4H-imidazoles and imidazoles from anionic and dipolar electrocyclization reactions of 2,4-diazapenta-1,3-dienes

FULL PAPER

4H-Imidazoles and Imidazoles from Anionic and Dipolar Electrocyclization

Reactions of 2,4-Diazapenta-1,3-dienes

Nils Habersaat,^[a]Roland Fröhlich,^[a]and Ernst-Ulrich Würthwein*^[a]

Dedicated to Prof. Dr. Christian Reichardt on the occasion of his 70th birthday

Keywords: Electrocyclization reaction / 2,4-Diazapentadienes / Lithium compounds / 1,5-Dipoles / Quantum chemical

calculations / Imidazoles

1-Amino-2,4-diazapenta-1,3-dienes 5 are synthesized by the

activation of N-acylamidines 2 with trifluoromethanesulfonic

ing the anionic 1,5-electrocyclization reaction. Results of

quantum chemical model calculations (RHF, MP2, SCS-MP2,

anhydride and subsequent condensation with amino com- G3, DFT) performed on the parent 2,4-diazapentadienyl an-

pounds 4. When the amino compounds 4 possess electron-

withdrawing substituents (e.g. alkoxycarbonyl groups, fluor-

enyl derivatives) this condensation leads instead to 4H-imid-

ion 9a, its lithium compound 9a-Li, the corresponding 1,5-

dipole 12 and their substituted derivatives are in accordance

with the suggested reaction mechanism. X-ray data are

azoles 6 and imidazoles 7. These reactions are considered to given for the 2,4-diazapenta-1,3-dienes 5a·F₃CSO₃H, 5c,

be 1,5-dipolar electrocyclization reactions of 1,5-dipoles that 5d·F₃CSO₃H, 5e,f and the spirocyclic 4H-imidazole deriva-

are tautomers of the 2,4-diazapenta-1,3-dienes 5. Depro- tives 6b−d.

tonation of 5b,f by the use of strong organic bases yields the

( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,

corresponding imidazoles 7b,c after amine elimination dur-

Germany, 2004)

Introduction

dicted for anionic cyclic polyenyl systems with heteroatoms

in even-numbered positions and for cations with het-

eroatoms in odd-numbered positions.

The cyclization of open-chain compounds presents a

straightforward and versatile method for the synthesis of

carbo- and heterocyclic compounds. From the mechanistic

and stereochemical points of view, pericyclic reactions, in

this case electrocyclization reactions, are of special interest

because of the sterically defined mode in which the ring-

closure reactions proceed.^[1,2]Whereas neutral compounds

often require higher temperatures, anionic and dipolar in-

termediates are sufficiently reactive to allow the formation

of cyclic products under well-controlled mild reaction con-

ditions.

In this report we describe the results of the ring-closure

reactions of 2,4-diazapentadienyl anions and the corre-

sponding dipoles. The aim of this work was to investigate

the scope and limitations of this approach, for example, in

the synthesis of non-aromatic heterocycles such as 4H-imid-

azoles. Furthermore, we have studied the influence of elec-

tron-withdrawing substituents on the mechanism of these

cyclization reactions; there are two mechanisms that seem

reasonable, the anionic mode and the 1,5-dipolar mode

(Scheme 1).

In earlier work, we developed a set of rules that allows

to predict the thermodynamics of electrocyclization reac-

tions of open-chain compounds that contain heteroatoms

depending on the position of the heteroatoms.^[3,4]Thus,

anionic azapolyenyl-type precursors readily cyclize if the

nitrogen atom is at an even-numbered position within the

unsaturated chain. In contrast, cationic precursors lead to

heterocycles if the nitrogen atom occupies an odd-num-

bered position.^[5]On the other hand, if the thermodynamic

barriers are not prohibitive, ring-opening reactions are pre-

Scheme 1

There are only a few publications that report such reac-

tions. Hunter and Sim^[6,7]observed the formation of 4,5-

dihydro-2,4,5-triphenylimidazole (‘‘amarine’’) from 1,3,5-

triphenyl-2,4-diazapenta-1,4-diene (‘‘hydrobenzamide’’) via

intermediate 2,4-diazapentadienyl anions^[8,9]after depro-

[a]

Organisch-Chemisches Institut, Universität Münster,

Corrensstrasse 40, 48149 Münster, Germany

Fax: (internat.) ϩ49-251-83-39772

E-mail: wurthwe@uni-muenster.de

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DOI: 10.1002/ejoc.200400057

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tonation with phenyllithium and subsequent work up with

acetic acid. For 2-azapentadienyl anions^[10]Hunter and co-

workers also observed similar ring-formation reactions that

produced dihydropyrroles.^[11,12]Later, this reaction was ap-

plied to the synthesis of 2,3-dihydroindoles^[13,14]and pyrrol-

izines.^[15]2-Azapentadienes also undergo thermal cycliza-

tion reactions to yield five-membered ring systems. Grigg

and co-workers^[16,17]attributed this behavior to an inter-

mediate proton shift which leads to transient 1,5-dipoles

that cyclize readily or may be trapped by appropriate dieno-

philes.^[18]

Scheme 2

Results and Discussion

2,4-Diazapenta-1,3-dienes 5 and 2,4-diazapenta-1,4-di-

enes may be envisaged as precursors for 2,4-diazapentadi-

enyl anions and the corresponding lithium compounds. To

allow the formation of doubly unsaturated (aromatic)

heterocycles an amino functionality was incorporated into

the 1-position as a potential leaving group.

From our experience of oligonitrile synthesis we designed

the following pathway to synthesize the 1-amino-substi-

tuted 2,4-diazapenta-1,3-dienes 5.^[19]The preparation of 5

Scheme 3

is summarized in Schemes 2Ϫ4. The secondary amidines 1 acylamidines 2, as described by Katritzky and co-work-

were prepared by the nucleophilic addition of amines to ers.^[20]For the subsequent condensation with primary am-

nitriles, which were subsequently acylated to yield the N- ines the N-acylamidines 2 were activated by use of trifluoro-

Scheme 4

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Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

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methanesulfonic anhydride^[21]to give the cationic inter- N2ϪC3ϭN4 torsional angles: 5c: 132.9°; 5e: 129.4°; 5f:

mediates 3, which were then treated at a low temperature 81.8°), which is a characteristic feature of 1,3-diazabuta-1,3-

with primary amines 4 (or with equimolar mixtures of the dienes^[23,24](see Figure 1 for 5c). The CN bonds differ in

˚

ammonium hydrochlorides 4·HCl and triethylamine) to give length (e.g. 5c: C1ϭN2 1.303 A, N2ϪC3 1.393 A, C3ϭN4

˚

the 1-amino-2,4-diazapenta-1,3-dienes 5aϪg in 45Ϫ57% 1.287 A) as is expected for such an alignment of amidine

yield (5a was isolated as the corresponding triflate, pro- and imine functions. The protonated compounds 5a and

tonated at N4) (Scheme 4). This reaction works well for aro- 5d are less twisted [C1ϭN2ϪC3ϭN4 torsional angles: 5a:

matic amines as well as for trifluoromethylamines and am- 155.9° (see Figure 1); 5d: 159.1°] and the differences in the

˚

ino acids, for example, alaninates and valinates. The (R)- CN bond lengths (e.g. 5a: C1ϭN2 1.341 A, N2ϪC3 1.313

˚

methoxymethyl-pyrrolidine (RMP) derivative 5h was formed A, C3ϭN4 1.330 A) are not as pronounced due to better

in a low yield.

π-conjugation in the cationic species.

The molecular structures of the new 1-amino-2,4-diaza-

In several cases, however, the condensation reactions of

penta-1,3-dienes 5a·F₃CSO₃H, 5c, 5d·F₃CSO₃H, 5e,f were 3 and 4 took a surprising alternative route. Instead of the

determined by X-ray crystallography.^[22]The neutral com- 2,4-diazapentadienes 5, 4H-imidazole derivatives 6 and imi-

pounds 5c,e,f have non-planar CϭNϪCϭN skeletons (C1ϭ dazoles 7 were obtained in moderate (15%) to good (80%)

yields. The 4H-imidazoles deserve special attention because

their non-aromatic cyclic structure, with a fixed s-cis-1,3-

diazabutadiene subunit, makes them attractive starting ma-

terials for further transformations, for example, in hetero-

DielsϪAlder reactions. Inspection of the substitution pat-

terns of the reagents shows that the condensation reactions

occur mainly when the primary amines contain strongly

acidifying functions, such as two ester functionalities

(aminomalonate) or a fluorenyl group (Scheme 4). From

the products obtained it is clear that after the condensation

step a cyclization reaction must occur in the presence of the

two moles of trifluoromethanesulfonic acid that are liber-

ated during the condensation reaction. Finally elimination

of the secondary amine leads to the protonated imidazole

derivatives 6 and 7 and the corresponding ammonium salts.

Imidazole 7b, which was obtained from 2a after triflate an-

hydride activation and reaction with ethyl phenylglycinate,

deserves special attention. Its formation requires the com-

plete loss of an ethoxycarbonyl group in order to achieve

the aromatic electron sextet of the imidazole. It is surprising

that this unusual reaction (43% yield) occurs under the mild

reaction conditions (Ϫ78 °C, room temperature) applied.

In contrast, the aminomalonate-derived compound 6a was

isolated as the corresponding 4H-imidazole.

The molecular structures of the spiro-fluorene com-

pounds 6bϪd were obtained by X-ray crystallography (for

6b, see Figure 2) and exhibit features typical of spiro com-

Figure 1. Molecular structures of 5c (top) and of 5a·F₃CSO₃H

(bottom) (determined by X-ray crystallography)

Figure 2. Molecular structure of 6b (determined by X-ray crystal-

lography)

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pounds. The additional aromatic substituents lie in the

plane with the 4H-imidazole ring system.

With regard to the mechanism of such cyclization reac-

tions, in the absence of base we assume an equilibrium be-

tween 5 and its tautomeric 1,5-dipolar form (azavinylogous

azomethine ylide, in the presence of trifluoromethanesul-

fonic acid), which has the ability to undergo 1,5-dipolar

electrocyclizations (Scheme 5).^[16]Note that CF₃groups are

not sufficiently active as acidifying functionalities to induce

proton shift and subsequent cyclization. On the other hand,

it is surprising that the corresponding 2,4-diazapentadienes

5 are accessible from ethyl alaninate and ethyl valinate, but

not from the glycinate; the presence of alkyl groups seems

to reduce the CH acidity sufficiently to prevent the proton

shift and the subsequent cyclization.

Scheme 6

Scheme 7

Quantum Chemical Calculations

In order to understand and interpret the experimentally

observed cyclization reactions the thermodynamics and ki-

netics of the ring-closing step were calculated by means of

quantum chemical model calculations. Based on previous

experience^[25]we have used RHF theory (6-31G* basis set)

and MP2 single points to evaluate the relative energies of

Scheme 5

In order to convert the 2,4-diazapenta-1,3-dienes 5 into the species in question. The SCS-MP2 single points^[26]pro-

the corresponding lithium compounds, 5b and 5f were ved to be especially useful, and are available at no extra

treated at a low temperature with strong base (1:1 KOtBu/ cost from the MP2-outputs. To calibrate the unsubstituted

nBuLi for 5b, lithium diisopropylamide for the more acidic systems we employed the G3 theory,^[27]which indeed dem-

5f) (Scheme 6). At first, a deep purple color was observed, onstrated the superior performance of the SCS-MP2 data

which we attribute to the intermediate anion. After a few (see below). The DFT method B3LYP/6-31G* was also

minutes, the color disappeared, and after aqueous work up used, but, according to our findings, it seems to be less well

the imidazoles 7a and 7c were obtained in 42 and 63% yield. suited to anionic systems since it both overestimates acti-

The formation of these compounds is interpreted as being vation barriers and underestimates heats of reaction.^[25]All

the result of an anionic 6π-cyclization with subsequent β- stationary points were checked by frequency analyses (mini-

elimination of the heterocyclic amine to realize the energeti- mum or transition state); the relative energies include zero

cally favorable aromatic 6π-electron system of the imidaz- point corrections (unscaled, except for G3). These calcu-

ole. Deprotonation of 5d did not lead to the corresponding lations were performed using the Gaussian98 suite of pro-

imidazole, but to the elimination of HF to furnish the corre- grams.^[28]For comparison, semiempirical PM3^[29,30]data,

sponding 2,4-diazahexa-1,3,5-triene 8 (Scheme 7). The obtained from the MOPAC93 package, are included.^[31]

other 2,4-diazapenta-1,3-dienes (5a, 5c, 5e, 5h, 5i) were re-

First, we discuss the results of the quantum chemical cal-

covered in 30Ϫ80% yield after deprotonation and aqueous culations performed on the anionic cyclization of the un-

work up without cyclization, although the deep purple substituted model system 2,4-diazapentadienyl anion 9a.

color of the intermediate anions was always observed at The results for the parent system 9a in three configurations

low temperatures.

