College of Life and Materials Systems Engineering Graduate ... · Synthesis of fully substituted 1,1ʹ-linked-bipyrrole Tetramethyl substituted 1,1ʹ- ethylene-bipyrrole, 1,1ʹ-ethylene-bis(2,5-dimethyl-1H-pyrrole)

Synthesis of Novel Polysubstituted 1,1ʹ-Linked-Bipyrroles

via the Double 1,3-Dipolar Cycloaddition Reaction

March 2015

Huijun Liu

College of Life and Materials Systems Engineering

Graduate School of Advanced Technology and Science

The University of Tokushima, Japan

Acknowledgment

The study presented in this thesis has been carried out under the direction of Professor and

Dr. Yasuhiko Kawamura at Graduate School of Advanced Technology and Science of

Tokushima University during the period of April 2012 to March 2015.

The author wishes to express his sincerest gratitude to Professor Yasuhiko Kawamura for

his kind guidance, valuable discussions, and affectionate encouragement throughout this

work. The author would like to show his deep appreciation to Assistant Professor and Dr.

Fumitoshi Yagishita for his helpful suggestions and teaching.

The author is grateful to Ms. Shoko Ueta at Technology Center Graduate Institute of

Technology and Science of Tokushima University for the work of NMR spectra, mass spectra

and her valuable collaboration in the X-ray crystallographic analysis.

The author is grateful to Mr. Hirokazu Hashizume, Mr. Kazunori Mifune, Mr. Satoshi

Nishino, Mr. Toshimasa Kato for their helpful suggestions and kind friendship.

The author is grateful to his family and friends for their help and understanding about his

study and research.

The author also appreciates all other members of Professor Kawamura research group.

Huijun Liu

College of Life and Materials Systems Engineering

Graduate School of Advanced Technology and Science

Tokushima University

2015. 03

Contents

Abstract ....................................................................................................................................... 1

1. Introduction ............................................................................................................................ 2

1.1 Background .................................................................................................................... 2

1.2 The Objective of This Study .......................................................................................... 9

2. Synthesis of Symmetric Polysubstituted 1,1ʹ-(1,4-Phenylene)bis(pyrrole-3,4-dicarboxylates)

.................................................................................................................................................. 10

2.1 Synthesis of N,Nʹ-Biacyl-N,Nʹ-(1,4-phenylene)bis(2-arylglycine) .............................. 11

2.2 Synthesis of Symmetric Polysubstituted 1,1ʹ-(1,4-Phenylene)bis(pyrrole-3,4-dicarbo-

xylates) .............................................................................................................................. 12

2.3 Results and Discussions .............................................................................................. 13

2.4 Experimental and Characterization ............................................................................. 18

3. Synthesis of Asymmetric Polysubstituted 1,1 -́(1,4-Phenylene)bis(pyrrole-3,4-dicarboxyl-

ates) ........................................................................................................................................... 28

3.1 Synthesis of N-Acyl-Nʹ-acyl-N,Nʹ-(1,4-phenylene)bis(2-arylglycine) ........................ 29

3.2 Synthesis of Asymmetric Polysubstituted 1,1ʹ-(1,4-Phenylene)bis(pyrrole-3,4-dicarb-

oxylates) ............................................................................................................................ 29


3.4 Experimental and Characterization ............................................................................. 35

4. Synthesis of Polysubstituted Tetramethyl 1,1ʹ-(Propane-1,3-diyl)bis(1H-pyrrole-3,4-dicarb-

oxylates) ................................................................................................................................... 46

4.1 Synthesis of N,Nʹ-Diacyl-N,Nʹ-(propane-1,3-diyl)bis(2-arylglycine) ......................... 47

4.2 Synthesis of Polysubstituted Tetramethyl 1,1ʹ-(Propane-1,3-diyl)bis(1H-pyrrole-3,4-

dicarboxylates)................................................................................................................... 47


4.4 Experiment and Characterization ................................................................................ 54

5. Conclusion ............................................................................................................................ 62

6. References and Notes ........................................................................................................... 63

1

Abstract

Bipyrroles and their derivatives are structural units in many natural products and

pharmaceuticals, key intermediates for the synthesis of a variety of biologically active

molecules and functional materials.

A new method for synthesis of polysubstituted 1,1ʹ-linked-bipyrrole compounds have been

developed. The 1,1ʹ-linked-bipyrroles were successfully synthesized by the double [3+2]

cycloaddition-extrusion reactions of linked bimünchnones and dipolarophiles. Bimünchnones

were prepared by cyclodehydration reaction of N,Nʹ-bisacylglycine with N,Nʹ-diisopropyl

carbodiimide in dry toluene at 0–5 ℃ for 1.5–2 h, then, reacted with dimethyl acetylene

dicarboxylate in dry toluene at 80–100 ℃, the novel polysubstituted 1,1ʹ-linked-bipyrrole

derivatives have been obtained.

Three types of N,Nʹ-bisacylglycine were prepared:

1) 1,4-Phenylenediamine as a starting material is subjected to successive double

N-alkylation, double N-acylation, and hydrolysis, gave the target molecule;

2) 1,4-Phenylenediamine as a starting material is subjected to successive double

N-alkylation, single N-acylation, different single N-acylation, and hydrolysis, gave the target

molecule;

3) Propane-1,3-dilydiamine as a starting material is subjected to successive double

N-alkylation, double N-acylation, and hydrolysis, gave the target molecule.

The structures of 1,1′-linked-bipyrroles were characterized by 1H and

13C NMR spectroscopy

and X-ray crystallography. In addition, the optical properties of 1,1′-linked-bipyrroles were

investigated by UV–Vis absorption and fluorescence spectroscopic methods.

Keyword:

Bimünchnone; 1,3-Dipolar cycloaddition reaction; Bipyrrole; Characterization; UV–Vis

spectroscopy; Fluorescence spectroscopy.

2

1. Introduction

1.1 Background

Bipyrroles and their derivatives are important structural elements of many natural products

and pharmaceutically active substances such as antibacterial, antiviral, anti–inflammatory,

antitumoral, and antioxidant activities.1 As shown in Fig 1.1, prodigiosin is a red pigment

produced by various bacteria including S. marcescens, Gram–negative, Gamma

proteobacteria, prodigiosin is able to induce apoptosis in many different human cancer cell

lines with little effect on nonmalignant cells. Roseophilin is an antibiotic isolated from

Streptomyces griscovirides shown to have antitumor activity. Cultivation of the marine

Streptomyces strain CNQ–418 in a sea water based medium provided marinopyrroles.

Marinopyrroles A−F (1−6)

Fig 1.1. Natural products and pharmaceuticals of bipyrrole

Moreover, they are widely used in materials science.2 Bipyrroles in which electron–donor

pyrrole rings are linked through an aromatic or other electron–acceptor bridge attract interest

3

as precursors of extended π–systems that are widely used in the field of optical technologies

(as sensors, optical switchers, light–emitting diodes, semiconductors with a narrow band gap,

molecular crystals for frequency transduction), as shown in Fig 1.2.

Fig 1.2. N,Nʹ-bipyrroles

Because of the importance of bipyrroles, they have attracted the interest of many

researchers. Some methods of synthesizing bipyrrole and its derivatives have been reported,

including the Paal–Knorr condensation reaction,3,1a

Clauson–Kass reaction,4 cascade

reaction,5 catalytic dehydrogenation reactions,

6 C–N cross–coupling reactions,

7 a double

Michael addition reaction,8 and the metal–catalyzed 1,3-dipolar cycloaddition of azomethine

ylides.9

However, the literatures containing few reports of the synthesis of polysubstituted

1,1ʹ-bipyrroles or 1,1ʹ-linked-bipyrroles, suggesting that approaches to its synthesis are

limited. So far, two main methods have been developed to access 1,1ʹ-bipyrroles or

1,1ʹ-linked-bipyrroles. One is the Paal–Knorr condensation reaction. The first 1,1ʹ-bipyrrole

of 2,2ʹ,5,5ʹ-tetramethyl-1,1ʹ-bipyrrole-3,3ʹ-dicarboxylic acid (3) had been synthesized by

Korschun et al in 1904.10

Compound 3 was obtained as a byproduct in the condensation

reaction of hydrazine with methyl 2-acetyl-4-oxopentanoate. Afterwards, a slightly different

procedure was described by Chang and Adams in 1931.11

Compound 3 could be produced in

quantity and more readily. N-Amino-2,5-dimethyl-3-carboethoxypyrrole (1) was formed by

first condensation reaction of hydrazine with methyl 2-acetyl-4-oxopentanoate alcohol

solution in the presence of catalytic acetic acid. This latter substance was then condensed

again with methyl 2-acetyl-4-oxopentanoate giving 2,2ʹ,5,5ʹ-tetramethyl-1,1ʹ-bipyrrole-3,3ʹ-di

carboxylic acid ester (2). Compound 2 was hydrolyzed to give compound 3 (Scheme 1.1).

