Synthesis, structures, and aggregation properties of N-acylamidines

FULL PAPER

DOI: 10.1002/ejoc.201001155

Synthesis, Structures, and Aggregation Properties of N-Acylamidines^[‡]

Christof Wigbers,^[a]Jörg Prigge,^[a]Zhongchen Mu,^[b]Roland Fröhlich,^[a]Lifeng Chi,^[b]and

Ernst-Ulrich Würthwein*^[a]

Dedicated to Prof. Dr. Paul von Ragué Schleyer on the occasion of his 80th birthday

Keywords: Aggregation / Computational chemistry / Conformation analysis / Scanning probe microscopy / Self-assembly /

Tautomerism

N-Acylamidines 1a–q, which are important ligands for metal

ion complexation, were easily prepared either by acylation of

amidines 2 or by treatment of N-acylimidates 3 with amines.

Additionally, the reaction of amidinium salts with aroyl ha-

3–17 (C–N) and 15–27 (C=N) kcal/mol. Due to their excellent

ability to form intra- and intermolecular hydrogen bonds,

these molecules show very variable aggregation behavior in

the solid state (X-ray analysis) as well as on surfaces, de-

lides in the presence of sodium hydroxide gave the aryl de- pending on the substitution pattern. Thus, dimeric (1c, 1d,

rivatives 1r–1ad and three azobenzene derivatives 1ae–1ag.

The respective substitution pattern of these novel derivatives

was selected with respect to possible steric and electronic

effects in coordination reactions as well as with regard to the

aggregation properties. N-Acylamidines 1 may exist as three

types of tautomers, which were examined in solution by

NMR spectroscopic analysis and by quantum chemical DFT

and SCS-MP2-calculations for single molecules in the gas

phase. Internal rotations require activation energies between

and 1u) and tetrameric (1f) aggregates with strong NH···OC

hydrogen bonding, as well as polymeric chain structures (1x

and 1z) were observed in the solid state. Furthermore, a di-

mer 1k involving only the amidine subunits, rather than the

carbonyl function, was found. Monolayers of molecules 1u

and 1ab physisorbed at the liquid/HOPG (high orientated

pyrolytic graphite) interface in 1-phenyloctane solution were

examined by Scanning Tunneling Microscopy (STM).

Introduction

In coordination chemistry of metal ions and Lewis acids,

N-acylamidines 1 and their anions are valuable nitrogen-

and oxygen-containing monodentate or bidentate ligands

(Scheme 1).^[1–6]Structurally, they resemble the better-

known β-iminoketones (β-ketoiminates).^[7]However, the

additional nitrogen atom in the 3-position strongly influ-

ences the electronic structure and allows extended conjuga-

tion over all five carbon, nitrogen and oxygen atoms of the

parent species, even in the neutral form. Consequently,

these ligands are able to generate robust complexes, for ex-

ample, of transition metals and ions. Some of them show

high activities in cross-coupling reactions based on good

thermal stability and low loadings.^[8–10]

Scheme 1. Tautomers and conformers of primary (R¹= H) and

secondary N-acylamidines 1.

One may expect the formation of three different tauto-

meric forms of N-acylamidines 1 (Scheme 1): tautomer A,

with an N-acylimine subunit, tautomer B, being an amide

derivative, and tautomer C with its imidate substructure.

All of the tautomers are subject to extensive conformational

and configurational isomerism, and all may be involved in

intermolecular hydrogen bonding; some of them may also

involve intramolecular hydrogen bonding (see below). Be-

sides the synthesis of such compounds with novel substitu-

tion patterns, a careful evaluation of their structural proper-

ties in the solid state (X-ray spectroscopic analysis), in

[‡] Unsaturated Hetero Chains, XIX. Part XVIII: Ref.^[22]

[a] Organisch-Chemisches Institut, Westfälische Wilhelms-

Universität,

Corrensstraße 40, 48149 Münster, Germany

Fax: +49-251-83-39772

E-mail: wurthwe@uni-muenster.de

[b] Physikalisches Institut, Westfälische Wilhelms-Universität,

Wilhelm-Klemm-Straße 10, 48149 Münster, Germany

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201001155.

Eur. J. Org. Chem. 2011, 861–877

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monolayers (scanning tunneling microscopy, STM), in solu- Table 1. Substitution patterns and yields of the N-monosubstituted

N-acylamidines 1a–q.

tion (NMR spectroscopic analysis), and in the gas phase

R¹

R²

R³

Route Yield [%]

(quantum chemical calculations) is the subject of this study.

The synthesis of the first N-acylamidines, reported in

1889 by A. Pinner, involved the reaction of benzamidine

1a

1b

nBu

Mes

4-MeOC₆H₄

4-CF₃C₆H₄

3,5-Xyl

Mes

nBu

Mes

Ph

nBu

Ph

tBu

Ph

4-Tol 4-Tol

tBu

Et

tBu

Ph

tBu

Ph

tBu

Mes

4-MeOC₆H₄

4-CF₃C₆H₄

4-Tol

A

B

A

58

45

73

39

9

42

80

61

73

74

30

91

17

89

96

92

66

hydrochloride with benzoic acid anhydride.^[11]More re- 1c

1d

cently, additional synthetic pathways for the synthesis of

primary (without substituent at a nitrogen atom), second-

ary (one substituent at one of the nitrogen atoms) and terti-

ary N-acylamidines have been studied in our labora-

tory.^[12,13]A principal synthetic pathway is based on the re-

action of carboxylic acyl chlorides with amidines^[14,15]2 as

published by Katritzky and co-workers (see Scheme 2).^[16]

1e

1f

1g

1h

1i

4-Tol

nPr

CH(Ph)₂

4-Tol

tBu

1j

1k

1l

1m

1n

1o

1p

1q

2,6-Xyl

Mes

2,6-(iPr)₂C₆H₃Ph

Ph

tBu

4-Tol tBu

tBu

In another series of experiments, several new primary N-

acylamidines 1r–1ag were prepared by acylation of the re-

spective amidinium salts in the presence of sodium hydrox-

ide using acetone as solvent at 0 °C (Scheme 3 and

Table 2).^[16]The substitution patterns of compounds 1r–1ad

were selected with regard to possible molecular aggregation

phenomena by dispersion interaction, which is caused by

extended alkoxy moieties in the para-position of the aro-

matic group (see below). Furthermore, three red azo com-

pounds 1ae–1ag were synthesized for evaluation of their op-

tical properties. As expected for azobenzene derivatives,

they show UV absorption near 446 nm.

Scheme 2. Preparation of the secondary N-acylamidines 1a–q.

Secondary N-acylamidines provoked interest in our

group as ligands for catalytically active Pd complexes,^[12]

whereas primary N-acylamidines carrying alkoxyphenyl

and azophenyl substituents attracted our attention because

of their aggregation properties on surfaces.^[17]

Results and Discussion

In a first series of experiments, a library of secondary N-

acylamidines 1 with aliphatic and aromatic substituents was

prepared either by acylation of amidines 2 with acyl chlo-

rides or, in the case of 1f, from the reaction of ethyl N-

acylimidate 3 with a primary amine. Amidines 2 were syn-

thesized from nitriles and primary amines, in the case of

aliphatic nitriles the reaction proceeded best in the presence

of aluminum chloride, whereas for aromatic amidines the

use of lithiated amines was superior. For N-acylimidate 3,

a route through the corresponding Pinner salt was applied.

These alternative pathways allow a relatively free and inde-

pendent choice of the respective substituents: R¹, intro-

duced by the choice of the primary amine; R², stemming

from the nitrile, and R³, from the acyl chloride. The substit-

uents may either be aliphatic or aromatic, and can carry

various electronically and sterically effective groups. Thus,

we were able to synthesize one derivative 1a with three ali-

phatic groups of varying steric demand, several with three

aromatic substituents (1b–h), others with two aliphatic and

one aromatic moiety (1i–l), and derivatives with one ali-

phatic and two aromatic residues (1m–r) (see Scheme 2 and

Table 1).

Scheme 3. Preparation of the primary N-acylamidines 1r–1ag.

Table 2. Substitution patterns and yields of the primary N-acyl-

amidines 1r–1ag.

R¹

R²

R³

R⁴

Yield [%]

1r

Ph

tBu

Me

Ph

nBuO

nHexO

nOctO

n-hexadecyl-O

nBuO

nHexO

nOctO

nBuO

nHexO

H

nDecO

nHexO

H

nHexO

H

78

72

83

12

59

86

66

52

21

26^[a]

54

33

55

91

52

45

1s

1t

1u

1v

1w

1x

1y

1z

1aa

1ab

1ac

1ad

1ae

1af

1ag

nOctO

nHexadecO

nDecO

Ph

tBu

Me

nHexO

–N=N–Ph

H

[a] Purity: 90%.

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Synthesis and Properties of N-Acylamidines

Tautomerism

ever, in the course of our investigations we also prepared

some examples that exist in both solution and the solid state

in the tautomeric form B (see below).

It is known that N-acylamidines 1 are subject to taut-

omerism in both the solid state and in solution; the two

main tautomers A and B shown in Scheme 1. For the gas

phase, we performed quantum chemical calculations on all

the tautomers of the parent compound C₂H₄N₂O [SCS-

MP2/B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p)] using

the GAUSSIAN 03 suite of programs including frequency

calculations.^[18,19]All the tautomers may adopt many dif-

ferent conformations and configurations based on three

principal types, namely W-, U- and sickle-shapes, with low

to medium barriers for bond rotation. All tautomers A, B,

and C may take part in intermolecular hydrogen bonding,

but the U-shaped forms of tautomer A and C additionally

offer the possibility of intramolecular hydrogen bonding.

One of the structures of the tautomeric form B is predicted

to be lowest in energy (see Figure 1 for the lowest energy

species and the Supporting Information for all 28 possible

conformers and configurational isomers). The best struc-

ture of type A is 3.4 kcal/mol higher in energy (Sickle-

shape) with a second, chelate-type isomer (U-shape) very

close in energy, whereas the best form of tautomer C, in

spite of the intramolecular hydrogen bond, is higher in en-

ergy by approximately 10 kcal/mol. The structure of the

predominant conformation/configuration depends on the

steric and electronic properties and also on the overall di-

pole moment. Thus, amide tautomers with structures of

type B are preferred over N-acylimine tautomers of type A,

which, in turn, are much better in energy than the imidate

structures of type C tautomers. Internal rotations were also

studied by localization of the corresponding transition

states: for tautomers A, rotation about the C=N bond re-

quires about 15 kcal/mol, and rotation about the C–N bond

approximately 3 kcal/mol. For tautomers B and C, barriers

for NC=NH rotation of 23–27 kcal/mol, for NC–N rotation

of 4–10 kcal/mol, and for OC–N (amide bond) of 9–17 kcal/

mol were calculated. Thus, as expected, facile rotations

about amidine type C–N bonds and higher barriers for

amide-type bonds are typical for the dynamic behavior of

these species.

Structures in the Solid State and in Solution

Several X-ray diffraction structures of N-acylamidines 1

revealed that both types of tautomers A and B are present

in the solid state. Compounds 1c and 1d (Figure 2) are ex-

amples of type A tautomers (“U shape”) with strong intra-

molecular hydrogen bonds. Typical N–H···O distances of

1.97 Å for 1c, and 1.80 Å for 1d (N···O distances of 2.63 Å

for 1c and 2.61 Å for 1d; sum of the van-der-Waals radii:^[20]

H + O 2.74 Å, N + O 3.14 Å). The angles around the bridg-

ing hydrogen atom are 134.4° (1c) and 126.6° (1d), respec-

tively. The N–C–N–C–O moieties are almost planar, with

dihedral angles less than 2.4°.

Figure 2. Molecular structure of the homodimer of 1c in the solid

state. NH–O distances, intra: 1.97 Å, inter: 2.37 Å.

Additionally, some of the compounds, for example 1c

and 1d, are able to form homodimers using the same system

of hydrogen bonding in a bifurcated way, so that each bind-

ing proton is surrounded by three heteroatoms (N and O).

Possibly because of the steric bulk, the intermolecular hy-

drogen bonds are long (1c: 2.37 Å, 1d: 2.53 Å).

For the parent N-acylamidine C₂H₄N₂O, the calculated

heat of dimerization for this type of dimer amounts to ap-

proximately 8 kcal/mol (Figure 3); SCS-MP2/6-311+G(D,P

+ZPE) resp. 9 kcal/mol (DFT-B97-D/TZVP,^[21]a method

including dispersion correction) with respect to the mono-

mer of the same structural type. The calculated NH–O-dis-

tances indicate similar bond strengths for the intra- and

intermolecular hydrogen bonding.

For the trifluoromethyl compound 1f (Figure 4), a super-

structure consisting of four “head-to-tail”-oriented N-acyl-

amidines is formed by hydrogen bonding in the solid state,

resembling a slightly distorted rectangle (Figures 5 and 6).

Figure 1. Calculated best structures for tautomers of type A, B,

and C in the gas phase for the parent compound 1 (R¹= R²= R³

= H). Relative energies E_rel[kcal/mol] and dipole moments D [De-

bye]. SCS-MP2-B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p)

ZPE.

+

For the substituted examples studied here, the nature of A closer look at the crystalline ensemble shows that in this

the particular substituents, crystal packing effects, and the orientation a system of parallel channels is formed. Inter-

solvent, are also quite important. In the majority of the estingly, a close neighborhood of fluorine atoms in one mo-

examples described in the literature,^[16]as well as in our lecule and hydrogen atoms of adjacent molecules seems to

studies, tautomer A was found to be predominant. How- contribute to the overall stabilization of the system.

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Figure 3. Calculated structure of the hydrogen bonded dimer of

tautomer A of the parent compound of N-acylamidines 1. Dimeris-

ation energy: 7.94 kcal/mol [SCS-MP2/6-311+G(d,p) +ZPE] with

respect to the corresponding monomer (see Figure 1, second struc-

ture from left). Calculated NH–O distances: intra: 2.109 Å, inter,

2.073 Å.

Figure 6. Molecular arrangement of the tetrameric subunits of 1f

in the crystal lattice (fluorine atoms in light-grey, hydrogen atoms

in white). (Left) linear substructure; (right) two-dimension packing.

close to the ideal linear orientation. In this respect, this di-

meric structure resembles a dimer of a 1-unsubstituted 1,3-

diazabutadiene, which was recently observed in the solid

state in our laboratory.^[22]

Figure 4. Molecular structure of a single molecule of 1f in the solid

state.

Figure 7. Molecular structure of the homodimer of 1j in the solid

state.

The different tautomers that are present in the crystalline

materials, as shown from the X-ray data, also exhibit dis-

tinct IR spectra (recorded from the solids as KBr disks).

Thus, two ranges were found for the C=O and C=N stretch-

ing vibrations. For the derivatives 1b, 1j, 1k, and 1m–q,

these absorptions were found to be in the range of 1625

to 1715 cm^–1, which corresponds to tautomer B (compare

Figure 7 for 1j). In contrast, derivatives 1c–h, which prefer

to adopt the tautomeric structure A with direct, conjugative

interaction of the C=N and the C=O moieties, show ab-

Figure 5. Molecular structure of the tetrameric aggregate of 1f in

the solid state. The hydrogen bonds (dotted lines) are 1.95 Å in

length.

Derivative 1j presents an example of the formation of sorptions at lower energies between 1540 and 1625 cm^–1.

tautomer B, which crystallizes in the sickle-type structure Because, in each case, only one of the two ranges of absorp-

(Figure 7). The dihedral angles of –2.2° (OCNC) and 161.7° tions was detected, the presence of mixtures of tautomers

(CNCN) indicate a slight twisting of the molecule. Again, in the solid state can be excluded.

intermolecular hydrogen bonding is realized, resulting in

For the assignment of the tautomers in solution, a com-

the formation of homodimers, in this case, of the amidine parison of the ¹³C NMR spectroscopic data of the mesityl

subunits, whereas acyl moieties are not involved in hydro- derivatives 1b, 1c, 1h, 1j, and 1p is indicative. Again, two

gen bonding. Here, N–H···N interactions with distances of groups with typical shifts in the range of ipso-mesityl, C=N

2.12 Å, N···N distances of 3.03 Å, and 2.97 Å (sum of van- and CO signals may be distinguished, corresponding to the

der-Waals radii:^[20]HN 2.80 Å, NN 3.20 Å) between the two tautomers A and B (Table 3). For the derivatives 1c and

amino groups of one molecule and the imino function of 1h, we found relatively high-field signals for ipso-mesityl

the other, lead to the formation of antiparallel orientated and low-field C=N and C=O signals, which is in agreement

ensembles (Figure 7). In this example, the angles around the with the presence of tautomer A, whereas for 1b, 1j, and 1p

bridging hydrogen atoms are 169.1° and 170.3°, which are the ipso-mesityl signals at low field and the C=N and C=O

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Synthesis and Properties of N-Acylamidines

signals at high field indicate the presence of tautomer B. We Intermolecular interactions of the long alkyl chains by dis-

conclude from these observations that, in the crystalline persion seem to be the reason for the sheet-like aggregation

state as well as in solution, the same kind of tautomer is of the molecules in the crystal lattice (Figure 8, b).

preferentially formed. Hence, lattice forces in the solid state

do not exclusively determine the nature of the tautomer

formed.

Table 3. ¹³C NMR shifts of selected nuclei for some derivatives of

1.

¹³C NMR: δ [ppm]

Tautomer in

solution

Tautomer in

solid state

i-mesityl

1c 133.6

1h 133.5

1b 142.3

CN

CO

167.7 179.7

167.7 179.9

151.2 167.8

154.3 170.1

152.1 175.6

A

B

A

–

B

–

1j

141.1

1p 142.5

In summary, it is difficult to predict the preferred tauto-

mer simply by examining its substitution pattern. However,

most of the fully aryl-substituted derivatives 1b–h adopt the

conformation of tautomer A, with the exception of 1b.

When R¹and R²are aryl groups and R³is tert-butyl (1n–

q), tautomer B is observed. All compounds with R¹= alkyl

(1a, 1i, and 1l) form tautomer A, independent of the nature

of R²and R³.