(W-shape, sickle-shape and U-shape), the transition states

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Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

FULL PAPER

Table 1. Relative energies (kcal·mol^Ϫ1) of the stationary points of the cyclization of the 2,4-diazapentadienyl anion 9a at various levels

of theory

Method

W

TS (WϪS)

Sickle

TS (SϪU)

U

TS (UϪCycle)

Cycle

PM3

1.05

0.00

13.47

22.35

24.06

22.56

20.71

27.30

0.59

1.69

1.41

1.43

1.13

2.08

14.38

20.69

22.13

20.75

17.67

25.60

0.00

4.48

3.04

3.66

1.10

4.77

28.91

25.52

9.51

12.34

11.14

19.41

Ϫ24.90

Ϫ32.60

Ϫ30.14

Ϫ29.90

Ϫ25.34

Ϫ17.81

RHF/6-31G*

MP2/6-31G*

SCS-MP2/6-31G*

G3

B3LYP/6-31G*

Table 2. Relative energies (kcal·mol^Ϫ1) of the stationary points in the cyclization of the 2,4-diazapentadienyllithium compound 9a-Li at

various levels of theory

Method

W

TS (WϪS)

Sickle

TS (SϪU)

U

TS (UϪCycle)

Cycle

PM3

0.00

20.32

19.45

29.33

26.77

30.05

31.68

33.27

12.08

6.38

9.21

9.17

9.85

8.98

11.25

23.46

15.58

19.74

19.40

Ϫ^[a]

21.72

24.74

20.87

13.13

11.79

13.50

14.46

17.60

38.60

23.47

12.54

15.59

17.11

20.66

24.21

Ϫ12.52

Ϫ24.26

Ϫ15.88

Ϫ16.05

Ϫ12.72

Ϫ6.90

RHF/6-31G*

MP2/6-31G*

SCS-MP2/6-31G*

G3

B3LYP/6-31G*

B3LYP/6-311ϩϩG**

Ϫ4.92

[a]

No transition state could be localized using G3 theory (M2/6-31G* optimization).

form a surprisingly small barrier has been calculated (11.1

kcal·mol^Ϫ1). As seen in Table 1 the relative energies are

strongly dependent on the method employed. The MP2 re-

sults, especially the SCS-MP2 data, are not far off the G3

values, but the B3LYP data overestimate the barriers and

underestimate the heat of reaction. The semiempirical PM3

method predicts the reaction enthalpy quite well, but has

problems with the relative energies of the conformers and

with the activation barriers. In summary, from the calcu-

lations performed on the unsubstituted anion 9a without a

counterion, an exothermic cyclization reaction of the U-

shaped form is expected, but substantial barriers may delay

the interconversion of the different isomers.

The calculated energies for all stationary points in the

electrocyclization of 2,4-diazapentadienyllithium 9a-Li,

which is taken as a model for the contact ion pair (without

further coordination by aggregation or solvation), are sum-

marized in Table 2, Figure 4. The best structure corre-

sponds to a W-shaped form with Li^ϩcoordinating to both

nitrogen lone pairs; the sickle- and U-forms have signifi-

cantly higher energies. According to the G3 data, the bar-

riers for internal rotations and for the electrocyclization are

predicted to be higher than those of the anion by ca. 6 to

10 kcal·mol^Ϫ1, probably due to the less favorable coordi-

nation of lithium. For the same reason the ring closure is

less exothermic since lithium is only mono-hapto coordi-

nated in this model structure. Nevertheless, these data are

in accordance with the experimental results under the con-

ditions employed.

Figure 3. Molecular structures corresponding to the stationary

points in the cyclization of the 2,4-diazapentadienyl anion 9a

(MP2/6-31G*//MP2/6-31G*)

of the internal rotations and the pericyclic (disrotatory)

electrocyclization, and for the cyclic isomer are summarized

in Table 1 and Figure 3. The lowest energy form of the 2,4-

diazapentadienyl anion is predicted to be a W-shaped struc-

ture, followed by sickle- and U-shaped forms. To convert

the lowest energy W-form into the ring isomer two internal

rotations have to take place. For the WϪsickle interconver-

sion we calculate an activation barrier of 20.7 kcal·mol^Ϫ1

(G3), which is the highest barrier en route to the cyclic iso-

We also investigated the influence of substituents on the

mer. The sickle- and U-forms are only slightly higher in structures, thermodynamics and kinetics of the electrocy-

energy than the W-form (ca. 1.1 kcal·mol^Ϫ1). For the rather clization reaction of substituted model anions 9aϪh (in the

exothermic cyclization (∆H_rഠ Ϫ25.3 kcal·mol^Ϫ1) of the U- absence of a counterion, see Table 3, Figure 5). Since G3

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Figure 4. Molecular structures corresponding to the stationary

points in the cyclization of the 2,4-diazapentadienyllithium com-

pound 9a-Li (MP2/6-31G*//MP2/6-31G*)

Table 3. Relative energies (kcal·mol^Ϫ1) of the stationary points in

the cyclization of substituted 2,4-diazapentadienyl anions 9aϪh at

the MP2/6-31G*, SCS-MP2/6-31G* and B3LYP/6-31G* levels

Compound Method

W

Sickle U

TS (UϪCycle) Cycle

9a

9b

9c

9d

9e

9f

MP2

0.00 1.41 3.04 9.51

Ϫ30.41

Ϫ29.90

Ϫ17.81

Ϫ27.48

Ϫ27.97

Ϫ17.11

Ϫ6.53

Ϫ6.81

12.14

SCS-MP2 0.00 1.43 3.66 12.34

B3LYP

MP2

SCS-MP2 8.41 2.47 0.00 12.10

B3LYP

MP2

SCS-MP2 0.00 0.82 5.71 14.47

B3LYP

MP2

SCS-MP2 3.58 0.30 0.00 8.73

B3LYP

MP2

SCS-MP2 0.00 0.03 5.06 17.43

B3LYP

MP2

SCS-MP2 0.00 0.70 3.42 13.66

B3LYP

MP2

SCS-MP2 0.00 0.78 4.22 15.88

B3LYP

MP2

SCS-MP2 0.28 0.00 7.07 14.72

B3LYP 0.00 1.09 9.65 21.20

0.00 2.08 4.77 19.41

8.41 2.70 0.00 9.43

9.61 2.90 0.00 18.10

0.00 0.71 5.24 11.76

Figure 5. Molecular structures of various substituted 2,4-diazapen-

tadienyl anions 9aϪh (MP2/6-31G*//RHF/6-31G*)

0.00 1.64 6.92 24.73

3.84 0.43 0.00 6.33

Ϫ10.85

Ϫ11.91

4.37

4.64 0.65 0.00 17.46

0.00 0.09 4.58 15.04

shaped forms, and consequently the U-shaped structure is

favored. According to the calculations, the barrier to ring

closure is strongly reduced for the 1,3,5-triphenyl-2,4-diaza-

pentadienyl anion 9d (SCS-MP2: 8.7 kcal·mol^Ϫ1), both for

steric and electronic reasons; otherwise there is little varia-

tion (12Ϫ18 kcal·mol^Ϫ1) in this barrier.

To model the 1,5-dipolar electrocyclization reaction, we

performed calculations on the 2,4-diazapenta-1,3-diene 10a,

its isomer the 2,4-diazapenta-1,4-diene 11a, the 1,5-dipole

12a and the transition states for its internal rotations and

cyclization, and the ring form 13a (see Table 4, Figure 6).

Again we find a strong dependence on the method em-

Ϫ14.54

Ϫ14.22

Ϫ0.41

Ϫ27.96

Ϫ27.52

Ϫ14.35

Ϫ18.83

Ϫ18.76

Ϫ4.91

Ϫ5.58

Ϫ5.57

8.25

0.00 1.49 6.19 22.63

0.00 0.69 2.86 11.60

0.00 1.20 4.90 18.91

0.00 0.75 3.72 13.73

9g

9h

0.00 1.24 5.61 21.12

0.26 0.00 6.95 11.82

calculations on these species are not feasible due to the size ployed. Here, SCS-MP2/6-31G* single point data are not

of the molecules, we consider the SCS-MP2 data to be the as close to the G3 values as was the case for the anions

most reliable. All substituents lead to a less exothermic (Table 1), which might be due to the relatively poor descrip-

cyclization reaction, probably due to a better stabilization tion of the electronic structure of such 1,5-dipoles by this

of the open form relative to the cyclic structure, as seen for basis set. In this case, B3LYP is not far off the G3 data.

the 1-methoxycarbonyl (9e), phenyl (9bϪd) and fluorenyl The best structure for the 2,4-diazapenta-1,3-dienes 10a is

(9h) derivatives. Phenyl groups in the 3-position exert a not a planar penta-1,3-diene-like structure but a strongly

strong steric effect, which destabilizes the W- and sickle- twisted gauche conformation, as found in 1,3-diazabutadi-

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Table 4. Relative energies (kcal·mol^Ϫ1) of 2,4-diazapenta-1,3-diene 10a, 2,4-diazapenta-1,4-diene 11a and the corresponding 1,5-dipole

12a, the stationary points in the cyclization of 12a and for dihydroimidazole (13a) at various levels of theory

Method

1,3-Diene 1,4-Diene 1,5-Dipole W TS

TS

Sickle 1 Sickle 2 TS

TS

U

TS

Cycle

10a

11a

12a

(WϪS1) (WϪS2)

(S1ϪU) (S2ϪU)

(UϪCycle) 13a

PM3

AM1

0.00

6.77

17.08

21.12

48.24

31.00

33.21

27.05

26.09

22.03

25.65

27.95

64.79

48.27

49.40

42.64

46.01

40.84

41.46

45.91

71.38

69.23

69.25

60.76

63.48

56.69

22.83

19.76

56.28

37.93

40.33

32.99

33.08

29.15

20.11

22.27

50.45

33.55

35.70

28.47

28.71

24.09

46.49

42.61

73.45

68.48

69.27

59.92

61.68

55.87

26.39

28.00

62.87

45.87

47.21

39.53

44.21

38.24

22.41 44.80

19.78 35.69

55.44 62.72

37.31 40.38

40.26 44.57

31.64 35.38

33.04 38.23

28.02 33.45

Ϫ18.36

Ϫ12.43

Ϫ13.90

Ϫ17.20

Ϫ15.38

Ϫ17.42

Ϫ13.36

Ϫ14.53

2.86

9.19

9.63

8.96

8.52

10.21

9.53

RHF/6-31G*

MP2/6-31G*//6-31G* 0.00

SCS-MP2

G3

B3LYP/6-31G*

0.00

B3LYP/6-311ϩϩG** 0.00

enes.^[23]It is more stable than the non-conjugated 2,4-diaza-

penta-1,4-diene 11a by approximately 8.5 kcal·mol^Ϫ1. The

best corresponding 1,5-dipolar form 12a is predicted to be

planar, but is about 27 kcal·mol^Ϫ1more energy rich than

the 2,4-diazapenta-1,3-diene 10a. Thus, it is unlikely that

such an intermediate will exist in equilibrium with the other

C₃N₂H₆compounds under experimental conditions. If such

a W-shaped 1,5-dipole was formed, barriers to internal ro-

tation (of the iminium moiety) would amount to an ad-

ditional 33 kcal·mol^Ϫ1, whereas only a small barrier (ca. 8

kcal·mol^Ϫ1) is associated with the formation of the cyclic

tautomer imidazoline 13a, which is predicted to have a

lower energy (by ca. 44 kcal·mol^Ϫ1) than the 1,5-dipole.

However, one can also envisage the direct formation of the

U-shaped 1,5-dipole 12a from an appropriate conformer of

the 2,4-diazapenta-1,3-diene 10a without involving internal

rotations of the 1,5-dipole.

Figure 7. Various substituted 2,4-diazapenta-1,3-dienes 10 and the

corresponding 1,5-dipoles 12, 12Ј

The accessibility of the 1,5-dipoles 12 under experimental

conditions depends very much on the nature of the elec-

tron-withdrawing groups present in the 2,4-diazapenta-1,3-

dienes 10 (Figure 7, Table 5). We present model calculations

for some of the experimentally investigated systems in

Table 5. In all cases the 1,5-dipoles 12, which have the pro-

tonated nitrogen atom close to the electron-withdrawing

group, are more stable than the tautomeric 1,5-dipoles 12Ј.

It is clear that a trifluoromethyl group (10d, 12d) has rela-

tively little effect on the possible tautomeric (intermolecu-

lar) equilibrium between the 2,4-diazapenta-1,3-diene 10d

and the corresponding dipoles 12d. Two phenyl groups in

the 1,5-positions (10b, 12b), or a cyano group (10e, 12e),

acidify the respective compounds considerably; the effect is

even more pronounced for the methoxycarbonyl and fluor-

enyl moieties (10c,f, 12c,f). If the additional substituents

that are present in the experimentally investigated com-

pounds are taken into account, these qualitative data agree

well with the experimental results.