4

Scheme 1.1. The preparation route to 2,2ʹ,5,5ʹ-tetramethyl-1,1ʹ-bipyrrole-3,3ʹ-

dicarboxylic acid

2,5-Disubstituted-1,1ʹ-bipyrroles (4) had been synthesized by Flitsch et al in 1969.12

Condensation reaction of N-amino-pyrrole with 1,4-diketones had been carried out giving

compound 4, an intermediate N-amino-pyrrole has been prepared through reaction with

hydrazine and N-(pyrrole-1-yl) phthalimid (Scheme 1.2).

Scheme 1.2. Synthesis of 2,5-disubstituted-1,1ʹ-bipyrroles

Fully substituted 1,1ʹ-bipyrrole, 2,2ʹ,3,3ʹ,4,4ʹ,5,5ʹ-octamethyl-1,1ʹ-bipyrrole (6) had been

synthesized by Kuhn et al in 2000.13

1-Amino-2,3,4,5-tetramethylpyrrole (5) was prepared by

the condensation reaction of hydrazine with 3,4-dimethylhexane-2,5-dione, it have treated

with 3,4-dimethylhexane-2,5-dione to give 2,2ʹ,3,3ʹ,4,4ʹ,5,5ʹ-octamethyl-1,1ʹ-bipyrrole

(Scheme 1.3).

The five kinds of fully substituted 1,1ʹ-linked-bipyrrole was reported by Hua and Wu in

1990.3a

Tetraethyl 1,1ʹ-linked-bis(2,5-dimethyl-1H-pyrrole-3,4-dicarboxyl ate) (7) compouds

were synthesized by the condensation reaction of diethyl 2,3-diacetylsuccinate with diamines

5

in the presence of organic acid (Scheme 1.4).

Scheme 1.3. Synthesis of 2,2ʹ,3,3ʹ,4,4ʹ,5,5ʹ-octamethyl-1,1ʹ-bipyrrole

Scheme 1.4. Synthesis of fully substituted 1,1ʹ-linked-bipyrrole

Tetramethyl substituted 1,1ʹ- ethylene-bipyrrole, 1,1ʹ-ethylene-bis(2,5-dimethyl-1H-pyrrole)

(8) was obtained by Banik and co-workers via modified Paal–Knorr condensation reaction in

2004.14

Either iodine–catalyzed or montmorillonite KSF clay–induced modified Paal–Knorr

reaction of 1,2-ethylenediamine with 2,5-hexanedione was executed to give 1,1ʹ-ethylene

-bis(2,5-dimethyl -1H-pyrrole) (Scheme 1.5).

Scheme 1.5. Synthesis of 1,1ʹ-ethylene-bis(2,5-dimethyl-1H-pyrrole)

A conceptually new synthetic approach to octa-substituted 1,1ʹ-phenylene-bipyrroles was

reported by Binder and Kirsch in 2006.15

Fully substituted 1,1ʹ-phenylene-bipyrrole (9) was

produced utilizing a transition-metal-catalyzed domino reaction of a formal [3,3]-sigmatropic

rearrangement, an amine condensation, and a heterocyclization reaction of substituted

propargyl vinyl ethers with 1,4-phenylenediamine (Scheme 1.6).

Tetraaryl substituted 1,1ʹ-linked-bipyrrole (10) was reported by Sagyam and co-workers

6

in 2007.16

The condensation reaction of 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-

methyl-3-oxo-N-phenylpentanamide with the corresponding diamine (1,2-ethylenediamine,

1,3-propanediamine, 1,4-butanediamine) in the presence of an acetic acid was executed to

give compounds 10 (Scheme 1.7).

Scheme 1.6. Synthesis of fully substituted 1,1ʹ-phenylene-bipyrrole

Scheme 1.7. Synthesis of fully substituted 1,1ʹ-alkylene-bipyrrole

Another method is double 1,3-dipolar cycloaddition of bimesoionic compound with

alkynes. Fully substituted 1,1ʹ-ethylene-bipyrrole was synthesized by Iyer and co-workers in

1986 utilizing double 1,3-dipolar cycloaddition,17

the salt analog mesoionic form (11) was

reacted with DMAD (10 equivalents, 70–80 ℃, 12 hours), which could then undergo

cycloreversion with loss of HNCO via a retro–Diels–Alder process, the bispyrrole (12) was

obtained in 40–45 % yield (Scheme 1.8).

Fully substituted 1,1ʹ-linked-bipyrrole, 1,1ʹ-(1,3-propanediyl)bis(pyrrole-3,4-dicarboxylate)

and 1,1ʹ-(1,3-ethylenediyl)bis(pyrrole-3,4-dicarboxylate) (13) were synthesized by Abdulla

and co-workers18

in 2011 via double 1,3-dipolar cycloaddition. The reaction of bis-oxazolium

perchlorate salt and dimethyl acetylenedicarboxylate was carried out in the presence of

trifluoroacetic acid or 98 % sulfuric acid for about 22 days. However, this method has some

native disadvantage, such as, long reaction time, using strong acid, and unworkability etc.

(Scheme 1.9).

7

Scheme 1.8. Synthesis of fully substituted 1,1ʹ-ethylene-bipyrrole

Scheme 1.9. Synthesis of fully substituted 1,1ʹ-alkylene-bipyrrole

Other methods have been developed to access 1,1ʹ-linked-bipyrroles. Fully substituted

1,1ʹ-ethylene-bipyrrole (14) were reported by Meyer in 1981.19

The principle of a general

pyrrole synthesized by cyclizing Michael addition of enamine to nitroalkene is outlined.

Condensation of the nitroalkene with bienamine was executed to yield compound 14 in 64%

(Scheme 1.10).

Scheme 1.10. Synthesis of 1,1ʹ-(1,2-ethandiyl)bis[(2,5-dimethyl-4-

phenyl-pyrrol-3-yl)acetate)

Potikha and Kovtunenko20

studied the reaction of 4-bromo-1,3-diphenyl-2-buten-1-one

(γ-bromodypnone) with ethylenediamine and 1,3-diaminopropane in 2006. The reaction takes

place quickly without heat at both amino groups with the formation of

1-[2-(2,4-diphenyl-1H-pyrrol-1-yl)ethyl]- and 1-[2-(2,4-diphenyl-1H-pyrrol-1-yl)propyl]-2,4-

diphenyl-1H-pyrroles (15) in 69 % and 71 % (Scheme 1.11).

1,1'-(1,3-Propanediyl)bis-1H-pyrrole (16) was reported by Polshettiwar and co-workers in

2009.21

Reaction of tetrahydro-2,5-dimethoxyfuran and 1,3-propanediamine was carried out

8

under the nano–organocatalyst (Nano–FGT) and microwave (MW) irradiation conditions to

give 16 (Scheme 1.12).

Scheme 1.11. Synthesis of tetraaryl substituted 1,1'-alkylene-bipyrrole

Scheme 1.12. Synthesis of 1,1'-(1,3-propanediyl)bis-1H-pyrrole (16)

Zhou et al22

have achieved cyclization reactions of zirconacyclopentadienes with various

azides in the presence of CuCl in 2013. The formation of 1,2-bis(azidomethyl)benzene was

used, a double–cyclization reaction proceeded to give the 1,2-bis((1H-pyrrol-1-yl)methyl)

benzene derivative (17) in 39% isolated yield (Scheme 1.13).