Figure 8. Molecular structure of the homodimer (a), and a sheet

(b) of 1u in the solid state.

Clearly, due to steric repulsion in compound 1ac, the two

alkyl groups attached to the R²-substituent differ strongly

in their spatial orientation (Figure 9). The decyloxy-substit-

uent in the 4-position lies well within the plane of the rest

of the molecule, whereas the decyloxy moiety in the 3-posi-

tion is twisted by about 70° out of the plane of the mole-

cule. In addition to the intramolecular hydrogen bond, 1ac

forms a complicated three-dimensional network involving

hydrogen bonding of both NH₂protons.

Compared to the ¹³C NMR and IR data, we found that

the ¹H NMR signals of the NH protons measured either in

CDCl₃or [D₆]dimethyl sulfoxide ([D₆]DMSO) were only of

minor diagnostic value. Due to rapid exchange on the

NMR time scale in CDCl₃, line-broadening of these signals

(mostly between δ = 10 and 13 ppm) was observed; in [D₆]-

DMSO, broad signals were also observed, generally at

higher field (δ = 8–11 ppm) that were sometimes split into

several signals of lower intensity.

Structures of the N-Unsubstituted N-Acylamidines in the

Solid State

We were further able to obtain X-ray diffraction struc-

tures of the primary N-acylamidines 1u, 1x, 1z, 1aa, and

1ac. In general, most of the molecular structures are close

to planarity, with certain deviations observed for the deriva-

tives 1u and 1ac (17 and 25°, respectively, for the C=N–

C=O dihedral angle), which have aryl substituents as R¹. In

all cases, tautomer A in its cyclic form with intramolecular

hydrogen bonding is realized. The distances between the

terminal oxygen and nitrogen atoms vary from 2.584–

2.653 Å, all being significantly smaller than the sum of the

van-der-Waals radii (see above).

Figure 9. Molecular structure of a single molecule of 1ac in the

solid state.

As observed for 1c and 1d, in addition to the intramolec-

The structural parameters of 1ac obtained in this study

ular hydrogen bond, 1u also forms homodimers in the solid bear some resemblance to the data reported by Hvoslef et

state; these are interconnected by additional intermolecular al. for N-pivaloylpivalamidine.^[23]Korbonits et al. reported

hydrogen bonds again involving the terminal oxygen and on primary N-acylamidines, synthesized by hydrogenation

nitrogen atoms of the N-acylamidine subunits (Figure 8, a). of 1,2,4-oxadiazols.^[24]They found a U-shape structure

The amine hydrogen atoms involved in hydrogen bonds are (type A) in one of the 2-aminobenzamidine derivatives in

1.918 and 2.220 Å away from the respective oxygen atoms. the solid state. Here, along with intermolecular hydrogen

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bonding, an additional intramolecular hydrogen bond to and its lattice constants were determined to be a =

the central nitrogen bond was observed with the 2-amino (3.52Ϯ0.1) nm, b = (0.94Ϯ0.1) nm, and α = (71Ϯ3)°.

group acting as a hydrogen bridge donor.

Within a bright stripe, two acylamidine and phenyl moieties

Compounds 1x and 1z again show different superstruc- originating from two adjacent molecules form a pair, and

tures (see Figure 10 for 1z). In the latter case, in addition two adjacent pairs have a dislocation, as indicated with red

to the intramolecular chelate hydrogen bond, a polymeric bars. Based on the molecular structure seen in the single-

fishbone-like, essentially planar orientation of the N-acyl- crystal 3D experiment, this suggests that the two molecules

amidine molecules is found that is interconnected by hydro- of 1u form a dimer from intermolecular hydrogen bonding.

gen bonds. In 1x, a similar pattern of hydrogen bonds is A model of the molecular alignment in the 2D structure is

realized. The 4-(n-octyl)phenyl chains, however, are ordered shown in Figure 11 (b), which is very similar to the struc-

in two planes tilted by approximately 60° with respect to ture of a sheet in 3D, as shown in Figure 8, satisfying the

each other.

requirements of intermolecular interactions, hydrogen

bonding and van-der-Waals interactions between the alkyl

chains.

Figure 10. Molecular arrangement of 1z in the solid state.

Similar orientation phenomena forming polymeric net-

works are also present in the solid-state structure of 1aa. In

this case, similar to 1z, large polymeric sheets are formed

in which the polar groups (NH₂, O) form continuous net-

works on one hand, whereas, on the other hand, the apolar

alkyl groups also show a common aggregation behavior due

to dispersion interactions. Surprisingly, small differences,

for example, in the nature of the substituent R¹, generate

quite different aggregation patterns.

STM Measurements

To understand the molecular interactions of N-acyl-

amidines on surfaces (2D) compared to hydrogen bonding

involving the terminal oxygen and nitrogen atoms of the N-

acylamidine subunits in 3D, we also investigated the as-

sembled structures of N-unsubstituted N-acylamidines at

the liquid/high orientated pyrolytic graphite (HOPG) inter-

face by means of Scanning Tunneling Microscopy (STM).

Figure 11 (a) shows an STM image of a monolayer of mole-

cule 1u physisorbed at the liquid/graphite interface in 1-

phenyloctane solution. In the STM image, the bright stripes

correspond to the aromatic moieties of the molecules due

Figure 11. (a) STM image of compound 1u on HOPG in phenyl-

octane (17.1 nmϫ17.1 nm, U = –950 mV, I = 520 pA). (b) Pro-

posed structural model, deduced from STM image.

For molecules of compound 1ab adsorbed on graphite,

to their high electron density; the dim areas correspond to we also observed striped structures, as shown in Figure 12

the alkoxy substituents, in which alkyl chains are interdigi- (a). The phenyl moieties of the molecules 1ab form bright

tated. The length of an alkoxy chain (ΔL) is about stripes, whereas the interdigitated alkoxy chains, with the

(2.15Ϯ0.1) nm, which compares well with the distance of same orientation, form the dim areas. The length of an alk-

20.8 Å between the alkoxy oxygen atom and the terminal oxy chain (ΔL) is about (2.05Ϯ0.1) nm, and the angle (θ)

methyl group as measured by X-ray spectroscopic analysis. between the direction of an alkyl chain and that of a bright

The angle (θ) between the direction of an alkyl chain and stripe is about (124Ϯ3)°, as indicated with white arrows. A

that of a bright row is about (108Ϯ3)°, as indicated with 2D unit cell is shown in the image, and its lattice constants

white arrows. A comparable parameter is not present in the were determined to be

a = (3.41Ϯ0.1) nm, b =

3D X-ray structure. A 2D unit cell is shown in the image, (1.13Ϯ0.1) nm, and α = (63Ϯ3)°. Examining each bright

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Synthesis and Properties of N-Acylamidines

stripe, we suggest that the phenyl moieties of molecule 1ab studied by spectroscopic, crystallographic, and STM meth-

are interlaced with each other, so that the acylamidine ods. The formation of homodimers and tetramers, as well

moieties of two adjacent molecules approach each other as higher aggregates in solution, in the solid state, and on

close enough, as indicated with red bars (Figure 12, a). surfaces due to hydrogen bonding is typical for such com-

Therefore, we consider that two adjacent molecules form a pounds. High-level quantum chemical calculations for the

dimer by means of intermolecular hydrogen bonding and parent C₂H₄N₂O compound 1 support and quantify the ex-

that the dimers construct stripes, as presented in Figure 12 perimental findings. We will report on the coordination

(b). The 2D structure of 1ab is different to the 3D structures chemistry of the N-acylamidines 1 and on the catalytic

of 1aa and 1z, the analogues of 1ab, in which the polar properties of the resulting complexes in a separate paper.

groups (NH₂, O) form continuous networks with the alkyl

chains having different orientations. The differences can be

attributed to the many possible intermolecular hydrogen

bonding and molecule–substrate interactions.

Experimental Section

Materials and Methods: IR spectra were recorded with a Nicolet

5DXC spectrometer (KBr pellets). ¹H NMR spectra were recorded

with Bruker WM 300 (300.13 MHz) or Bruker AMX 400

(400.13 MHz) spectrometers, with tetramethylsilane as internal ref-

erence. ¹³C NMR were recorded with Bruker WM 300 (75.47 MHz)

or Bruker AMX 400 (100.61 MHz) spectrometers with solvent as

internal reference. CHN elemental analyses were recorded with an

Elementar Vario El III. All solvents were rigorously dried by stan-

dard methods. When necessary, the experiments were carried out

with complete exclusion of moisture (argon, septum/syringe tech-

nique) in glassware that had been thoroughly dried by repeated

heating under argon and subsequent evacuation.

The corresponding amidines were prepared either from the respec-

tive lithiated amines (using n-butyllithium as base) and the respec-

tive nitriles,^[25]or by reaction of amines with nitriles in the presence

of aluminum chloride.^[14]

Scanning Tunneling Microscopy: STM investigations were per-

formed with a commercial multimode Nanoscope III scanning tun-

neling microscope (Digital Instrument Co., Santa Barbara, CA)

with mechanically cut Pt/Ir (90:10) tips at ambient temperature.

The images shown were recorded in the constant-current mode.

For measurements at the solution–substrate interface, a saturated

solution of N-unsubstituted N-acylamidines was applied to a

freshly cleaved surface of highly orientated pyrolytic graphite

(HOPG; MaTeck GmbH). Measurement conditions are given in

the corresponding Figure captions. Different tips and samples were

used to check for reproducibility. Measurements obtained from

STM images, including unit cell parameters, are corrected against

the substrate lattice parameters obtained from HOPG images. Flat-

tening of the images was carried out to compensate for tilting of

the substrate and scan line artefacts, and a lowpass filtered trans-

form was employed to remove scanning noise in the STM images.

Figure 12. (a) STM image of compound 1ab on HOPG in phen-

yloctane (15.0 nmϫ15.0 nm, U = –524 mV, I = 300 pA). (b) Pro-

posed structural model, deduced from the STM images.

In conclusion, molecules of N-unsubstituted N-acyl-

amidines adsorbed at a liquid/graphite interface can form

dimers by means of intermolecular hydrogen bonds,

whereas dimeric basic units self-organize as ordered stripes

with the same orientation as the alkyl chains.

Preparation of N-Acylamidines 1. General Procedure: To a solution

of an amidine (10.0 mmol) in dichloromethane (10.0 mL) was

added an excess of triethylamine (1.5 mL, 11.0 mmol). The mixture

was stirred and cooled to 0 °C. A solution of acyl chloride

(9.5 mmol) in dichloromethane (10.0 mL) was added dropwise to

the reaction mixture using a dropping funnel. Then, the suspension

was warmed to 10 °C over the course of 1.5 h and was subsequently

washed with water (2 ϫ 10.0 mL). The organic layer was dried with

magnesium sulfate and the solvent was removed in vacuo to yield

the crude product.

Conclusions

In this study we have reported on the synthesis of 33

novel primary and secondary N-acylamidines 1 with quite

varied substitution patterns incorporating many combina-

tions of aliphatic and aromatic substituents. This class of

N-Pivaloyl-NЈ-(n-butyl)pivalamidine (1a): From N-(n-butyl)pival-

amidine (1.62 g, 10.0 mmol; prepared from lithiated n-butylamine

and pivalonitrile according to Konokahara et al.^[25]) and pivaloyl

chloride (1.14 g, 9.5 mmol), colorless crystals (1.33 g, 5.5 mmol,

compound shows versatile aggregation behavior, which was 58%) were obtained after washing of the crude product with water.

Eur. J. Org. Chem. 2011, 861–877

www.eurjoc.org

867

E.-U. Würthwein et al.

FULL PAPER

This material was used without further purification for the metal

CH_aliph.), 2837 (m, OCH₃), 1923 (vw), 1805 (vw), 1609 (s), 1587

(vs, C=O/C=N), 1553 (vs, C=O/C=N), 1506 (s, C=C_arom.), 1441 (s),

ion complexation experiments;^[12]m.p. 138 °C. IR (KBr): ν = 3400

˜

(vs, NH), 3294 (m, NH), 3204 (s, ν-CH_arom.), 2960 (s), 2928 (s), 1416 (s), 1327 (vs), 1254 (vs), 1198 (s), 1151 (vs), 1070 (m), 1022 (s),

1

2869 (m), 2770 (w, ν-CH_aliph), 1655 (vs, C=O/C=N), 1624 (vs, C=O/

810 (s), 772 (m), 698 (m, δ-CH_arom.) cm^–1. H NMR (300.13 MHz,

C=N), 1543 (s), 1485 (s), 1458 (s), 1410 (m), 1379 (m), 1225 (s), CDCl₃): δ = 2.14 (s, 6 H, o-CH₃R¹), 2.23 (s, 3 H, p-CH₃R¹), 3.86

1111 (m), 737 (m), 621 (m) cm^–1. H NMR (400.13 MHz, CDCl₃): (s, 3 H, CH₃O), 6.80 (s, 2 H, m-CH_arom.R¹), 6.95 (d, J = 8.7 Hz,

1

3

δ = 0.93 (t, ³J = 7.3 Hz, 3 H, CH₂CH₃), 1.19 [s, 9 H, COC- 2 H, m-CH_arom.R³), 7.23 (t, J = 7.5 Hz, 2 H, m-CH_arom.R²), 7.35

3

(CH₃)₃], 1.24 [s, 9 H, C(CH₃)₃], 1.36 (m, 2 H, CH₂CH₃), 1.53 (m,

2 H, CH₂CH₂CH₃), 3.04 (br., 2 H, NCH₂), 5.20 (br., NH) ppm. CH_arom.R²), 8.36 (d, ³J = 8.2 Hz, 2 H, o-CH_arom.R³), 11.23 (br.,

¹³C NMR (100.61 MHz, CDCl₃): δ = 13.6 (CH₂CH₃), 20.0 NH) ppm. ¹³C NMR (75.48 MHz, CDCl₃): δ = 18.5 (o-CH₃R¹),

(t, ³J = 7.5 Hz, 1 H, p-CH_arom.R²), 7.55 (d, ³J = 7.6 Hz, 2 H, o-

(CH₂CH₃), 28.2 [C(CH₃)₃], 28.5 [C(CH₃)₃], 31.0 (CH₂CH₂CH₃), 20.9 (p-CH₃R¹), 55.4 (OCH₃), 113.3 (m-CH_arom.R³), 127.0 (o-

38.5 [C(CH₃)₃], 40.8 [C(CH₃)₃], 43.2 (NCH₂), 165.3 (C=N), 187.1

C_arom.R¹), 127.8 (m-CH_arom.R²), 129.0 (o-CH_arom.R²), 129.2 (m-

CH_arom.R¹), 130.2 (i-C_arom.R³), 130.8 (p-CH_arom.R²), 131.6 (o-

(C=O) ppm. MS (70 eV): m/z (%) = 240 (5) [M]⁺, 225 (2) [M⁺

–

CH₃], 211 (2) [M⁺– C₂H₅], 183 (100) [M⁺– C₄H₉], 157 (4) [M⁺

CH_arom.R³), 133.6 (i-C_arom.R¹), 135.2 (i-C_arom.R²), 136.9 (p-C_arom.

-

C₄H₉CO + 2 H], 139 (3), 127 (4), 110 (3), 84 (7) [C₄H₉CNH]⁺, 72 R¹), 162.9 (p-C_arom.R³), 167.7 (CN), 179.7 (CO) ppm. MS (70 eV):

(5) [C₄H₉NH]⁺, 57 (50) [C₄H₉]⁺.

m/z (%) = 372 (21) [M]⁺, 269 (2), 237 (2) [M – CO(PhOMe)]⁺, 221

(30), 135 (100) [MeOPhCO]⁺, 104 (5), 92 (5), 77 (12) [Ph]⁺, 43 (2)

[NHCO]⁺. C₂₄H₂₄N₂O₂(372.46): calcd. C 77.39, H 6.49, N 7.52;

found C 77.22, H 6.58, N 7.43.

2,4,6-Trimethyl-N-[phenyl(2,4,6-trimethylphenylamino)methylene]-

benzamide (1b): Synthesized from 2,4,6-trimethylbenzoyl chloride

(1.73 g, 9.5 mmol) and N-(2,4,6-trimethylphenyl)benzamidine^[26]

(2.38 g, 10.0 mmol). Purification by column chromatography

X-ray Crystal Structure Analysis of 1c:^[27,28]Formula C₂₄H₂₄N₂O₂,

(TBME/n-pentane, 1:10

+

10% triethylamine); yield 1.64 g

M = 372.745, colorless crystal, 0.40ϫ0.25ϫ0.15 mm, a =

(4.3 mmol, 45%); pale yellow crystals; m.p. 148 °C. IR (KBr): ν =

3445 (m, NH), 3213 (m, NH), 3059 (m, ν-CH_arom.), 2959 (m), 2918

(m), 2858 (m), 2733 (w, ν-CH_aliph.), 1655 (s, C=O/C=N), 1628 (vs,

13.778(1), b = 9.289(1), c = 16.823(2) Å, β = 111.07(1)°, V =

2009.1(4) Å³, ρ_calc= 1.231 gcm^–3, μ = 0.623 mm^–1, empirical ab-

sorption correction (0.789Յ T Յ0.912), Z = 4, monoclinic, space

˜

C=O/C=N), 1611 (s), 1491 (s), 1477 (s), 1448 (s, C=C_arom.), 1267 group P2₁/n (No. 14), λ = 1.54178 Å, T = 223(2) K, ω/2θ scans,

(s), 1209 (s), 1175 (m), 1107 (m), 1034 (w), 1020 (m), 932 (vw),

8254 reflections collected (+h, Ϯk, Ϯl), [(sinθ)/λ] = 0.62 Å^–1, 4092

851 (m), 762 (m), 689 (m, δ-CH_arom.) cm^–1. ¹H NMR (300.13 MHz, independent (R_int= 0.045) and 2972 observed reflections [I

CDCl₃): δ = 2.10 (s, 6 H, o-CH₃R¹), 2.19 (s, 6 H, o-CH₃R³), 2.22 Ն2σ(I)], 261 refined parameters, R = 0.040, wR²= 0.123, max.