Experimentally, the spiro-fluorene-4H-imidazoles 6bϪd

are formed in a fast cyclization process even in the absence

of base; the intermediate 2,4-diazapenta-1,3-dienes 5 could

not be isolated under the reaction conditions employed (see

above). Therefore, we have studied this system in more de-

tail. Based on the SCS-MP2 data (Figure 8, Table 6), which

are possibly too high by 6Ϫ8 kcal·mol^Ϫ1for the 1,5-dipole

and its transition states, as estimated from the data in

Table 4, we have calculated an energy difference between

the fluorenyl-substituted 1,3-diene 10f and the better of its

two 1,5-dipolar forms 12f (ca. 14 kcal·mol^Ϫ1) that is drasti-

cally reduced compared with the parent system 10a

(Table 4). Phenyl groups, present in the experimentally stud-

ied system, will further reduce this energy difference. From

the calculated transition state energy for cyclization (27.7

Figure 6. Molecular structures of 2,4-diazapenta-1,3-diene 10a, 2,4-

diazapenta-1,4-diene 11a and the corresponding 1,5-dipole 12a, the

stationary points in the cyclization of 12a and for 4,5-dihydroimi-

dazole (13a) (RHF/6-31G*)

kcal·mol^Ϫ1) we estimate a barrier of ca. 20 kcal·mol^Ϫ1

,

Eur. J. Org. Chem. 2004, 2567Ϫ2581

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FULL PAPER

Table 5. Relative energies (kcal·mol^Ϫ1) of various substituted 2,4-diazapenta-1,3-dienes 10 and its 1,5-dipoles 12 and 12Ј at three levels

of theory

Nr.

R¹

H

R²

H

R³

H

Method

1,3-Diene 10

Dipole 12

Dipole 12Ј

[a]

a

MP2

0.00

31.00

33.21

26.09

18.21

21.97

13.24

14.88

17.76

8.03

27.43

29.85

22.31

18.23

21.17

11.96

9.58

31.00

33.21

26.09

18.21

21.97

13.24

[a]

SCS-MP2

B3LYP

MP2

SCS-MP2

B3LYP

MP2

SCS-MP2

B3LYP

MP2

SCS-MP2

B3LYP

MP2

SCS-MP2

B3LYP

MP2

SCS-MP2

B3LYP

[a]

b

c

d

e

f

Ph

H

Ph

H

[a]

CO₂Me

CF₃

23.60

26.69

17.06

28.73

31.21

22.92

19.68

22.98

13.88

15.05

19.01

8.19

CN

N-fluorenyl

13.83

3.95

[a]

Owing to symmetry the energies are equal to those of dipole 12.

Conclusions

A new synthetic route to 1-amino-2,4-diazapenta-1,3-di-

enes 5 has been developed, that is based on the activation

of N-acylamidines 2 by trifluoromethanesulfonic anhydride

and subsequent condensation with amino compounds 4. If

the amino compounds 4 are substituted with electron-with-

drawing substituents (e.g. alkoxycarbonyl groups, fluorenyl

derivatives) the condensation reaction surprisingly gives

4H-imidazoles 6 and imidazoles 7 instead of the 2,4-diaza-

penta-1,3-dienes 5. We consider these reactions to occur by

1,5-dipolar electrocyclization of 1,5-dipoles, which are

formed from the relatively acidic 2,4-diazapenta-1,3-dienes

5 by tautomerism. In the case of 5b,f, electrocyclization

could be achieved by using strong organic bases to yield the

corresponding imidazoles 7b,c after amine elimination in

an anionic ring-closure reaction. The anionic and the 1,5-

dipolar reaction mechanisms have been studied by per-

forming quantum chemical model calculations (RHF, MP2,

SCS-MP2, G3, DFT) on the parent 2,4-diazapentadienyl

anion 9a, its lithium compound 9a-Li, the corresponding

1,5-dipole 12, and substituted derivatives as model systems

for the experimentally studied species. We have sup-

plemented our experimental and theoretical work by X-ray

analyses of the 2,4-diazapenta-1,3-dienes 5a·F₃CSO₃H, 5c,

5d·F₃CSO₃H, 5e,f and the spirocyclic 4H-imidazole deriva-

tives 6bϪd.

Figure 8. Molecular structures of the fluorenyl-substituted 2,4-di-

azapenta-1,3-diene 10f, its 1,5-dipoles 12f and 12Јf, the transition

state of the cyclization and the corresponding cyclic product 13f

(4,5-dihydroimidazole) (RHF/6-31G*)

Experimental Section

Materials and Methods: IR: Nicolet 5DXC. ¹H NMR: Bruker WM

300 (300.13 MHz), Bruker AMX 400 (400.13 MHz) and Varian

Unity plus (599.86 MHz), internal reference tetramethylsilane. ¹³C

NMR: Bruker WM 300 (75.47 MHz), Bruker AMX 400

(100.61 MHz) and Varian Unity plus (150.85 MHz), internal refer-

ence tetramethylsilane or solvent. ¹⁹F NMR: Bruker WM 300

which is easily overcome even under mild experimental con-

ditions, assuming an intermolecular proton shift occurs.

Again, the cyclization to form 13f is predicted to be rather

exothermic (Ϫ18 kcal·mol^Ϫ1).

2574

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Eur. J. Org. Chem. 2004, 2567Ϫ2581

Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

FULL PAPER

Table 6. Relative energies (kcal·mol^Ϫ1) of the fluorenyl-substituted 2,4-diazapenta-1,3-diene 10f, its 1,5-dipoles 12f and 12Јf, the transition

state of the cyclization and the corresponding cyclic product (4,5-dihydroimidazole 13f) at various levels of theory

Method

1,3-Diene 10f

Dipole 12f

Dipole 12Јf

TS (UϪCycle)

Cycle 13f

PM3

AM1

0.00

4.05

5.91

29.93

9.58

13.83

3.95

8.99

10.59

35.24

15.05

19.01

8.19

33.42

19.54

42.97

21.88

27.69

17.50

Ϫ20.27

Ϫ15.82

Ϫ17.62

Ϫ23.71

Ϫ21.22

Ϫ17.86

RHF/6-31G*

MP2/6-31G*//6-31G*

SCS-MP2

B3LYP/6-31G*

(282.37 MHz), internal reference trichlorofluoromethane. CHN el-

emental analysis: Elementar Vario El III. Melting points are uncor-

rected. All solvents were rigorously dried by standard methods.

When necessary, the experiments were carried out with complete

exclusion of moisture (argon, septum-syringe technique) in glass-

1562 (s, CϭN), 1516 (s, CϭC), 1437 (s), 1344 (s), 1296 (s), 1250

1

(vs), 1175 (s), 1111 (m), 1030 (s), 839 (s), 793 (m) cm^Ϫ1. H NMR

(300.13 MHz, CDCl₃): δ ϭ 1.76 (m, 4 H, NCH₂CH₂), 3.22 (m, 4

H, NCH₂CH₂), 3.67 (s, 3 H, OCH₃), 5.94 (br. s, 1 H, NH), 6.74 (m,

2 H, CH_arom.), 7.17 (m, 2 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz,

ware that had been thoroughly dried by repeated heating under CDCl₃): δ ϭ 25.3 (NCH₂CH₂), 47.8 (NCH₂CH₂), 54.9 (OCH₃),

argon and subsequent evacuation.

113.3 (m-C_arom.), 127.6 (o-C_arom.), 131.8 (i-C_arom.), 159.6 (i-COCH₃),

166.8 (CϭN) ppm. MS (EI, 70 eV): m/z (%) ϭ 204 (88) [M^ϩ], 203

(78) [M^ϩϪ H], 175 (80), 134 (87) [M^ϩϪ (CH₂)₄N], 91 (23), 70

(100) [(CH₂)₄N^ϩ]. C₁₂H₁₆N₂O (204.27): calcd. C 70.56, H 7.89,

N 13.71; found C 70.58, H 7.83, N 13.50.

Amidines 1aϪd. General Procedure: An equimolar amount of the

appropriate amine was added to a solution of n-butyllithium (1.6 

in n-hexane) in dry tetrahydrofuran at Ϫ78 °C. This solution was

stirred at room temperature for 15 min. At Ϫ78 °C an equimolar

amount of nitrile was added. The reaction mixture was warmed

slowly to room temperature and stirred for 2 h. For hydrolysis

(R)-1-Benzimidoyl-2-methoxymethylpyrrolidine (1d): Following the

general procedure 1d was prepared from (R)-2-methoxymethylpyr-

methanol (80 mL) and water (80 mL) were subsequently added. rolidine (3.7 mL, 30.0 mmol) in dry tetrahydrofuran (100 mL), n-

The aqueous layer was separated from the organic layer and ex-

tracted three times with tert-butyl methyl ether. The combined or-

ganic layers were dried with sodium sulfate and the solvent was

removed in vacuo.

butyllithium (18.8 mL, 1.6  in n-hexane) and benzonitrile (3.1 mL,

30.0 mmol). The crude product was purified by distillation (104 °C,

1 mbar). Yield 4.17 g (64%), colorless oil. IR (film): ν˜ ϭ 3312 (s,

NH), 3059 (m, CH_arom.), 2972 (s, CH_aliph.), 2874 (s, CH_aliph.), 2826

(s, CH_aliph.), 1585 (vs, CϭN), 1566 (vs, CϭN), 1499 (s, CϭC), 1447

(vs, CϭC), 1344 (s), 1310 (m), 1223 (s), 1188 (s), 1111 (vs), 1028

1-Benzimidoylpyrrolidine (1a): Following the general procedure 1a

was prepared from pyrrolidine (5.0 mL, 60.0 mmol) in dry tetra-

hydrofuran (100 mL), n-butyllithium (37.5 mL, 1.6  in n-hexane)

and benzonitrile (6.2 mL, 60.0 mmol). The crude product was puri-

fied by distillation (100 °C, 1 mbar). Yield 8.37 g (80%) (ref.^[32]

70%, 104 °C/1 hPa), colorless oil. C₁₁H₁₄N₂(174.24): calcd.

C 75.82, H 8.10, N 16.08; found C 75.61, H 8.09, N 15.86.

(m), 972 (m), 872 (m), 775 (vs), 704 (vs) cm^Ϫ^{1 1}H NMR

.

(300.13 MHz, CDCl₃): δ ϭ 1.72Ϫ1.96 (m, 4 H, NCH₂CH₂), 3.18

(s, 3 H, OCH₃), 3.20Ϫ3.40 (m, 4 H, NCH₂, OCH₂), 4.09 (m, 1 H,

NCH), 5.98 (br. s, 1 H, NH), 7.26 (m, 5 H, CH_arom.) ppm. ¹³C

NMR (75.47 MHz, CDCl₃): δ ϭ 23.6, 28.2 (NCH₂CH₂), 48.9

(NCH₂), 56.7 (OCH₃), 58.7 (NCH), 72.7 (OCH₂), 126.2, 128.1 (o-,

m-C_arom.), 128.4 (p-C_arom.), 139.5 (i-C_arom.), 167.1 (CϭN) ppm. MS

(EI, 70 eV): m/z (%) ϭ 218 (9) [M^ϩ], 203 (44) [M^ϩϪ CH₃], 187 (15)

[M^ϩϪ OCH₃], 173 (6) [M^ϩϪ CH₂OCH₃], 104 (39) [PhCNH^ϩ], 77

(20) [Ph^ϩ], 70 (100) [(CH₂)₄N^ϩ]. C₁₃H₁₈N₂O (218.29): calcd.

C 71.53, H 8.31, N 12.83; found C 71.37, H 8.35, N 12.69.

1-(4-Methylbenzimidoyl)pyrrolidine (1b): Following the general pro-

cedure 1b was prepared from pyrrolidine (5.3 mL, 64.0 mmol) in

dry tetrahydrofuran (100 mL), n-butyllithium (40.0 mL, 1.6  in n-

hexane) and 4-methylbenzonitrile (7.49 g, 64.0 mmol). The crude

product was purified by distillation (105 °C, 1 mbar). Yield 6.83 g

(57%), pale-yellow oil. IR (film): ν˜ ϭ 3312 (m, NH), 3022 (m,

CH_arom.), 2968 (m, CH_aliph.), 2868 (m, CH_aliph.), 1583 (s, CϭN),

1560 (s, CϭN), 1445 (s), 1344 (s), 1215 (s), 1176 (m), 827 (s), 789

N-Acylamidines 2aϪd. General Procedure. Method A: An excess of

2  sodium hydroxide solution (100 mL) was added to N,N-dialkyl-

amidine 1 (30.0 mmol). The mixture was stirred and cooled to 0

°C. A solution of acyl chloride (30.0 mmol) in acetone (15 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.

The remaining solid was filtered off, washed with water (50 mL),

and the solvent removed in vacuo.

