Secondary
and the tertiary amides were prepared by the reaction of
amines with carboxylic esters[38a] or acids[38b] in the pres-
ence of AlMe3. In this connection, we wished to verify the
Scheme 2. Reactivity comparison of primary and secondary
scope of this AlMe3-mediated transformation for the amid- carboxamides in the presence of AlMe3.
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Convenient Synthesis of Amidines and Indole-3-acylimines
We also observed that when a mixture of benzamide (1b), (entry 3) showed good tolerance towards these conditions,
benzanilide (10b) and N,N-dimethylbenzamide (11b) were with aliphatic primary amines derived from valine, 14a and
treated with aniline in the presence of AlMe3, amidine 9c 15a exhibiting good reactivity.
was formed as the sole product (Scheme 2). Furthermore,
The success of this amidine formation seems to depend
the AlMe3-mediated reaction of p-aminoacetanilide (5a) on the ease of formation of the aluminium-amide from the
with aniline afforded the amidine 5c in 71% yield (Table 2, reaction of AlMe3 with the amines. Aromatic amines are
entry 5). The rest of the starting material remained unre- more readily deprotonated by AlMe3 to form the more nu-
acted. No polymeric product arising out of the self-conden- cleophilic aluminium amide, whereas the more basic ali-
sation of 5a could be detected. Thus, this transformation is phatic amines form only the Lewis acid–base adduct with
found to display an exclusive chemoselectivity in favour of AlMe3.[41] The reactions are also found to be faster in the
the primary carboxamide (Scheme 2).
cases of aromatic primary amine compared with that of ali-
Aromatic secondary amines 12a and 13a (Table 4, entries phatic amines (Table 2, entry 10 and Table 5, entries 2 and
1–5) gave the respective amidines in good yields under these 3), which may be due to the ease of formation of the alu-
conditions. Sterically hindered 2,6-diisopropylaniline 7a minium amide in the case of aromatic amines (B, see
(Table 2, entry 7) and 2,6-diethylaniline 11a (Table 3, entries Scheme 4 below).
1–4) also underwent this transformation to afford the re-
Benzylamine is known to form a Lewis acid:base com-
spective amidines in good yields. Heteroaromatic primary plex with trimethylaluminium. The formation of the alu-
carboxamides 12–14b, were also successfully transformed minium amide from this complex is evidently a slow pro-
into the corresponding amidines 22–26c (Table 5, entries 1– cess. This is supported by the findings from the reaction of
5). Silyl protecting groups OTBS (entry 2) and OSi(iBu)3 carboxamide 4b with aliphatic secondary amines 16a, 17a
and 18a, and a hindered aromatic amine 11a (see Table 6).
Whereas no conversion was observed in the case of any of
Table 5. Scope of the reaction with heterocyclic carboxamide and
different amines.[a]
the aliphatic amines (entries 2–4), moderate conversion
(42%) into amidine 14c was observed in the case of 2,6-
diethylaniline, despite it being a sterically hindered aromatic
amine (entry 1).
Table 6. Nucleophilicity of amines with less reactive aliphatic
carboxamide in the presence of AlMe3.
Entry
Amine
Amidine (conversion, %)
1
2
3
4
2,6-diethylaniline (11a)
dibenzylamine (16a)
piperidine (17a)
14c (42)[a]
27c (0)[b]
28c (0)[b]
29c (0)[b]
N-benzylpiperazine (18a)
[a] By HPLC analysis. [b] Not observed by HPLC or LCMS analy-
ses.
In addition to the above observation, we can compare
the results from Table 2, in which 1.1 equiv. aniline 9a (en-
try 9) was treated with 1b to give amidine 9c in good yield.
When 1.1 equiv. benzylamine (10a, Table 2, entry 10) was
used, the conversion by TLC was not attractive and excess
benzylamine (2.0 equiv.) was required for complete conver-
sion. Thus, it is clear that aliphatic amines are relatively
poor substrates for the AlMe3-mediated amidine synthesis.
With such amines, the reaction could still be realised by
employing the amine in excess (2.0–3.0 equiv.).[38b,42,43]
We also compared the reaction of benzonitrile and
benzamide with diphenylamine under identical conditions
(heating in toluene at 75 °C for 3 h using 2.8 equiv. AlMe3;
Table 7). HPLC analysis revealed the complete absence of
benzonitrile after 3 h, with the maximum conversion of
89% into amidine (entry 1), whereas in the case of benz-
[a] Reaction conditions: amine (1.1 mmol), primary carboxamide
(1.0 mmol). [b] Isolated yield. [c] Amine (2.0 equiv.) was used.
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amide (entry 2) only 25% conversion into amidine 17c was the behaviour of indoles towards primary carboxamide in
observed, with the major amount being the starting materi- the presence of AlMe3.
als benzamide and diphenylamine. No benzonitrile interme-
When an equimolar mixture of indole, 4-chlorobenz-
diate was detected in this reaction (entry 2). In another re- amide and AlMe3 (2.5 equiv.) were heated at 100 °C in tolu-
action, conducted under the same conditions in the absence ene for 15 h, the reaction was incomplete as revealed by
of diphenylamine, benzamide was completely dehydrated to TLC. The reaction was driven to completion by employing
benzonitrile (Scheme 3). Thus, it is evident that the reaction 3.0 equiv. AlMe3 and continuing the reaction for 24 h. We
of the nitrile with amine is faster than the dehydration of were pleased to observe the formation of indole-3-acylimine
the amide to nitrile.