(s, 3 H, p-CH₃R¹), 2.23 (s, 3 H, p-CH₃R³), 6.77 (s, 2 H, m- (min.) residual electron density 0.22 (–0.18) e·Å^–3. Hydrogen atom

CH_arom.R³), 6.84 (s, 2 H, m-CH_arom.R¹), 7.45–7.53 (m, 3 H, m,p-

at N5 from difference Fourier map, others calculated and refined

CH_arom.R²), 7.88 (dd, ³J = 7.7, ⁴J = 1.7 Hz, 2 H, o-CH_arom.R²), as riding atoms.

12.90 (br., NH) ppm. ¹³C NMR (100.63 MHz, CDCl₃): δ = 17.9

4-Methoxy-N-[(4-methoxyphenylamino)phenylmethylene]benzamide

(o-CH₃R¹), 19.2 (o-CH₃R³), 20.7 (p-CH₃R³),21.0 (p-CH₃R¹), 126.4

(o-C_arom.R¹), 128.0 (o-CH_arom.R²), 128.1 (m-CH_arom.R²), 128.5 (m-

CH_arom.R³), 129.1 (m-CH_arom.R¹), 130.5 (p-CH_arom.R²), 133.2 (p-

(1d): Synthesized from 4-methoxybenzoyl chloride (1.62 g,

9.5 mmol) and N-(4-methoxyphenyl)benzamidine^[15](2.26 g,

10.0 mmol). Purification by column chromatography (acetone/n-

Pentane, 1:3 + 5% triethylamine); yield 1.32 g (3.7 mmol, 39%);

C_arom.R¹), 133.3 (i-C_arom.R³), 134.3 (o-C_arom.R³), 135.4 (i-C_arom.

-

R²), 139.2 (p-C_arom.R³), 142.3 (i-C_arom.R¹), 151.2 (CN), 167.8

(CO) ppm. MS (70 eV): m/z (%) = 384 (37) [M]⁺, 369 (8) [M –

CH₃]⁺, 341 (2), 265 (1) [M – Mes]⁺, 250 (7) [OC(Mes)NC(Ph)]⁺,

221 (11), 147 (100) [MesCO]⁺, 119 (28) [Mes]⁺, 91 (7), 77 (2)

[Ph]⁺. C₂₆H₂₈N₂O (384.52): calcd. C 81.21, H 7.34, N 7.29; found

C 80.82, H 7.21, N 7.65.

colorless crystals; m.p. 199 °C. IR (KBr): ν = 3437 (s, NH), 3059

˜

(m), 3007 (m, ν-CH_arom.), 2945 (m), 2831 (m, OCH₃), 2052 (vw),

1902 (vw), 1603 (vs, C=C_arom.), 1589 (vs, C=O/C=N), 1555 (vs,

C=O/C=N), 1512 (vs, C=C_arom.), 1441 (s), 1429 (s), 1331 (vs), 1250

(vs), 1202 (s), 1184 (s), 1167 (vs), 1070 (m), 1032 (s), 829 (m), 810

(m), 787 (m), 696 (m, δ-CH_arom.) cm^–1. ¹H NMR (400.13 MHz,

CDCl₃): δ = 3.73 (s, 3 H, CH₃OR¹), 3.85 (s, 3 H, CH₃OR³), 6.73

X-ray Crystal Structure Analysis of 1b:^[27,28]Formula C₂₆H₂₈N₂O,

M = 384.50, colorless crystal, 0.25ϫ0.20ϫ0.10 mm, a = 11.188(1),

b = 12.427(1), c = 16.875(1) Å, α = 93.55(1), β = 106.58(1), γ =

3

(d, J = 8.9 Hz, 2 H, o-CH_arom.R¹), 6.93 (d, J = 8.9 Hz, 4 H, m-

CH_arom.R¹, m-CH_arom.R³), 7.29 (t, ³J = 7.5 Hz, 2 H, m-CH_arom.R²),

100.27(1)°, V = 2196.7(3) Å³, ρ_calc= 1.163 gcm^–3, μ = 0.547 mm^–1, 7.38 (t, J = 7.4 Hz, 1 H, p-CH_arom.R²), 7.59 (d, J = 7.4 Hz, 2 H,

3

empirical absorption correction (0.875Յ T Յ0.947), Z = 4, tri- o-CH_arom.R²), 8.30 (d, J = 8.6 Hz, 2 H, o-CH_arom.R³), 12.44 (br.,

3

clinic, space group P1 (No. 2), λ = 1.54178 Å, T = 223(2) K, ω

NH) ppm. ¹³C NMR (100.62 MHz, CDCl₃): δ = 55.3 (2·CH₃O),

113.3 (m-CH_arom.R³), 114.2 (o-CH_arom.R¹), 122.7 (i-C_arom.R¹),

125.2 (m-CH_arom.R¹), 128.1 (m-CH_arom.R²), 129.5 (o-CH_arom.R²),

130.1 (i-C_arom.R³), 130.6 (p-CH_arom.R²), 131.6 (o-CH_arom.R³), 134.7

(i-C_arom.R²), 157.4 (p-C_arom.R¹), 162.9 (p-C_arom.R³), 165.0 (CN),

179.1 (CO) ppm. MS (70 eV): m/z (%) = 360 (20) [M]⁺, 257 (11)

[OC(PhOMe)NH(PhOMe)]⁺, 135 (100) [MeOPhCO]⁺, 107 (6) [Me-

OPh]⁺, 77 (9) [Ph]⁺, 43 (5) [NHCO]⁺. C₂₂H₂₀N₂O₃(360.41): calcd.

C 73.32, H 5.59, N 7.77; found C 73.04, H 5.45, N 7.70.

¯

and φ scans, 22510 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] =

0.60 Å^–1, 7506 independent (R_int= 0.039) and 6545 observed reflec-

tions [I Ն2σ(I)], 543 refined parameters, R = 0.046, wR²= 0.122,

max. (min.) residual electron density 0.18 (–0.14) e·Å^–3. Hydrogen

atoms at N3 from difference Fourier map, others calculated and

refined as riding atoms, two almost identical molecules in the asym-

metric unit.

4-Methoxy-N-[phenyl(2,4,6-trimethylphenylamino)methylene]benz-

amide (1c): Synthesized from 4-methoxybenzoyl chloride (1.62 g,

9.5 mmol) and N-(2,4,6-trimethylphenyl)benzamidine^[26](2.38 g,

10.0 mmol). Purification by washing with n-pentane and recrystalli-

zation from n-pentane; yield 2.58 g (6.9 mmol, 73%); colorless crys-

X-ray Crystal Structure Analysis of 1d:^[27,28]Formula C₂₂H₂₀N₂O₃,

M = 360.40, colorless crystal, 0.40ϫ0.05ϫ0.05 mm, a = 14.189(1),

b = 5.706(1), c = 22.694(1) Å, β = 92.86(1)°, V = 1835.1(4) Å³, ρ_calc

= 1.304 gcm^–3, μ = 0.708 mm^–1, empirical absorption correction

(0.765Յ T Յ0.966), Z = 4, monoclinic, space group P2₁/n (No.

14), λ = 1.54178 Å, T = 223(2) K, ω and φ scans, 8769 reflections

tals; m.p. 178 °C. IR (KBr): ν = 3439 (m, NH), 3144 (m, NH),

˜

3074 (m), 3022 (m, ν-CH_arom.), 2970 (m), 2945 (m), 2856 (m, ν-

868

www.eurjoc.org

Eur. J. Org. Chem. 2011, 861–877

Synthesis and Properties of N-Acylamidines

collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.59 Å^–1, 2705 independent (R_int

= 0.058) and 1431 observed reflections [I Ն2σ(I)], 250 refined pa-

rameters, R = 0.050, wR²= 0.117, max. (min.) residual electron

MS (70 eV): m/z (%) = 436 (23) [M]⁺, 417 (2), 382 (1), 333 (8), 291

(2) [M – CF₃Ph]⁺, 248 (7), 173 (100) [CF₃PhCO]⁺, 145 (22) [CF₃-

Ph]⁺, 104 (9) [C₆H₄CO]⁺. C₂₂H₁₄F₆N₂O (436.35): calcd. C 60.56,

density 0.22 (–0.27) e·Å^–3. Hydrogen atom at N5 from difference H 3.23, N 6.42; found C 60.69, H 3.20, N 6.34.

Fourier map, others calculated and refined as riding atoms.

X-ray Crystal Structure Analysis of 1f:^[27,28]Formula C₂₂H₁₄F₆N₂O,

M = 436.35, colorless crystal, 0.40ϫ0.30ϫ0.20 mm, a = 23.767(1),

c = 14.412(1) Å, V = 8140.9(7) Å³, ρ_calc= 1.424 g cm^–3, μ =

1.106 mm^–1, empirical absorption correction (0.666Յ T Յ0.809),

Z = 16, tetragonal, space group I4₁/a (No. 88), λ = 1.54178 Å, T

= 223(2) K, ω and φ scans, 15794 reflections collected (Ϯh, Ϯk,

Ϯl), [(sinθ)/λ] = 0.60 Å^–1, 3577 independent (R_int= 0.034) and 3065

observed reflections [I Ն2σ(I)], 340 refined parameters, R = 0.051,

wR²= 0.134, max. (min.) residual electron density 0.14 (–0.21)

e·Å^–3. Hydrogen atom at N5 from difference Fourier map, others

calculated and refined as riding atoms, both CF₃-groups are con-

siderably disordered, refined with split position using geometrical

and thermal restraints.

N-[(4-Methoxyphenylamino)phenylmethylene]-4-(trifluoromethyl)-

benzamide (1e): Synthesized from 4-trifluoromethylbenzoyl chlo-

ride (1.98 g, 9.5 mmol) and N-(4-methoxyphenyl)benzamidine^[15]

(2.26 g, 10.0 mmol). Purification by kugelrohr distillation (208 °C,

2ϫ10^–2mbar); yield 345 mg (0.9 mmol, 9%); yellow viscous oil/

solid; m.p. 53 °C. IR (KBr): ν = 3276 (m, NH), 3065 (m, ν-

˜

CH_arom.), 2957 (m), 2936 (m), 2910 (w), 2837 (m, CH₃O), 1944

(vw), 1813 (vw, C=C_arom.), 1611 (vs, C=O/C=N), 1593 (vs,

C=C_arom.), 1557 (vs, C=O/C=N), 1510 (vs, C=C_arom.), 1443 (s),

1410 (s), 1321 (vs), 1250 (vs), 1169 (vs), 1126 (vs, CF₃), 1069 (vs),

1034 (s), 1016 (s), 901 (m), 829 (s), 777 (s), 694 (s, δ-CH_arom.) cm^–1.

¹H NMR (400.13 MHz, CDCl₃): δ = 3.76 (s, 3 H, CH₃O), 6.77 (d,

³J = 8.8 Hz, 2 H, o-CH_arom.R¹), 6.96 (d, ³J = 7.3 Hz, 2 H, m-

N-[(2,6-Dimethylphenylamino)phenylmethylene]-4-methylbenzamide

(1g): Synthesized from 4-methylbenzoyl chloride (1.47 g, 9.5 mmol)

and N-(2,6-dimethylphenyl)benzamidine^[30](2.24 g, 10.0 mmol).

Purification by kugelrohr distillation (190 °C, 3.7 ϫ 10^–2mbar);

yield 2.61 g (7.6 mmol, 80%); slight-green viscous oil/solid; m.p.

3

CH_arom.R¹), 7.33 (t, J = 7.7 Hz, 2 H, m-CH_arom.R²), 7.42 (t, J =

7.2 Hz, 1 H, p-CH_arom.R²), 7.60 (d, ³J = 7.3 Hz, 2 H, o-CH_arom.R²),

7.70 (d, ³J = 8.3 Hz, 2 H, m-CH_arom.R³), 8.43 (d, ³J = 7.7 Hz, 2

H, o-CH_arom.R³), 12.92 (br., NH) ppm. ¹³C NMR (100.62 MHz,

CDCl₃): δ = 55.4 (CH₃O), 114.4 (o-CH_arom.R¹), 122.7 (i-C_arom.R¹),

123.4 (q, ¹J = 229.8 Hz, CF₃), 125.0 (q, ³J = 3.7 Hz, m-CH_arom.R³),

125.4 (m-CH_arom.R¹), 128.3 (m-CH_arom.R²), 129.6 (o-CH_arom.R²),

58 °C. IR (KBr): ν = 3395 (s, NH), 3267 (s, NH), 3061 (m), 3028

˜

(s, ν-CH_arom.), 2951 (m), 2920 (s), 2856 (m, ν-CH_aliph.), 1925 (vw),

1803 (vw, C=C_arom.), 1638 (s), 1597 (vs, C=O/C=N), 1551 (vs,

C=O/C=N), 1474 (vs, C=C_arom.), 1445 (s), 1414 (s), 1321 (vs), 1277

(vs), 1173 (s), 1067 (s), 1018 (s), 922 (m), 901 (m), 839 (m), 768 (s),

129.9 (o-CH_arom.R³), 131.0 (p-CH_arom.R²), 133.3 (q, J = 32.2 Hz,

2

p-C_arom.R³), 134.3 (i-C_arom.R²), 140.6 (i-C_arom.R³), 157.8 (p-

C_arom.R¹), 166.6 (CN), 178.1 (CO) ppm. MS (70 eV): m/z (%) = 398

(22) [M]⁺, 295 (29) [OC(PhCF₃)NH(PhOMe)]⁺, 210 (13) [(MeO-

Ph)NCPh]⁺, 173 (100) [CF₃PhCO]⁺, 145 (27), 105 (44) [PhCO]⁺,

77 (11) [Ph]⁺. C₂₂H₁₇F₃N₂O₂(398.38): calcd. C 66.33, H 4.30, N

7.03; found C 65.84, H 4.17, N 6.77.

1

694 (s, δ-CH_arom.) cm^–1. H NMR (400.14 MHz, CDCl₃): δ = 2.17

3

(s, 6 H, o-CH₃R¹), 2.41 (s, 3 H, p-CH₃R³), 6.98 (d, J = 7.5 Hz, 2

H, m-CH_arom.R¹), 7.07–7.09 (m, 1 H, p-CH_arom.R¹), 7.20–7.25 (m,

4 H, m-CH_arom.R², m-CH_arom.R³), 7.34 (t, ³J = 7.3 Hz, 1 H, p-

3

CH_arom.R²), 7.55 (d, J = 7.5 Hz, 2 H, o-CH_arom.R²), 8.29 (br., 2

H, o-CH_arom.R³), 13.08 (br., NH) ppm. ¹³C NMR (100.63 MHz,

CDCl₃): δ = 18.6 (o-CH₃R¹), 21.6 (p-CH₃R³), 124.0 (p-CH_arom.R¹),

127.2 (o-C_arom.R¹), 127.8 (m-CH_arom.R²), 128.5 (m-CH_arom.R¹),

128.8 (m-CH_arom.R³), 129.0 (o-CH_arom.R²), 129.6 (o-CH_arom.R³),

131.0 (p-CH_arom.R²), 133.7 (i-C_arom.R¹), 134.8 (i-C_arom.R³), 135.0

(i-C_arom.R²), 142.5 (p-C_arom.R³), 167.4 (CN), 179.9 (CO) ppm. MS

(70 eV): m/z (%) = 342 (28) [M]⁺, 251 (1) [M Tol]⁺, 239 (4), 223 (4)

[M – COTol]⁺, 207 (50), 119 (100) [TolCO]⁺, 91 (42) [Tol]⁺, 77 (9)

[Ph]⁺. C₂₃H₂₂N₂O (342.44): calcd. C 80.67, H 6.48, N 8.18; found

C 80.27, H 6.40, N 7.60.