Scheme 1.13. Synthesis of 1,2-bis((1H-pyrrol-1-yl)methyl)-benzene

Scheme 1.14. Synthesis of α,ω-di(N-pyrrolyl)alkanes

In 2011, Attanasiwe23

has reported the procedure of α,ω-di(N-pyrrolyl)alkanes. The double

nucleophilic attack of the 1,3-diaminopropane or 1,6-diaminohexane, to two equivalents of

4-aminocarbonyl-1,2-diaza-1,3-dienes furnishes the bis-α-aminocarbonyl-α-aminohydrazones

9

(18), which in turn, are converted into the corresponding bis-α-aminocarbonyl

-α-(N-enamino)-hydrazones by reaction with two equivalents of dialkyl acetylene

dicarboxylates. Their final acid–catalyzed ring closure produces new and amply

functionalized α,ω-di(N-pyrrolyl)alkanes (19) (Scheme 1.14).

1.2 The Objective of This Study

To achieve the develop of more efficient and convenient routes to prepared linked

bipyrrole compounds, we have become interested in generating double cycloaddition reaction

reagent. That exhibits superior the reactivity, is easily generated, and is well diversified.

Through numerous investigation, we observed that mono-münchnone (1,3-oxazolium-5-

olates) was satisfy all of these. Münchnone cycloaddition reaction was first reported by

Huisgen in 1964.24

Upon treatment with alkynes, 1,3-dipolar cycloaddition reaction of

münchnone is usually followed by the elimination of CO2 and provides an efficient route for

synthesizing a number of biologically relevant products, including such common cores as

pyrroles (20) (see Scheme 1.15), pyrrolines, imidazoles, imidazolines, and other

heterocycles.25

Scheme 1.15. Cycloaddition-extrusion reactions of münchnones and alkynes

We believe that bimünchnone may have similar advantages with mono-münchnone. So our

main goals were formulated in the following way:

1) Study on the preparation and characterization of N,Nʹ-bisacylglycines;

2) Study on the preparation and characterization of bimünchnones;

3) Study on the synthesis and characterization of objective compounds.

10

2. Synthesis of Symmetric Polysubstituted

1,1ʹ-(1,4-Phenylene)bis(pyrrole-3,4-dicarboxylates)

11

2.1 Synthesis of N,Nʹ-Biacyl-N,Nʹ-(1,4-phenylene)bis(2-arylglycine)

The general synthetic route for preparation of compounds 2a-b is depicted in Scheme 2.1.

Bromination of ethyl 2-phenylacetate 1a or its analogue 1b with N-bromosuccinimide (NBS)

in carbon tetrachloride gave ethyl 2-bromo-2-phenylacetate (2a) and ethyl 2-bromo-2-(4

-methoxyphenyl)acetate (2b).26

A 2–3% excess of NBS was used generally along with

benzoyl peroxide or HBr as a catalyst (see Scheme 2.1). In this article, the desired ethyl

2-bromo-2-phenylacetates were prepared by the reaction of NBS and the corresponding ethyl

2-arylacetate in carbon tetrachloride containing a catalytic amount of 2,2ʹ-azobisiso-

butyronitrile (AIBN) (see Scheme 2.2).

Scheme 2.1. Synthesis of compound 2 with benzoyl peroxide or HBr as a catalyst

Scheme 2.2. Synthesis of compound 2 with AIBN as a catalyst

1,4-Bis[(ethoxycarbonylmethyl)amino]benzene was efficiently synthesized from ethyl

chloroacetate and p-phenylenediamine (PPD) in triethylamine under reflux27

(Scheme 2.3).

According to this method, diethyl N,N′-(1,4-phenylene)bis(2-arylglycinate) (3a-b) was

synthesized by the reaction of compound 2 and PPD in triethylamine at 80 ℃ under a

nitrogen atmosphere (Scheme 2.4).

Scheme 2.3. Synthesis of 1,4-bis[(ethoxycarbonylmethyl)amino]benzene

12

Diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate) (5a-f) was synthesized by the

acylation of diethyl N,N′-(1,4-phenylene)bis(2-arylglycinate) using the corresponding acyl

chloride (Scheme 2.5); N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate) was hydrolyzed

to give N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycine) (6a-f) (Scheme 2.6).

Scheme 2.4. Synthesis of diethyl N,N′-(1,4-phenylene)bis(2-arylglycinate) (3a-b)

Scheme 2.5. Synthesis of 5a-f

Scheme 2.6. Synthesis of 6a-f

2.2 Synthesis of Symmetric Polysubstituted 1,1ʹ-(1,4-Phenylene)bis(pyrrole

-3,4-dicarboxylates)

Typically acetic anhydride is used as a water–removing agent simultaneously for the

acylation of the amino acid. Huisgen et al24

has firstly described preparation of 3-methyl-2,4-

13

diphenyloxazolium-5-oxide, when N-benzoyl-N-methylphenylglycine is treated with acetic

anhydride at 55 ℃ for a few minutes, bright yellow crystals of the mesoionic compound are

obtained in 90 % yield. But other reagents, such as N,Nʹ-dicyclohexylcarbodiimide (DCC),28

has some problem, for example, the resultant dicyclohexylurea is difficult to remove

completely from the reaction mixture. N-(3-Dimethylaminopropyl)-Nʹ-ethylcarbodiimide

(EDC)29

and DIC30

have been used for the dehydration of N-acylated amino acids in the

cycloaddition reactions.

We examined a standard method22

to synthesize bimünchnones 7a-f from the N,

Nʹ-bisacyl-bis(2-arylglycine) 6a-f. The bimünchnone were not isolated, but instead generated

in situ by cyclodehydration with DIPC in dry toluene. Thus, a mixture of the bimünchnone

7a-f and DMAD in dry toluene was heated at 80–100 ℃ for 24 h to yield the desired

substituted bipyrroles 8a-f by one-pot.

2.3 Results and Discussions

In the general case, secondary amines are more basic than primary amines, but are more

steric hindrance. The reactivity toward acyl chlorides is a weighted mean of both factors. The

reaction of compound 3a or 3b with different aromatic acid chlorides in the presence of

K2CO3 gave compound 5a-f and byproduct of mono-acylation, and starting material was

completely consumed. The yield of compound 5 influenced by the steric hindrance of the

substituents R and R1 and acylation activity of acyl chlorides. The results are summarized in

Table 2.1. When the benzoyl chloride (R1 = H) was used, yield of compound 5a was higher

than compound 5d (Table 2.1, entries 1 and 4). The results indicated that the steric hindrance

of starting material had a profound effect on the overall isolated yield. When starting material

was compound 3a (R = H), yield of compound 5a was higher than that of the compound 5b

and compound 5c (Table 2.1, entries 1, 2 and 3). The results indicated that the steric

hindrance of acyl chloride had a profound effect on the overall isolated yield. When starting

material was compound 3b (R = OCH3), yield of compound 5b was higher than that of the

compound 5c (Table 2.1, entries 2 and 3), acylation ability of 4-nitrobenzoyl chlorides is the

strongest in comparison with benzoyl chloride or 4-methoxybenzoyl chloride, but yield of

compound 5f was lower than that of the compound 5d and 5e (Table 2.1, entries 4, 5 and 6),

14

the results indicated that the acylation activity of acyl chloride had a profound effect on the

overall isolated yield.

Table 2.1. Sythesis of diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate)

Entry R R1 Reaction Time (h) Compound 5 Yield (%)

1 H H 24 5a 80.4

2 H OCH3 24 5b 57.5

3 H NO2 24 5c 65.8

4 OCH3 H 48 5d 52.1

5 OCH3 OCH3 48 5e 51.7

6 OCH3 NO2 48 5f 26.1

Table 2.2. Hydrolysis of diethyl N,N′-biacyl-N,N′-(1,4-phenylene)-bis(2-arylglycinate)

Entry R R1 time (h) / hydrolysis Compound 6 Yield (%)

1 H H 6 6a 96.3

2 H OCH3 3 6b 79.1

3 H NO2 9 6c 63.0

4 OCH3 OCH3 3 6d 47.0

5 OCH3 H 4 6e 73.1

6 OCH3 NO2 12 6f 27.8

15

Table 2.2 shows the hydrolysis reaction of the compound 5. For instance, while the

hydrolysis reaction proceeds, the reaction rate of hydrolysis is high when the compound 5

possesses –OCH3 group, (Table 2.2, entries 2, 4, and 5). In contrast, the rate of hydrolysis is

low when the compound 5 possesses –NO2 group (Table 2.2, entries 3 and 6). This difference

in rates may result from solubility of the compound 5 in the aqueous alcohol solution.