(30c; Table 8, entry 1) as the only product. We did not ob-
serve any amidine product arising from the attack of indole
nitrogen. Indole C3, being a soft centre, preferentially re-
acted with the nitrile to give imines.
Table 7. Reactivity comparison of benzonitrile and benzamide.
Table 8. Indole-3-acylimine synthesis.
Entry
Electrophile
Conversion [%][a]
1
2
benzonitrile
benzamide
89
25
[a] Conversion based on HPLC analysis.
Scheme 3. Dehydration of benzamide mediated by AlMe3.
We have not observed any transamidation[44] product or
triazine[22,32,33] in any of our reactions. These observations
suggest that amidine formation probably proceeds via ni-
trile intermediate F, as depicted in Scheme 4. An alternative
mechanistic possibility, involving tetrahedral intermediate
C formed by attack of aluminium amide B on imidate A
(Scheme 4), seems to be less probable from the findings that
the reaction takes place readily even in the case of hindered
amines. Formation of tetrahedral intermediate C from imid-
ate A would be sterically less favoured in the case of hin-
dered amines such as 2,6-disubstituted anilines (Table 2, en-
try 7). Furthermore, nitriles have been isolated in some of
these reactions (Scheme 3 and Scheme 1), and nitriles have
been converted into the amidines by reacting with amines
in the presence of Lewis acid catalysts.[23–26] Because indoles
are ambident nucleophiles, it was of interest to investigate
[a] Isolated yield. [b] Not observed.
Primary carboxamides have never been considered to be
convenient candidates for Friedel–Crafts acylation reac-
tions because of their weak electrophilic nature. It is worth
mentioning here that this is the first report to demonstrate
the use of primary carboxamides as electrophiles in the
Friedel–Crafts acylation of indoles. There are only a few
reports on Friedel–Crafts acylation reactions involving ni-
triles as electrophiles.[45] Indole C3-acyl imines are potential
precursors for many transformations. All these imines are
stable towards the aqueous work up conditions involving
saturated ammonium chloride. Acylimine 31c was hydro-
lysed to the corresponding ketone 34c by using 50% sulfuric
acid upon heating at 50 °C for 1 h (Scheme 5).
Unsymmetrical amidines are known to exist as tauto-
mers in solution associated with proton transfer between
the two nitrogen centres, and the existence of tautomerism
was established by proton NMR spectroscopy.[46,47] It was
observed that the predominant tautomer at equilibrium was
Scheme 4. Possible mechanistic pathways.
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Convenient Synthesis of Amidines and Indole-3-acylimines
as on the basis of previously reported data. The 13C NMR
spectrum of 24c displayed more signals than can be ac-
counted for on the basis of tautomers.
Conclusions
Scheme 5. Hydolysis of imine 31c.
We have demonstrated a simple, general and high-yield-
ing method for the synthesis of substituted amidines from
the reaction of primary carboxamides and amines. This
methodology is complementary to existing methodologies,
which are restricted to secondary carboxamides. The pres-
ent methodology is applicable for aliphatic primary amines
and aromatic amines of diverse nucleophilicity. A variety of
amines, including hindered aromatic amines, less nucleo-
philic amines and heterocyclic amines, undergo this reac-
tion. Whereas aromatic and heterocyclic primary carbox-
amides are excellent substrates for this transformation, ali-
phatic carboxamides also exhibited reasonable reactivity.
This methodology showed high functional group tolerance,
with -OTBS, -OSi(iBu)3, -Cl, -I, -F, -OCHF2, -OMe, -OEt,
and -CONHR being stable under the conditions of the
AlMe3-mediated amidine formation. Primary carboxamides
are chemoselectively transformed into amidines in the pres-
ence of secondary and tertiary carboxamides. This reaction
is free from the formation of side products from transamid-
ation or cyclotrimerisation (s-triazine). It is noteworthy that
primary carboxamides, which have been useful only for
transamidation,[49] or nitrile synthesis,[50] have been found
to be a useful electrophile in Friedel–Crafts acylation of
indoles. Because inexpensive halobenzoic acids could be
preferred over the more expensive halogenated benzonitrile
for amidine synthesis, this methodology provides conve-
nient access to amidines directly from primary carboxam-
ides and serves as an alternative to routes starting from ni-
triles.