N-{Phenyl[4-(trifluoromethyl)phenylamino]methylene}-4-(trifluoro-

methyl)benzamide (1f): A mixture of 4-(trifluoromethyl)aniline

(1.61 g, 10.0 mmol) and N-(ethoxyphenylmethylene)-4-(trifluoro-

methyl)benzamide (from ethyl benzimidate hydrochloride and 4-

(trifluormethyl)benzoyl chloride according to Kupfer et al.^[29]

;

3.21 g, 10.0 mmol) was stirred for 3 h at 60 °C. The excess of amine

was removed by distillation, to give the crude product, which re-

mained as a highly viscous oil that crystallized after 2 d. The com-

pound was purified by washing the solid with diethyl ether and

subsequent recrystallisation from ethanol or by column chromatog-

raphy (ethanol/n-pentane, 1:7 + 10% triethylamine); yield 1.85 g

4-Methyl-N-[p-tolyl(2,4,6-trimethylphenylamino)methylene]benz-

amide (1h): Synthesized from 4-methylbenzoyl chloride (1.47 g,

(4.2 mmol, 42%); colorless crystals; m.p. 186 °C. IR (KBr): ν =

˜

3433 (m, NH), 3269 (s, NH), 3204 (s), 3125 (m), 3076 (m, ν- 9.5 mmol) and 4-methyl-N-(2,4,6-trimethylphenyl)benzamidine^[26]

CH_arom.), 2988 (w), 2928 (w), 1917 (vw), 1809 (vw, C=C_arom.), 1624

(vs, C=O/C=N), 1591 (vs), 1578 (vs, C=C_arom.), 1539 (vs, C=O/ 2.0ϫ10^–2mbar); yield 2.13 g (5.7 mmol, 61%); yellow viscous oil/

C=N), 1412 (vs), 1377 (s), 1325 (vs), 1271 (vs), 1236 (s), 1167 (vs), solid; m.p. 136 °C. IR (KBr): ν = 3437 (s, NH), 3069 (m), 3024 (s,

(2.52 g, 10.0 mmol). Purification by kugelrohr distillation (189 °C,

˜

1124 (vs, CF₃), 1065 (vs), 1016 (s), 899 (m), 849 (s), 775 (s), 758

ν-CH_arom.), 2953 (s), 2920 (s), 2860 (s), 2735 (m, ν-CH_aliph.), 1933

(s), 698 (s, δ-CH_arom.) cm^–1. ¹H NMR (400.13 MHz, CDCl₃): δ = (vw), 1813 (vw, C=C_arom.), 1638 (m), 1611 (vs), 1585 (vs, C=O/

3

7.23 (d, J = 7.7 Hz, 2 H, o-CH_arom.R¹), 7.36 (t, J = 7.6 Hz, 2 H,

C=N), 1545 (vs, C=O/C=N), 1410 (vs), 1317 (vs), 1202 (s), 1153

m-CH_arom.R²), 7.46 (t, J = 7.4 Hz, 1 H, p-CH_arom.R²), 7.51 (d, J (s), 1069 (s), 1016 (s), 907 (m), 860 (m), 789 (s), 698 (m, δ-

3

= 8.5 Hz, 2 H, m-CH_arom.R¹), 7.54 (d, ³J = 7.4 Hz, 2 H, o-

CH_arom.) cm^–1. H NMR (300.13 MHz, CDCl₃): δ = 2.14 (s, 6 H,

1

CH_arom.R²), 7.70 (d, J = 8.2 Hz, 2 H, m-CH_arom.R³), 8.35 (d, J = o-CH₃R¹), 2.24 (s, 3 H, p-CH₃R¹), 2.30 (s, 3 H, p-CH₃R²), 2.41 (s,

3

7.9 Hz, 2 H, o-CH_arom.R³), 11.45 (br., NH) ppm. ¹³C NMR 3 H, p-CH₃R³), 6.80 (s, 2 H, m-CH_arom.R¹), 7.03 (d, J = 8.0 Hz,

3

(100.61 MHz, CDCl₃): δ = 122.8 (o-CH_arom.R¹), 123.8 (q, ¹J =

2 H, m-CH_arom.R²), 7.24 (d, J = 7.9 Hz, 2 H, m-CH_arom.R³), 7.47

3

280.5 Hz, CF₃R¹), 125.2 (q, J = 3.7 Hz, m-CH_arom.R³), 126.3 (q,

(d, J = 8.2 Hz, 2 H, o-CH_arom.R²), 8.28 (d, J = 7.4 Hz, 2 H, o-

3

³J = 3.6 Hz, m-CH_arom.R¹), 127.8 (q, ²J = 32.5 Hz, p-C_arom.R¹),

CH_arom.R³), 11.20 (br., NH) ppm. ¹³C NMR (100.63 MHz,

128.7 (m-CH_arom.R²), 129.0 (o-CH_arom.R²), 129.9 (o-CH_arom.R³), CDCl₃): δ = 18.5 (o-CH₃R¹), 20.9 (p-CH₃R¹), 21.4 (p-CH₃R²), 21.6

131.6 (p-CH_arom.R²), 133.7 (i-C_arom.R²), 133.8 (²J = 32.5 Hz, p- (p-CH₃R³), 127.0 (o-C_arom.R¹), 128.5 (m-CH_arom.R²), 128.7 (m-

C_arom.R³), 139.6 (i-C_arom.R³), 141.5 (i-C_arom.R¹), 164.2 (CN), 177.6

(CO) ppm; signal of CF₃R³partially under the signal of CF₃R¹.

CH_arom.R³), 129.0 (o-CH_arom.R²), 129.2 (m-CH_arom.R¹), 129.6 (o-

CH_arom.R³), 132.2 (i-C_arom.R²), 133.5 (i-C_arom.R¹), 135.1 (i-

Eur. J. Org. Chem. 2011, 861–877

www.eurjoc.org

869

E.-U. Würthwein et al.

FULL PAPER

C_arom.R³), 136.9 (p-C_arom.R¹), 141.4 (p-C_arom.R²), 142.3 (p-

C_arom.R³), 167.7 (CN), 179.9 (CO) ppm. MS (70 eV): m/z (%) =

370 (35) [M]⁺, 235 (46), 221 (4), 134 (5), 119 (100) [TolCO]⁺, 91

(36) [PhCH₂]⁺, 65 (5) [C₅H₅]⁺. C₂₅H₂₆N₂O (370.49): calcd. C 81.05,

H 7.07, N 7.56; found C 80.95, H 7.01, N 7.38.

cules B disordered, refined with split positions using geometrical

and thermal restraints, two almost identical molecules in the asym-

metric unit.

N-(2,2-Dimethyl-1-phenylaminopropylidene)-2,2-diphenylacetamide

(1k): Synthesized from diphenylacetyl chloride (2.19 g, 9.5 mmol)

and 2,2-dimethyl-N-phenylpropionamidine^[32](1.76 g, 10.0 mmol).

N-(4-Methylbenzoyl)-NЈ-(n-butyl)pivalamidine (1i): Synthesized

from N-(n-butyl)pivalamidine (1.56 g, 10.0 mmol) and 4-meth- Purification by column chromatography (acetone/n-pentane, 1:5 +

oxybenzoyl chloride (1.47 g, 9.5 mmol); yield 1.89 g (6.9 mmol, 5% triethylamine); yield 1.05 g (2.8 mmol, 30%); colorless solid;

73%); colorless solid; m.p. 87 °C. IR (KBr): ν = 3431 (br., NH), m.p. 139–148 °C. IR (KBr): ν = 3433 (m, NH), 3304 (s), 3252 (s,

˜

3267 (br., NH), 3101 (m, CH_arom.), 2959 (s, CH_aliph.), 2928 (s, NH), 3061 (m), 3032 (m, ν-CH_arom.), 2976 (s), 2932 (m), 2905 (w),

CH_aliph.), 2872 (m, CH_aliph.), 1597 (vs, C=O/C=N), 1570 (vs, C=O/ 2870 (w, ν-CH_aliph.), 1948 (vw), 1882 (vw), 1811 (vw, C=C_arom.),

C=N), 1553 (vs, C=C_arom.), 1531 (vs), 1506 (s), 1458 (s), 1437 (s), 1678 (vs, C=O/C=N), 1643 (vs, C=O/C=N), 1595 (s, C=C_arom.),

1389 (vs), 1362 (s), 1362 (s), 1304 (m), 1279 (s), 1231 (m), 1204 (m), 1493 (vs), 1448 (s), 1366 (m), 1236 (m), 1205 (s), 1169 (m), 1105

1173 (m), 1111 (m), 945 (w), 849 (m), 789 (m), 746 (m), 727 (m), (s), 1030 (m), 976 (w), 802 (w), 756 (s), 731 (s), 698 (vs, δ-

1

708 (m), 685 (s) cm^–1. ¹H NMR (300.13 MHz, CDCl₃): δ = 0.87 (t,

³J = 7.3 Hz, 3 H, CH₂CH₃), 1.30 [s, 9 H, C(CH₃)₃], 1.31 (m, 2 H,

CH_arom.) cm^–1. H NMR (400.14 MHz, CDCl₃): δ = 1.15 [s, 9 H,

3

4

C(CH₃)₃], 4.78 (s, 1 H, CHPh₂), 6.74 (td, J = 8.4, J = 1.1 Hz, 2

CH₂CH₃), 1.50 (m, 2 H, CH₂CH₂CH₃), 2.38 [s, 3 H, Ph(CH₃)], H, o-CH_arom.R¹), 6.88–6.90 (m, 4 H, o-CH_arom.R³), 7.07 (tt, ³J =

3.13 (br., 2 H, NCH₂), 5.50 (br., NH), 7.20 (m, 2 H, CH_arom.), 7.92

7.1, ⁴J = 1.1 Hz, 1 H, p-CH_arom.R¹), 7.21–7.28 (m, 8 H, m-

(m, 2 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ = 13.6 CH_arom.R¹, m,p-CH_arom.R³) ppm. ¹³C NMR (75.48 MHz, CDCl₃):

(CH₂CH₃), 19.9 (CH₂CH₃), 28.5 [C(CH₃)₃], 31.0 (CH₂CH₂CH₃), δ = 27.4 [C(CH₃)₃], 39.4 [C(CH₃)₃], 59.3 (CHPh₂), 119.6 (o-

39.0 [C(CH₃)₃], 43.3 (NCH₂), 128.5, 129.1 (o-, m-CH_arom.), 134.4 CH_arom.R¹), 123.3 (p-CH_arom.R¹), 127.4 (p-CH_arom.R³), 128.7 (m-

(i-C_arom.), 141.3 (i-C_arom.), 166.7 (C=N), 173.4 (C=O) ppm. MS CH_arom.R¹), 2ϫ128.8 (o,m-CH_arom.R³), 138.6 (i-C_arom.R³), 149.3

(70 eV): m/z (%) = 274 (27) [M]⁺, 245 (6) [M⁺– C₂H₅], 217 (23) (i-C_arom.R¹), 157.9 (CN), 168.4 (CO) ppm. MS (70 eV): m/z (%) =

[M⁺– C₄H₉], 203 (6), 183 (10) [M⁺– PhCH₃], 161 (4), 139 (12),

370 (76) [M]⁺, 203 (24) [M – CHPh₂]⁺, 194 (100) [Ph₂CCO]⁺, 175

119 (100) [CH₃PhCO]⁺, 110 (15), 91 (36) [PhCH₃]⁺, 72 (30) (60) [M – COCHPh₂]⁺, 167 (72), 160 (78) [PhNCtBu]⁺, 118 (12),

[C₄H₉NH]⁺, 57 (17) [C₄H₉]⁺. C₁₇H₂₆N₂O (274.20): calcd. C 74.41,

H 9.55, N 10.21; found C 74.10, H 9.44, N 10.06.

104 (59) [PhNCH]⁺, 93 (37) [PhNH₂]⁺, 57 (28) [C₄H₉]⁺. C₂₅H₂₆N₂O

(370.20): calcd. C 81.05, H 7.07, N 7.56; found C 80.82, H 7.06, N

7.37.

N-[1-(2,4,6-Trimethylphenylamino)propylidene]butyramide (1j): Syn-

thesized from butyric acid (1.01 g, 9.5 mmol) and N-(2,4,6-trimeth-

ylphenyl)propionamidine^[31](1.90 g, 10.0 mmol), and purified by

kugelrohr distillation (112 °C, 5 ϫ 10^–3mbar); yield 1.82 g

N-(4-Methylbenzoyl)-NЈ-(n-butyl)benzamidin (1l): Synthesized from

N-(n-butyl)benzamidine^[33](1.76 g, 10.0 mmol) and 4-methylbenz-

oyl chloride (1.47 g, 9.5 mmol), and purified by kugelrohr distil-

lation (180 °C, 0.004 hPa); yield 2.54 g (8.6 mmol, 91%); light-yel-

(7.0 mmol, 74%); colorless solid; m.p. 82 °C. IR (KBr): ν = 3437

˜

(m, NH), 3229 (m), 3171 (m, NH), 3117 (m), 2961 (s), 2937 (s), low viscous oil; b.p. 180 °C (0.004 hPa); m.p. 87 °C. IR (KBr): ν =

˜

2876 (m), 2735 (w, CH_aliph.), 1715 (vs, C=O/C=N), 1655 (vs, C=O/ 3447 (br., NH), 3261 (br., NH), 3094 (s, CH_arom.), 3063 (s,

C=N), 1510 (s), 1475 (s, C=C_arom.), 1466 (m), 1431 (m, δ-CH₂),

1377 (s, δ-CH₃), 1335 (s), 1242 (s), 1221 (m), 1177 (s), 1151 (m),

CH_arom.), 3034 (s, CH_arom.), 2961 (s, CH_aliph.), 2930 (s, CH_aliph.),

2870 (s, CH_aliph.), 1610 (s, C=O/C=N), 1589 (s, C=O/C=N), 1562

854 (m), 748 (w, δ-CH_arom.) cm^–1. ¹H NMR (400.13 MHz, CDCl₃): (vs, C=C_arom.), 1502 (m), 1493 (m), 1462 (m), 1441 (m), 1385 (m),

3

δ = 0.79 (t, J = 7.1 Hz, 3 H, CH₃CH₂CH₂), 0.99 (t, J = 7.5 Hz, 1312 (m), 1285 (m), 1163 (w), 1088 (w), 1020 (vw), 922 (vw), 893

3 H, CH₃CH₂), 1.45–1.56 (m, 2 H, CH₃CH₂CH₂), 2.03 (br., 2 H, (w), 881 (w), 841 (w), 793 (w), 766 (w), 744 (w), 696 (m) cm^–1. H

1

CH₃CH₂CH₂), 2.06 (s, 6 H, o-CH₃R¹), 2.27 [s (br.), 3 H, p-CH₃R¹], NMR (300.13 MHz, CDCl₃): δ = 0.90 (br., 3 H, CH₂CH₃), 1.38

2.45 (br., 2 H, CH₃CH₂), 6.87 [s (br.), 2 H, m-CH_arom.], 9.68 (br., (br., 2 H, CH₂CH₃), 1.60 (br., 2 H, CH₂CH₂CH₃), 2.38 [s, 3 H,

NH), 12.43 (br., NH) ppm. ¹³C NMR (100.63 MHz, CDCl₃): δ =

Ph(CH₃)], 3.41 (br., 2 H, NCH₂), 5.43 (br., NH), 7.18–8.15 (m, 9 H,

10.8 (CH₃CH₂), 13.3 (CH₃CH₂CH₂), 17.5 (o-CH₃R¹), 18.4 CH_arom.), 11.68 (br., NH) ppm. ¹³C NMR (100.61 MHz, CDCl₃): δ

(CH₃CH₂CH₂), 20.7 (p-CH₃R¹), 23.9 (CH₃CH₂), 39.3

= 13.5 (CH₂CH₃), 19.7 (CH₂CH₃), 21.5 (PhCH₃), 32.4

(CH₃CH₂CH₂), 127.3 (o-C_arom.), 128.8 (m-CH_arom.), 132.8 (p (CH₂CH₂CH₃), 45.3 (NCH₂), 128.3, 128.6, 129.4 (o-, m-CH_arom.),

C_arom.), 141.1 (i-C_arom.), 154.3 (CN), 170.1 (CO) ppm. MS (70 eV): 130.4 (p-CH_arom.), 134.7 (i-C_arom.), 135.1 (i-C_arom.), 141.9 (i-C_arom.),

m/z (%) = 260 (81) [M]⁺, 245 (25) [M – CH₃]⁺, 217 (18) [M – 161.9 (C=N), 180.0 (C=O) ppm. MS (70 eV): m/z (%) = 294 (60)

nPr]⁺, 205 (16) [OC(nPr)NH(Mes)]⁺, 174 (100) [MesNCEt]⁺, 161

(37), 120 (21) [Mes]⁺, 71 (23) [nPrCO]⁺, 43 (45) [nPr]⁺. C₁₆H₂₄N₂O

(260.37): calcd. C 73.81, H 9.29, N 10.76; found C 74.05, H 9.26,

N 10.44.

[M]⁺, 251 (22) [M⁺– C₃H₇], 237 (23) [M⁺– C₄H₉], 203 (18) [M⁺

–

PhCH₃], 175 (4) [M⁺– COPhCH₃], 159 (10), 130 (13). 119 (100)

[CH₃PhCO]⁺, 104 (34) [PhCNH]⁺, 91 (39) [CH₃Ph]⁺, 72 (26)

[C₄H₉NH]⁺. C₁₉H₂₂N₂O (294.39): calcd. C 77.52, H 7.53, N 9.52;

found C 77.29, H 7.54, N 9.52.

X-ray Crystal Structure Analysis of 1j:^[27,28]Formula C₁₆H₂₄N₂O,

M = 260.37, colorless crystal, 0.30 ϫ 0.25 ϫ 0.20 mm, a = N-[2,2-Dimethyl-1-(phenylamino)propylidene]-4-methylbenzamide

10.1936(2), b = 24.6608(7), c = 13.0369(2) Å, β = 99.911(1)°, V

= 3228.34(12) Å³, ρ_calc= 1.071 gcm^–3, μ = 0.067 mm^–1, empirical

absorption correction (0.980 Յ T Յ 0.987), Z = 8, monoclinic,

space group P2₁/c (No. 14), λ = 0.71073 Å, T = 198(2) K, ω and φ

scans, 20315 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] =

0.66 Å^–1, 7681 independent (R_int= 0.055) and 4109 observed reflec-

tions [I Ն2σ(I)], 369 refined parameters, R = 0.071, wR²= 0.210,

max. (min.) residual electron density 0.86 (–0.32) e·Å^–3. Hydrogen

atoms calculated and refined as riding atoms, propyl group in mole-

(1m): Synthesized from 4-methylbenzoyl chloride (1.47 g,

9.5 mmol) and 2,2-dimethyl-N-phenylpropionamidine^[32](1.76 g,

10.0 mmol). Purification by kugelrohr distillation (148 °C,

6ϫ10^–3mbar); yield 0.47 g (1.6 mmol, 17%); colorless solid; m.p.

152 °C. IR (KBr): ν = 3373 (vs, NH), 3061 (m), 3034 (m, ν-

˜

CH_arom.), 2963 (s), 2928 (s), 2909 (s), 2866 (m, ν-CH_aliph.), 1944

(vw), 1873 (vw), 1803 (vw, C=C_arom.), 1672 (vs, C=O/C=N), 1639

(vs, C=O/C=N), 1612 (s), 1593 (s), 1520 (s, C=C_arom.), 1475 (vs),

1443 (vs), 1364 (m), 1261 (s), 1198 (s), 1132 (s), 1090 (s), 1020 (m),

870

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Eur. J. Org. Chem. 2011, 861–877

Synthesis and Properties of N-Acylamidines

910 (m), 841 (s), 824 (m), 752 (vs), 698 (s, δ-CH_arom.) cm^–1. ¹H 2,2-Dimethyl-N-[p-tolyl-(2,4,6-trimethylphenylamino)methylene]prop-

NMR (400.14 MHz, CDCl₃): δ = 1.38 [s, 9 H, C(CH₃)₃], 2.37 (s, 3 ionamide (1p): Synthesized from pivaloyl chloride (1.15 g,

H, p-CH₃R³), 7.06–7.11 (m, 1 H, p-CH_arom.R¹), 7.15 (d, ³J = 9.5 mmol) and 4-methyl-N-(2,4,6-trimethylphenyl)benzamidine^[34]

8.1 Hz, 2 H, m-CH_arom.R³), 7.21 (d, ³J = 7.3 Hz, 2 H, o,m-

(2.52 g, 10.0 mmol). Purification by kugelrohr distillation (147 °C,

3

CH_arom.R¹), 7.29 (d, J = 7.5 Hz, 2 H, o,m-CH_arom.R¹), 7.78 (d, J

1.7ϫ10^–2mbar). The compound was isolated as a mixture of tau-

= 8.1 Hz, 2 H, o-CH_arom.R³) ppm. ¹³C NMR (100.63 MHz, tomers; yield 2.93 g (8.7 mmol, 92 %); yellow viscous oil; m.p.