1

(m), 734 (m) cm^Ϫ1. H NMR (300.13 MHz, CDCl₃): δ ϭ 1.76 (m,

4 H, NCH₂CH₂), 2.23 (s, 3 H, CH₃), 3.23 (m, 4 H, NCH₂CH₂),

5.92 (br. s, 1 H, NH), 7.03 (m, 2 H, CH_arom.), 7.13 (m, 2 H, CH_arom.

)

ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 20.8 (CH₃), 25.3

(NCH₂CH₂), 47.7 (NCH₂CH₂), 126.0, 128.6 (C_arom.), 136.5, 138.2

(i-C_arom.), 167.1 (CϭN) ppm. MS (EI, 70 eV): m/z (%) ϭ 188 (81)

[M^ϩ], 187 (90) [M^ϩϪ H], 159 (66), 145 (54), 118 (79) [TolCN^ϩ], Method B: An excess of 2  sodium hydroxide solution (100 mL)

91 (33) [Tol^ϩ], 70 (100) [(CH₂)₄N^ϩ]. C₁₂H₁₆N₂(188.27): calcd. was added to N,N-dialkylamidine 1 (30.0 mmol). The mixture was

C 76.56, H 8.57, N 14.88; found C 76.22, H 8.90, N 14.73.

stirred and cooled to 0 °C. A solution of acyl chloride (30.0 mmol)

in acetone (15 mL) was added dropwise to the reaction mixture

using a dropping funnel. Then the solution was warmed to 10 °C

over the course of 1.5 h. The solution was extracted with chloro-

form (3 ϫ 30 mL). The combined organic layers were dried with

sodium sulfate, and the solvent removed in vacuo.

1-(4-Methoxybenzimidoyl)pyrrolidine (1c): Following the general

procedure 1c was prepared from pyrrolidine (5.3 mL, 64.0 mmol)

in dry tetrahydrofuran (100 mL), n-butyllithium (40.0 mL, 1.6  in

n-hexane) and 4-methoxybenzonitrile (8.51 g, 64.0 mmol). The

crude product was purified by distillation (115 °C, 1 mbar). Yield

10.71 g (82%), pale-yellow oil. IR (film): ν˜ ϭ 3312 (m, NH), 2966 N-[(Phenyl)(pyrrolidin-1-yl)methylene]benzamide (2a): Following

(m, CH_aliph.), 2869 (m, CH_aliph.), 1609 (s, CϭN), 1585 (vs, CϭN), method A 2a was prepared from 1a (10.44 g, 60.0 mmol) and ben-

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FULL PAPER

zoyl chloride (6.9 mL, 60.0 mmol). Yield 14.10 g (85%), colorless

137.2 (i-C_arom.), 163.2 (CϭN), 176.2 (CϭO) ppm. MS (EI, 70 eV):

solid; m.p. 119 °C (ref.^[32]96.5%, 119 °C). C₁₈H₁₈N₂O (278.35): m/z (%) ϭ 322 (13) [M^ϩ], 307 (9) [M^ϩϪ CH₃], 237 (12) [M^ϩ

Ϫ

calcd. C 77.67, H 6.52, N 10.06; found C 77.61, H 6.28, N 9.99.

PhCO], 174 (10), 105 (100) [PhCO^ϩ], 77 (30) [Ph^ϩ]. C₂₀H₂₂N₂O₂

(322.40): calcd. C 74.51, H 6.88, N 8.69; found C 74.60, H 7.08,

N 8.21.

4-Methyl-N-[(4-methylphenyl)(pyrrolidin-1-yl)methylene]benzamide

(2b): Following method A 2b was prepared from 1b (5.65 g,

30.0 mmol) and 4-methylbenzoyl chloride (4.0 mL, 30.0 mmol).

Yield 8.22 g (90%), colorless solid; m.p. 142 °C. IR (KBr): ν˜ ϭ

3022 (m, CH_arom.), 2974 (s, CH_aliph.), 2947 (s, CH_aliph.), 2920 (m,

CH_aliph.), 2876 (s, CH_aliph.), 1634 (vs, CϭO/CϭN), 1606 (s, CϭO/

CϭN), 1545 (vs, CϭC), 1477 (vs, CϭC), 1339 (s), 1308 (vs), 1285

(vs), 1209 (s), 1167 (vs), 1069 (vs), 1018 (s), 951 (s), 916 (s), 825

(vs), 779 (s), 758 (vs), 729 (s), 696 (s) cm^Ϫ1. ¹H NMR (300.13 MHz,

CDCl₃): δ ϭ 1.90Ϫ1.97 (br. m, 4 H, NCH₂CH₂), 2.30 (s, 3 H,

CH₃), 2.36 (s, 3 H, CH₃), 3.31 (br. s, 2 H, NCH₂CH₂), 3.76 (br. s,

2 H, NCH₂CH₂), 7.09Ϫ7.21 (m, 6 H, CH_arom.), 7.99 (m, 2 H, o-

CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 21.2, 21.3

(CH₃), 24.5, 25.7 (NCH₂CH₂), 48.1, 49.5 (NCH₂CH₂), 127.0,

128.4, 128.9, 129.4 (o-, m-C_arom.), 132.3, 134.6 (i-C_arom.), 139.2,

141.3 (i-CCH₃), 163.0 (CϭN), 176.1 (CϭO) ppm. MS (EI, 70 eV):

m/z (%) ϭ 306 (51) [M^ϩ], 237 (17), 215 (22) [M^ϩϪ Tol], 119 (83)

[TolCO^ϩ], 91 (53) [Tol^ϩ], 70 (100) [(CH₂)₄N^ϩ]. C₂₀H₂₂N₂O

(306.40): calcd. C 78.40, H 7.24, N 9.14; found C 78.11, H 6.97,

N 9.09.

2,4-Diazapenta-1,3-dienes 5aϪh and Imidazoles 6 and 7. General

Procedure. Method A: An equimolar amount of N-acylamidine 2,

dissolved in dichloromethane, was added to a solution of trifluoro-

methanesulfonic anhydride in dry dichloromethane at Ϫ78 °C. This

solution was stirred for 1.5 h at Ϫ50 °C. At Ϫ78 °C an equimolar

amount of amine 4 was added. The reaction mixture was stirred at

Ϫ78 °C for 1 h and additionally for 3 h at room temperature. The

reaction mixture was washed with saturated sodium hydrogen car-

bonate solution (3 ϫ 30 mL), dried with sodium sulfate, and the

solvent removed in vacuo.

Method B: An equimolar amount of N-acylamidine 2, dissolved in

dichloromethane, was added to a solution of trifluoromethanesul-

fonic anhydride in dry dichloromethane at Ϫ78 °C. This solution

was stirred for 1.5 h at Ϫ50 °C. Subsequently, equimolar amounts

of the appropriate ammonium salt and triethylamine were added

at Ϫ78 °C. The reaction mixture was warmed slowly to room tem-

perature and was stirred for 16 h. The reaction mixture was washed

with saturated sodium hydrogen carbonate solution (3 ϫ 30 mL),

dried with sodium sulfate, and the solvent removed in vacuo.

4-Methoxy-N-[(4-methoxyphenyl)(pyrrolidin-1-yl)methylene]-

benzamide (2c): Following method B 2c was prepared from 1c

(6.12 g, 30.0 mmol) and 4-methoxybenzoyl chloride (4.1 mL,

30.0 mmol). The crude product was purified by column chromatog-

raphy (SiO₂) using tert-butyl methyl ether as eluent (R_fϭ 0.08).

Yield 5.80 g (57%), colorless solid; m.p. 110 °C. IR (KBr): ν˜ ϭ

3070 (m, CH_arom.), 2972 (s, CH_aliph.), 2878 (m, CH_aliph.), 2837 (m,

CH_aliph.), 1728 (m), 1607 (vs, CϭO/CϭN), 1516 (vs, CϭC), 1458

(vs), 1364 (m), 1339 (s), 1283 (vs), 1248 (vs), 1205 (s), 1178 (vs),

1153 (vs), 1069 (s), 1028 (vs), 933 (m), 848 (s), 783 (s), 766 (s), 700

N-(1-Phenylethyl)-NЈ-[(phenyl)(pyrrolidin-1-yl)methylene]benz-

amidine Hydrotrifluoromethanesulfonate (5a): Following the general

procedure (method A) 5a was prepared from 2a (5.56 g,

20.0 mmol),

trifluoromethanesulfonic

anhydride

(3.4 mL,

20.0 mmol) and -1-phenylethylamine (2.6 mL, 20.0 mmol) in dry

dichloromethane (60 mL). The crude product was purified by crys-

tallization from dichloromethane/petroleum ether. Yield 5.73 g

(54%), colorless crystals; m.p. 194 °C. IR (KBr): ν˜ ϭ 3258 (s, NH),

3065 (m, CH_arom.), 2990 (m, CH_aliph.), 2888 (w, CH_aliph.), 1584 (vs,

CϭN), 1539 (vs, CϭC), 1459 (vs), 1339 (s), 1280 (vs), 1256 (vs),

(m) cm^Ϫ^{1 1}H NMR (300.13 MHz, CDCl₃): δ ϭ 1.94 (br. s, 4 H,

.

NCH₂CH₂), 3.33Ϫ3.63 (m, 4 H, NCH₂CH₂), 3.77 (s, 3 H, OCH₃),

3.83 (s, 3 H, OCH₃), 6.81Ϫ6.88 (m, 4 H, CH_arom.), 7.24 (m, 2 H,

CH_arom.), 8.04 (m, 2 H, o-CH_arom.) ppm. ¹³C NMR (75.47 MHz,

CDCl₃): δ ϭ 24.6, 25.7 (NCH₂CH₂), 48.1, 49.6 (NCH₂CH₂), 55.0,

55.2 (OCH₃), 112.9, 113.7 (m-C_arom.), 127.5 (i-C_arom.), 128.7

(o-C_arom.), 129.0 (i-C_arom.), 131.3 (o-C_arom.), 160.2, 162.1 (i-COCH₃),

162.7 (CϭN), 176.0 (CϭO) ppm. MS (EI, 70 eV): m/z (%) ϭ 338

(60) [M^ϩ], 269 (20), 231 (10) [M^ϩϪ PhOMe], 136 (23), 135 (90)

[MeOPhCO^ϩ], 134 (35), 107 (8) [PhOMe^ϩ], 77 (13) [Ph^ϩ], 70 (100)

[(CH₂)₄N^ϩ]. C₂₀H₂₂N₂O₃(338.40): calcd. C 70.99, H 6.55, N 8.28;

found C 70.85, H 6.36, N 8.28.

1157 (vs), 1029 (vs), 774 (s), 709 (s), 643 (s) cm^Ϫ^{1 1}H NMR

.

(300.13 MHz, CD₃CN): δ ϭ 1.68 (d, ³J ϭ 6.9 Hz, 3 H, CH₃),

2.08Ϫ2.14 (m, 4 H, NCH₂CH₂), 3.38 (m, 1 H, NCH₂CH₂), 3.55

(m, 1 H, NCH₂CH₂), 3.77 (m, 1 H, NCH₂CH₂), 3.91 (m, 1 H,

NCH₂CH₂), 5.40 (q, ³J ϭ 6.9 Hz, 1 H, CH), 6.54 (m, 2 H, CH_arom.),

7.01 (m, 2 H, CH_arom.), 7.15Ϫ7.27 (m, 5 H, CH_arom.), 7.39 (m, 2 H,

CH_arom.), 7.44Ϫ7.55 (m, 4 H, CH_arom.), 8.30 (br. s, 1 H, NH) ppm.

¹³C NMR (75.47 MHz, CD₃CN): δ ϭ 22.0 (CH₃), 25.1, 26.5

(NCH₂CH₂), 51.3, 53.1 (NCH₂CH₂), 55.0 (CH), 127.9, 128.7,

128.8, 129.1, 129.2, 129.6, 129.9 (o-, m-, p-C_arom.), 132.0, 133.2 (p-

C_arom.), 134.1, 134.5, 144.1 (i-C_arom.), 168.1, 168.5 (CϭN) ppm. MS

(R)-N-{[2-(Methoxymethyl)pyrrolidin-1-yl]phenylmethylene}-

benzamide (2d): Following method B 2d was prepared from 1d

(3.93 g, 18.0 mmol) and benzoyl chloride (2.1 mL, 18.0 mmol). The

crude product was purified by column chromatography (SiO₂)

using tert-butyl methyl ether/petroleum ether (1:1) as eluent (R_fϭ

0.11). Yield 4.12 g (71%), colorless oil. IR (film): ν˜ ϭ 3059 (m,

CH_arom.), 3028 (m, CH_arom.), 2974 (s, CH_aliph.), 2928 (s, CH_aliph.),

(EI, 70 eV): m/z (%) ϭ 382 (23) [M Ϫ F₃CSO₃^Ϫ], 381 (45) [M^ϩ

F₃CSO₃H], 366 (25) [M^ϩ

F₃CSO₃H CH₃], 276 (5)

Ϫ

[(CH₂)₄NPhCNPhCN^ϩ], 207 (100) [PhCNPhCNH^ϩ], 194 (12), 158

(12), 105 (54) [PhCHCH₃^ϩ], 104(50) [PhCNH^ϩ], 70 (12)

[(CH₂)₄N^ϩ]. C₂₇H₂₈F₃N₃O₃S (531.58): calcd. C 61.00, H 5.31,

N 7.90; found C 61.00, H 5.20, N 7.76.