that with the more basic nitrogen atom bearing the
hydrogen. The rotational isomerism was studied by using
variable-temperature NMR spectroscopy. Tautomerism in
amidines has also been studied by infrared spectroscopy.[48]
In the IR spectrum (CHCl3), primary amidines exhibit
three bands in the N–H stretching region. The first is a
weak band at 3400–3300 cm–1, which corresponds to the
asymmetric N–H stretching, and a second band in the re-
gion 3330–3250 cm–1, corresponding to the symmetric N–
H stretch. The third band occurs near 3450 cm–1, and corre-
sponds to the N–H stretch of a secondary amino group. In
addition to these bands, a band due to N-H bending vi-
bration is also observed near 1650–1580 cm–1. N,N,NЈ-Tri-
substituted amidines were found to be the least basic. With
a view to gain some insight into the tautomerism of the
amidines that we have synthesised, we analysed the proton
NMR spectrum of amidine 1c. The proton NMR spectrum
of 1c (CDCl3) exhibited a signal due to the NH2 protons
(integrated for two protons) at δ = 4.58 ppm, which disap-
peared on D2O exchange. No evidence could be found in
the NMR spectrum for the presence of the second tauto-
mer, i.e., the imino form. Indeed, no additional signals were
1
seen in the H NMR spectrum. Likewise, the 13C NMR
spectrum also suggested it to be homogeneous compound
and did not contain any additional carbon signals. In con-
trast, amidines 23c and 24c were found to exist as a mixture
of two tautomers, as revealed by their H and 13C NMR
1
spectra (see NMR and IR spectra in the Supporting Infor-
mation), although HPLC analysis indicated that amidine
24c was 99% pure. Evidently, the mixture of tautomers
could not be resolved by HPLC. HRMS of 24c was consis-
tent with the expected molecular formula. Although ac-
cording to the literature reports, the amino and imino forms
show distinguishable characteristic NH stretching bands in
the IR spectrum, the IR spectrum of 24c (neat) recorded in
NaCl disc and in CHCl3 did not clearly show =N-H and
-NH2 stretching vibrations. The region 3584–3012 cm–1 was
broad and was not informative. A band of medium intensity
was, however, seen at 1654 cm–1, which corresponds to
C=N stretching vibration. Amidines 23c and 24c exist as a
mixture of tautomers in solution. The proton NMR spec-
trum of 24c in [D6]DMSO displayed two broad signals, with
an appreciable chemical shift separation, one at δ =
6.22 ppm and one at δ = 5.11 ppm and both these signals
disappeared upon D2O exchange. The upfield exchangeable
signal at δ = 5.11 ppm is due to the amino proton and the
more downfield signal at δ = 6.22 ppm is due to the imino
Experimental Section
General Information: NMR spectra were recorded in CDCl3 or
[D6]DMSO with 300, 400 or 500 MHz spectrometers and reso-
nances are reported relative to TMS. Melting points were recorded
by the open capillary method and are uncorrected. All reagents
were purchased from commercial suppliers and were used without
further purification unless noted. AlMe3 (2 m in toluene) was used.
Toluene was dried with sodium, distilled and stored over molecular
sieves. All reactions were conducted under an atmosphere of nitro-
gen. The products were purified with an automated flash chro-
matographer on silica gel (200–400 mesh). High-resolution mass
spectroscopy was carried out in electron spray ionisation mode.
Typical Procedure for Amidine Synthesis: A solution of AlMe3 (2 m
in toluene, 5.6 mmol, 2.8 equiv.) was added dropwise to a mixture
of aromatic amine (2.2 mmol, 1.1 equiv.) and primary carboxamide
(2 mmol, 1.0 equiv.) in anhydrous toluene (3 mL) at 0 °C in a
flame-dried two-necked flask, under nitrogen. The resulting mix-
ture was stirred for 30 min at room temp. and heated to 110 °C (oil
bath temperature) for the given time. The mixture was cooled to
0 °C and diluted with CH2Cl2 (20 vol) and then slowly poured into
proton. This assignment is based on the integration as well ice-cold saturated NH4Cl solution (4 mL). THF (15 vol) was added
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A. Velavan, S. Sumathi, K. K. Balasubramanian
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and the mixture was stirred for 30 min at room temp. then filtered
through a Celite bed, dried with sodium sulphate, and concentrated
to give the crude product.
TMS, CDCl3): δ = 155.4, 143.9, 134.8, 133.3, 131.0, 129.3, 128.6,
128.4, 127.6, 127.1, 123.9 ppm. HRMS (ESI): m/z calcd. for
C13H11Cl2N2 [M + H]+ 265.0294; found 265.0291.
Note: Different amounts of amine are necessary [aliphatic primary
amine (2.0 equiv.) or aromatic amine (1.1 equiv.)] for maximum
conversion where primary carboxamide is the limiting reagent.
N-(2,6-Diisopropylphenyl)benzamidine (7c): Yield 90 mg (89%);
white solid; m.p. 160–163 °C (ref.[32] m.p. 162–163 °C). 1H NMR
(300 MHz, TMS, [D6]DMSO): δ = 8.0 (d, J = 6 Hz, 2 H), 7.54–
7.44 (m, 3 H), 7.13–7.10 (m, 2 H), 7.04–6.90 (m, 1 H), 6.50–6.10
(br., 2 H), 2.98–2.89 (m, 2 H), 1.17–1.15 (m, 12 H) ppm. HRMS
(ESI): m/z calcd. for C19H25N2 [M + H]+ 281.2012; found 281.2029.
NЈ-(4-Ethoxyphenyl)benzamidine (1c): Yield 211 mg (88%); off-
white solid; m.p. 106–108 °C. IR (KBr): ν
= 3446, 3144, 1633,
˜
max
1568, 1502, 1477, 1386, 1277, 1240, 1225 cm–1. 1H NMR
(400 MHz, TMS, CDCl3): δ = 7.81 (d, J = 7.2 Hz, 2 H), 7.45–7.38
(m, 3 H), 6.94–6.85 (m, 4 H), 4.58 (br., 2 H), 4.00 (q, J = 6.8 Hz,
2 H), 1.40 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, TMS,
CDCl3): δ = 155.2, 141.7, 136.3, 130.6, 128.7, 128.6, 126.9, 122.8,
115.6, 63.8, 15.0 ppm. HRMS (ESI): m/z calcd. for C15H17N2O [M
+ H]+ 241.1335; found 241.1334.