CDCl₃): δ = 21.5 (p-CH₃R³), 28.8 [C(CH₃)₃], 40.2 [C(CH₃)₃], 122.9 83 °C. IR (KBr): ν = 3408 (vs, NH), 3061 (m), 3015 (m, ν-CH_arom.),

˜

(o,m-CH_arom.R¹), 125.1 (p-CH_arom.R¹), 128.6 (m-CH_arom.R³), 128.8 2980 (s), 2961 (s), 2934 (s), 2918 (s), 2868 (s, ν-CH_aliph.), 1923 (vw,

(o,m-CH_arom.R¹), 129.1 (o-CH_arom.R³), 133.7 (i-C_arom.R³), 141.9 (p-

C_arom.R³), 149.0 (i-C_arom.R¹), 161.5 (CN), 174.6 (CO) ppm. MS

(70 eV): m/z (%) = 294 (20) [M]⁺, 279 (5) [M – CH₃]⁺, 211 (5), 119

(100) [TolCO]⁺, 91 (31) [Tol]⁺, 57 (5) [C₄H₉]⁺. C₁₉H₂₂N₂O (294.39):

calcd. C 77.52, H 7.53, N 9.52; found C 77.51, H 7.36, N 9.30.

C=C_arom.), 1699 (vs, C=O/C=N), 1632 (vs, C=O/C=N), 1572 (m),

1514 (m, C=C_arom.), 1477 (vs), 1315 (s), 1215 (s), 1161 (s), 1020 (w),

935 (w), 864 (m), 799 (m, δ-CH_arom.) cm^–1. ¹H NMR (400.14 MHz,

CDCl₃): δ = 0.99 [s, 6 H, C(CH₃)₃], 1.32 [s, 3 H, C(CH₃)₃], 2.06 (s,

6 H, o-CH₃R¹), 2.27 (s, 3 H, p-CH₃R¹), 2.39 (s, 3 H, p-CH₃R²),

6.90 (s, 2 H, m-CH_arom.R¹), 7.23 (d, ³J = 7.4 Hz, 2 H, m-

CH_arom.R²), 7.63 (d, ³J = 7.7 Hz, 2 H, o-CH_arom.R²), 12.29 (br.,

NH) ppm. ¹³C NMR (100.63 MHz, CDCl₃): δ = 17.6 (o-CH₃R¹),

20.7 (p-CH₃R¹), 21.4 (p-CH₃R²), 26.9 [C(CH₃)₃], 39.8 [C(CH₃)₃],

126.8 (o-C_arom.R¹), 127.9 (o-CH_arom.R²), 128.7 (m-CH_arom.R²),

129.1 (m-CH_arom.R¹), 132.2 (i-C_arom.R²), 133.1 (p-C_arom.R¹), 140.7

(p-C_arom.R²), 142.5 (i-C_arom.R¹), 152.1 (CN), 175.6 (CO) ppm. MS

(70 eV): m/z (%) = 336 (53) [M]⁺, 321 (6) [M – CH₃]⁺, 279 (100)

[M – C₄H₉]⁺, 235 (54), 221 (9), 135 (13) [MesNH₂]⁺, 118 (21)

[TolCNH]⁺, 91 (13) [Tol]⁺, 57 (31) [C₄H₉]⁺. C₂₂H₂₈N₂O (336.47):

calcd. C 78.53, H 8.39, N 8.33; found C 78.33, H 8.27, N 8.37.

2,2-Dimethyl-N-(phenylphenylaminomethylene)propionamide (1n):

Synthesized from pivaloyl chloride (1.15 g, 9.5 mmol) and N-phen-

ylbenzamidine^[32](1.96 g, 10.0 mmol), and purified by kugelrohr

distillation (190 °C, 4.0ϫ10^–3mbar). The compound was isolated

as a mixture of tautomers; yield 2.36 g (8.4 mmol, 89%); pale yel-

low viscous oil, which began to crystallize after two weeks; m.p.

90 °C. IR (KBr): ν = 3466 (br., NH), 3234 (br. NH), 3088 (m,

˜

CH_arom.), 3059 (m, CH_arom.), 3028 (m, CH_arom.), 2993 (m), 2974

(s), 2957 (s), 2934 (m), 2870 (m, CH_aliph.), 1664 (vs, C=O/C=N),

1630 (vs, C=O/C=N), 1593 (vs), 1578 (s), 1504 (vs), 1477 (vs,

C=C_arom.), 1448 (s), 1402 (s), 1373 (m), 1313 (s), 1294 (vs), 1279

(s), 1215 (s), 1175 (vs), 1072 (s), 1024 (m), 951 (m), 920 (m), 843

N-[(2,6-Diisopropylphenylamino)phenylmethylene]-2,2-dimethylprop-

ionamide (1q): Synthesized from pivaloyl chloride (1.15 g,

9.5 mmol) and N-(2,6-diisopropylphenyl)benzamidine^[35](2.80 g,

10.0 mmol), and purified by recrystallization from diethyl ether.

The compound was isolated as a mixture of tautomers; yield 2.27 g

1

(m), 808 (m), 766 (s), 750 (vs), 694 (vs, δ-CH_arom.) cm^–1. H NMR

(300.13 MHz, CDCl₃): δ = 1.06 [s, 4.9 H, C(CH₃)₃], 1.28 [s, 4.1 H,

C(CH₃)₃], 6.91–7.49 (m, 9 H, CH_arom.), 7.70–7.74 (m, 1 H,

CH_arom.), 9.30 (br., 1 H, NH) ppm. ¹³C NMR (75.47 MHz,

CDCl₃): δ = 27.0 [C(CH₃)₃], 27.6 [C(CH₃)₃], 39.8 [C(CH₃)₃], 120.1

(o-CH_arom.R¹), 122.8, 124.0, 128.1, 128.8, 129.2, 129.6, 130.4, 130.8

(CH_arom.), 135.2 (i-C_arom.R²), 148.1 (i-C_arom.R¹), 152.4 (CN), 176.2

(CO) ppm. MS (70 eV): m/z (%) = 280 (11) [M]⁺, 265 (3), 237 (2),

223 (100) [M – C₄H₉]⁺, 196 (15), 195 (33) [M – COtBu]⁺, 180 (31)

[PhCNPh]⁺, 127 (4), 119 (5), 104 (29) [PhCNH]⁺, 93 (37)

[PhNH₂]⁺, 92 (17) [PhNH]⁺, 77 (59) [Ph]⁺, 57 (81) [C₄H₉]⁺.

(6.2 mmol, 66%); colorless crystals; m.p. 127 °C. IR (KBr): ν =

˜

3410 (s, NH), 3393 (s, NH), 3354 (s, NH), 3063 (m, ν-CH_arom.),

2963 (vs), 2928 (s), 2868 (s, ν-CH_aliph.), 1919 (vw, C=C_arom.), 1695

(vs, C=O/C=N), 1630 (vs, C=O/C=N), 1580 (s, C=C_arom.), 1479 (s),

1454 (vs), 1362 (m), 1317 (s), 1302 (s), 1244 (m), 1194 (s), 1157 (s),

937 (m), 787 (s), 764 (s), 746 (s), 694 (s, δ-CH_arom.) cm^–1. ¹H NMR

3

(300.13 MHz, CDCl₃): δ = 0.96 [s, 8.5 H, C(CH₃)₃], 1.18 [d, J =

C

₁₈H₂₀N₂O (280.36): calcd. C 77.11, H 7.19, N 9.99; found C

1.0 Hz, 6 H, (CH₃)₂CH], 1.20 [d, ³J = 1.1 Hz, 6 H, (CH₃)₂CH],

77.12, H 6.97, N 10.58.

3

1.35 [s, 0.5 H, C(CH₃)₃], 2.90 [sep., J = 6.9 Hz, 2 H, (CHCH₃)₂],

7.04–7.23 (m, 3 H, CH_arom.R¹), 7.41–7.51 (m, 3 H, m,p-CH_arom.R²),

7.69–7.73 (m, 2 H, o-CH_arom.R²) ppm. ¹³C NMR (75.48 MHz,

CDCl₃): δ = 23.1 [CH(CH₃)₂], 23.4 [CH(CH₃)₂], 27.0 [C(CH₃)₃],

28.2 [CH(CH₃)₂], 39.8 [C(CH₃)₃], 123.7 (m-CH_arom.R¹), 124.7 (p-

CH_arom.R¹), 127.9, 128.1 (o,m-CH_arom.R²), 130.4 (p-CH_arom.R²),

135.0 (i-C_arom.R²), 137.6 (o-C_arom.R¹), 142.8 (i-C_arom.R¹), 151.9

(CN), 175.5 (CO), 194.4 (CO) ppm. MS (70 eV): m/z (%) = 364

(76) [M]⁺, 321 (9) [M – iPr]⁺, 307 (54) [M – C₄H₉]⁺, 263 (61) [M –

OC(tBu)NH₂]⁺, 248 (74), 235 (100) [M – COtBu – iPr – 1]⁺, 220

(12) [M – OC(tBu)NH₂– iPr]⁺, 175 (11), 160 (6), 127 (11), 104 (11)

[PhCNH]⁺, 57 (47) [C₄H₉]⁺. C₂₄H₃₂N₂O (364.53): calcd. C 79.08,

H 8.85, N 7.68; found C 79.09, H 8.76, N 7.62.

N-[(2,6-Dimethylphenylamino)phenylmethylene]-2,2-dimethylprop-

ionamide (1o): Synthesized from pivaloyl chloride (1.15 g,

9.5 mmol) and N-(2,6-dimethylphenyl)benzamidine^[30](2.24 g,

10.0 mmol). Purification by kugelrohr distillation (150 °C,

3.0ϫ10^–2mbar). The compound was isolated as a mixture of tau-

tomers; yield 2.81 g (9.1 mmol, 96%); pale yellow viscous oil; m.p.

67 °C. IR (KBr): ν = 3402 (s, NH), 3354 (vs, NH), 3065 (m), 3055

˜

(m), 3026 (m, ν-CH_arom.), 2964 (s), 2922 (s), 2866 (m, ν-CH_aliph.),

1954 (vw, C=C_arom.), 1686 (vs, C=O/C=N), 1626 (vs, C=O/C=N),

1593 (s), 1578 (s, C=C_arom.), 1477 (vs), 1288 (s), 1250 (s), 1213 (s),

1200 (s), 1163 (s), 1151 (vs), 1096 (s), 1026 (m), 843 (m), 781 (s),

766 (vs), 690 (vs, δ-CH_arom.) cm^–1. ¹H NMR (400.14 MHz, CDCl₃):

δ = 0.98 [s, 7 H, C(CH₃)₃], 1.33 [s, 2 H, C(CH₃)₃], 2.11 (s, 6 H, o-

CH₃R¹), 6.97 (t, ³J = 7.4 Hz, 1 H, p-CH_arom.R¹), 7.10 (d, ³J = X-ray Crystal Structure Analysis of 1q:^[27,28]Formula C₂₄H₃₂N₂O,

7.5 Hz, 2 H, m-CH_arom.R¹), 7.38–7.49 (m, 3 H, m,p-CH_arom.R²), M = 364.52, colorless crystal, 0.30ϫ0.30ϫ0.20 mm, a = 11.590(1),

7.75 (d, ³J = 7.7 Hz, 2 H, o-CH_{ar om .}R²) ppm. ¹³C NMR

(100.61 MHz, CDCl₃): δ = 17.6 (o-CH₃R¹), 26.9 [C(CH₃)₃], 27.7

b = 13.321(1), c = 16.715(1) Å, α = 99.29(1), β = 100.21(1), γ =

114.64(1)°, V = 2117.1(3) Å³, ρ_calc= 1.087 gcm^–3, μ = 0.508 mm^–1,

[C(CH₃)₃], 39.8 [C(CH₃)₃], 124.0 (p-CH_arom.R¹), 127.0 (o-C_arom.R¹), empirical absorption correction (0.863Յ T Յ0.905), Z = 4, tri-

127.9 (m-CH_arom.R¹), 128.0 (o,m-CH_arom.R²), 128.4 (m-CH_arom.R¹), clinic, space group P1 (No. 2), λ = 1.54178 Å, T = 223(2) K, ω

¯

130.6 (p-CH_arom.R²), 134.9 (i-C_arom.R²), 145.1 (i-C_arom.R¹), 152.1

(CN), 175.6 (CO) ppm. MS (70 eV): m/z (%) = 308 (60) [M]⁺, 265

and φ scans, 34464 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] =

0.60 Å^–1, 7795 independent (R_int= 0.035) and 7104 observed reflec-

(2), 251 (100) [M – C₄H₉]⁺, 207 (82), 193 (7), 147 (3), 121 (16) tions [I Ն2σ(I)], 557 refined parameters, R = 0.057, wR²= 0.155,

[XylNH₂]⁺, 104 (27), 77 (20) [Ph]⁺, 57 (47) [C₄H₉]⁺. C₂₀H₂₄N₂O max. (min.) residual electron density 0.50 (–0.31) e·Å^–3. Hydrogen

(308.42): calcd. C 77.89, H 7.84, N 9.08; found C 77.86, H 7.65, N

9.14.

atoms at N3 from difference Fourier map, others calculated and

refined as riding atoms, tert-butyl groups are considerably disor-

Eur. J. Org. Chem. 2011, 861–877

www.eurjoc.org

871

E.-U. Würthwein et al.

FULL PAPER

dered, refined with split positions using geometrical restraints, two

almost identical molecules in the asymmetric unit.

[M⁺– 1], 239 (6) [M⁺– C₆H₁₃], 205 (73) [H₁₃C₆OC₆H₄CO]⁺, 147

(7) [H₂NC(Ph)NCO]⁺, 138 (5), 137 (7), 121 (100) [HOC₆H₄CO]⁺,

120 (6), 104 (9) [C₆H₄CO]⁺, 103 (9) [PhCN]⁺, 99 (12), 97 (6), 93

(10) [C₆H₄OH]⁺, 85 (6) [C₆H₁₃]⁺, 83 (9), 77 (4) [C₆H₅]⁺, 71 (9)

[C₅H₁₁]⁺, 70 (7), 69 (10), 65 (7), 58 (6), 57 (18) [C₄H₉]⁺, 56 (7), 55

(13). C₂₀H₂₄N₂O₂(324.42): calcd. C 74.05, H 7.46, N 8.63; found

C 73.89, H 7.57, N 8.53.

General Procedure for the Synthesis of N-Acylamidines 1r–x: At

0 °C, amidine hydrochloride (1 equiv.) was suspended in acetone

(20 mL) and treated with aqueous NaOH (2 n, 2.5 equiv.). After

5 min of stirring, acyl chloride (1 equiv.), dissolved in acetone

(10 mL), was added slowly. After 1.5 h stirring at 0 °C, the solvent

was removed in vacuo as completely as possible. The residue was

treated with water (100 mL), and the mixture was extracted with

chloroform (3ϫ50 mL). After removal of the chloroform in vacuo

from the organic phase, the remaining residue was purified by col-

umn chromatography.

N-[4-(n-Octyloxy)benzoyl]benzamidine (1t): Synthesized from 4-(n-

octyloxy)benzoyl chloride^[37](0.537 g, 2.00 mmol), benzamidine hy-

drochloride (0.378 g, 2.00 mmol), and NaOH (2 n, 2.50 mL). Puri-

fied by column chromatography (ethyl acetate, 5:1); yield 0.584 g

(83%); colorless solid; R_f= 0.66 (ethyl acetate/petroleum ether,

1:1); m.p. 76 °C. IR (KBr): ν = 3337 (br. m, NH), 3198 (br. m,

˜

N-[4-(n-Butyloxy)benzoyl]benzamidine (1r): Synthesized from 4-(n-

butyloxy)benzoyl chloride^[36](0.328 g, 1.54 mmol), benzamidine

hydrochloride (0.291 g, 1.54 mmol) and NaOH (2 n, 1.93 mL).

Purified by column chromatography (ethyl acetate/petroleum ether,

5:1); yield 0.355 g (78%); colorless amorphous solid; R_f= 0.58

NH), 3080 (w), 3053 (w, CH_arom.), 2955 (s), 2937 (s), 2924 (m),

2872 (m), 2854 (m, CH_alk), 1609 (sh), 1591 (s), 1562 (m), 1514 (s),

1501 (s), 1473 (m), 1359 (m), 1333 (sh), 1321 (s), 1294 (m), 1285

(m), 1259 (sh), 1252 (s), 1175 (m), 1151 (m), 1040 (m), 1030 (m),

997 (m), 865 (m), 852 (m), 725 (m), 698 (m), 653 (m), 634 (m) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 0.85–0.93 (m, 3 H, CH₃), 1.22–

1.54 (m, 10 H, CH₂), 1.74–1.87 (m, 2 H, CH₂), 4.02 (t, ³J = 6.6 Hz,

2 H, OCH₂), 6.7 (br. s, 1 H, NH), 6.92 (m, 2 H, m-CH_arom., CO),

7.45–7.60 (m, 3 H, m-/p-CH_arom.), 8.02 (m, 2 H, o-CH_arom.), 8.33

(m, 2 H, o-CH_arom., CO), 10.56 (br. s, 1 H, NH) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 14.0 (CH₃), 22.6, 26.0, 29.2, 29.3, 31.7

(ethyl acetate/petroleum ether, 1:1); m.p. 86–87 °C. IR (KBr): ν =

˜

3321 (br. m, NH), 3184 (br. m, NH), 3070 (w), 3031 (w, CH_arom.),

2959 (m), 2934 (m), 2872 (m), 2841 (sh, CH_alk), 1622 (sh), 1595 (s),

1580 (m), 1560 (m), 1553 (sh), 1508 (s), 1475 (s), 1468 (sh), 1443

(s), 1389 (m), 1331 (s), 1292 (m), 1252 (s), 1227 (sh), 1173 (m), 1159

(sh), 1148 (m), 1103 (m), 1069 (m), 1028 (m), 1007 (m), 1001 (m),

970 (m), 957 (sh), 854 (m), 820 (sh), 810 (m), 783 (s), 770 (m), 704

(sh), 698 (m), 669 (m), 658 (m), 633 (m), 579 (m), 546 (m), 509

(CH₂), 68.1 (OCH₂), 113.8 (m-CH_arom.