2878 (s, CH_aliph.), 2827 (s, CH_aliph.), 1678 (s, CϭO/CϭN), 1632 (vs, X-ray Crystal Structure Analysis of 5a: formula C₂₆H₂₈N₃·CF₃SO₃,

CϭO/CϭN), 1539 (vs, CϭC), 1456 (vs), 1337 (s), 1310 (vs), 1277

M ϭ 531.58, colorless crystal, 0.35 ϫ 0.25 ϫ 0.10 mm, a ϭ

˚

(vs), 1161 (s), 1113 (vs), 1059 (vs), 1024 (s), 974 (m), 927 (m), 802

25.279(1), b ϭ 11.379(1), c ϭ 19.037(1) A, β ϭ 105.13(1)°, V ϭ

3

(s), 777 (vs), 723 (vs), 702 (vs) cm^Ϫ1

.

¹H NMR (300.13 MHz,

5286.2(6) A , ρ_calcd.ϭ 1.336 g·cm^Ϫ3, µ ϭ 15.65 cm^Ϫ1, empirical

˚

CDCl₃): δ ϭ 1.97Ϫ2.09 (m, 4 H, NCH₂CH₂), 3.20 (s, 3 H, OCH₃), absorption correction (0.610 Յ T Յ 0.859), Z ϭ 8, monoclinic,

˚

3.30Ϫ3.50 (m, 4 H, NCH₂, OCH₂), 4.67 (m, 1 H, NCH), 7.25Ϫ7.42 space group C2/c (No. 15), λ ϭ 1.54178 A, T ϭ 223 K, ω and

(m, 8 H, CH_arom.), 8.03 (m, 2 H, CH_arom.) ppm. ¹³C NMR scans, 13421 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.59

(75.47 MHz, CDCl₃): δ ϭ 24.3, 27.9 (NCH₂CH₂), 50.5 (NCH₂),

^Ϫ1, 4427 independent (R_intϭ 0.041) and 3184 observed reflec-

˚

A

58.0 (OCH₃), 59.0 (NCH), 72.3 (OCH₂), 127.1, 127.7 (o-, m-C_arom.), tions [I Ն 2σ(I)], 340 refined parameters, R ϭ 0.045, wR²ϭ 0.110,

128.1 (p-C_arom.), 128.2, 129.3 (o-, m-C_arom.), 131.2 (p-C_arom.), 135.3, max. residual electron density 0.41 (Ϫ0.28) e·A^Ϫ3, hydrogen at N3

˚

2576

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Eur. J. Org. Chem. 2004, 2567Ϫ2581

Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

FULL PAPER

from difference Fourier map, other hydrogens calculated and all

refined as riding atoms.

was prepared from 2a (2.78 g, 10.0 mmol), trifluoromethanesul-

fonic anhydride (1.7 mL, 10.0 mmol), 2,2,2-trifluoroethylamine hy-

drochloride (1.21 g, 10.0 mmol) and triethylamine (1.4 mL,

10.0 mmol) in dry dichloromethane (30 mL). The crude product

was purified by column chromatography (SiO₂) using n-pentane/

triethylamine (20:1) as eluent (R_fϭ 0.17). Yield 1.83 g (51%), color-

less crystals; m.p. 134 °C. IR (KBr): ν˜ ϭ 3053 (m, CH_arom.), 3024

(m, CH_arom.), 2972 (s, CH_aliph.), 2949 (s, CH_aliph.), 2878 (s, CH_aliph.),

1616 (vs, CϭN), 1522 (vs, CϭC), 1458 (vs), 1441 (vs), 1348 (vs),

1308 (vs), 1288 (vs, CF), 1204 (s), 1059 (s), 1024 (s), 947 (s), 922

N-Benzyl-NЈ-[(phenyl)(pyrrolidin-1-yl)methylene]benzamidine (5b):

Following the general procedure (method A) 5b was prepared from

2a (5.56 g, 20.0 mmol), trifluoromethanesulfonic anhydride

(3.4 mL, 20.0 mmol) and benzylamine (2.2 mL, 20.0 mmol) in dry

dichloromethane (60 mL). The crude product was purified by col-

umn chromatography (SiO₂) using tert-butyl methyl ether/n-pen-

tane/triethylamine (10:10:1) as eluent (R_fϭ 0.20). Yield 3.45 g

(47%), pale-yellow oil. IR (film): ν˜ ϭ 3061 (m, CH_arom.), 3026 (m,

CH_arom.), 2976 (s, CH_aliph.), 2878 (m, CH_aliph.), 1622 (vs, CϭN),

1502 (s, CϭC), 1463 (s), 1253 (s), 1155 (s), 1061 (m), 1030 (s), 939

(s), 804 (s), 781 (vs), 744 (s), 719 (vs), 704 (vs) cm^{Ϫ1 1}H NMR

.

(400.13 MHz, CDCl₃): δ ϭ 1.89 (s, 4 H, NCH₂CH₂), 3.13Ϫ3.58

3

(br. m, 4 H, NCH₂CH₂), 3.82 (q, J_H,Fϭ 10.2 Hz, 2 H, CH₂CF₃),

(m), 849 (m), 766 (s), 710 (s) cm^{Ϫ1 1}H NMR (300.13 MHz,

.

6.82 (m, 2 H, CH_arom.), 7.02Ϫ7.14 (m, 6 H, CH_arom.), 7.50 (m, 2

CDCl₃): δ ϭ 1.99 (s, 4 H, NCH₂CH₂), 3.28 (br. s, 2 H, NCH₂CH₂),

3.76 (br. s, 2 H, NCH₂CH₂), 4.62 (s, 2 H, CH₂), 6.66 (m, 1 H,

CH_arom.), 7.00 (m, 2 H, CH_arom.), 7.10Ϫ7.20 (m, 3 H, CH_arom.),

7.25Ϫ7.35 (m, 5 H, CH_arom.), 7.37Ϫ7.42 (m, 3 H, CH_arom.), 8.05

(m, 1 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 24.6,

25.8 (NCH₂CH₂), 48.2, 49.6 (NCH₂CH₂), 50.4 (CH₂), 126.7, 126.9,

127.0, 127.7, 127.8, 128.0, 128.1, 128.2, 128.3 (o-, m-, p-C_arom.),

134.4, 136.7, 139.7 (i-C_arom.), 162.0, 166.2 (CϭN) ppm. MS (EI,

70 eV): m/z (%) ϭ 367 (51) [M^ϩ], 297 (12) [M^ϩϪ (CH₂)₄N], 194

(27) [PhCNCH₂Ph^ϩ], 193 (100), 104 (26) [PhCNH^ϩ], 91 (79)

[PhCH₂^ϩ], 70 (14) [(CH₂)₄N^ϩ]. C₂₅H₂₅N₃(M ϭ 367.49)

H, CH_arom.) ppm. ¹³C NMR (100.61 MHz, CDCl₃): δ ϭ 25.4 (br.,

2

NCH₂CH₂), 47.8, 49.5 (br., NCH₂CH₂), 51.8 (q, J_C,Fϭ 30.5 Hz,

1

CH₂CF₃), 117.3 (q, J_C,Fϭ 336.5 Hz, CF₃), 126.5, 127.5, 127.7,

128.3 (o-, m-C_arom.), 129.1, 129.2 (p-C_arom.), 135.2, 139.3 (i-C_arom.),

158.4, 166.3 (CϭN) ppm. ¹⁹F NMR (282.37 MHz, CDCl₃): δ ϭ

3

Ϫ71.3 (t, J_F,Hϭ 9.5 Hz, CF₃) ppm. MS (EI, 70 eV): m/z (%) ϭ

359 (60) [M^ϩ], 290 (26) [M^ϩϪ CF₃], 186 (78) [PhCNCH₂CF₃^ϩ],

104 (100) [PhCNH^ϩ], 77 (16) [Ph^ϩ], 70 (40) [(CH₂)₄N^ϩ].

C₂₀H₂₀F₃N₃(359.39): calcd. C 66.84, H 5.61, N 11.69; found

C 66.86, H 5.27, N 11.63.

From the crude reaction mixture a small crystal of the correspond-

ing triflate was isolated, which was subjected to X-ray analysis.

N-Benzhydryl-NЈ-[phenyl(pyrrolidin-1-yl)methylene]benzamidine

(5c): Following the general procedure (method A) 5c was prepared

from 2a (5.56 g, 20.0 mmol), trifluoromethanesulfonic anhydride

(3.4 mL, 20.0 mmol) and α-aminodiphenylmethane (3.4 mL,

20.0 mmol) in dry dichloromethane (60 mL). The crude product

was purified by column chromatography (SiO₂) using n-pentane/

triethylamine (20:1) as eluent (R_fϭ 0.17). Yield 4.47 g (50%), color-

less crystals; m.p. 137 °C. IR (KBr): ν˜ ϭ 3059 (m, CH_arom.), 3022

(m, CH_arom.), 2976 (s, CH_aliph.), 2868 (m, CH_aliph.), 2854 (w,

CH_aliph.), 1610 (s, CϭN), 1584 (vs, CϭN), 1489 (s, CϭC), 1452

(vs), 1441 (vs), 1342 (s), 1296 (s), 1097 (m), 1069 (s), 1028 (m), 916

X-ray Crystal Structure Analysis of 5d·CF₃SO₃H: Formula

C₂₀H₂₁F₃N₃·CF₃SO₃, M ϭ 509.47, colorless crystal, 0.50 ϫ 0.50

˚

ϫ 0.25 mm, a ϭ 12.593(1), b ϭ 14.028(1), c ϭ 14.326(1) A, β ϭ

3

108.77(1)°, V ϭ 2396.2(3) A , ρ_calcd.ϭ 1.412 g·cm^Ϫ3, µ ϭ 18.85

˚

cm^Ϫ1, empirical absorption correction by ψ scan data (0.453 Յ T

Յ 0.650), Z ϭ 4, monoclinic, space group P2₁/n (No. 14), λ ϭ

˚

1.54178 A, T ϭ 223 K, ω/2θ scans, 5076 reflections collected (Ϯh,

ϩk, ϩl), [(sinθ)/λ] ϭ 0.62 A^Ϫ1, 4882 independent (R_intϭ 0.028)

˚

and 4229 observed reflections [I Ն 2σ(I)], 313 refined parameters,

(m), 850 (m), 771 (s), 743 (s), 698 (vs) cm^Ϫ1

.

¹H NMR

R ϭ 0.043, wR²ϭ 0.130, max. residual electron density 0.24

(300.13 MHz, CDCl₃): δ ϭ 1.90 (s, 4 H, NCH₂CH₂), 3.37 (br. s, 4

H, NCH₂CH₂), 6.16 (s, 1 H, CHPh₂), 6.44 (m, 2 H, CH_arom.), 6.82

(m, 2 H, CH_arom.), 6.96 (m, 1 H, p-CH_arom.), 7.05Ϫ7.17 (m, 5 H,

CH_arom.), 7.19Ϫ7.24 (m, 4 H, CH_arom.), 7.42 (m, 4 H, CH_arom.), 7.59

(m, 2 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 25.5

(NCH₂CH₂), 48.3 (NCH₂CH₂), 65.4 (CH), 126.0, 126.8, 127.3,

127.6, 127.8, 127.9, 128.2, 128.4 (o-, m-, p-C_arom.), 135.2, 140.7,

145.9 (i-C_arom.), 158.1, 162.2 (CϭN) ppm. MS (EI, 70 eV): m/z

(%) ϭ 443 (57) [M^ϩ], 373 (12) [M^ϩϪ (CH₂)₄N], 270 (35)

[PhCNCHPh₂^ϩ], 269 (100), 167 (50) [CHPh₂^ϩ], 166 (53), 165 (54),

159 (29) [(CH₂)₄NCPh^ϩ], 104 (24) [PhCNH^ϩ], 70 (11) [(CH₂)₄N^ϩ].

C₃₁H₂₉N₃(443.57): calcd. C 83.94, H 6.59, N 9.47; found C 83.60,

H 6.56, N 9.44.

(Ϫ0.33) e·A^Ϫ3, hydrogen at N4 from difference Fourier map, others

˚

calculated and all refined as riding atoms.