NЈ-(6-Chloropyridin-3-yl)benzamidine (8c): Yield 170 mg (81%);
brown solid; m.p. 132–135 °C. IR (KBr): ν
= 3394, 3320, 3197,
˜
max
1638, 1605, 1571, 1460, 1385, 1100, 855, 699 cm–1. 1H NMR
(300 MHz, TMS, CDCl3): δ = 8.05 (s, 1 H), 7.84–7.82 (m, 2 H),
7.51–7.43 (m, 3 H), 7.29 (m, 2 H), 5.12–4.98 (br., 2 H) ppm. 13C
NMR (75 MHz, TMS, CDCl3): δ = 156.7, 145.0, 144.9, 143.1,
134.8, 132.6, 131.1, 128.7, 126.9, 124.6 ppm. HRMS (ESI): m/z
calcd. for C12H11ClN3 [M + H]+ 232.0636; found 232.0642.
NЈ-(4-Fluorophenyl)benzamidine (2c): Yield 180 mg (87%); off-
white solid; m.p. 126–128 °C (ref.[32] m.p. 127–129 °C). IR (CHCl3):
ν
= 3405, 1639, 1576, 1500, 1367 cm–1. 1H NMR (300 MHz,
˜
max
N-Phenylbenzamidine (9c): Yield 190 mg (80%); white solid; m.p.
1
111–113 °C (ref.[32] m.p. 114–115 °C). H NMR (300 MHz, TMS,
TMS, CDCl3): δ = 7.82 (d, J = 7.2 Hz, 2 H), 7.51–7.40 (m, 3 H),
7.07–7.01 (m, 2 H), 6.94–6.89 (m, 2 H), 4.87 (br., 2 H) ppm. HRMS
(ESI): m/z calcd. for C13H12FN2 [M + H]+ 215.0979; found
215.0942.
[D6]DMSO): δ = 7.96–7.94 (m, 2 H), 7.45–7.43 (m, 3 H), 7.33–7.28
(m, 2 H), 6.97–6.88 (m, 3 H), 6.29–6.26 (br., 1.4 H) ppm.
N-Benzyl-benzamidine (10c):[51] Yield 280 mg (88%); off-white so-
N-Biphenyl-4-yl-benzamidine (3c): Yield 292 mg (81%); white solid;
1
lid; m.p. 228–230 °C. H NMR (300 MHz, TMS, [D6]DMSO): δ =
m.p. 179–182 °C. IR (KBr): ν
= 3468, 3352, 1614, 1592, 1570,
˜
max
10.53–9.55 (br., 2 H), 7.82 (d, J = 7.5 Hz, 2 H), 7.73 (t, J = 7.5 Hz,
1 H), 7.61 (t, J = 7.8 Hz, 2 H), 7.48–7.32 (m, 5 H), 4.73 (s, 2
H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ = 162.5, 135.8,
133.2, 128.7, 128.6, 128.3, 128.2, 127.7, 127.5, 45.0 ppm.
1485, 1377 cm–1. H NMR (500 MHz, TMS, CDCl3): δ = 7.89 (s,
2 H), 7.60 (d, J = 8.0 Hz, 4 H), 7.50–7.41 (m, 5 H), 7.33–7.30 (m,
1 H), 7.08 (d, J = 7.5 Hz, 2 H), 4.90 (br., 2 H) ppm. 13C NMR
(125 MHz, TMS, CDCl3): δ = 155.5, 149.2, 141.0, 136.0, 135.9,
130.8, 128.8, 128.7, 128.3, 126.9, 126.8, 126.7, 122.2 ppm. HRMS
(ESI): m/z calcd. for C19H17N2 [M + H]+ 273.1386; found 273.1392.
1
N-(2,6-Diethylphenyl)benzamidine (11c): Yield 160 mg (89%); white
solid; m.p. 97–99 °C. IR (KBr): ν
= 3456, 3326, 3181, 2962,
˜
max
2925, 1626, 1575, 1449, 1380 cm–1. 1H NMR (400 MHz, TMS,
CDCl3): δ = 7.92 (dd, J = 8, 1.6 Hz, 2 H), 7.50–7.45 (m, 3 H), 7.11
(d, J = 7.6 Hz, 2 H), 7.01 (d, J = 7.6 Hz, 1 H), 4.62–4.40 (br., 2
H), 2.59–2.45 (m, 4 H), 1.19 (t, J = 7.6 Hz, 6 H) ppm. 13C NMR
(100 MHz, TMS, CDCl3): δ = 153.2, 144.7, 135.8, 134.7, 130.6,
128.6, 126.7, 126.3, 123.1, 24.6, 14.4 ppm. HRMS (ESI): m/z calcd.
for C17H21N2 [M + H]+ 253.1699; found 253.1686.
N-(4-Difluoromethoxyphenyl)benzamidine (4c): Yield 210 mg
(79%); brown solid; m.p. 74–77 °C. IR (KBr): ν
= 3467, 3332,
˜
max
1618, 1572, 1499, 1383, 1213, 1126, 1046, 868 cm–1. 1H NMR
(500 MHz, TMS, CDCl3): δ = 7.81–7.79 (m, 2 H), 7.43–7.41 (m, 3
H), 7.10–6.94 (m, 4 H), 6.47 (t, JH,F = 58 Hz, 1 H), 5.30–4.50 (br.,
2 H) ppm. 13C NMR (125 MHz, TMS, CDCl3): δ = 155.9, 146.9,
135.4, 130.9, 128.7, 126.9, 123.0, 121.2, 118.3 (OCHF2), 116.3
(OCHF2), 116.2, 114.2 (JC,F = 257.5 Hz, OCHF2) ppm. HRMS
(ESI): m/z calcd. for C14H13F2N2O [M + H]+ 263.0990; found
263.1007.