, CO), 127.4, 128.7

(CH_arom.), 130.3 (C_ipso, C=O), 131.7, 132.1 (CH_arom.), 135.3 (C_ipso),

162.5 (p-C_arom., CO), 166.1 (C_quat., C=N), 180.0 (C_quat., C=O) ppm.

MS (70 eV): m/z (%) = 352 (48) [M]⁺, 351 (34) [M⁺– 1], 324 (3)

[M⁺– C₂H₄], 239 (6), 233 (85) [H₁₇C₈OC₆H₄CO]⁺, 147 (9)

[H₂NC(Ph)NCO]⁺, 138 (5), 137 (7) [HOC₆H₄CONH₂]⁺, 121 (100)

[HOC₆H₄CO]⁺, 120 (5), 104 (12) [C₆H₄CO]⁺, 103 (12) [PhCN]⁺, 93

(11) [C₆H₄OH]⁺, 77 (6) [C₆H₅]⁺, 76 (5), 71 (6) [C₅H₁₁]⁺, 69 (6), 65

(7), 57 (14) [C₄H₉]⁺, 55 (10). C₂₂H₂₈N₂O₂(352.48): calcd. C 74.97,

H 8.01, N 7.95; found C 74.76, H 8.17, N 7.93.

1

3

(m) cm^–1. H NMR (300 MHz, CDCl₃): δ = 0.97 (t, J = 7.4 Hz, 3

H, CH₃), 1.41–1.57 (m, 2 H, CH₂), 1.68–1.83 (m, 2 H, CH₂), 4.00

3

(t, J = 6.6 Hz, 2 H, OCH₂), 6.91 (m, 2 H, m-CH_arom., CO), 7.43

(m, 2 H, m-CH_arom.), 7.52 (m, 1 H, p-CH_arom.), 7.98 (m, 2 H, o-

CH_arom.), 8.32 (m, 2 H, o-CH_arom., CO), 10.4 (br. s, 1 H, NH) ppm.

¹³C NMR (75 MHz, CDCl₃): δ = 13.7 (CH₃), 19.1, 31.2 (CH₂),

67.8 (OCH₂), 113.7 (m-CH_arom., CO), 127.3, 128.6 (CH_arom.), 130.3

(p-C_ipso, CO), 131.6, 132.0 (CH_arom.), 135.3 (C_ipso), 162.4 (p-C_ipso

,

CO), 166.1 (C_quat., C=N), 179.9 (C_quat., C=O) ppm. MS (70 eV):

m/z (%) = 296 (42) [M]⁺, 295 (25) [M⁺– 1], 239 (3) [M⁺– C₄H₉],

177 (100) [C₄H₉OC₆H₄CO]⁺, 147 (7) [H₂NC(Ph)NCO]⁺, 121 (99)

[HO – C₆H₄CO]⁺, 104 (16) [C₆H₄CO]⁺, 103 (6) [PhCN]⁺, 93 (18)

[C₆H₄OH]⁺, 92 (5), 77 (9) [C₆H₅]⁺, 65 (15), 57 (6) [C₄H₉]⁺.

C₁₈H₂₀N₂O₂(296.37): calcd. C 72.95, H 6.80, N 9.45; found C

73.10, H 6.82, H 9.46.

N-[4-(n-Hexadecyloxy)benzoyl]benzamidine (1u): Synthesized from

4-(n-hexadecyloxy)benzoyl chloride (0.552 g, 1.45 mmol), benzami-

dine hydrochloride (0.274 g, 1.45 mmol), and NaOH (2 n,

1.80 mL). Purified by column chromatography (ethyl acetate, 10:1);

yield 0.080 g (12%); colorless solid; R_f= 0.70 (ethyl acetate/petro-

leum ether, 1:1); m.p. 78–79 °C. IR (KBr): ν = 3458 (br. m, NH),

˜

3252 (br. m, NH), 3069 (w), 3059 (w), 3030 (w, CH_arom.), 2955 (m),

2939 (s), 2916 (s), 2860 (sh), 2851 (s, CH_alk), 2766 (w), 1630 (s),

1603 (s), 1566 (s), 1508 (s), 1472 (s), 1445 (s), 1416 (s), 1391 (m),

1313 (s), 1298 (s), 1290 (sh), 1246 (s), 1180 (sh), 1171 (s), 1161 (sh),

1146 (s), 1099 (m), 1026 (m), 999 (m), 881 (m), 847 (m), 820 (m),

800 (m), 783 (s), 770 (m), 719 (m), 700 (m), 694 (m), 675 (m), 662

(m), 575 (m), 548 (m), 530 (m), 511 (m) cm^–1. ¹H NMR (300 MHz,

CDCl₃): δ = 0.81–0.95 (m, 3 H, CH₃), 1.17–1.55 (m, 26 H, CH₂),

N-[4-(n-Hexyloxy)benzoyl]benzamidine (1s): Synthesized from 4-(n-

hexyloxy)benzoyl chloride^[36](0.481 g, 2.00 mmol), benzamidine

hydrochloride (0.378 g, 2.00 mmol), and NaOH (2 n, 2.50 mL).

Purified by column chromatography (ethyl acetate/petroleum ether,

5:1); yield 0.467 g (72%); colorless solid; R_f= 0.61 (ethyl acetate/

petroleum ether, 1:1); m.p. 89–90 °C. IR (KBr): ν = 3325 (br. m,

˜

NH), 3186 (br. m, NH), 3070 (w), 3032 (w, CH_arom.), 2955 (s), 2930

(s), 2872 (m), 2858 (m, CH_alk), 1622 (sh), 1597 (s), 1582 (m), 1560

3

1.73–1.87 (m, 2 H, CH₂), 4.01 (t, J = 6.6 Hz, 2 H, OCH₂), 6.67

(s), 1508 (s), 1475 (s), 1443 (s), 1333 (s), 1319 (sh), 1292 (m), 1252 (br. s, 1 H, NH), 6.94 (m, 2 H, m-CH_arom., CO), 7.47 (m, 2 H, m-

(s), 1229 (sh), 1175 (m), 1159 (m), 1150 (s), 1126 (m), 1001 (m), CH_arom.), 7.55 (m, 1 H, p-CH_arom.), 8.02 (m, 2 H, o-CH_arom., CO),

938 (m), 928 (sh), 891 (m), 851 (m), 843 (sh), 812 (m), 783 (s), 702

(m), 696 (m), 675 (m), 669 (m), 660 (m), 635 (m), 579 (m), 542 (75 MHz, CDCl₃): δ = 14.0 (CH₃), 22.7, 26.0, 29.2, 29.3, 29.4, 29.6,

(m) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.87–0.96 (m, 3 H,

29.7, 31.9 (CH₂), 68.1 (OCH₂), 113.8 (m-CH_arom., CO), 127.3, 128.7

CH₃), 1.27–1.55 (m, 6 H, CH₂), 1.74–1.87 (m, 2 H, CH₂), 4.02 (t, (CH_arom.), 130.3 (C_ipso, CO), 131.7, 132.1 (CH_arom.), 135.4 (C_ipso),

³J = 6.6 Hz, 2 H, OCH₂), 6.50 (br. s, 1 H, NH), 6.93 (m, 2 H, m-

162.5 (p-C_arom., CO), 166.0 (C_quat., C=N), 180.0 (C_quat., C=O) ppm.

8.33 (m, 2 H, o-CH_arom.), 10.51 (br. s, 1 H, NH) ppm. ¹³C NMR

CH_arom., CO), 7.49 (m, 2 H, m-CH_arom.), 7.57 (m, 1 H, p-CH_arom.), MS (70 eV): m/z (%) = 464 (40) [M]⁺, 463 (16) [M⁺– 1], 435 (4)

8.03 (m, 2 H, o-CH_arom.), 8.33 (m, 2 H, o-CH_arom., CO), 10.60 (br.

[M⁺– C₂H₅], 421 (3) [M⁺– C₃H₇], 407 (3) [M⁺– C₄H₉], 365 (3)

[M⁺– C₇H₁₅], 361 (7), 346 (14), 345 (47) [H₃₃C₁₆OC₆H₄CO]⁺, 253

s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 13.9 (CH₃),

22.5, 25.7, 29.1, 31.5 (CH₂), 68.1 (OCH₂), 113.8 (m-CH_arom., CO), (20) [M⁺– C₁₅H₃₁], 241 (6), 240 (29) [M⁺– C₁₆H₃₂], 147 (13)

127.3, 128.7 (CH_arom.), 130.3 (C_ipso, C=O), 131.7, 132.1 (CH_arom.), [H₂NC(Ph)NCO]⁺, 138 (13), 137 (19) [HOC₆H₄CONH₂]⁺, 121

135.4 (C_ipso), 162.5 (p-C_arom., CO), 166.1 (C_quat., C=N), 180.1 (100) [HOC₆H₄CO]⁺, 120 (10), 104 (19) [C₆H₄CO]⁺, 103 (75)

(C_quat., C=O) ppm. MS (70 eV): m/z (%) = 324 (39) [M]⁺, 323 (27)

[PhCN]⁺, 99 (22) [C₇H₁₁]⁺, 97 (7), 93 (7), 85 (10) [C₆H₁₃]⁺, 83 (13),

872

www.eurjoc.org

Eur. J. Org. Chem. 2011, 861–877

Synthesis and Properties of N-Acylamidines

81 (7), 77 (12) [C₆H₅]⁺, 76 (25), 75 (9), 71 (21) [C₅H₁₁]⁺, 70 (9), 69 [H₂NC(tBu)NCO]⁺, 121 (100) [HOC₆H₄CO]⁺, 120 (7), 99 (18)

(20), 57 (52) [C₄H₉]⁺, 56 (13), 55 (33), 51 (9), 50 (11). C₃₀H₄₄N₂O₂[H₂NC(tBu)N]⁺, 93 (13) [C₆H₄OH]⁺, 92 (6), 85 (5), 84 (5), 69 (6),

(464.69): calcd. C 77.54, H 9.54, N 6.03; found C 77.33, H 9.58, N

6.03.

65 (9), 57 (17) [C₄H₉]⁺, 56 (4), 55 (12). C₁₈H₂₈N₂O₂(304.43): calcd.

C 71.01, H 9.27, N 9.20; found C 71.04, H 9.25, N 9.31.

X-ray Crystal Structure Analysis of 1u:^[27,28]Formula C₃₀H₄₄N₂O₂,

M = 464.67, colorless crystal, 0.35ϫ0.20ϫ0.10 mm, a = 44.009(3),

b = 5.483(1), c = 23.630(2) Å, β = 107.72(1)°, V = 5431.4(12) Å³,

ρ_calc= 1.137 g cm^–3, μ = 0.542 mm^–1, empirical absorption correc-

tion (0.833Յ T Յ0.948), Z = 8, monoclinic, space group C2/c (No.

15), λ = 1.54178 Å, T = 223(2) K, ω/2θ scans, 5685 reflections col-

N-[4-(n-Octyloxy)benzoyl]pivalamidine (1x): Synthesized from 4-n-

octyloxybenzoyl chloride^[37](0.331 g, 1.23 mmol), pivalamidine hy-

drochloride (0.168 g, 1.23 mmol), NaOH (2 n, 1.5 mL). Purified by

column chromatography (ethyl acetate, 5:1); yield 0.270 g (66%);

colorless solid; R_f= 0.66 (ethyl acetate/petroleum ether, 1:1); m.p.

66–67 °C. IR (KBr): ν = 3335 (br. s, NH), 3186 (br. m, NH), 3072

˜

lected (-h, +k, Ϯl), [(sinθ)/λ] = 0.62 Å^–1, 5534 independent (R_int

=

(w, CH_arom.), 2988 (sh), 2974 (m), 2953 (s), 2937 (s), 2922 (s), 2905

(sh), 2868 (m), 2853 (m), 1623 (sh), 1603 (s), 1589 (s), 1560 (s),

1508 (s), 1493 (s), 1474 (m), 1466 (sh), 1443 (sh), 1418 (w), 1394

(m), 1371 (m), 1329 (sh), 1317 (s), 1286 (s), 1254 (s), 1227 (m), 1207

(sh), 1167 (s), 1042 (m), 1036 (m), 1005 (sh), 999 (m), 860 (m), 854

(m), 822 (m), 814 (sh), 804 (sh), 723 (m), 689 (m), 669 (sh), 640

(m), 635 (m), 546 (m) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.89

(m, 3 H, CH₃), 1.21–1.53 [m, 19 H, CH₂, C(CH₃)₃], 1.78 (m, 2 H,

CH₂), 3.99 (t, ³J = 6.6 Hz, 2 H, OCH₂), 6.26 (br. s, 1 H, NH), 6.88

(m, 2 H, m-CH_arom.), 8.23 (m, 2 H, o-CH_arom.), 10.47 (br. s, 1 H,

NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 14.0 (CH₃), 22.58,

26.0 (CH₂), 28.0 [C(CH₃)₃], 29.2, 29.3, 31.7 (CH₂), 38.5 [C(CH₃)₃],

68.1 (OCH₂), 113.6 (m-CH_arom.), 130.7 (C_ipso), 131.6 (o-CH_arom.),

0.024) and 4093 observed reflections [I Ն2σ(I)], 315 refined pa-

rameters, R = 0.042, wR²= 0.139, max. (min.) residual electron

density 0.18 (–0.19) e·Å^–3. Hydrogen atoms at N5 from difference

Fourier map, others calculated and refined as riding atoms.

N-[4-(n-Butyloxy)benzoyl]pivalamidine (1v): Synthesized from 4-(n-

butyloxy)benzoyl chloride^[36](0.393 g, 1.85 mmol), pivalamidine

hydrochloride (0.252 g, 1.85 mmol), and NaOH (2 n, 2.30 mL).

Purified by column chromatography (ethyl acetate, 5:1); yield

0.300 g (59%, 93% purity); colorless solid; R_f= 0.62 (ethyl acetate/

petroleum ether, 1:1); m.p. 95 °C. IR (KBr): ν = 3362 (m, NH),

˜

3238 (w, NH), 3074 (w, CH_arom.), 2961 (m), 2932 (m), 2872 (m,

CH_alk), 1622 (sh), 1603 (s), 1591 (s), 1560 (m), 1508 (s), 1475 (s),

1466 (s), 1366 (m), 1333 (sh), 1319 (s), 1290 (s), 1250 (s), 1229 (sh),

1165 (s), 1146 (m), 1132 (m), 1117 (m), 1067 (m), 1029 (m), 1004

(m), 972 (m), 874 (m), 856 (s), 851 (s), 821 (m), 806 (m), 744 (m),

162.2 (p-C_arom.), 178.8, 179.9 (C_quat.

, C=N, C=O) ppm. MS

(70 eV): m/z (%) = 332 (42) [M]⁺, 331 (8) [M⁺– 1], 318 (7), 317 (41)

[M⁺– CH₃], 290 (4), 262 (3), 234 (11), 233 (63) [H₁₇C₈OC₆H₄CO]⁺,

191 (4), 138 (4), 137 (6) [HOC₆H₄CONH₂]⁺, 127 (5) [H₂NC(tBu)

NCO]⁺, 121 (100) [HOC₆H₄CO]⁺, 120 (8), 104 (3), 99 (3)

[H₂NC(tBu)N]⁺, 97 (3), 93 (10) [C₆H₄OH]⁺, 92 (4), 84 (4), 71 (6),

65 (7) [C₅H₅]⁺, 57 (17) [C₄H₉]⁺, 55 (8). C₂₀H₃₂N₂O₂(332.49): calcd.

C 72.25, H 9.70, N 8.43; C 72.27, H 9.67, N 8.54.

1

696 (m), 638 (s), 540 (m) cm^–1. H NMR (300 MHz, CDCl₃): δ =

0.97 (m, 3 H, CH₃), 1.32 (s, 9 H, tBu), 1.50 (m, 2 H, CH₂), 1.77

3

(m, 2 H, CH₂), 4.01 (t, J = 6.6 Hz, 2 H, OCH₂), 6.27 (br. s, 1 H,

NH), 6.88 (m, 2 H, m-CH_arom.), 8.23 (m, 2 H, o-CH_arom.), 10.52

(br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 13.9

(CH₂CH₃), 22.5, 25.6 (CH₂), 28.0 [C(CH₃)₃], 31.5 (CH₂), 38.5

[C(CH₃)₃], 68.0 (OCH₂), 113.6 (m-CH_arom.), 130.6 (C_ipso, C=O),

131.6 (o-CH_arom.), 162.2 (p-C_arom.), 178.8, 179.9 (C_quat., C=O,

X-ray Crystal Structure Analysis of 1x:^[27,28]Formula C₂₀H₃₂N₂O₂,

M = 332.48, colorless crystal, 0.40ϫ0.15ϫ0.15 mm, a = 10.059(2),

b = 8.570(1), c = 23.878(5) Å, β = 90.67(2)°, V = 2058.3(6) Å³, ρ_calc

= 1.073 gcm^–3, μ = 0.539 mm^–1, empirical absorption correction

(0.813Յ T Յ0.924), Z = 4, monoclinic, space group P2₁/c (No.