N-[(Phenyl)(pyrrolidin-1-yl)methylene]-NЈ-(2,2,2-trifluoro-1-phenyl-

ethyl)benzamidine (5e): Following the general procedure (method

B) 5e was prepared from 2a (2.78 g, 10.0 mmol), trifluoromethane-

sulfonic anhydride (1.7 mL, 10.0 mmol), 2,2,2-trifluoro-1-phenyl-

ethylamine hydrochloride (2.18 g, 10.0 mmol) and triethylamine

(1.4 mL, 10.0 mmol) in dry dichloromethane (30 mL). The crude

product was purified by column chromatography (SiO₂) using n-

pentane/triethylamine (25:1) as eluent (R_fϭ 0.13). Yield 2.46 g

(57%), colorless crystals; m.p. 152 °C. IR (KBr): ν˜ ϭ 3053 (m,

CH_arom.), 3030 (m, CH_arom.), 2966 (m, CH_aliph.), 2928 (m, Ch_aliph.),

2868 (m, CH_aliph.), 1602 (s, CϭN), 1555 (vs, CϭN), 1499 (s, Cϭ

C), 1452 (vs), 1342 (s), 1250 (s, CF), 1161 (s), 1113 (s), 775 (m),

708 (s), 696 (s) cm^Ϫ1. ¹H NMR (300.13 MHz, CDCl₃): δ ϭ 1.93 (s,

4 H, NCH₂CH₂), 2.90Ϫ3.80 (br. m, 4 H, NCH₂CH₂), 5.49 (q,

³J_H,Fϭ 8.3 Hz, 1 H, CHCF₃), 6.27 (m, 2 H, CH_arom.), 6.85 (m, 2

H, CH_arom.), 7.00 (m, 1 H, CH_arom.), 7.05Ϫ7.14 (m, 3 H, CH_arom.),

7.28Ϫ7.36 (m, 3 H, CH_arom.), 7.40 (m, 2 H, CH_arom.), 7.55 (m, 2

H, CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 25.4 (br.,

X-ray Crystal Structure Analysis of 5c: Formula C₃₁H₂₉N₃, M ϭ

443.57, colorless crystal, 0.25 ϫ 0.15 ϫ 0.10 mm, a ϭ 10.415(1),

˚

b ϭ 13.133(1), c ϭ 18.964(1) A, β ϭ 104.72(1)°, V ϭ 2508.8(3)

3

A , ρ_calcd.ϭ 1.174 g·cm^Ϫ3, µ ϭ 0.69 cm^Ϫ1, empirical absorption

˚

correction (0.983 Յ T Յ 0.993), Z ϭ 4, monoclinic, space group

˚

P2₁/c (No. 14), λ ϭ 0.71073 A, T ϭ 198 K, ω and scans, 15257

reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.67 A^Ϫ1, 6174 inde-

˚

pendent and 3384 observed reflections [I Ն 2σ(I)], 307 refined par-

2

NCH₂CH₂), 47.6 (br., NCH₂CH₂), 64.3 (q, J_C,Fϭ 28.0 Hz,

ameters, R ϭ 0.058, wR²ϭ 0.111, max. residual electron density

1

CHCF₃), 117.4 (q, J_C,Fϭ 337.0 Hz, CF₃), 126.7, 127.4, 127.7,

0.16 (Ϫ0.22) e·A^Ϫ3, hydrogens calculated and refined as riding

˚

127.9 (o-, m-C_arom.), 128.0 (p-C_arom.), 128.1 (o-, m-C_arom.), 128.7,

128.8 (p-C_arom.), 129.7 (o-, m-C_arom.), 135.2, 137.1, 140.3 (i-C_arom.),

159.2, 166.4 (CϭN) ppm. ¹⁹F NMR (282.37 MHz, CDCl₃): δ ϭ

atoms.

N-[(Phenyl)(pyrrolidin-1-yl)methylene]-NЈ-(2,2,2-trifluoroethyl)-

benzamidine (5d): Following the general procedure (method B) 5d

3

Ϫ74.1 (d, J_F,Hϭ 9.5 Hz, CF₃) ppm. MS (EI, 70 eV): m/z (%) ϭ

Eur. J. Org. Chem. 2004, 2567Ϫ2581

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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2577

N. Habersaat, R. Fröhlich, E.-U. Würthwein

FULL PAPER

435 (87) [M^ϩ], 366 (44) [M^ϩϪ CF₃], 261 (96), 194 (49), 159 (100) (m), 1246 (m), 1175 (m), 1033 (m), 771 (m), 698 (s) cm^Ϫ1. ¹H NMR

3

[PhCHCF₃^ϩ], 131 (18), 109 (58), 104 (78) [PhCNH^ϩ], 91 (30), 70 (300.13 MHz, CDCl₃): δ ϭ 0.99 (d, J ϭ 6.7 Hz, 6 H, CH(CH₃)₂],

(38) [(CH₂)₄N^ϩ]. C₂₆H₂₄F₃N₃(435.48): calcd. C 71.71, H 5.55, 1.27 (t, ³J ϭ 6.9 Hz, 3 H, OCH₂CH₃), 1.94 (s, 4 H, NCH₂CH₂),

N 9.65; found C 71.37, H 5.35, N 9.37.

2.23 [m, 1 H, CH(CH₃)₂], 3.43 (br. s, 4 H, NCH₂CH₂), 4.06 (d,

³J ϭ 7.6 Hz, 1 H, CHCH(CH₃)₂], 4.18 (q, ³J ϭ 7.2 Hz, 2 H,

OCH₂CH₃), 6.92 (m, 2 H, CH_arom.), 7.04Ϫ7.15 (m, 6 H, CH_arom.),

7.47 (m, 2 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ

14.4 (OCH₂CH₃), 19.3, 19.5 [CH(CH₃)₂], 25.4 (br., NCH₂CH₂),

32.7 [CH(CH₃)₂], 48.2 (br., NCH₂CH₂), 59.8 [CHCH(CH₃)₂], 68.6

(OCH₂CH₃), 126.9, 127.2, 128.0 (o-, m-C_arom.), 128.5, 128.7

(p-C_arom.), 135.4, 140.4 (i-C_arom.), 157.8, 164.8 (CϭN), 173.7

(COOEt) ppm. MS (EI, 70 eV): m/z (%) ϭ 405 (30) [M^ϩ], 362 (100)

[M^ϩϪ iPr], 332 (84) [M^ϩϪ COOEt], 158 (45), 104 (42)

[PhCNH^ϩ]. C₂₅H₃₁N₃O₂(405.54): calcd. C 74.04, H 7.70, N 10.36;

found C 73.33, H 8.02, N 10.12.

X-ray Crystal Structure Analysis of 5e: Formula C₂₆H₂₄F₃N₃, M ϭ

435.48, colorless crystal, 0.40 ϫ 0.25 ϫ 0.10 mm, a ϭ 8.792(1), b ϭ

3

˚

9.332(1), c ϭ 27.193(1) A, β ϭ 93.52(1)°, V ϭ 2226.9(4) A ,

ρ

_calcd.ϭ 1.299 g·cm^Ϫ3, µ ϭ 7.84 cm^Ϫ1, empirical absorption correc-

tion (0.744 Յ T Յ 0.926), Z ϭ 4, monoclinic, space group P2₁/c

˚

(No. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω and scans, 14645 reflec-

tions collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.59 A^Ϫ1, 3779 indepen-

˚

dent (R_intϭ 0.054) and 2618 observed reflections [I Ն 2σ(I)], 290

refined parameters, R ϭ 0.043, wR²ϭ 0.119, max. residual electron

density 0.21 (Ϫ0.17) e·A^Ϫ3, hydrogens calculated and refined as

˚

riding atoms.

Ethyl

(S)-2-[({Phenyl[(phenyl)(pyrrolidin-1-yl)methylene]amino}-

(R,R)-N-{[(2-Methoxymethyl)pyrrolidin-1-yl](phenyl)methylene}-NЈ-

(1-phenylethyl)benzamidine (5h): Following the general procedure

(method A) 5a was prepared from 2d (3.74 g, 11.6 mmol), trifluoro-

methylene)amino]propionate (5f): Following the general procedure

(method B) 5f was prepared from 2a (5.56 g, 20.0 mmol), trifluoro-

methanesulfonic anhydride (3.4 mL, 20.0 mmol), ethyl -alaninate methanesulfonic anhydride (2.0 mL, 11.6 mmol) and (R)-1-phenyl-

hydrochloride (3.07 g, 20.0 mmol) and triethylamine (2.8 mL, ethylamine (1.5 mL, 11.6 mmol) in dry dichloromethane (40 mL).

20.0 mmol) in dry dichloromethane (60 mL). The crude product

The crude product was purified by column chromatography (SiO₂)

was purified by column chromatography (SiO₂) using n-pentane/

using n-pentane/triethylamine (20:1) as eluent (R_fϭ 0.25). Yield

triethylamine (10:1) as eluent (R_fϭ 0.13). Yield 3.40 g (45%), color- 0.70 g (14%), colorless oil. IR (film): ν˜ ϭ 3059 (m, CH_arom.), 3024

less crystals; m.p. 101 °C. IR (KBr): ν˜ ϭ 3061 (m, CH_arom.), 2980 (m, CH_arom.), 2968 (s, CH_aliph.), 2924 (s, CH_aliph.), 2874 (s, CH_aliph.),

(m, CH_aliph.), 2881 (m, CH_aliph.), 1740 (s, CϭO), 1533 (vs, CϭN), 1722 (m), 1609 (vs, CϭN), 1591 (vs, CϭN), 1574 (vs, CϭN), 1493

1452 (s), 1339 (s), 1275 (s), 1157 (s), 1032 (s), 735 (m), 698 (m)

(s, CϭC), 1447 (s), 1423 (s), 1310 (s), 1281 (s), 1113 (s), 1055 (s),

1

3

cm^Ϫ1. H NMR (300.13 MHz, CDCl₃): δ ϭ 1.28 (t, J ϭ 7.2 Hz, 1026 (s), 756 (s), 723 (s), 700 (vs) cm^Ϫ1

.

¹H NMR (300.13 MHz,

3 H, OCH₂CH₃), 1.44 (d, ³J ϭ 6.7 Hz, 3 H, CHCH₃), 1.94 (s, 4 H,

CDCl₃): δ ϭ 1.33 (d, J ϭ 5.0 Hz, 3 H, CHCH₃), 1.70Ϫ2.10 (m, 4

3

NCH₂CH₂), 3.30Ϫ3.70 (br. m, 4 H, NCH₂CH₂), 4.18 (q, ³J ϭ H, NCH₂CH₂CH₂), 3.07 (s, 3 H, OCH₃), 3.10Ϫ3.70 (m, 4 H,

3

7.2 Hz, 2 H, OCH₂CH₃), 4.54 (q, J ϭ 6.7 Hz, 1 H, CHCH₃), 6.93

OCH₂, NCH₂), 4.55 (m, 1 H, NCH), 4.92 (q, ³J ϭ 5.0 Hz, 1 H,

(m, 2 H, CH_arom.), 7.07Ϫ7.14 (m, 6 H, CH_arom.), 7.44 (m, 2 H, CHCH₃), 6.83 (m, 2 H, CH_arom.), 6.96 (m, 1 H, CH_arom.), 7.02Ϫ7.07

CH_arom.

)

ppm. ¹³C NMR (75.47 MHz, CDCl₃):

δ

ϭ

14.3

(m, 3 H, CH_arom.), 7.10Ϫ7.25 (m, 5 H, CH_arom.), 7.40 (m, 4 H,

(OCH₂CH₃), 18.8 (CHCH₃), 25.4 (br., NCH₂CH₂), 48.0 (br., CH_arom.) ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 24.5 (CH₃),

NCH₂CH₂), 57.2 (CHCH₃), 60.1(OCH₂CH₃), 126.9, 127.3, 127.7, 26.5, 28.2 (NCH₂CH₂CH₂), 46.3 (NCH₂), 56.9 (OCH₃), 57.1, 59.0

127.9 (o-, m-C_arom.), 128.5, 128.8 (p-C_arom.), 135.3, 140.2 (i-C_arom.), (CH), 72.8 (OCH₂), 125.9 (p-C_arom.), 126.9, 127.2, 127.4, 127.5,

158.2, 164.3 (CϭN), 175.0 (COOEt) ppm. MS (EI, 70 eV): m/z

(%) ϭ 377 (34) [M^ϩ], 304 (100) [M^ϩϪ COOEt], 176 (10), 132 (15), 147.4 (i-C_arom.), 158.1, 161.7 (CϭN) ppm. MS (EI, 70 eV): m/z

130 (20), 104 (20) [PhCNH^ϩ]. C₂₃H₂₇N₃O₂(377.48): calcd. C 73.18, (%) ϭ 425 (48) [M^ϩ], 410 (19) [M^ϩϪ CH₃], 320 (7) [M^ϩ

127.6, 128.0 (o-, m-C_arom.), 128.3, 128.5 (p-C_arom.), 135.2, 140.7,

Ϫ

H 7.21, N 11.13; found C 73.08, H 7.32, N 11.16.