N-(2,6-Diethylphenyl)-2-phenyl-acetamidine (12c): Yield 121 mg
(81%); white solid; m.p. 148–150 °C. 1H NMR (300 MHz, TMS,
CDCl3): δ = 7.39–7.30 (m, 5 H), 7.06–6.95 (m, 3 H), 4.14–4.10 (br.,
2 H), 3.75 (s, 2 H), 2.62–2.41 (m, 4 H), 1.22–1.12 (m, 6 H) ppm.
13C NMR (75 MHz, TMS, CDCl3): δ = 155.0, 145.0, 136.7, 134.8,
129.0, 128.8, 127.1, 125.7, 123.0, 43.0, 24.4, 14.3 ppm. HRMS
(ESI): m/z calcd. for C18H23N2 [M + H]+ 267.1855; found 267.1864.
N-[4-(-Benzamido)phenyl]acetamide (5c): The crude material was
washed with 15% EtOAc in hexane to obtain a solid, and filtered;
yield 71%; off-white solid; mp 179–181 °C. IR (KBr): νmax = 3295,
˜
1655, 1630, 1597, 1562, 1539, 1502, 1384, 1370, 1315 cm–1. 1H
NMR (300 MHz, TMS, [D6]DMSO): δ = 9.79 (s, 1 H), 7.96–7.94
(m, 2 H), 7.53–7.44 (m, 5 H), 6.82–6.81 (m, 2 H), 6.35–6.20 (m, 2
H), 2.02 (s, 3 H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ
= 167.5, 164.0, 136.7, 134.5, 132.4, 131.8, 128.8, 127.9, 126.8, 120.1,
119.0, 20.3 ppm. HRMS (ESI): m/z calcd. for C15H16N3O
[M + H]+ 254.1289; found 254.1287.
NЈ-(2,6-Diethylphenyl)cinnamamidine (13c): Yield 360 mg (81%);
off-white solid; m.p. 146–148 °C. IR (KBr): ν
= 3436, 3289,
˜
max
3116, 2960, 1634, 1579, 1571, 1442, 1391 cm–1. 1H NMR
(300 MHz, TMS, CDCl3): δ = 7.53 (d, J = 6.6 Hz, 2 H), 7.38–7.32
(m, 3 H), 7.20 (d, J = 16.2 Hz, 1 H), 7.09 (d, J = 7.5 Hz, 2 H),
7.02–6.99 (m, 1 H), 6.75 (d, J = 16.8 Hz, 1 H), 4.39 (br., 2 H),
2.51–2.46 (m, 4 H), 1.17 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR
(75 MHz, TMS, [D6]DMSO): δ = 152.4, 146.8, 136.1, 134.6, 134.2,
129.3, 129.1, 127.5, 126.9, 126.3, 125.5, 122.4, 24.6, 14.8 ppm.
HRMS (ESI): m/z calcd. for C19H23N2 [M + H]+ 279.1855; found
279.1863.
NЈ-(2,6-Dichlorophenyl)benzamidine (6c): Purified by silica gel col-
umn chromatography using an automated flash column chro-
matographer, eluted at the flow rate of 20 mL/min, with column
packing of 25 g silica gel. Silica gel (230–400 mesh) washed with
2% Et3N in hexanes before elution. 2% Et3N used as an additive
in both solvents. Product eluted out in 40% EtOAc in hexanes to
give 6c; yield 230 mg (85%); white solid; m.p. 80–83 °C. IR (KBr):
(S)-NЈ-(2,6-Diethylphenyl)-2-(4-isobutylphenyl)propanamidine (14c):
Purified by column chromatography. Silica gel (230–400 mesh) was
washed with 2% Et3N in hexanes before elution. 2% Et3N used as
an additive in both solvents. Product eluted out of column in 6–
10% EtOAc in hexanes; yield 292 mg (81%); off-white solid; m.p.
ν
= 3482, 3458, 3179, 1685, 1630, 1572, 1432, 1390, 1244,
˜
max
1025 cm–1. 1H NMR (300 MHz, TMS, CDCl3): δ = 7.95 (d, J =
6.6 Hz, 2 H), 7.52–7.42 (m, 3 H), 7.34 (d, J = 7.8 Hz, 2 H), 6.94
(t, J = 7.8 Hz, 1 H), 4.88–4.72 (br., 2 H) ppm. 13C NMR (75 MHz,
70–72 °C. IR (KBr): νmax = 3434, 3282, 2963, 2930, 2867, 1634,
˜
5812
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5806–5815

Convenient Synthesis of Amidines and Indole-3-acylimines
1
1586, 1514, 1449, 1390 cm–1. H NMR (300 MHz, TMS, CDCl3):
160.6, 145.6, 130.3, 129.7, 129.2, 126.8, 124.9, 113.4, 55.2 ppm.