Next, we examined the double 1,3-dipolar cycloaddition reaction of bimünchnone 7 with

DMAD. When bimünchnones bearing phenyl and 4-methoxyphenyl substituents were reacted

with DMAD, the corresponding substituted bipyrrole 8 were obtained in moderate yield

(Table 2.3). Unfortunately, the use of bimünchnone 7c or 7f having powerful

electron-withdrowing groups gave 8c or 8f in low yield, resulting from low reactivity of

bimünchnone 7c or 7f with DMAD.

Table 2.3. The double 1,3-dipolar cycloaddition of bismünchnone 7 with DMAD

Entry R R1 Reaction Time (h) Compd 8 Y (%)

1 H H 24 8a 36.1

2 H OCH3 24 8b 50.9

3 H NO2 24 8c 25.0

4 OCH3 H 24 8d 40.1

5 OCH3 OCH3 24 8e 20.0

6 OCH3 NO2 24 8f 18.8

The optical properties of compounds 8a-f were studied by UV-Vis and fluorescent

spectroscopy. The UV-Vis spectra of 8a-f are shown in Figure 2.1. Electronic absorption

spectra of 8a-f in CH3OH exhibit absorption bands with maxima at 200–400 nm. The

compound 8a-b, 8d-e possessed the electron-donating groups appearing at longer

wavelengths than compound 8c, 8f possessed the electron-withdrawing groups.

16

Fig 2.1. UV-Vis spectra of 8a-f in CH3OH (saturated solution)

Fig 2.2. Fluorescence spectra of 8a-f in CHCl3 ( 1×10-5

mol/L)

The fluorescence spectra of the obtained 1,1-(1,4-phenylene)bipyrrole 8a-f were also

measured in CHCl3, as shown in Figure 2.2. All of those compounds showed blue

fluorescence emissions in CHCl3 when the phenyl C4 position was occupied by the aromatic

moiety with electron-donating group (such as CH3O), and all exhibited stronger blue

fluorescence. In each of the spectra, five main fluorescence maxima were observed. The

fluorescence maxima of bipyrrole 8b 8d-f are red–shifted compared to bipyrrole 8a. The

intense fluorescence band of 8b (8d) at 414 nm is slightly red–shifted from that of 8a (397

nm), the fluorescence maxima of bipyrrole 8e (423 nm), 8f (419) are slightly red–shifted

0

0.2

0.4

0.6

0.8

1

1.2

200 250 300 350 400 450 500

AB

S

UV-Vis wavelength (nm)

8a

8b

8c

8d

8e

8f

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

200 250 300 350 400 450 500 550 600 650

Rel

ati

ve

inte

nsi

ty

Wavelength (nm)

8a

8b

8c

8d

8e

8f

17

from that of 8a (397 nm). The intense fluorescence band of 9c at 389 nm is drastically blue–

shifted from that of 8a (397 nm). The fluorescence of bipyrrole 8c, 8f can be quenched

efficiently as the introduction of an electron–withdrawing substituent (NO2).

The product 8 were characterized spectroscopically. 1H NMR spectra of compounds 8a-f

showed resonances at 3.6–3.7 ppm (–COOCH3) (see Figure 2.3), It is noteworthy that in the

NMR spectra of all bis-pyrrole esters, with the exception of the symmetrically substituted 8a

and 8d analogs, two sets of the methoxycarbonyl (COOCH3) protons corresponding to each

ester group were observed, indicated different electronic environments imposed by the

neighboring phenyl and substituted phenyl substituents. 13

C NMR spectra of compounds 8a-f

showed resonances at 51–52 ppm (signals due to a carbon of methyl of COOCH3); 114–116

ppm (carbons of pyrrole with methoxycarbonyl group) and 165 ppm (carbons of carbonyl

group of COOCH3)14

, both consistent with the presence of the heterocyclic ring. Further

verification was obtained by the X–ray diffraction analysis (see Figure 2.4).

Fig 2.3. 1H NMR (CDCl3, 400 HMz) spectra of compound 8a and 8b

18

Fig 2.4. ORTEP drawing of compound 8e

2.4 Experimental and Characterization

General remarks

All reactions were carried out under an atmosphere of nitrogen in flame–dried glassware

with magnetic stirring. All reagents and solvents were obtained from commercial suppliers

and used without further purification. All reagents were weighed and handled in air at room

temperature. Melting points were recorded on a Yanaco hot–stage melting point apparatus

and uncorrected. Purification of the reaction products was carried out by flash

chromatography using EM Reagent silica gel 60 (230–400 mesh). Analytical thin layer

chromatography was performed on EM Reagent 0.25 mm silica gel 60–F plates. 1H NMR

spectra were recorded at 400 MHz and 13

C NMR spectra were recorded at 100 MHz using a

JEOL ECA 400 or ECX 400 spectrometer. Chemical shifts were reported in parts per million

(δ) relative to tetramethylsilane (TMS). Data are reported as (ap = apparent, s = singlet, d =

doublet, t = triplet, q = quartet, m = multiplet, b = broad; coupling constant(s) in Herz;

integration). Elemental analyses were performed with a Yanaco MT–5 CHN–Corder. The

UV–vis absorption and fluorescence spectra were recorded at HITACHI U–2000 and

HITACHI F–7000; Single crystal X–ray diffraction data were obtained on a Rigaku R–Axis

Rapid II diffractometer equipped with a curved imaging plate detector and a

monochromatized Cu–Kα radiation source.

19

The preparation of compounds 2a-b.

A two–neck round bottom flask equipped with a magnetic bar, was charged with

N-bromosuccinimide (18 mmol, 1.2 equiv.) and 2,2ʹ-azobisisobutyronitrile (0.15 mmol, 0.01

equiv.). To this mixture, a starting material 1a-b (15 mmol, 1 equiv.) in carbon tetrachloride

(30 mL) was added. Under the atmosphere of nitrogen, the suspension was refluxed for 4-6 h,

cooled to room temperature, the reaction mixture was filtered to remove the precipitate, after

filtrate were concentrated in vacuo, the residual mixture was subjected to column

chromatography (hexane–dichloromethane, 9:1, and hexane–dichloromethene, 1:1, v/v) and

the corresponding compound 2 was separated.

Ethyl 2-bromo-2-phenylacetate (2a).26(a)

Colorless oil, yield: 98 %. 1H NMR (CDCl3, 400 MHz): δ = 1.24–1.28 (t, J = 7.60 Hz, 3H,

CH3), 4.17–4.26 (m, 2H, CH2), 5.34 (s, 1H, CH), 7.30–7.37 (m, 3H, ArH), 7.52–7.55 (d, J =

8.0 Hz, 3H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.0, 46.9, 62.6, 128.7, 128.8, 129.0,

129.2, 129.4, 135.9, 168.3.

Ethyl 2-bromo-2-(4-methoxyphenyl)acetate (2b).26(b)

Colorless oil, yield: 80 %. 1H NMR (CDCl3, 400 MHz): δ = 1.25–1.29 (t, J = 7.20 Hz, 3H,

CH3), 3.80 (s, 1H, CH), 4.17–4.25 (m, 2H, CH2), 5.32 (s, 1H, CH), 6.86–6.88 (d, J = 8.80 Hz,

2H, ArH), 7.47–7.79 (d, J = 8.80 Hz, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.0, 46.9,

55.4, 62.5, 114.3, 127.9, 130.1, 160.3, 168.5.

2.4.2 General procedure for the preparation of compounds 3a-b.

In a nitrogen atmosphere, 2a (2b) (11 mmol) was added slowly to a stirred solution of

p-phenylenediamine (0.54 g, 5 mmol) in triethylamine (5 mL) at 80 ℃. After vigorous

stirring for 30 min under reflux, the reaction mixture was cooled down to 50 ℃, then

solidified with distilled water, washed with distilled water 3 times, the precipitate was

20

collected by filtration, dried in vacuo. Purification by column chromatography (silica gel;

ethyl acetate/hexane, 1:2, v/v) gave compounds 3a-b.

Diethyl N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (3a).

1.94 g, pale yellow solid, yield: 89.0 %. Mp: 123–125 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.17–1.20 (t, J = 7.20 Hz, 6H, CH3), 4.07–4.24 (m, 4H, CH2), 4.52 (s, 2H, NH), 4.77 (s, 2H,

CH), 6.44 (s, 4H, ArH), 7.27–7.34 (m, 6H, ArH), 7.46–7.47 (d, J = 7.20 Hz, 4H, ArH). 13

C

NMR (CDCl3, 100 MHz): δ = 14.1, 61.7, 61.9, 115.2, 127.3, 128.1, 128.8 138.2, 138.9, 172.2.