PhCHCH₃], 207 (100) [PhCNPhCNH^ϩ], 194 (11), 105 (70)

[PhCHCH₃^ϩ]. C₂₈H₃₁N₃O (425.57): calcd. C 79.02, H 7.34, N 9.87;

found C 78.41, H 7.79, N 9.22.

X-ray Crystal Structure Analysis of 5f: Formula C₂₃H₂₇N₃O₂, M ϭ

377.48, light yellow crystal, 0.30 ϫ 0.15 ϫ 0.10 mm, a ϭ 8.974(1),

3

˚

b ϭ 14.361(1), c ϭ 16.272(1) A, V ϭ 2097.1(3) A , ρ_calcd.

ϭ

Ethyl 2,5-Diphenyl-3H-imidazole-4-carboxylate (7a): Following the

general procedure (method B) 7a was prepared from 2a (5.56 g,

1.196 g·cm^Ϫ3, µ ϭ 0.77 cm^Ϫ1, empirical absorption correction

(0.977 Յ T Յ 0.992), Z ϭ 4, orthorhombic, space group P2₁2₁2₁

20.0 mmol),

trifluoromethanesulfonic

anhydride

(3.4 mL,

˚

(No. 19), λ ϭ 0.71073 A, T ϭ 198 K, ω and scans, 13808 reflec-

20.0 mmol), ethyl glycinate hydrochloride (2.77 g, 20.0 mmol) and

triethylamine (2.8 mL, 20.0 mmol) in dry dichloromethane

(60 mL). The crude product was purified by recrystallization from

acetonitrile. Yield 4.21 g (72%), colorless solid; m.p. 168 °C (ref.^[33]

166Ϫ167.5 °C). IR (KBr): ν˜ ϭ 3053 (m, CH_arom.), 2957 (m, CH_aliph.),

2901 (m, CH_aliph.), 1713 (vs, CϭO), 1583 (m, CϭN), 1531 (m,

CϭN), 1491 (s, CϭC), 1383 (s), 1312 (s), 1236 (s), 1130 (vs), 1022

(s), 966 (s), 781 (m), 717 (s), 692 (s) cm^Ϫ1. ¹H NMR (300.13 MHz,

tions collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.66 A^Ϫ1, 4901 indepen-

˚

dent (R_intϭ 0.045) and 3343 observed reflections [I Ն 2σ(I)], 255

refined parameters, R ϭ 0.055, wR²ϭ 0.125, max. residual electron

density 0.22 (Ϫ0.17) e·A^Ϫ3, hydrogens calculated and refined as

˚

riding atoms.

Ethyl

(S)-3-Methyl-2-[({phenyl[(phenyl)pyrrolidin-1-ylmethylene]-

amino}methylene)amino]butanoate (5g): Following the general pro-

cedure (method B) 5g was prepared from 2a (2.78 g, 10.0 mmol),

trifluoromethanesulfonic anhydride (1.7 mL, 10.0 mmol), ethyl -

3

[D₆]DMSO): δ ϭ 1.24 (t, J ϭ 6.9 Hz, 3 H, OCH₂CH₃), 4.25 (q,

³J ϭ 6.9 Hz, 2 H, OCH₂CH₃), 7.37Ϫ7.52 (m, 6 H, CH_arom.), 7.83

valinate hydrochloride (1.82 g, 10.0 mmol) and triethylamine (m, 2 H, CH_arom.), 8.18 (m, 2 H, CH_arom.), 13.08 (s, 1 H, NH) ppm.

(1.4 mL, 10.0 mmol) in dry dichloromethane (30 mL). The crude

product was purified by column chromatography (SiO₂) using n-

pentane/triethylamine (20:1) as eluent (R_fϭ 0.18). Yield 2.32 g

¹³C NMR (75.47 MHz, [D₆]DMSO): δ ϭ 14.0 (CH₃), 59.8 (OCH₂),

126.0, 127.6, 128.2, 128.6, 129.1, 129.4, 129.5, 131.8 (o-, m-, p-, i-

C_arom., C_imidazol.), 146.9 (NCN), 161.3 (COOEt) ppm. MS (EI,

(57%), pale-yellow oil. IR (film): ν˜ ϭ 3061 (w, CH_arom.), 2968 (s, 70 eV): m/z (%) ϭ 292 (100) [M^ϩ], 246 (93) [M^ϩϪ EtOH], 218

CH_aliph.), 2871 (m, CH_aliph.), 1730 (s, CϭO), 1609 (vs, CϭN), 1587 (33) [M^ϩϪ HCOOEt], 115 (38), 89 (42). C₁₈H₁₆N₂O₂(292.33):

(vs, CϭN), 1568 (vs, CϭN), 1448 (s), 1340 (m), 1310 (m), 1283

calcd. C 73.95, H 5.52, N 9.58; found C 73.66, H 5.26, N 9.60.

2578

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjoc.org

Eur. J. Org. Chem. 2004, 2567Ϫ2581

Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

FULL PAPER

2,4,5-Triphenyl-1H-imidazole (7b): Following the general procedure

(method B) 7b was prepared from 2a (5.56 g, 20.0 mmol), trifluoro-

methanesulfonic anhydride (3.4 mL, 20.0 mmol), ethyl -phenyl- 8.727(2), c ϭ 11.191(1) A, β ϭ 109.31(1)°, V ϭ 1010.1(3) A ,

X-ray Crystal Structure Analysis of 6b: C₂₇H₁₈N₂, M ϭ 370.45,

colorless crystal, 0.35 ϫ 0.20 ϫ 0.05 mm, a ϭ 10.959(1), b ϭ

3

˚

glycinate hydrogen p-toluenesulfonate (7.02 g, 20.0 mmol) and tri-

ρ_calcd.ϭ 1.218 g·cm^Ϫ3, µ ϭ 5.51 cm^Ϫ1, no absorption correction

ethylamine (2.8 mL, 20.0 mmol) in dry dichloromethane (60 mL). (0.830 Յ T Յ 0.973), Z ϭ 2, monoclinic, space group P2₁(No. 4),

˚

The crude product was purified by recrystallization from aceto-

nitrile. Yield 2.53 g (43%), colorless solid; m.p. 278 °C (ref.^[34]

278Ϫ279 °C). IR (KBr): ν˜ ϭ 3045 (m, CH_arom.), 2966 (m, CH_aliph.),

λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2301 reflections collected

(Ϯh, ϩk, Ϫl), [(sinθ)/λ] ϭ 0.62 A^Ϫ1, 2191 independent (R_int

ϭ

˚

0.031) and 1542 observed reflections [I Ն 2σ(I)], 263 refined param-

2853 (m, CH_aliph.), 1601 (m, CϭN), 1587 (m, CϭN), 1489 (s, Cϭ eters, R ϭ 0.069, wR²ϭ 0.214, max. residual electron density 0.45

C), 1460 (s, CϭC), 1396 (m), 1202 (w), 1128 (m), 1070 (m), 1028 (Ϫ0.37) e·A^Ϫ3, hydrogens calculated and refined as riding atoms.

˚

1

(m), 966 (m), 916 (m), 834 (m), 766 (s), 735 (s), 698 (vs) cm^Ϫ1. H

2Ј,5Ј-Bis(4-methylphenyl)spiro[9H-fluorene-9,4Ј-(4H)-imidazole]

NMR (400.14 MHz, [D₆]DMSO): δ ϭ 7.20Ϫ7.60 (m, 13 H,

(6c): Following the general procedure (method B) 6c was prepared

CH_arom.), 8.11 (m, 2 H, CH_arom.), 12.73 (s, 1 H, NH) ppm. ¹³C

NMR (100.63 MHz, [D₆]DMSO): δ ϭ 125.2, 126.5, 127.1, 127.8,

128.2, 128.3, 128.5, 128.6, 128.7, 130.4 (o-, m-, p-C_arom., C_imidazol.),

from 2b (3.06 g, 10.0 mmol), trifluoromethanesulfonic anhydride

(1.7 mL, 10.0 mmol), 9-aminofluorene hydrochloride (2.18 g,

10.0 mmol) and triethylamine (1.4 mL, 10.0 mmol) in dry dichloro-

methane (30 mL). The crude product was purified by crystallization

from chloroform/n-pentane. Yield 3.19 g (80%), colorless crystals;

m.p. 223 °C. IR (KBr): ν˜ ϭ 3018 (w, CH_arom.), 2964 (w, CH_aliph.),

2920 (w, CH_aliph.), 1610 (s, CϭN), 1593 (s, CϭN), 1558 (s, CϭN),

131.1, 135.2, 137.1 (i-C_arom.), 145.5 (NCN) ppm. MS (EI, 70 eV):

m/z (%) ϭ 296 (100) [M^ϩ], 195 (29) [M^ϩϪ H], 165 (30), 127 (30),

84 (11). C₂₁H₁₆N₂(296.37): calcd. C 85.11, H 5.44, N 9.45; found

C 84.64, H 5.48, N 9.25.

Diethyl 2,5-Diphenyl-4H-imidazole-4,4-dicarboxylate (6a): Follow-

ing the general procedure (method B) 6a was prepared from 2a

(2.78 g, 10.0 mmol), trifluoromethanesulfonic anhydride (1.7 mL,

10.0 mmol), ethyl 2-aminomalonate hydrochloride (2.12 g,

10.0 mmol) and triethylamine (1.4 mL, 10.0 mmol) in dry dichloro-

methane (30 mL). The crude product was purified by column chro-

matography (SiO₂) using tert-butyl methyl ether/n-pentane/triethyl-

amine (10:10:1) as eluent (R_fϭ 0.20). Yield 0.54 g (15%), colorless

oil. IR (film): ν˜ ϭ 3063 (w, CH_arom.), 2982 (m, CH_aliph.), 2937 (w,

CH_aliph.), 1738 (vs, CϭO), 1605 (s, CϭN), 1566 (s, CϭN), 1448 (m,

1497 (s, CϭC), 1448 (s), 1315 (s), 1279 (s), 1175 (s), 1072 (s), 1028

(m), 835 (m), 764 (vs), 733 (vs) cm^Ϫ^{1 1}H NMR (300.13 MHz,

.

CDCl₃): δ ϭ 2.21 (s, 3 H, CH₃), 2.43 (s, 3 H, CH₃), 6.89 (m, 2 H,

CH_arom.), 6.91 (m, 2 H, CH_arom.), 7.15 (m, 2 H, CH_arom.), 7.32 (m,

2 H, CH_arom.), 7.39 (m, 2 H, CH_arom.), 7.47 (m, 2 H, CH_arom.),

7.82 (m, 2 H, CH_arom.), 8.38 (m, 2 H, CH_arom.) ppm. ¹³C NMR

(75.47 MHz, CDCl₃): δ ϭ 21.5, 21.6 (CH₃), 94.1 (C_q), 121.0, 124.0,

128.3, 128.8, 129.1, 129.2, 129.3, 129.4 (o-, m-C_arom., C_fluoren.),

141.8, 141.9, 142.2, 142.8 (i-C_arom.), 175.6, 192.3 (CϭN) ppm. MS

(EI, 70 eV): m/z (%) ϭ 398 (35) [M^ϩ], 281 (100) [M^ϩϪ TolCN],

164 (44) [M^ϩϪ 2 TolCN]. C₂₉H₂₂N₂(398.49): calcd. C 87.41,

H 5.56, N 7.03; found C 87.10, H 5.65, N 6.97.

CϭC), 1323 (s), 1283 (s), 1229 (vs), 1063 (s), 733 (m), 690 (s) cm^Ϫ1

.

¹H NMR (300.13 MHz, CDCl₃): δ ϭ 1.19 (t, ³J ϭ 7.2 Hz, 6 H,

3

OCH₂CH₃), 4.23 (q, J ϭ 7.2 Hz, 4 H, OCH₂CH₃), 7.46Ϫ7.59 (m,

X-ray Crystal Structure Analysis of 6c: Formula C₂₉H₂₂N₂, M ϭ

398.49, colorless crystal, 0.30 ϫ 0.20 ϫ 0.05 mm, a ϭ 12.881(1),

6 H, CH_arom.), 8.25 (m, 2 H, CH_arom.), 8.46 (m, 2 H, CH_arom.) ppm.

¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 13.7 (OCH₂CH₃), 63.0

(OCH₂CH₃), 95.3 (C_q), 128.4, 128.5, 129.7 (o-, m-C_arom.), 130.2 (i-

˚

b ϭ 11.202(1), c ϭ 15.664(1) A, β ϭ 108.69(1)°, V ϭ 2141.0(3)

3

A , ρ_calcd.ϭ 1.236 g·cm^Ϫ3, µ ϭ 5.54 cm^Ϫ1, empirical absorption

˚

C_arom.), 130.4 (o-, m-C_arom.), 130.9 (i-C_arom.), 132.1, 132.9 (o-C_arom.),

correction (0.851 Յ T Յ 0.973), Z ϭ 4, monoclinic, space group

164.1 (COOEt), 177.9, 187.8 (CϭN) ppm. MS (EI, 70 eV): m/z

(%) ϭ 364 (19) [M^ϩ], 320 (27), 292 (100) [M^ϩϪ COOCH₂CH₂],

291 (75) [M^ϩϪ COOEt], 274 (11), 246 (99), 218 (38) [M^ϩϪ 2

COOEt], 187 (51), 127 (17), 115 (38), 105 (81), 104 (62) [PhCNH^ϩ],

89 (60), 77 (25) [Ph^ϩ]. C₂₁H₂₀N₂O₄(364.40): calcd. C 69.22, H 5.53,

N 7.69; found C 68.24, H 6.00, N 7.55.