δ = 7.34 (d, J = 7.8 Hz, 2 H), 7.15 (d, J = 8.1 Hz, 2 H), 7.04–7.02
HRMS (ESI): m/z calcd. for C20H19N2O [M + H]+ 303.1492; found
(m, 2 H), 6.93 (t, J = 7.5 Hz, 1 H), 4.2–3.9 (br., 2 H), 3.82–3.75 303.1493.
(m, 1 H), 2.48–2.40 (m, 6 H), 1.88–1.84 (m, 1 H), 1.67 (d, J =
NЈ-(2,6-Diethylphenyl)thiophene-2-carboxamidine (22c): Purified by
7.2 Hz, 3 H), 1.17–1.11 (m, 6 H), 0. 90 (d, J = 6.6 Hz, 6 H) ppm.
13C NMR (75 MHz, TMS, CDCl3): δ = 158.7, 144.9, 140.5, 139.5,
134.8, 129.4, 127.1, 126.2, 123.0, 45.4, 30.2, 24.4, 22.3, 18.6,
14.4 ppm. HRMS (ESI): m/z calcd. for C23H33N2 [M + H]+
337.2638; found 337.2646.
silica gel column chromatography using an automated flash column
chromatographer, eluted at the flow rate of 20 mL/min, 25 g silica
gel. Silica gel (230–400 mesh) washed with 2% Et3N in hexane be-
fore elution. 2% Et3N used as an additive in both solvents. Product
eluted out in 10% EtOAc in hexane to give 22; yield 222 mg (81%);
colourless sticky mass. IR (CHCl ): νmax = 3396, 2969, 1636, 1583,
˜
N-(4-Chlorophenyl)-N-methylbenzamidine (16c): Yield 188 mg
3
1030 cm–1. H NMR (300 MHz, TMS, CDCl3): δ = 7.41–7.35 (m,
1
(81%); white solid; m.p. 195–197 °C. IR (KBr): ν
= 2887 (br),
˜
max
1601, 1571, 1491, 1132, 1090, 1017 cm–1. 1H NMR (500 MHz,
TMS, CDCl3): δ = 7.41 (d, J = 7.5 Hz, 2 H), 7.37 (d, J = 7.5 Hz,
1 H), 7.28 (t, J = 7.5 Hz, 2 H), 7.21 (d, J = 9.0 Hz, 2 H), 7.01 (d,
J = 8.5 Hz, 2 H), 3.85 (s, 3 H) ppm. 13C NMR (125 MHz, TMS,
CDCl3): δ = 165.9, 142.0, 133.9, 132.0, 129.8, 129.4, 129.3, 128.7,
128.0, 43.5 ppm. HRMS (ESI): m/z calcd. for C14H14ClN2 [M +
H]+ 245.0840; found 245.0847.
2 H), 7.07–6.97 (m, 4 H), 4.56 (br., 2 H), 2.58–2.40 (m, 4 H), 1.19–
1.14 (m, 6 H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ =
148.6, 146.0, 142.1, 134.6, 129.5, 127.8, 126.7, 126.3, 126.0, 122.6,
24.8, 14.7 ppm. HRMS (ESI): m/z calcd. for C15H19N2S [M + H]+
259.1263; found 259.1271.
N-[1-(tert-Butyl-dimethylsilanyloxymethyl)-2-methylpropyl]iso-
nicotinamidine (23c): Mixture of tautomers; yield 370 mg (81%);
yellow gum; HPLC purity: 92%. IR (KBr): ν
= 2958, 2930,
˜
N,N-Diphenylbenzamidine (17c): Purified by reverse-phase column
chromatography using an automated flash column chromatogra-
pher, column size (50 g with C18 packing material; MeCN–H2O);
flow rate: 50 mL/min, eluted out of column using 30–40% of
MeCN–H2O; yield 163 mg (84%); off-white solid; m.p. 62–64 °C.
max
2857, 1652, 1601, 1255 cm–1. 1H NMR (300 MHz, TMS, [D6]-
DMSO): δ = 8.63–8.57 (m, 2 H), 7.72–7.70 (m, 2 H), 6.4–6.3 (br.,
1.4 H, NH), 3.69–3.64 (m, 1.2 H), 3.53–3.34 (m, 3 H), 1.94–1.83
(m, 1 H), 0.93–0.89 (m, 6 H), 0.88–0.83 (m, 10 H), 0.006–0.004 (m,
6 H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ = 161.1,
150.8, 149.9, 145.1, 134.6, 122.0, 121.5, 72.5, 70.7, 64.9, 61.6, 32.6,
29.9, 26.2, 20.3, 19.0, 18.6, 18.4, 18.2, –2.7, –4.8, –4.98 ppm.
HRMS (ESI): m/z calcd. for C17H32N3OSi [M + H]+ 322.2309;
found 322.2315.
IR (KBr): ν
= 3268, 3055, 1605, 1588, 1568, 1487, 1446,
˜
max
1
1358 cm–1. H NMR (300 MHz, TMS, CDCl3): δ = 7.57–7.55 (m,
2 H), 7.27–7.22 (m, 7 H), 7.11–7.06 (m, 6 H) ppm. 13C NMR
(75 MHz, TMS, CDCl3): δ = 167.2, 145.3, 137.5, 129.5, 128.7,
128.3, 127.3, 127.2 ppm. HRMS (ESI): m/z calcd. for C19H17N2 [M
+ H]+ 273.1386; found 273.1397.