Found: C, 72.07; H, 6.53; N, 6.40. Calcd for. C26H28N2O4: C, 72.20; H, 6.53; N, 6.48 %.

Diethyl N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycinate] (3b).

4.55 g, pale yellow solid, yield: 93.4%. Mp: 102–105 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.15–1.19 (t, J = 7.20 Hz, 6H, CH3), 3.77 (s, 3H, CH), 4.07–4.21 (m, 4H, CH2), 4.42 (s, 2H,

NH), 4.86 (s, 2H, CH), 6.41 (s, 4H, ArH), 6.83–6.85 (d, J = 8.00 Hz, 4H, ArH), 7.34–7.36 (d,

J = 7.20 Hz, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 55.3, 61.3, 61.5, 114.1, 115.2,

128.4, 130.1, 138.9, 159.4, 172.5. Found: C, 68.19; H, 6.50; N, 5.42. Calcd for. C28H32N2O6:

C, 68.28; H, 6.55; N, 5.69 %.

2.4.3 General procedure for the preparation of compounds 5a-f.

A two–neck round bottom flask equipped with a magnetic bar was charged with CH2Cl2 (4

mL), aroyl chloride (4.8 mmol, 2.2 equiv.) and KCO3 (4.8 mmol, 2.4 equiv.). To this mixture,

21

solution of 3a (3b) (2 mmol, 1 equiv.) dissolved in CH2Cl2 (6 mL) was dripped slowly via an

addition funnel. After the addition was complete, the reaction mixture was slowly warmed to

room temperature and stirred for 1 d. The reaction mixture was then washed with distilled

water 3 times. The organic layer was separated, and dried with anhydrous MgSO4, removal of

the solvent, dried in vacuo. The crude products were purified by column chromatography

(silica gel; ethyl acetate/hexane, 1:2, v/v), to give compound 5a-f.

Diethyl N,Nʹ-bisbenzoyl-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (5a).

1.03 g, colorless solid, yield 80.4 %. Mp: 210–212 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.20–1.24 (t, J = 7.20 Hz, 6H, CH3), 4.18–4.26 (m, 4H, CH2), 6.20 (s, 2H, CH), 6.48 (s, 4H,

ArH), 6.89–6.91 (d, J = 7.60 Hz, 4H, ArH), 7.07–7.26 (m, 16H, ArH). 13

C NMR (CDCl3, 125

MHz): δ = 14.1, 61.5, 64.5, 127.8, 128.3, 128.4, 128.5, 129.6, 130.2, 130.5, 133.9, 135.5,

139.2, 170.1, 171.1. Found: C, 74.96; H, 5.77; N, 4.48. Calcd for. C40H36N2O6: C, 74.98; H,

5.66; N, 4.37 %.

Diethyl N,Nʹ-bis(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (5b).


1.17–1.20 (t, J = 7.20 Hz, 6H, CH3), 4.07–4.24 (m, 4H, CH2), 4.52 (s, 2H, NH), 4.77 (s, 2H,

CH), 6.44 (s, 4H, ArH), 7.27–7.34 (m, 6H, ArH), 7.46–7.47 (d, J = 7.20 Hz, 4H, ArH). 13

C

NMR (CDCl3, 100 MHz): δ = 14.2, 55.2, 61.5, 64.9, 113.0, 127.4, 127.5, 128.3, 128.4, 128.5,

130.3, 130.4, 130.9, 134.0, 139.6, 139.7, 160.7, 170.3, 170.6. Found: C, 71.89; H, 5.89; N,

4.08. Calcd for. C26H28N2O4: C, 71.98; H, 5.75; N, 4.00 %.

Diethyl N,Nʹ-bis(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (5c).

0.96 g, pale yellow solid, yield 65.8 %. Mp: 215–216 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.20–1.24 (t, J = 7.20 Hz, 6H, CH3), 4.19–4.28 (m, 4H, CH2), 6.2 (s, 2H, CH), 6.56 (s, 4H,

ArH), 6.85–6.87 (d, J = 7.20 Hz, 2H, ArH), 7.07–7.11 (t, 4H, ArH), 7.19–7.23 (d, J = 7.60 Hz,

2H, ArH), 7.26–7.28 (d, J = 8.80 Hz, 4H, ArH), 7.95–7.97 (d, J = 8.80 Hz, 4H, ArH). 13

C

NMR (CDCl3, 125 MHz): δ = 14.1, 62.0, 64.1, 123.1, 128.5, 128.8, 129.3, 130.1, 130.7,

132.8, 138.5, 141.5, 148.0, 169.0, 170.0. Found: C, 65.68; H, 4.88; N, 7.63. Calcd for.

C26H28N2O4: C, 65.75; H, 4.69; N, 7.67 %.

22

Diethyl N,Nʹ-bis(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)

glycinate] (5d).


1.21–1.23 (t, J = 7.20 Hz, 6H, CH3), 3.73 (s, 6H, CH3), 3.77 (s, 6H, CH3), 4.16–4.25 (m, 4H,

CH2), 6.12 (s, 2H, CH), 6.52 (s, 4H, ArH), 6.60–6.62 (d, J = 8.80 Hz, 4H, ArH), 6.61–6.63 (d,

J = 9.20 Hz, 4H, ArH), 6.81–6.83 (d, J = 8.80 Hz, 4H, ArH), 7.16–7.18 (d, J = 9.20 Hz, 4H,

ArH); 13

C NMR (CDCl3, 125 MHz): δ = 14.2, 55.2, 61.4, 64.1, 112.9, 113.7, 126.0, 127.6,

130.6, 131.1, 131.6, 139.5, 159.6, 160.7, 170.5, 170.6. Found: C, 69.51; H, 5.90; N, 3.60.

Calcd for. C44H44N2O10: C, 69.46; H, 5.83; N, 3.68 %.

Diethyl N,Nʹ-bisbenzoyl-N,Nʹ-(1,4-phenylenediyl)bis[2-(4-methoxyphenyl)glycinate]

(5e).


1.20–1.24 (t, J = 7.20 Hz, 6H, CH3), 3.75 (s, 6H, CH3), 4.15–4.27 (m, 4H, CH2), 6.17 (s, 2H,

CH), 6.50 (s, 4H, ArH), 6.60–6.62 (d, J = 8.40 Hz, 4H, ArH), 6.79–6.81 (d, J = 8.40 Hz, 4H,

ArH), 7.08–7.10 (d, J = 7.60 Hz, 4H, ArH), 7.14–7.15 (d, J = 7.60 Hz, 4H, ArH), 7.22–7.26 (t,

J = 7.20 Hz, 4H, ArH). 13

C NMR (CDCl3, 125 MHz): δ = 14.2, 55.2, 61.5, 63.8, 113.7, 125.8,

127.7, 128.6, 129.6, 130.6, 131.6, 135.6, 139.1, 159.5, 170.5, 171.1；Found: C, 72.23; H, 5.91;

N, 4.04. Calcd for. C42H40N2O8: C, 71.98; H, 5.75; N, 4.00 %.

Diethyl N,Nʹ-bis(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylenediyl)bis[2-(4-methoxyphenyl)glycin

-ate] (5f).

0.41 g, slight yellow solid, yield 26.1 %. Mp: 235–237 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.20–1.24 (t, J = 7.20 Hz, 6H, CH3), 3.78 (s, 6H, CH3), 4.16–4.28 (m, 4H, CH2), 6.16 (s, 2H,

CH), 6.57 (s, 4H, ArH), 6.64–6.66 (d, J = 8.80 Hz, 4H, ArH), 6.77–6.80 (d, J = 8.80 Hz, 4H,

ArH), 7.28–7.30 (d, J = 8.00 Hz, 4H, ArH), 7.96–7.98 (d, J = 8.00 Hz, 4H, ArH). 13

C NMR

(CDCl3, 100 MHz): δ = 14.1, 55.3, 61.8, 63.9, 113.9, 123.0, 124.8, 129.4, 130.9, 131.4, 138.7,


C, 63.79; H, 4.84; N, 7.09 %.