˚

P2₁/c (No. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω and scans, 12291

reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.59 A^Ϫ1, 3575 inde-

˚

pendent (R_intϭ 0.103) and 2026 observed reflections [I Ն 2σ(I)],

281 refined parameters, R ϭ 0.060, wR²ϭ 0.138, max. residual

electron density 0.21 (Ϫ0.18) e·A^Ϫ3, hydrogens calculated and re-

˚

fined as riding atoms.

2Ј,5Ј-Diphenylspiro[9H-fluorene-9,4Ј-(4H)imidazole] (6b): Following

the general procedure (method B) 6b was prepared from 2a (2.78 g,

2Ј,5Ј-Bis(4-methoxyphenyl)spiro[9H-fluorene-9,4Ј-(4H)imidazole]

(6d): Following the general procedure (method B) 6d was prepared

from 2c (3.38 g, 10.0 mmol), trifluoromethanesulfonic anhydride

10.0 mmol),

trifluoromethanesulfonic

anhydride

(1.7 mL,

10.0 mmol), 9-aminofluorene hydrochloride (2.18 g, 10.0 mmol)

and triethylamine (1.4 mL, 10.0 mmol) in dry dichloromethane (1.7 mL, 10.0 mmol), 9-aminofluorene hydrochloride (2.18 g,

(30 mL). The crude product was purified by column chromatogra-

phy (SiO₂) using n-pentane/triethylamine (20:1) as eluent (R_fϭ

0.18). Yield 1.52 g (41%), colorless crystals; m.p. 187 °C. IR (KBr):

ν˜ ϭ 3057 (w, CH_arom.), 3007 (w, CH_arom.), 1605 (m, CϭN), 1595 (s,

CϭN), 1562 (s, CϭN), 1531 (m, CϭN), 1447 (s), 1317 (s), 1277

10.0 mmol) and triethylamine (1.4 mL, 10.0 mmol) in dry dichloro-

methane (30 mL). The crude product was purified by crystallization

from chloroform/n-pentane. Yield 3.18 g (74%), colorless crystals;

m.p. 206 °C. IR (KBr): ν˜ ϭ 3065 (w, CH_arom.), 3005 (w, CH_arom.),

2937 (w, CH_aliph.), 2833 (w, CH_aliph.), 1607(s, CϭN), 1595 (s, Cϭ

(s), 1173 (m), 1080 (s), 1059 (s), 1020 (m), 933 (m), 771 (s), 737 (s), N), 1564 (w, CϭN), 1510 (s, CϭC), 1319 (s), 1258 (vs), 1165 (s),

1

710 (vs), 689 (s) cm^Ϫ1. H NMR (300.13 MHz, CDCl₃): δ ϭ 6.90

1074 (m), 1028 (m), 835 (m), 756 (m), 727 (m) cm^{Ϫ1 1}H NMR

.

(m, 2 H, CH_arom.), 7.15 (m, 4 H, CH_arom.), 7.27 (m, 1 H, CH_arom.), (300.13 MHz, CDCl₃): δ ϭ 3.70 (s, 3 H, OCH₃), 3.89 (s, 3 H,

7.41 (m, 2 H, CH_arom.), 7.47Ϫ7.60 (m, 5 H, CH_arom.), 7.83 (m, 2 OCH₃), 6.65 (m, 2 H, CH_arom.), 6.91 (m, 2 H, CH_arom.), 7.01 (m, 2

H, CH_arom.), 8.51 (m, 2 H, CH_arom.) ppm. ¹³C NMR (75.47 MHz,

CDCl₃): δ ϭ 94.4 (C_q), 121.1, 123.9, 128.3, 128.4, 128.5, 128.7,

H, CH_arom.), 7.17 (m, 2 H, CH_arom.), 7.40 (m, 2 H, CH_arom.), 7.53

(m, 2 H, CH_arom.), 7.83 (m, 2 H, CH_arom.), 8.43 (m, 2 H, CH_arom.

)

129.3, 129.4 (o-, m-C_arom., C_fluoren.), 130.3 (i-C_arom.), 131.4 (p-C_arom.), ppm. ¹³C NMR (75.47 MHz, CDCl₃): δ ϭ 55.2, 55.4 (OCH₃), 93.7

131.8 (i-C_arom.), 132.1 (p-C_arom.), 141.7, 141.8 (i-C_fluoren.), 175.4, (C_q), 113.9, 121.0, 123.2, 124.1, 124.8, 128.3, 129.1, 130.9, 131.2

192.7 (CϭN) ppm. MS (EI, 70 eV): m/z (%) ϭ 370 (29) [M^ϩ], 267

(o-, m-C_arom., C_fluoren.), 141.7, 142.8 (i-C_arom.), 162.3, 162.7 (i-

(100) [M^ϩϪ PhCN], 164 (59) [M^ϩϪ 2 PhCN]. C₂₇H₁₈N₂(370.45): COCH₃), 175.1, 191.5 (CϭN) ppm. MS (EI, 70 eV): m/z (%) ϭ

calcd. C 87.54, H 4.90, N 7.56; found C 87.45, H 4.89, N 7.48.

430 (26) [M^ϩ], 297 (100) [M^ϩϪ MeOC₆H₄CN], 164 (44) [M^ϩ

Ϫ

Eur. J. Org. Chem. 2004, 2567Ϫ2581

www.eurjoc.org

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2579

N. Habersaat, R. Fröhlich, E.-U. Würthwein

FULL PAPER

2 MeOC₆H₄CN]. C₂₉H₂₂N₂O₂(430.49): calcd. C 80.91, H 5.15,

N 6.51; found C 80.23, H 5.15, N 6.44.

(w, CH_arom.), 2972 (m, CH_aliph.), 2870 (m, CH_aliph.), 1717 (vs), 1583

(vs, CϭN), 1501 (m, CϭC), 1448 (s), 1339 (s), 1310 (s), 1288 (s),

1234 (s), 1202 (m), 1047 (m), 1022 (m), 943 (m), 766 (m), 719 (s),

X-ray Crystal Structure Analysis of 6d: Formula C₂₉H₂₂N₂O₂, M ϭ

430.49, colorless crystal, 0.70 ϫ 0.10 ϫ 0.05 mm, a ϭ 9.331(1), b ϭ

1

698 (s) cm^Ϫ1. H NMR (300.13 MHz, CHCl₃): δ ϭ 1.97 (s, 4 H,

NCH₂CH₂), 3.22 (br. s, 2 H, NCH₂CH₂), 3.68 (br. s, 2 H,

˚

9.187(1), c ϭ 14.522(1) A, α ϭ 90.74(1), β ϭ 94.05(1), γ ϭ

3

NCH₂CH₂), 6.38 [d, J(H,F) ϭ 19.6 Hz, 1 H, CHϭCF₂], 6.94 (m,

3

91.55(1)°, V ϭ 1108.2(2) A , ρ_calcd.ϭ 1.290 g·cm^Ϫ3, µ ϭ 6.45 cm^Ϫ1

,

˚

2 H, CH_arom.), 7.10Ϫ7.25 (m, 6 H, CH_arom.), 7.66 (m, 2 H, CH_arom.

)

no absorption correction (0.661 Յ T Յ 0.969), Z ϭ 2, triclinic,

ppm. ¹³C NMR (75.47 MHz, CHCl₃): δ ϭ 25.4 (br., NCH₂CH₂),

47.5, 49.2 (br., NCH₂CH₂), 94.2 [dd, ²J(C,F) ϭ 43.2 Hz, ²J(C,F) ϭ

11.5 Hz, CHϭCF₂], 115.1, 119.5 (i-C_arom.), 126.6, 127.6, 127.7,

128.2, 129.2 (o-, m-C_arom.), 135.0, 138.7 (p-C_arom.), 157.1 [dd,

1J(C,F) ϭ 300.1 Hz, 1J(C,F) ϭ 279.7 Hz, CHϭCF₂], 158.7 (Cϭ

N), 162.3 [d, 4_J(C,F) ϭ 7.6 Hz, CϭN] ppm. ¹⁹F NMR (282.37

˚

¯

space group P1 (No. 2), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans,

4856 reflections collected (Ϫh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.62 A^Ϫ1, 4529

˚

independent (R_intϭ 0.032) and 3830 observed reflections [I Ն

2σ(I)], 301 refined parameters, R ϭ 0.044, wR²ϭ 0.124, max. re-

sidual electron density 0.32 (Ϫ0.19) e·A^Ϫ3, hydrogens calculated

˚

and refined as riding atoms.

2

3

MHz, CHCl₃): δ ϭ Ϫ91.1 [dd, J(F,F) ϭ 38.2 Hz, J(F,H) ϭ 19.1

Hz], Ϫ102.6 [d, ²J(F,F) ϭ 38.1 Hz] ppm. MS (EI, 70 eV): m/z (%) ϭ

339 (100) [M^ϩ], 220 (23), 167 (80), 166 (86) [PhCNCHCF₂^ϩ], 158

(40), 127 (73), 104 (34) [PhCNH^ϩ], 103 (25) [PhCN^ϩ], 84 (60), 77

(31) [Ph^ϩ], 70 (35) [(CH₂)₄N^ϩ]. C₂₀H₁₉F₂N₃(339.38): calcd. C

70.78, H 5.64, N 12.38; found C 70.60, H 5.45, N 12.33.

2,4,5-Triphenyl-1H-imidazole (7b): A solution of 5b (920 mg,

2.5 mmol) in dry tetrahydrofuran (10 mL) was added to a solution

of potassium tert-butoxide (336 mg, 3.0 mmol) and n-butyllithium

(1.9 mL, 1.6  in n-hexane) in dry tetrahydrofuran (40 mL) at Ϫ78

°C. The reaction mixture was stirred at Ϫ40 °C for 3 h. After

warming to room temperature the reaction mixture was washed

with saturated sodium hydrogen carbonate solution (3 ϫ 15 mL),

dried with sodium sulfate, and the solvent removed in vacuo. The

crude product was purified by crystallization from dichlorometh-

ane/diethyl ether. Yield 310 mg (42%), colorless solid; m.p. 278 °C

(ref.^[34]278Ϫ279 °C). C₂₁H₁₆N₂(296.37).

Acknowledgments

The authors thank the Sonderforschungsbereich 424 [Deutsche

Forschungsgemeinschaft (DFG)], the Fonds der Chemischen Indu-

strie (Frankfurt) and the European Graduate College ‘‘Template

Directed Chemical Synthesis’’ for support.

4-Methyl-2,5-diphenyl-1H-imidazole (7c): A solution of 5f (950 mg,

2.5 mmol) in dry tetrahydrofuran (10 mL) was added dropwise at

Ϫ78 °C over a period of 20 min to a solution of lithium diisopro-

pylamide [3.0 mmol, prepared in situ from diisopropylamine

(300 mg) and n-butyllithium (1.9 mL, 1.6  in n-hexane)] in dry

tetrahydrofuran (40 mL). The reaction mixture was stirred at Ϫ40

°C for 3 h. After warming to room temperature the reaction mix-

ture was washed with saturated sodium hydrogen carbonate solu-

tion (3 ϫ 15 mL), dried with sodium sulfate and the solvent re-

moved in vacuo. The crude product was purified by column chro-

matography (SiO₂) using tert-butyl methyl ether/n-pentane (1:1) as

eluent (R_fϭ 0.18). Yield 370 mg (63%), pale-yellow oil. IR (film):

ν˜ ϭ 3211 (m, NH), 3063 (m, CH_arom.), 2978 (s, CH_aliph.), 2924 (m,

CH_aliph.), 2876 (m, CH_aliph.), 1672 (s, CϭN), 1591 (m, CϭN), 1498

(m, CϭC), 1462 (s, CϭC), 1182 (m), 1128 (m), 1111 (m), 910 (s),

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˜

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2580

 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjoc.org

Eur. J. Org. Chem. 2004, 2567Ϫ2581

Anionic and Dipolar Electrocyclization Reactions of 2,4-Diazapenta-1,3-dienes

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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2581

Article Doi

4H-imidazoles and imidazoles from anionic and dipolar electrocyclization reactions of 2,4-diazapenta-1,3-dienes

DOI: 10.1002/ejoc.200400057

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