Compound (24c): Mixture of tautomers; yield 360 mg (79%); yellow
gum; HPLC purity: 99%. IR (KBr): νmax = 2955, 2929, 2869, 1654,
˜
4-Chloro-N,N-diphenylbenzamidine (18c): Purified by silica gel col-
umn chromatography using an automated flash column chro-
matographer, eluted at the flow rate of 20 mL/min, with column
packing of 25 g silica gel. Silica gel (230–400 mesh) washed with
2% Et3N in hexane before elution. 2% Et3N was used as an addi-
tive in both solvents. Product eluted out in 10% EtOAc in hexane;
1
1601, 1465, 1364 cm–1. H NMR (300 MHz, TMS, [D6]DMSO): δ
= 8.71 (d, J = 6 Hz, 1 H), 8.57 (d, J = 6 Hz, 1.92 H), 7.75 (d, J =
6 Hz, 1 H), 7.69 (d, J = 6 Hz, 1.92 H), 6.5–6.1 (br., 1.35 H), 5.3–
5.18 (br., 0.42 H), 4.51–4.44 (m, 0.62 H, NH), 4.19–4.05 (m, 1.39
H, NH), 3.68–3.63 (m, 1.07 H), 3.53–3.48 (m, 1.4 H), 1.95–1.69
(m, 7 H), 0.96–0.86 (m, 37 H), 0.56–0.53 (m, 5.4 H), 0.48–0.46 (m,
3.8 H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ = 161.0,
150.8, 149.8, 145.0, 135.1, 122.0, 121.4, 72.5, 70.7, 64.3, 32.6, 29.9,
27.5, 26.8, 26.6, 25.2, 24.3, 24.2, 20.2, 18.9, 18.6, 18.4 ppm. HRMS
(ESI): m/z calcd. for C23H44N3OSi [M + H]+ 406.3248; found
406.3221.
yield 177 mg (81%); brown solid; m.p. 118–120 °C. IR (KBr): ν
˜
max
= 3436 (br), 3265, 3044, 1610, 1587, 1564, 1490, 1349 cm–1. 1H
NMR (300 MHz, TMS, CDCl3): δ = 7.52 (d, J = 8.4 Hz, 2 H),
7.28–7.19 (m, 6 H), 7.13–7.04 (m, 6 H), 6.40–5.90 (br., 1 H) ppm.
13C NMR (75 MHz, TMS, CDCl3): δ = 165.8, 144.9, 135.8, 135.5,
130.1, 129.3, 128.4, 126.9, 125.4 ppm. HRMS (ESI): m/z calcd. for
C19H16ClN2 [M + H]+ 307.0997; found 307.0999.
NЈ-(4-Ethoxyphenyl)isonicotinamidine (25c): Crude material washed
with 10% EtOAc in hexanes; yield 191 mg (81%); off-white solid;
2-Iodo-N,N-diphenylbenzamidine (19c): Purified by silica gel col-
umn chromatography using an automated flash column chro-
matographer, eluted at the flow rate of 20 mL/min, with column
packing of 25 g silica gel. Silica gel (230–400 mesh) washed with
2% Et3N in hexane before elution. 2% Et3N used as an additive in
both solvents. Product eluted out in 30% of EtOAc in hexane; yield
m.p. 123–125 °C. IR (KBr): ν
= 3307, 3161, 1636, 1503, 1549,
˜
max
1
1503, 1377, 1238, 1046 cm–1. H NMR (300 MHz, TMS, CDCl3):
δ = 8.61 (d, J = 4.8 Hz, 2 H), 7.66 (d, J = 4.2 Hz, 2 H), 6.86 (m, 4
H), 5.19 (br., 2 H), 3.99 (q, J = 6.9 Hz, 2 H), 1.39 (t, J = 6.9 Hz,
3 H) ppm. 13C NMR (75 MHz, TMS, CDCl3): δ = 155.4, 153.2,
150.1, 143.1, 141.7, 122.4, 121.1, 115.6, 63.7, 14.9 ppm. HRMS
(ESI): m/z calcd. for C14H16N3O [M + H]+ 242.1288; found
242.1286.
149 mg (78%); white solid; m.p. 105–109 °C; IR (KBr): ν
=
˜
max
3302, 3061, 3037, 1589, 1575, 1491, 1389, 1231 cm–1. 1H NMR
(300 MHz, TMS, CDCl3): δ = 7.66 (dd, J = 8.1, 0.6 Hz, 1 H), 7.44
(dd, J = 7.8, 1.3 Hz, 1 H), 7.28–7.21 (m, 9 H), 7.14–7.06 (m, 2 H),
6.87 (td, J = 15.3, 7.5 Hz, 1 H) ppm. 13C NMR (100 MHz, TMS,
CDCl3): δ = 167.0, 144.1, 142.5, 139.6, 130.5, 129.9, 128.9, 127.6,
125.7, 95.1 ppm. HRMS (ESI): m/z calcd. for C19H16IN2
[M + H]+ 399.0346; found 399.0352.