23

A two–neck round bottom flask equipped with a magnetic bar was charged compound 5 (1

mmol, 1 equiv), ethanol (5 mL) and water (10 mL). To this mixture, potassium hydroxide (4.2

mmol, 4.2 equiv)was added. The mixture was heated, refluxed for 6 h. The aqueous solution

was acidifized with HCl (10 %) to pH 2, The acidic solution was extracted with ethyl acetate

3 times, The combined extracts were washed successively with H2O, 1 % Na2CO3, and H2O.

The organic layer was separated, and dried with anhydrous MgSO4, removal of the solvent, to

give compounds 6a-f.

N,Nʹ-Bisbenzoyl-N,Nʹ-(1,4-phenylene)bis(2-phenylglycine) (6a).

White power, yield: 96.3 %. Mp: 241–244 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 5.91 (s,

2H, CH), 6.52 (s, 4H, ArH), 6.95–7.15 (m, 20H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ =

65.1, 128.0, 128.2, 128.3, 129.7, 129.8, 130.3, 130.5, 134.8, 136.4, 139.8, 170.3, 171.0.


N,Nʹ-Bis(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycine) (6b).

White power, yield: 79.1 %. Mp: 233–234℃; 1H NMR (DMSO-D6, 400 MHz): δ = 3.71 (s,

6H, CH3), 5.86 (s, 2H, CH), 6.57 (s, 4H, ArH), 6.64–6.70 (d, J = 8.8, 4H, ArH) 6.98–7.00

(d, J = 7.2, 4H, ArH), 7.02–7.05 (d, J = 8.8, 4H, ArH), 7.11–7,14 (t, J = 7.6, 4H, ArH), 7.18–

7.21 (t, J = 7.6, 2H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 55.6, 65.5, 113.5, 127.9,

128.4, 130.1, 130.6, 130.9, 134.8, 140.1, 160.6, 169.6, 171.5. Found: C, 70.65; H, 5.19; N,


N,Nʹ-Bis(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycine) (6c)32

.

White power, yield: 63.0 %. Mp: 252–254 ℃; 1H NMR (DMSO-D6, 400 MHz): δ = 5.96 (s,

2H, CH), 6.63 (s, 4H, ArH), 6.93–6.95 (d, J = 6.8, 4H, ArH), 7.04–7.10 (m, 6H, ArH), 7.26–

24

7.29 (d, J =8.8, 4H, ArH), 7.94–7.96 (d, J =8.8, 4H, ArH). 13

C NMR (DMSO-D6, 100 MHz):

δ = 64.9, 123.5, 128.4, 129.5, 130.5, 133.9, 138.9, 142.5, 147.8, 168.6, 171.2. Found: C,

63.94; H, 4.04; N, 8.28. Calcd for. C36H26N4O10: C, 64.09; H, 3.88; N, 8.31 %.

N,Nʹ-Bis(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycine] (6d).


6H, CH3), 3.71 (s, 6H, CH3), 5.84 (t, 2H, CH), 6.56 (s, 4H, ArH), 6.64–6.67 (d, J = 8.8, 8H,

ArH), 6.87–6.89 (d, J = 8.4, 4H, ArH), 7.04–7.06 (d, J = 8.8, 4H, ArH). 13

C NMR (DMSO-D6,

100 MHz): δ = 55.5, 55.6, 64.8, 113.4, 113,7, 126.7, 127.9, 130.3, 131.0, 132.0, 140.0, 159.3,


5.15; N, 3.98 %.

N,Nʹ-Bisbenzoyl-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycine] (6e).32

White power, yield: 73.0 %. Mp: 241–243 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 3.69 (s,

6H, CH3), 5.83 (s, 2H, CH), 6.53 (s, 4H, ArH), 6.68–6.71 (d, J = 8.4, 4H, ArH), 6.83–6.89 (q,

J = 8.4, 4H, ArH), 7.00–7.02 (d, J =7.2, 4H, ArH),7.06–7.10 (t, J =7.2, 4H, ArH), 7.25–7.28 (t,

J =7.2, 2H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 55.7, 64.5, 114.2, 127.0, 128.0,

128.3, 129.7, 130.4, 131.8, 136.5, 139.8, 139.9, 159.7, 170.3, 171.2. Found: C, 69.63; H, 5.10;


N,Nʹ-Bis(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycine] (6f).


6H, CH3), 5.58 (s, 2H, CH), 6.60–6.63 (d, J = 8.8, 4H, ArH), 6.82–6.84 (d, J = 8.8, 4H, ArH),

7.29–7.31 (d, J = 8.8, 4H, ArH), 7.94–7.96 (t, J =8.8, 2H, ArH). 13

C NMR (DMSO-D6, 100

MHz): δ = 55.5, 64.4, 113.7, 123.4, 125.8, 129.9, 130.7, 131.9, 138.9, 142.4, 147.9, 159.4,

168.4, 171.4. Found: C, 61.97; H, 4.33; N, 7.44. Calcd for. C38H30N4O12: C, 62.12; H, 4.12; N,

7.63 %.


25

A two-neck round bottom flask equipped with a magnetic bar was charged the compound 6

(0.1 mmol, 1 equiv) and toluene (5 mL). Under atmosphere of nitrogen, at 0–5 ℃, to this

mixture, DIC (0.22 mmol, 2.2 equiv) dissolved in toluene (2 mL) was dropped, and stirring

for 2h, then DMAD (0.22 mmol, 2.2 equiv) dissolved in toluene (3 mL) was added. When

DMAD was added, the mixture heated to 80 ℃ with an oil bath, stirred for 1 d, The reaction

mixture was then washed with distilled water 3 times. The organic layer was separated, and

dried with anhydrous MgSO4, removal of the solvent, dried in vacuo. The crude products was

subjected to column chromatography (ethyl acetate–hexane, 2:3, v/v), to give the pure

bipyrrole compounds 8a-f.

Tetramethyl 1,1ʹ-(1,4-phenylene)bis(2,5-diphenyl-1H-pyrrole-3,4-dicarboxylate) (8a).

Colorless solid, yield: 36.1 %. Mp: 289–292 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.68 (s,

12H, CH3), 6.54 (s, 4H, ArH), 6.99–7.01 (d, J = 7.6 Hz, 8H, ArH), 7.12–7.16 (t, J = 7.6 Hz,

8H, ArH), 7.22–7.24 (d, J = 7.6 Hz, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 115.2,

127.8, 128.3, 128.6, 129.0, 129.4, 129.8, 130.7, 136.5, 165.3. Found: C, 73.43; H, 5.27; N,


Tetramethy 1,1ʹ-(1,4-phenylene)bis[2-phenyl-5-(4-methoxyphenyl)-1H-pyrrole-3,4-

dicarboxylate] (8b).

White crystal, yield: 50.9 %. Mp: 262–265 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.68 (s, 6H,

CH3), 3.69 (s, 6H, CH3), 3.80 (s, 6H, CH3), 6.56 (s, 4H, ArH), 6.66–6.69 (d, J = 8.8, 4H,

ArH), 6.92–6.94 (d, J = 8.8, 4H, ArH), 6.99–7.01(d, J = 7.2, 4H, ArH), 7.12–7.15 (t, J = 7.2,

4H, ArH), 7.21–723 (b, J = 7.2, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 55.2,

113.3, 114.8, 115.1, 121.9, 127.7, 128.2, 129.0, 129.9, 130.7, 130.9, 132.0, 136.3, 136.4,


26

5.01; N, 3.48 %.

Tetramethyl 1,1ʹ-(1,4-phenylene)bis[2-phenyl-5-(4-nitrophenyl)-1H-pyrrole-3,4-di

carboxylate] (8c).33

Yellow solid, yield: 25 %. Mp: 275–278 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.67 (s, 6H,

CH3), 3.71 (s, 6H, CH3), 6.64 (s, 4H, ArH), 7.00–6.02 (d, J = 7.2, 4H, ArH), 7.14–7.18 (t, J =

7.2, 4H, ArH), 7.16–7.18 (d, J = 8.4, 4H, ArH), 7.27–7.29 (d, J = 7.2, 2H, ArH), 7.97–7.99 (d,

J = 8.4, 2H, ArH). Found: C, 66.06; H, 4.29; N, 6.60. Calcd for. C46H34N4O12: C, 66.18; H,

4.11; N, 6.71 %.

Tetramethyl 1,1ʹ-(1,4-phenylenediyl)bis[2,5-di(4-methoxyphenyl)-1H-pyrrole-3,4-di

carboxylate] (8d).