14), λ = 1.54178 Å, T = 223(2) K, ω/2θ scans, 4447 reflections col-

C=N) ppm. MS (70 eV): m/z (%) = 276 (38) [M]⁺, 275 (5) [M⁺

–

1], 262 (8), 261 (42) [M⁺– CH₃], 234 (5) [M⁺– C₃H₆], 206 (6), 177

(100) [H₉C₄OC₆H₄CO]⁺, 121 (96) [HOC₆H₄CO]⁺, 99 (17)

[H₂NC(tBu)N]⁺, 97 (6), 93 (17) [C₆H₄OH]⁺, 92 (7), 85 (5), 84 (5),

71 (8), 69 (10), 65 (17), 57 (36) [C₄H₉]⁺, 56 (6), 55 (16).

lected (–h, +k, Ϯl), [(sinθ)/λ] = 0.62 Å^–1, 4203 independent (R_int

=

0.029) and 2340 observed reflections [I Ն2σ(I)], 227 refined pa-

rameters, R = 0.051, wR²= 0.171, max. (min.) residual electron

density 0.13 (–0.18) e·Å^–3. Hydrogen atoms at N5 from difference

Fourier map, others calculated and refined as riding atoms.

N-[4-(n-Hexyloxy)benzoyl]pivalamidine (1w): Synthesized from 4-

(n-hexyloxy)benzoyl chloride^[36](0.303 g, 1.26 mmol), pivalamidine

hydrochloride (0.172 g, 1.26 mmol), and NaOH (2 n, 1.6 mL).

Purified by column chromatography (ethyl acetate, 5:1); yield

0.330 g (86%); colorless solid; R_f= 0.65 (ethyl acetate/petroleum

General Procedure for the Synthesis of the N-Acylacetamidines 1y–

1ab: At 0 °C, acetamidine hydrochloride (2 mmol) was suspended

in acetone (30 mL). An exact amount of NaOH ( 2 n, 4.0 mmol,

2.0 mL) was added and the mixture was stirred for 1 min at 0 °C.

Subsequently, acyl chloride (2 mmol) dissolved in acetone (5 mL),

was added slowly. After 1.5 h stirring at 0 °C, the solvent was re-

moved in vacuo as completely as possible. The residue was treated

with water (100 mL), which was extracted with chloroform

(3ϫ50 mL). After removal of the chloroform in vacuo, the remain-

ing residue was crystallized from chloroform/petroleum ether by

diffusion.

ether, 1:1); m.p. 97–99 °C. IR (KBr): ν = 3335 (br. s, NH), 3184

˜

(br. m, NH), 3057 (w, CH_arom.), 2991 (sh), 2976 (m), 2953 (s), 2937

(s), 2912 (sh), 2868 (m), 2856 (sh, CH_alk), 1622 (sh), 1605 (s), 1587

(s), 1558 (s), 1510 (s), 1493 (s), 1475 (s), 1466 (m), 1443 (m), 1396

(m), 1369 (m), 1358 (m), 1317 (s), 1290 (s), 1277 (sh), 1272 (s), 1227

(m), 1173 (s), 1128 (m), 1107 (m), 1061 (m), 1030 (s), 1007 (m), 989

(m), 895 (m), 860 (s), 827 (m), 820 (sh), 806 (m), 773 (m), 727 (m),

687 (m), 669 (sh), 640 (s), 633 (m), 546 (m) cm^–1. ¹H NMR

(300 MHz, CDCl₃): δ = 0.90 (m, 3 H, CH₃), 1.24–1.53 [m, 15 H,

CH₂, C(CH₃)₃], 1.78 (m, 2 H, CH₂), 3.99 (t, ³J = 6.7 Hz, 2 H,

OCH₂), 6.31 (br. s, 1 H, NH), 6.88 (m, 2 H, m-CH_arom.), 8.23 (m, N-[4-(n-Butyloxy)benzoyl]acetamidine (1y): Synthesized from 4-(n-

2 H, o-CH_arom.), 10.50 (br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz, butyloxy)benzoyl chloride^[36](0.419 g, 1.97 mmol), acetamidine hy-

CDCl₃): δ = 13.9 (CH₃), 22.5, 25.6 (CH₂), 28.0 [C(CH₃)₃], 29.1, drochloride (0.186 g, 1.97 mmol), and NaOH (2 n, 0.98 mL); yield

31.5 (CH₂), 38.5 [C(CH₃)₃], 68.0 (OCH₂), 113.6 (m-CH_arom.), 130.6

0.240 g (52%); colorless solid; m.p. 103 °C. IR (KBr): ν = 3331 (br.

˜

(C_ipso), 131.6 (o-CH_arom.), 162.2 (p-C_arom.), 178.8, 179.9 (C_quat.

,

m, NH), 3197 (br. m, NH), 3080 (w), 3062 (w, CH_arom.), 2956 (m),

2940 (m), 2928 (sh), 2920 (sh), 2873 (m), 2854 (w, CH_alk), 1617

(sh), 1603 (s), 1590 (s), 1559 (m), 1512 (s), 1497 (s), 1476 (m), 1462

(m), 1455 (sh), 1361 (m), 1328 (s), 1296 (m), 1270 (m), 1257 (s),

C=N, C=O) ppm. MS (70 eV): m/z (%) = 304 (33) [M]⁺, 303 (8)

[M⁺– 1], 290 (9), 289 (45) [M⁺– CH₃], 262 (7), 234 (6), 206 (12),

205 (79) [H₁₃C₆OC₆H₄CO]⁺, 137 (7) [HOC₆H₄CONH₂]⁺, 127 (3)

Eur. J. Org. Chem. 2011, 861–877

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873

E.-U. Würthwein et al.

FULL PAPER

1179 (s), 1038 (m), 1004 (m), 868 (m), 855 (m), 654 (m) cm^–1. H

NMR (300 MHz, CDCl₃): δ = 0.98 (t, ³J = 7.4 Hz, 3 H, CH₃), 1.49

(m, 2 H, CH₂), 1.78 (m, 2 H, CH₂), 2.18 (s, 3 H, CH₃, CH₃-amid-

N-[4-(n-Octyloxy)benzoyl]acetamidine (1aa): Synthesized from 4-(n-

octyloxy)benzoyl chloride^[37](0.895 g, 3.33 mmol), acetamidine hy-

drochloride (0.315 g, 3.33 mmol) and NaOH (2 n, 3.33 mL); yield

1

3

ine), 4.00 (t, J = 6.6 Hz, 2 H, OCH₂), 6.11 (br. s, 1 H, NH), 6.88

0.251 g (26%, purity 92%); colorless solid. IR (KBr): ν = 3325 (br.

˜

(m, 2 H, m-CH_arom.), 8.18 (m, 2 H, o-CH_arom.), 10.16 (br. s, 1 H,

s, NH), 3180 (br. m, NH), 3084 (w, CH_arom.), 2957 (m), 2941 (s),

2936 (m), 2918 (s), 2890 (sh), 2856 (m, CH_alk), 1604 (s), 1592 (s),

NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 13.7 (CH₃), 19.2

(CH₂), 24.7 (CH₃, CH₃-amidine), 31.2 (CH₂), 67.8 (OCH₂), 113.8 1560 (s), 1512 (m), 1493 (s), 1474 (s), 1393 (m), 1367 (m), 1321 (s),

(m-CH_arom.), 129.9 (C_ipso), 131.5 (o-CH_arom.), 162.4 (p-C_arom.),

169.3 (C_quat., C=N), 179.6 (C_quat., C=O) ppm. MS (70 eV): m/z (%)

1292 (s), 1275 (s), 1255 (s), 1173 (m), 1148 (m), 1107 (m), 1022 (m),

998 (m), 866 (m), 814 (m), 806 (m), 784 (m), 704 (m), 667 (m), 653

= 234 (37) [M]⁺, 233 (12) [M⁺– 1], 193 (5), 178 (8), 177 (75) (m) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.89 (m, 3 H, CH₃),

[H₉C₄OC₆H₄CO]⁺, 137 (5) [HOC₆H₄CONH₂]⁺, 121 (100) 1.20–1.52 (m, 10 H, CH₂), 1.78 (m, 2 H, CH₂), 2.14 (s, 3 H, CH₃,

[HOC₆H₄CO]⁺, 108 (7), 103 (3), 93 (16) [C₆H₄OH]⁺, 92 (8), 85 (6),

76 (5) [C₆H₄]⁺, 65 (15) [C₅H₅]⁺, 57 (10) [H₂NC(CH₃)N⁺, C₄H₉]⁺,

55 (4). C₁₃H₁₈N₂O₂(234.39): calcd. C 66.64, H 7.74, N 11.96;

found C 66.65, H 7.43, N 12.06.

CH₃-amidine), 3.99 (t, J = 6.6 Hz, 2 H, OCH₂), 6.37 (br. s, 1 H,

NH), 6.88 (m, 2 H, m-CH_arom.), 8.16 (m, 2 H, o-CH_arom.), 10.14

(br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 14.0 (CH₃),

22.5 (CH₂), 24.6 (CH₃, CH₃-amidine), 25.9, 29.1, 29.2, 31.7 (CH₂),

68.1 (OCH₂), 113.8 (m-CH_arom.), 129.9 (C_ipso), 131.5 (o-CH_arom.),

162.4 (p-C_arom.), 169.4 (C_quat., C=N), 179.6 (C_quat., C=O) ppm. MS

(70 eV): m/z (%) = 290 (41) [M]⁺, 289 (18) [M⁺– 1], 249 (3), 234

(14), 233 (74) [H₁₇C₈OC₆H₄CO]⁺, 177 (9), 161 (3), 149 (3), 138 (4),

137 (7), 121 (100) [HOC₆H₄CO]⁺, 120 (6), 104 (4), 93 (11)

[C₆H₄OH]⁺, 92 (7), 85 (11) [C₆H₁₃]⁺, 71 (3) [C₅H₁₁]⁺, 69 (6), 65 (8)

[C₅H₅]⁺, 57 (9) [H₂NC(CH₃)N⁺, C₄H₉]⁺, 55 (12).

3

If a surplus of NaOH was used or after chromatographic work

up, the hydrolysis product N-acetyl-(4-n-butyloxy)benzamide was

1

3

isolated. H NMR (300 MHz, CDCl₃): δ = 0.97 (t, J = 7.5 Hz, 3

H, CH₃), 1.42–1.57 (m, 2 H), 1.72–1.84 (m, 2 H, CH₂), 2.59 (s, 3

3

H, CH₃, Acetyl), 4.02 (t, J = 6.4 Hz, 2 H, OCH₂), 6.94 (m, 2 H,

m-CH_arom.), 7.87 (m, 2 H, o-CH_arom.), 9.23 (s, 1 H, NH) ppm. ¹³C

NMR (75 MHz, CDCl₃): δ = 13.7 (CH₃), 19.1 (CH₂), 25.4 (CH₃,

Acetyl), 31.0, 68.0 (OCH₂), 114.5 (m-CH_arom.), 124.4 (C_ipso), 130.0 X-ray Crystal Structure Analysis of 1aa:^[27,28]Formula

(o-CH_arom.), 163.2 (p-C_arom.), 165.2, 174.0 (C_quat., C=O) ppm. MS

C₁₇H₂₆N₂O₂, M = 290.40, colorless crystal, 0.30ϫ0.30ϫ0.25 mm,

(70 eV): m/z (%) = 235 (34) [M]⁺, 179 (15) [M⁺– C₄H₈], 177 (12) a = 8.270(1), b = 9.160(1), c = 22.462(1) Å, β = 93.74(1)°, V =

[M⁺– HNCOCH₃], 137 (11), 121 (100) [HOC₆H₄CO]⁺, 120 (9), 93

(15), 65 (21), 57 (15).

1697.9(3) Å³, ρ_calc= 1.136 gcm^–3, μ = 0.074 mm^–1, empirical ab-

sorption correction (0.978Յ T Յ0.982), Z = 4, monoclinic, space

group P2₁/n (No. 14), λ = 0.71073 Å, T = 198(2) K, ω and φ scans,

6990 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.66 Å^–1, 3993

independent (R_int= 0.029) and 2674 observed reflections [I

Ն2σ(I)], 198 refined parameters, R = 0.058, wR²= 0.144, max.

(min.) residual electron density 0.21 (–0.19) e·Å^–3. Hydrogen atoms

at N1 from difference Fourier map, others calculated and refined

as riding atoms.

N-[4-(n-Hexyloxy)benzoyl]acetamidine (1z): Synthesized from 4-(n-

hexyloxy)benzoyl chloride^[36](0.722 g, 3.00 mmol), acetamidine hy-

drochloride (0.284 g, 3.00 mmol), and NaOH (2 n, 3.00 mL); yield

0.165 g (21%); colorless solid; m.p. 109 °C. IR (KBr): ν = 3315 (br.

˜

s, NH), 3182 (br. m, NH), 3084 (w, CH_arom.), 2957 (m), 2941 (m),

2932 (m), 2912 (m), 2872 (m), 2856 (m, CH_alk), 1620 (sh), 1603 (s),

1589 (s), 1560 (s), 1512 (s), 1493 (s), 1474 (s), 1396 (m), 1360 (m),

1321 (s), 1292 (s), 1275 (s), 1256 (s), 1173 (s), 1148 (m), 1107 (m),

N-[4-(n-Hexadecyloxy)benzoyl]acetamidine (1ab): Synthesized from

1024 (m), 1011 (sh), 995 (m), 866 (m), 858 (m), 814 (m), 806 (m), 4-(n-hexadecyloxy)benzoyl chloride (1.33 g, 3.48 mmol), acetamid-

781 (m), 702 (m), 667 (sh), 653 (m), 635 (m) cm^–1. ¹H NMR

(300 MHz, CDCl₃): δ = 0.90 (m, 3 H, CH₃), 1.28–1.52 (m, 6 H,

ine hydrochloride (0.329 g, 3.48 mmol), and NaOH (2 n, 3.48 mL);

yield 0.751 g (54%); colorless needles; m.p. 83 °C. IR (KBr): ν =

˜

CH₂), 1.78 (m, 2 H, CH₂), 2.13 (s, 3 H, CH₃, CH₃-amidine), 3.99 3323 (br. s, NH), 3196 (br. m, NH), 3076 (w, CH_arom.), 2955 (m),

3

(t, J = 6.7 Hz, 2 H, OCH₂), 6.54 (br. s, 1 H, NH), 6.88 (m, 2 H,

m-CH_arom.), 8.13 (m, 2 H, o-CH_arom.), 10.10 (br. s, 1 H, NH) ppm. 1560 (m), 1510 (s), 1491 (s), 1473 (s), 1358 (m), 1327 (s), 1292 (s),

¹³C NMR (75 MHz, CDCl₃): δ = 13.9 (CH₃), 22.4 (CH₂), 24.5

1256 (s), 1175 (s), 1153 (m), 1105 (m), 1041 (m), 1022 (m), 1001

2935 (m), 2920 (m), 2872 (m), 2853 (m, CH_alk), 1622 (sh), 1599 (s),

(CH₃, CH₃-amidine), 25.5, 29.0, 31.4 (CH₂), 68.0 (OCH₂), 113.7 (m), 976 (m), 868 (m), 853 (m), 802 (m), 783 (m), 771 (m), 720 (m),

(m-CH_arom.), 129.8 (C_ipso), 131.4 (o-CH_arom.), 162.3 (p-C_arom.),

169.5 (C_quat., C=N), 179.5 (C_quat., C=O) ppm. MS (70 eV): m/z (%)

700 (m), 667 (sh), 654 (m), 635 (m) cm^–1. ¹H NMR (300 MHz,

CDCl₃): δ = 0.88 (m, 3 H, CH₃), 1.18–1.54 (m, 26 H, CH₂), 1.73–

= 262 (36) [M]⁺, 261 (14) [M⁺– 1], 221 (3), 206 (11), 205 (79) 1.84 (m, 2 H, CH₂), 2.18 (s, 3 H, CH₃, CH₃-amidine), 4.00 (t, ³J =

[H₁₃C₆OC₆H₄CO]⁺, 177 (6), 149 (3), 138 (3), 137 (7), 121 (100) 6.6 Hz, 2 H, OCH₂), 6.06 (br. s, 1 H, NH), 6.89 (m, 2 H, m-

[HOC₆H₄CO]⁺, 120 (6), 108 (9), 103 (3), 93 (12) [C₆H₄OH]⁺, 92

CH_arom.), 8.18 (m, 2 H, o-CH_arom.), 10.13 (br. s, 1 H, NH) ppm.

(8), 85 (8), 65 (9) [C₅H₅]⁺, 57 (3) [H₂NC(CH₃)N⁺, C₄H₉]⁺, 55 (6). ¹³C NMR (75 MHz, CDCl₃): δ = 14.1 (CH₃), 22.6 (CH₂), 24.7

C₁₅H₂₂N₂O₂(262.35): calcd. C 68.67, H 8.45, N 10.68; found C

68.77, H 8.51, N 10.75.

(CH₃, CH₃-amidine), 26.0, 29.2, 29.3, 29.4, 29.5, 29.6, 31.9 (CH₂),

68.1 (OCH₂), 113.8 (m-CH_arom.), 129.8 (C_ipso), 131.5 (o-CH_arom.),

162.4 (p-C_arom.), 169.3 (C_quat., C=N), 179.5 (C_quat., C=O) ppm. MS

(70 eV): m/z (%) = 402 (61) [M]⁺, 401 (24) [M⁺– 1], 362 (11), 361

(39) [M⁺– CH₃CN], 346 (20), 345 (76) [H₃₃C₁₆OC₆H₄CO]⁺, 191

(9), 178 (12) [M⁺– C₁₆H₃₂], 177 (7), 150 (10), 138 (38), 137 (54)

[HOC₆H₄CONH₂]⁺, 127 (7) [C₉H₁₉]⁺, 121 (100) [HOC₆H₄CO]⁺,

120 (7), 113 (11) [C₈H₁₇]⁺, 85 (14) [C₆H₁₃⁺, H₂NC(CH₃)NCO]⁺, 83

(9), 71 (14) [C₅H₁₁]⁺, 69 (14), 57 (36), 55 (22). C₂₅H₄₂N₂O₂

(402.62): calcd. C 74.58, H 10.51, N 6.96; found C 74.49, H 10.20,

N 6.86.