NЈ-(4-Ethoxyphenyl)-5-methylpyrazine-2-carboxamidine(26c): Recy-
stallised from IPA and hexane; yield 179 mg(80%); yellow solid;
1
m.p. 125–127 °C. H NMR (300 MHz, TMS, CDCl3): δ = 9.50 (s,
1 H), 8.38 (s, 1 H), 6.98–6.90 (m, 4 H), 5.73 (br., 2 H), 4.03 (q, J
= 6.8 Hz, 2 H), 2.64 (s, 3 H), 1.42 (t, J = 6.8 Hz, 3 H) ppm. 13C
NMR (75 MHz, TMS, CDCl3): δ = 155.2, 155.1, 151.4, 143.9,
142.9, 142.2, 141.7, 122.4, 115.5, 63.7, 21.6, 15.0 ppm. HRMS
(ESI): m/z calcd. for C14H17N4O [M + H]+ 257.1397; found
257.1402.
4-Methoxy-N,N-diphenylbenzamidine (20c): Yield 180 mg (81%);
off-white solid; m.p. 106–108 °C. IR (KBr): ν
= 3057, 3034,
˜
max
2967, 2932, 1607, 1587, 1573, 1508, 1487, 1356, 1247, 1232 cm–1.
1H NMR (300 MHz, TMS, CDCl3): δ = 7.52 (d, J = 8.7 Hz, 2 H),
7.27–7.22 (m, 4 H), 7.10–7.04 (m, 6 H), 6.74 (d, J = 8.7 Hz, 2 H), (4-Chlorophenyl)(1H-indol-1-yl)methanimine (30c): Crude material
3.75 (s, 3 H) ppm. 13C NMR (75 MHz, TMS, CDCl3): δ = 166.8, was washed with hexane; yield 282 mg (79%); light-pink solid; m.p.
Eur. J. Org. Chem. 2014, 5806–5815
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5813

A. Velavan, S. Sumathi, K. K. Balasubramanian
FULL PAPER
[12] J. A. Gautier, M. Miocque, C. C. Farnoux, in: The Chemistry
of Amidines and Imidates (Ed.: S. Patai), Wiley, London, 1975,
p. 283.
192–194 °C. IR (KBr): ν
= 3390 (br), 1582, 1558, 1519, 1242,
˜
max
1143, 1092 cm–1. 1H NMR (300 MHz, TMS, [D6]DMSO): δ =
13.0–9.5 (br., 2 H), 8.07 (s, 1 H), 7.61–7.45 (m, 6 H), 7.22–7.10 (m,
2 H) ppm. 13C NMR (75 MHz, TMS, [D6]DMSO): δ = 170.3,
140.2, 137.1, 133.9, 130.9, 129.3, 128.8, 128.2, 125.6, 122.2, 121.3,
120.5, 114.3, 112.0 ppm. HRMS (ESI): m/z calcd. for C15H12ClN2
[M + H]+ 255.0683; found 255.0686.
[13] V. G. Granik, Usp. Khim. 1983, 52, 669; Chem. Abstr. 1983, 99,
405265.
[14] P. J. Dunn, in: Comprehensive Organic Functional Group Trans-
formations II, vol. 5, Elsevier, Oxford, UK, 2005, p. 655–699.
[15] K. Ostrowska, A. Kolasa, in: Science of Synthesis, vol. 22,
Thieme, Stuttgart, Germany, 2005, p. 379–488.
[16] a) A. A. Aly, A. M. Nour-El-Din, ARKIVOC (Gainesville, FL,
U.S.) 2008, 153–194, and references cited therein; b) H. Soll,
Methoden Org. Chem. (Houben-Weyl) 1958, 9, 39.
[17] For recent heterocycle syntheses from amidines, see: a) S. K.
Alla, R. K. Kumar, P. Sadhu, T. Punniyamurthy, Org. Lett.
2013, 15, 1334–1337; b) D. Tejedor, S. López-Tosco, F. García-
Tellado, J. Org. Chem. 2013, 78, 3457–3463.
[18] R. Roger, D. G. Neilson, Chem. Rev. 1961, 61, 179.
[19] F. C. Schaefer, G. A. Peters, J. Org. Chem. 1961, 26, 412.
[20] S. Caron, L. Wei, J. Douville, A. Ghosh, J. Org. Chem. 2010,
75, 945–947.
[21] R. T. Boere, R. T. Oakley, R. W. Reed, J. Organomet. Chem.
1987, 331, 161–167.
(5-Chloro-1H-indol-1-yl)(4-chlorophenyl)methanimine (31c): Crude
material was washed with hexane; yield 290 mg (81%); light-pink
solid; m.p. 189–191 °C. IR (KBr): ν
= 3110, 1583, 1556, 1436,
˜
max
1236, 1092 cm–1. 1H NMR (300 MHz, TMS, [D6]DMSO): δ =
11.77 (s, 1 H), 9.78 (s, 1 H), 8.24–8.23 (m, 1 H), 7.61–7.46 (m, 6
H), 7.20 (dd, J = 8.7, 1.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
TMS, CDCl3, [D6]DMSO): δ = 172.2, 139.9, 135.7, 135.5, 131.3,
129.1, 128.6, 127.0, 126.8, 123.2, 121.0, 115.2, 112.9 ppm. HRMS
(ESI): m/z calcd. for C15H11Cl2N2 [M + H]+ 289.0293; found
289.0299.
(4-Chlorophenyl)(2-phenyl-1H-indol-1-yl)methanimine (32c): Crude
material was washed with hexane to give 32c; yield 321 mg (83%);
yellow solid; m.p. 185–188 °C. IR (KBr): ν
= 3401 (br), 3062,
˜
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7.62 (d, J = 8.1 Hz, 2 H), 7.50–7.48 (m, 3 H), 7.39–7.21 (m, 6 H),
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