Colorless solid, yield: 20 %. Mp: > 300 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.69 (s, 12H,

CH3), 3.79 (s, 12H, CH3), 6.58 (s, 4H, ArH), 6.67–6.69 (d, J = 8.8, 8H, ArH), 6.93–6.95(d, J

= 8.8, 8H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 51.8, 55.1, 113.2, 114.8, 122.0, 129.1,

132.1, 136.3, 136.4, 159.4, 165.3. Found: C, 69.38; H, 5.27; N, 3.13. Calc. for C50H44N2O12:

C, 69.43; H, 5.13; N, 3.24 %.

Tetramethy l,1ʹ-(1,4-phenylenediyl)bis[2-phenyl-5-(4-methoxyphenyl)-1H-pyrrole-3,4-di

carboxylate] (8e).

White crystal, yield: 50.9 %. Mp: 262–265 ℃; 1H NMR (CDCl3, 400 MHz): δ = 3.68 (s, 6H,


ArH), 6.92–6.94 (d, J = 8.8, 4H, ArH), 6.99–7.01(d, J = 7.2, 4H, ArH), 7.12–7.15 (t, J = 7.2,

4H, ArH), 7.21–7.23 (b, J = 7.2, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 55.2,

113.3, 114.8, 115.1, 121.9, 127.7, 128.2, 129.0, 129.9, 130.7, 130.9, 132.0, 136.3, 136.4,


5.01; N, 3.48 %. Crystal data: C50H44N2O12, M = 864.90, monoclinic; Z = 2, Dcalc = 1.322

g/cm3; a = 15.289(2) Å, b = 8.721(1) Å, c = 16.999(3) Å, b = 106.495(7)

o, V = 2173.4(6) Å

3,

space group P21/c (#14), R1 (I > 2.00 σ(I)) = 0.0669, R (All) = 0.1080, wR2 = 0.2160, GOF ≈

1.0.

Tetramethyl 1,1ʹ-(1,4-phenylenediyl)bis[2-(4-methoxy phenyl)-5-(4-nitrophenyl)-1H-

27

pyrrole-3,4-dicarboxylate] (8e).

Yellow solid, yield: 18.8 %. Mp: 75–78 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.67 (s, 6H,


ArH), 6.83–6.85 (d, J = 8.8, 4H, ArH), 7.27–7.29 (d, J = 8.8, 4H, ArH), 7.96–7.98 (d, J = 8.8,

2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 52.0, 55.3, 113.3, 114.8, 115.0, 122.8, 123.1,

129.4, 131.6, 131.9, 135.6, 138.9, 147.4, 152.9, 159.8, 160.2, 165.7, 167.1. Found: C, 64.23;

H, 4.53; N, 6.02. Calcd for. C48H38N4O14: C, 64.43; H, 4.28; N, 6.26 %.

28

3. Synthesis of Asymmetric Polysubstituted

1,1 -́(1,4-Phenylene)bis(pyrrole-3,4-dicarboxylates)

29

3.1 Synthesis of N-Acyl-Nʹ-acyl-N,Nʹ-(1,4-phenylene)bis(2-arylglycine)

When diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate) (5a-f) was

synthesized by the acylation of diethyl N,N′-(1,4-phenylene)bis(2-arylglycinate) using the

corresponding aroyl chloride, diethyl N-acyl-N,N′-(1,4-phenylene)bis(2-arylglycinate) (4a-f)

were obtained as byproducts (Scheme 3.1). N-Acyl-N′-acyl-N,N′-(1,4-phenylene)bis(2-aryl

glycine) (6g-l) was obtained by hydrolysis of N-acyl-N′-acyl-N,N′-(1,4-phenylene)bis

(2-arylglycinate) (5g-l), which were synthesized from diethyl N-acyl-N,N′-(1,4-phenylene)

bis(2-arylglycinate) (4a, b; 4d, e) via acylation (Scheme 3.2).

Scheme 3.1. Synthesis of diethyl N-acyl-N,N′-(1,4-phenylene)bis(2-arylglycinate)

Scheme 3.2. Acylation reaction of diethyl N-acyl-N,N′-(1,4-phenylene)bis(2-arylglycinate)

3.2 Synthesis of Asymmetric Polysubstituted 1,1ʹ-(1,4-Phenylene)bis

(pyrrole-3,4-dicarboxylates)

We examined a standard method to synthesize bimünchnones 7g-l from the N-acyl-

Nʹ-acyl-bis(2-arylglycine) 6g-l. The bimünchnones were not isolated, but instead generated

in situ by the cyclodehydration reation with N,Nʹ-diisopropylcarbodiimide in dry toluene.

Thus, a mixture of the bimünchnone 7g-l and DMAD in dry toluene was heated at 80–100 ℃

30

for 24 h to yield the desired 1,1ʹ-linked-bipyrroles 8g-l.


The reaction of compound 3a and 3b with various aromatic acid chlorides was carried

out in the presence of K2CO3 to give compound 4a-f as by–production, because of moiety

acylation of compound 3a, b. The yield of compound 4 influenced by the steric hindrance

of the substituents R and R1 and acylation activity of acyl chlorides (see Table 3.1).

Table 3.1. Synthesis of diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate)


1 H H 24 4a 15.5

2 H OCH3 24 4b 39.3

3 H NO2 24 4c 26.1

4 OCH3 H 24 4d 17.7

5 OCH3 OCH3 24 4e 62

6 OCH3 NO2 24 4f 16.9

Acylation reaction of compounds 4a, b and 4d, e with various aromatic acid chlorides was

carried out in the presence of K2CO3 to give compounds 5g-l. The results are summarized in

Table 3.2. The results indicated that the steric hindrance had a profound effect on the overall

isolated yield.

Table 3.3 shows that the hydrolysis reaction time of the compound 5, For instance, the rate

of hydrolysis is high when the compound 5 possesses –OCH3 group, (Table 3.2, entries 1, and

4). In contrast, the rate of hydrolysis is low when the compound 5 possesses –NO2 group

(Table 3.2, entries 2, 3, 5 and 6). This difference in rates may result from different solubility

31

of the compound 5 in the aqueous alcohol solution.

Table 3.2. Synthesis of diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycinate)

Entry R R1 R3 Reaction Time (h) Compound 5 Yield (%)

1 H OCH3 H 48 5g 63.1

2 H OCH3 NO2 48 5h 57.5

3 H H NO2 48 5i 47.7

4 OCH3 OCH3 H 48 5j 56.3

5 OCH3 OCH3 NO2 48 5k 61

6 OCH3 H NO2 48 5l 62.5

Table 3.3. Synthsis of diethyl N,N′-biacyl-N,N′-(1,4-phenylene)bis(2-arylglycine)

Entry R R1 R2 Reaction Time (h) Compound 6 Y (%)

1 H OCH3 H 1 6g 95

2 H OCH3 NO2 3 6h 68.5

3 H H NO2 3 6i 58.8

4 OCH3 OCH3 H 2 6j 63

5 OCH3 OCH3 NO2 3 6k 90

6 OCH3 H NO2 3 6l 60

32

Next, we examined the double 1,3-dipolar cycloaddition of bimünchnone 7g-l with DMAD.

When bimünchnone7g-l having phenyl and 4-methoxyphenyl substituents were treated with

DMAD with the double 1,3-dipolar cycloaddition, the corresponding substituted bipyrroles 8

were obtained in moderate yield (table 3.4). Unfortunately, bimünchnone 7h, 7i having

powerful electron–withdrowing groups produced 8h and 8i in low yield, due to electron–

withdrowing groups weaken reactivity of bimünchnone 7 with DMAD.