X-ray Crystal Structure Analysis of 1z:^[27,28]Formula C₁₅H₂₂N₂O₂,

M = 262.35, colorless crystal, 0.50ϫ0.30ϫ0.15 mm, a = 14.338(1),

b

= 22.277(1), c = 9.411(1) Å, V = =

3005.9(4) Å³, ρ_calc

1.159 gcm^–3, μ = 0.077 mm^–1, empirical absorption correction

(0.962Յ T Յ0.989), Z = 8, orthorhombic, space group Pccn (No.

56), λ = 0.71073 Å, T = 198(2) K, ω and φ scans, 25662 reflections

collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.71 Å^–1, 4407 independent (R_int

= 0.041) and 3103 observed reflections [I Ն2σ(I)], 180 refined pa-

rameters, R = 0.076, wR²= 0.240, max. (min.) residual electron

density 0.67 (–0.37) e·Å^–3. Hydrogen atoms at N5 from difference

Fourier map, others calculated and refined as riding atoms.

N-[3,4-Bis(n-decyloxy)benzoyl]benzamidine (1ac): KOH (0.122 g,

2.17 mmol) was dissolved in a little water and treated with acetone

874

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Eur. J. Org. Chem. 2011, 861–877

Synthesis and Properties of N-Acylamidines

(20 mL). The solution was cooled to 0 °C, then benzamidine hydro-

chloride (0.412 g, 2.17 mmol) was added. Subsequently, 3,4-bis(n-

decyloxy)benzoyl chloride (0.987 g, 2.17 mmol), dissolved in ace-

tone (10 mL), was added dropwise and the solution was stirred for

1.5 h at 0 °C. Acetone was distilled off and the residue was treated

with water (50 mL). The aqueous phase was extracted with chloro-

form (1 ϫ100 mL, 2ϫ50 mL) and the solvent of the organic phase

was removed in vacuo. The remaining substance was purified by

column chromatography (silica gel; petroleum ether/ethyl acetate,

132.7, 135.3, 142.1, 152.6 (C_ipso, OR), 166.3 (C_quat., C=N), 180.1

(C_quat., C=O) ppm. MS (ESI): m/z (%) = 547 (9) [M⁺+ Na], 525

(100) [M⁺+ 1].

General Procedure for the Synthesis of N-(4-Phenylazobenzoyl)amid-

ines 1ae-1ag: Amidine hydrochloride (1 mmol) was dissolved at

0 °C in a mixture of acetone (20 mL) and NaOH (2 n, 1 mL), then

4-phenylazobenzoyl chloride (1 mmol), dissolved in acetone

(5 mL), was added slowly. After 2 h stirring at 0 °C, the solvent was

removed in vacuo and the residue was treated with water (50 mL).

This mixture was extracted with chloroform (3 ϫ 50 mL) and the

combined organic extracts were dried with magnesium sulfate, the

solvent was removed in vacuo, and the residue was purified by col-

umn chromatography or crystallized from chloroform/petroleum

ether by diffusion of the solvents.

1:1); yield 0.383 g (33%); colorless plates; m.p. 85 °C. IR (KBr): ν

˜

= 3391 (m, NH), 3275 (m), 3194 (w), 3094 (w), 3075 (w), 3055 (w,

CH_arom.), 2955 (s), 2920 (s), 2870 (s), 2851 (s, CH_alk), 1601 (s), 1562

(s), 1512 (s), 1485 (s), 1470 (sh), 1443 (m), 1424 (s), 1385 (m), 1319

(s), 1296 (s), 1278 (s), 1258 (sh), 1223 (s), 1181 (m), 1130 (sh), 1119

(s), 1022 (m), 988 (m), 953 (m), 880 (m), 872 (m), 829 (m), 795 (m),

779 (s), 756 (m), 721 (m), 698 (m), 664 (m), 594 (m), 563 (m) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 0.88 (m, 6 H, CH₃), 1.98–1.54

N-(4-Phenylazobenzoyl)benzamidine (1ae): Synthesized from 4-

phenylazobenzoyl chloride^[38](0.489 g, 2.00 mmol) and benzamid-

ine hydrochloride (0.378 g, 2.00 mmol), and purified by column

chromatography (petroleum ether/ethyl acetate, 5:1); yield 0.593 g

(91%); orange felted needles; R_f= 0.61 (petroleum ether/ethyl acet-

3

(m, 29 H, CH₂), 1.83 (m, 4 H, CH₂), 4.05, 4.08 (t, J = 6.8 Hz, 2

3

H, OCH₂), 6.71 (s, br., 1 H, NH), 6.89 (d, J = 8.6 Hz, 1 H, C-5),

7.46 (m, 2 H, m-CH_arom., Ph), 7.53 (m, 1 H, p-CH_arom., Ph), 7.88

(d, ⁴J = 1.9 Hz, 1 H, C-2), 8.03 (m, 3 H, CH_arom., o-Ph, C-6), 10.55

(s, br., 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 14.0

(CH₃), 22.6, 26.0, 29.2, 29.3, 29.4, 29.5, 29.6, 31.9 (CH₂), 69.1, 69.3

(OCH₂), 112.1, 114.8 (CH_arom., C-2, C-5), 124.0, 127.3, 128.7, 130.7

(C_ipso), 132.1, 135.4, 148.5, 152.8 (C-3, C-4), 166.0 (C_quat., C=N),

180.1 (C_quat., C=O) ppm. MS (70 eV): m/z (%) = 536 (11) [M]⁺,

433 (9) [M⁺– PhCN], 293 (4) [M⁺– PhCN – C₁₀H₂₀], 171 (6), 154

(8), 153 (43), 149 (6), 137 (24), 136 (8), 128 (5), 124 (8), 121 (6),

104 (16), 103 (100) [C₆H₃CO⁺, PhCN]⁺, 86 (7), 85 (19), 83 (24), 81

(6), 77 (13) [Ph]⁺, 76 (49), 75 (16), 74 (9), 73 (8), 71 (17), 70 (10),

69 (17), 67 (9), 63 (7), 62 (4), 60 (8), 57 (38) [C₄H₉]⁺, 56 (10), 55

(30), 53 (7), 52 (12), 51 (22). C₃₄H₅₂N₂O₃(536.79): calcd. C 76.08,

H 9.76, N 5.22; found C 76.24, H 9.93, N 5.16.

ate); m.p. 160–161 °C. IR (KBr): ν = 3361 (br. m, NH), 3177 (w,

˜

br, NH), 3059 (w, CH_arom.), 1616 (sh), 1601 (s), 1556 (s), 1506 (s),

1474 (s), 1443 (s), 1333 (s), 1300 (sh), 1290 (m), 1221 (w), 1138

1

(m), 1126 (w), 783 (m), 700 (m), 689 (sh), 542 (w) cm^–1. H NMR

(300 MHz, CDCl₃): δ = 6.73 (br. s, 1 H, NH), 7.44–7.61 (m, 6 H,

m-/p-CH_arom.), 7.92–8.00 (m, 4 H, CH_arom.), 8.02–8.07 (m, 2 H,

CH_arom.), 8.52 (m, 2 H, o-CH_arom., CO), 10.75 (br. s, 1 H,

NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 122.4, 123.0, 127.4,

128.9, 129.1, 130.7, 131.3, 132.4 (CH_arom.), 135.0 (C_ipso, C=N),

139.7 (C_ipso, C=O), 152.8, 154.7 (C_ipso, N=N), 166.9 (C_quat., C=N),

179.7 (C_quat., C=O) ppm. MS (70 eV): m/z (%) = 328 (79) [M]⁺,

327 (4) [M⁺– 1], 251 (3) [M⁺– Ph], 225 (11), 224 (15), 223 (91)

[M⁺– PhN₂], 209 (18) [Ph-N=N-C₆H₄-CO]⁺, 181 (5), 180 (8), 152

(10) [C₆H₄-C₆H₄]⁺, 147 (12) [H₂N-C(Ph)N-CO]⁺, 120 (11), 105 (28)

[PhN₂]⁺, 104 (54) [C₆H₄CO]⁺, 103 (51) [PhCN]⁺, 92 (7), 78 (10), 77

(100) [C₆H₅]⁺, 76 (34), 75 (16), 69 (10), 65 (6), 57 (6), 55 (5), 51

(20) [C₄H₃]⁺. UV (acetonitrile): λ_max[lg(ε/M^–1cm^–1)] = 447 (2.60),

331 (4.50), 225 (4.11) nm. C₂₀H₁₆N₄O (328.37): calcd. C 73.15, H

4.91, N 17.06; found C 72.82, H 5.20, N 16.71.

X-ray Crystal Structure Analysis of 1ac:^[27,28]Formula C₃₄H₅₂N₂O₃,

M = 536.78, colorless crystal, 0.60ϫ0.40ϫ0.02 mm, a = 34.504(5),

b = 9.707(1), c = 9.777(2) Å, β = 93.08(1)°, V = 3269.9(9) Å³, ρ_calc

= 1.090 gcm^–3, μ = 0.532 mm^–1, empirical absorption correction

(0.741Յ T Յ0.989), Z = 4, monoclinic, space group P2₁/c (No.

14), λ = 1.54178 Å, T = 223(2) K, ω/2θ scans, 7087 reflections col-

lected (Ϯh, +k, +l), [(sinθ)/λ] = 0.62 Å^–1, 6662 independent (R_int

=

N-(4-Phenylazobenzoyl)pivalamidine (1af): Synthesized from 4-

phenylazobenzoyl chloride^[38](0.734 g, 3.00 mmol), pivalamidine

hydrochloride (0.410 g, 3.00 mmol), and purified by column

chromatography (petroleum ether/ethyl acetate, 5:1); yield 0.480 g

(52%); red solid; R_f= 0.66 (petroleum ether/ethyl acetate, 1:1); m.p.

0.045) and 3552 observed reflections [I Ն2σ(I)], 360 refined pa-

rameters, R = 0.065, wR²= 0.217, max. (min.) residual electron

density 0.39 (–0.25) e·Å^–3. Hydrogen atoms at N1 from difference

Fourier map, others calculated and refined as riding atoms.

N-[3,4,5-Tris(n-hexyloxy)benzoyl]benzamidine (1ad): Synthesized

from 3,4,5-tris(n-hexyloxy)benzoyl chloride (0.500 g, 1.13 mmol),

128–129 °C. IR (KBr): ν = 3342 (m, br), 3190 (br. m, NH), 3072

(w), 3053 (w, CH_arom.), 2966 (m, CH_alk), 1626 (sh), 1616 (sh), 1593

˜

benzamidine hydrochloride (0.214 g, 1.13 mmol), and NaOH (50%, (s), 1564 (s), 1493 (s), 1466 (m), 1458 (sh), 1373 (m), 1367 (m), 1325

0.090.8 g). Purified by column chromatography (petroleum ether/

ethyl acetate, 5:1); yield 0.326 g (55%, purity of 90%); colorless oil;

(sh), 1313 (s), 1304 (sh), 1225 (w), 1148 (w), 1009 (w), 870 (w), 858

1

(w), 698 (w), 683 (m) cm^–1. H NMR (300 MHz, CDCl₃): δ = 1.34

R = 0.21 (petroleum ether/ethyl acetate, 5:1). IR (Film): ν = 3380

[s, 9 H, C(CH₃)₃], 6.43 (br. s, 1 H, NH), 7.42–7.55 (m, 3 H, m-/p-

CH_arom.), 7.90–7.98 (m, 4 H, o-CH_arom., N=N), 8.43 (d, 2 H, o-

˜

f

(br. m, NH), 3193 (w, br, NH), 3067 (w, CH_arom.), 2955 (s), 2930

(s), 2870 (s), 2858 (s, CH_alk), 1618 (sh), 1607 (s), 1568 (s), 1508 (s), CH_arom., CO), 10.68 (br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz,

1474 (s), 1445 (s), 1425 (s), 1394 (sh), 1381 (m), 1333 (s), 1269 (m), CDCl₃): δ = 28.0 (CH₃), 38.7 [C(CH₃)₃], 122.3, 123.0, 129.0, 130.5,

1219 (m), 1138 (sh), 1128 (sh), 1111 (s), 1001 (w), 781 (m), 698

131.2 (CH_arom.), 140.0 (C_ipso, C=O), 152.7, 154.5 (C_ipso, N=N),

(m) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.91 (m, 9 H, CH₃), 179.4, 179.9 (C_quat., C=O, C=N) ppm. MS (70 eV): m/z (%) = 308

1.28–1.41 (m, 12 H), 1.44–1.54 (m, 6 H), 1.72–1.87 (m, 6 H, CH₂), (20) [M]⁺, 293 (10) [M⁺– CH₃], 209 (26) [Ph-N=N-C₆H₄-CO]⁺,

3

4.04 (t, J = 6.6 Hz, 2 H), 4.07 (t, J = 6.6 Hz, 4 H), 6.70 (br. s, 1

203 (27) [M⁺– PhN₂], 188 (9), 152 (10) [C₆H₄-C₆H₄]⁺, 146 (8), 127

H, NH), 7.44–7.51 (m, 2 H, m-CH_arom.), 7.52–7.58 (m, 1 H, p- (5), 105 (22) [PhN₂]⁺, 104 (45) [C₆H₄CO]⁺, 103 (14) [PhCN]⁺, 92

CH_arom.), 7.64 (s, 2 H, CH_arom.), 7.98–8.04 (m, 2 H, o-CH_arom.),

10.66 (br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 13.9,

14.0 (CH₃), 22.5, 22.6, 25.7, 25.8, 29.4, 30.3, 31.6, 31.7 (CH₂), 69.2,

73.5 (OCH₂), 108.5 (CH_arom., o-CO), 127.3, 128.8 (CH_arom.), 132.2,

(7), 84 (9), 78 (9), 77 (100) [Ph]⁺, 76 (39), 75 (9), 58 (5), 57 (23)

[C₄H₉]⁺, 51 (28), 50 (9). UV (acetonitrile): λ_max[lg(ε/M^–1cm^–1)] =

447 (2.53), 329 (4.43), 230 (4.02) nm. C₁₈H₂₀N₄O (308.38): calcd.

C 70.11, H 6.54, N 18.17; found C 70.00, H 6.67, N 17.91.

Eur. J. Org. Chem. 2011, 861–877

www.eurjoc.org

875

E.-U. Würthwein et al.

FULL PAPER

[13]

J. I. Clodt, V. D. Hack, R. Fröhlich, E.-U. Würthwein, Synthe-

sis 2010, 1485–1492.

F. C. Cooper, M. W. Partridge, Org. Synth. 1956, 36, 64.

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J. Prigge, Ph. D. Thesis, University of Münster, 2004.

N-(4-Phenylazobenzoyl)acetamidine (1ag): Synthesized from 4-

phenylazobenzoyl chloride^[38](0.734 g, 3.00 mmol) and acetamid-

ine hydrochloride (0.284 g, 3.00 mmol); yield 0.360 g (45%); red

[14]

[15]

[16]

needles; m.p. 126.5 °C. IR (KBr): ν = 3312 (br. m, NH), 3182 (br.

˜

m, NH), 3061 (w, CH_arom.), 2947 (m), 2847 (m, CH_alk), 1624 (sh),

1603 (s), 1570 (m), 1504 (s), 1491 (sh), 1466 (sh), 1404 (m), 1364

(m), 1325 (sh), 1308 (s), 1288 (sh), 864 (m), 777 (m), 698 (m), 679

(m) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 2.23 (s, 3 H, CH₃),

6.22 (br. s, 1 H, NH), 7.47–7.57 (m, 3 H, m-/p-CH_arom.), 7.90–7.98

(m, 4 H, o-CH_arom., N=N), 8.38 (m, 2 H, o-CH_arom., CO), 10.37

(br. s, 1 H, NH) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 24.8 (CH₃),

122.4, 123.0, 129.1. 130.5, 131.9 (CH_arom.), 139.4 (C_ipso, CO), 152.7,

154.6 (C_ipso, N=N), 170.4 (C_quat., C=N), 179.3 (C_quat., C=O) ppm.

MS (70 eV): m/z (%) = 266 (74) [M]⁺, 209 (16) [Ph-N=N-C₆H₄-

CO]⁺, 162 (10), 161 (86) [M⁺– PhN₂], 153 (5), 152 (10) [C₆H₄-

C₆H₄]⁺, 133 (5), 120 (6), 105 (27) [PhN₂]⁺, 104 (26) [C₆H₄CO]⁺,

103 (33) [PhCN]⁺, 93 (5), 92 (15), 85 (16) [H₂N-C(CH₃)=NCO]⁺,

78 (7), 77 (100) [C₆H₅]⁺, 76 (33), 75 (15), 71 (6), 69 (7), 65 (6), 57

(12) [H₂N-C(CH₃)=N]⁺, 56 (5), 55 (10), 51 (22). UV (acetonitrile):

λ_max[lg(ε/M^–1cm^–1)] = 446 (2.43), 330 (4.47), 229 (4.01) nm.

C₁₅H₁₄N₄O (266.30): calcd. C 67.65, H 5.30, N 21.04; found C

67.41, H 5.58, N 20.72.

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Eur. J. Org. Chem. 2011, 861–877

Synthesis and Properties of N-Acylamidines

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Published Online: December 22, 2010

Eur. J. Org. Chem. 2011, 861–877

www.eurjoc.org

877

Article Doi

Synthesis, structures, and aggregation properties of N-acylamidines

DOI: 10.1002/ejoc.201001155

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Article abstract of DOI:10.1002/ejoc.201001155

Full text of DOI:10.1002/ejoc.201001155

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