Table 3.4. The double 1,3–dipolar cycloaddition of bismünchnone 7 with DMAD

Entry R R1 R2 Reaction Time (h) Compound 8 Y (%)

1 H OCH3 H 24 8g 47.4

2 H OCH3 NO2 24 8h 17.6

3 H H NO2 24 8i 29.6

4 OCH3 OCH3 H 24 8j 52.0

5 OCH3 OCH3 NO2 24 8k 34.4

6 OCH3 H NO2 24 8l 60.0

The optical properties of compounds 8g-l were investigated. The UV/Vis spectra of the

obtained 1,1ʹ-(1,4-phenylene)bipyrrole derivatives 8g-l taken in CH3OH are shown in Figure

3.1. Compound 8g, 8j showed similar broad absorption band (200–400 nm), two maximum

absorption peaks of 8g, 8j were observed in the UV region (210 and 275 nm); Compound 8h

showed maximum absorptions at 210, 240 and 335nm. Compound 8i showed maximum

absorptions at 205, 250, 330 nm. Compound 8k showed maximum absorptions at 205, 260

nm. Compound 8l showed maximum absorptions at 205, 230 nm. In comparison to 8g, 8j

absorption band, the broad absorption band (200–410 nm) of 8h, 8i, 8k and 8l are slightly

red-shifted. The color of the solutions of compound 8 in CH3OH were colorless. The

fluorescence spectra of obtained 1,1ʹ-(1,4-phenylene)bipyrroles 8g-l were also measured in

33

Fig 3.1. UV-Vis spectra of 8g-l in CH3OH (saturated solution)

CHCl3, as shown in Figure 3.2. All of those compound showed fluorescence emissions in

CHCl3 when the phenyl C4 position was occupied by the aromatic moiety with electron–

donating group (such as CH3O), and all exhibited stronger blue fluorescence. In each of the

spectra, six main fluorescence maxima were observed. In comparison to bipyrrole 8a, the

fluorescence maxima of bipyrroles 8g-l are red–shifted (see Fig. 2.2) The fluorescence of

bipyrroles 8h-i, 8k-l can be quenched efficiently through the introduction of an electron–

withdrawing substituent (NO2).

Fig 3.2. Fluorescence spectra of 8g-l in CHCl3 ( 1×10-5

mol/L)

The products 8g-l were characterized spectroscopically. 1H NMR spectra of compound 8g-l

0

0.1

0.2

0.3

0.4

0.5

0.6

200 250 300 350 400 450 500

AB

S

UV-vis wavelength (nm)

8g

8h

8i

8j

8k

8l

0

100

200

300

400

500

600

700

800

900

1000

200 250 300 350 400 450 500 550 600

Rel

ati

ve

inte

nsi

ty

Wavelength (nm)

8g

8h

8i

8j

8k

8l

34

showed resonances at 3.6–3.7 ppm (COOCH3) (see Figure 3.3), It is noteworthy that in the

1H NMR spectra of bipyrrole (8g, 8i and 8j-k), three sets of the methoxycarbonyl (COOCH3)

protons corresponding to each ester group were observed, and those are indicative of different

electronic environment imposed by the neighboring phenyl and the substituted phenyl

substituents. In the 1H NMR spectra of bipyrrole (8h and 8l), four sets of the

methoxycarbonyl (COOCH3) protons corresponding to each ester group were observed, and

those are indicative of different electronic environment imposed by the neighboring phenyl

and the substituted phenyl substituents.13

C NMR spectra of compound 8g-l showed

resonances at 51–52 ppm (carbon of methyl of COOCH3); 114–116 ppm (carbons of the

pyrrole a with methoxycarbonyl group) and 165 ppm (carbon of carbonyl group of

COOCH3)31

, both consistent with the presence of the heterocyclic ring. Further verification

was obtained by X–ray crystallographic analysis (see Figure 3.4).

35

Fig 3.3. 1H NMR (CDCl3, 400 MHz) spectra of compound 8h, 8k, 8j

Fig 3.4. ORTEP drawing of compound 8j

3.4 Experimental and Characterization

3.4.1 Synthesis of compound 4

A two–neck round bottom flask equipped with a magnetic bar was charged CH2Cl2 (4 mL),

36

aroyl chloride (4.8 mmol, 2.2 equiv.) and KCO3 (4.8 mmol, 2.4 equiv.). To this mixture,

solution of 3a-b (2 mmol, 1 equiv.) dissolved in CH2Cl2 (6 mL) was dropped slowly via a

addition funnel. After the addition was complete, the reaction mixture was slowly warmed to

room temperature and stirred for 24 h. The reaction mixture was then washed with distilled

water 3 times. The organic layer was separated, and dried with anhydrous MgSO4, removal of

the solvent, dried in vacuo. the crude products were purified by column chromatography

(silica gel; ethyl acetate/hexane, 1:2, v/v), gave pure compound 4.

Diethyl N-benzoyl-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (4a).

Colorless solid, 0.20 g, yield: 15.5 %. Mp: 123–125 ℃. 1H NMR (CDCl3, 400 MHz): δ =

1.14–1.17 (t, J = 7.20 Hz, 3H, CH3), 1.23–1.29 (t, J = 7.20 Hz, 3H, CH3), 4.02–4.30 (m, 4H,

CH2), 4.79 (s, H, NH), 4.87 (s, H, CH), 6.16 (s, H, CH), 6.11-6.91 (d, J = 8.40 Hz, 2H, ArH),

6.59 (s, 2H, ArH), 7.07–7.32 (m, 15H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.0, 14.2,

60.6, 61.4, 61.9, 65.2, 113.0, 127.1, 127.5, 128.2, 128.5, 128.8, 129.2, 130.3, 130.9, 131.0,

131.4, 134.4, 136.1, 137.1, 144.8, 170.5, 171.3, 171.5. Found: C, 7.82; H, 6.14; N, 5.18.


Diethyl N-(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (4b).

Colorless solid, 0.80 g, yield: 57.5 %. Mp: 53–55 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.14–

1.18(m, 3H, CH3), 1.20–1.26 (m, J 3H, CH3), 3.71 (s, 3H, CH3), 4.05–4.26 (m, 4H, CH2),

4.28 (s, H, NH), 4.90 (s, H, CH), 6.13 (s, H, CH), 6.14–6.17 (d, J = 8.80 Hz, 2H, ArH), 6.58–

6.60 (d, J = 9.20 Hz, 4H, ArH), 7.06–7.08 (d, J = 6.80 Hz, 2H, ArH), 7.21–7.37 (m, 10H,

ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 14.2, 55.2, 60.7, 61.3, 61.9, 65.3, 65.4, 112.8,

113.0, 127.2, 128.1, 128.2, 128.3, 128.8, 130.3, 130.4, 130.9, 131.3, 131.5, 134.5, 137.2,

144.7, 160.4, 170.6, 171.5. Found: C, 71.94; H, 6.22; N, 4.95. Calcd for. C34H34N2O8: C,

72.07; H, 6.05; N, 4.94 %.

Diethyl N-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (4c).

Yellow solid, 0.3 g, yield: 26.1 %. Mp: 51–54 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.12–

1.17(m, 3H, CH3), 1.23–1.27 (m, 3H, CH3), 4.02–4.33 (m, 4H, CH2), 4.85–4.92 (m, 2H, CH,

NH), 6.09–6.11 (d, J = 7.60 Hz, 2H, ArH), 6.2 (s, 1H, CH), 6.59 (s, 2H, ArH), 7.04–7.06 (d, J

37

= 6.40 Hz, 2H, ArH), 7.13–7.31 (m, 8H, ArH), 7.36–7.37 (d, J = 7.20 Hz, 2H, ArH), 7.92–

7.95 (d, J = 8.80 Hz, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.0, 14,2, 60.4, 61.7, 62.0,

64.9, 113.0, 122.9 127.1, 128.4, 128.5, 128.7, 129.2, 130.3, 130.4, 131.5, 133.6, 136.8, 136.9,


C33H31N3O7: C, 68.15; H, 5.37; N, 7.22 %.

Diethyl N-benzoyl-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycinate] (4d).

Colorless solid, 0.21 g, yield 17.6 %. Mp: 82–85 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.13–

1.18 (m, 3H, CH3), 1.22–1.26 (m, 3H, CH3), 3.73 (s, 3H, CH3), 3.78 (s, 3H, CH3), 4.06–4.28

(m, 4H, CH2), 4.73 (s, H, NH), 4.83 (s, H, CH), 6.11 (s, H, CH), 6.13–6.15 (d, J = 8.0 Hz, 2H,

ArH), 6.59 (s, 2H, ArH), 6.66–6.71 (t, J = 8.80 Hz, 2H, ArH), 6.81–6.83 (t, J = 8.80 Hz, 2H,

ArH), 6.98–7.00 (t, J = 8.80 Hz, 2H, ArH), 6.98–7.00 (d, J = 8.80 Hz, 2H, ArH), 7.06–7.10 (t,

J = 7.20 Hz, 3H, ArH), 7.24–7.26 (m, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 14.2,

55.2, 55.3, 60.1, 61.3, 61.8, 64.5, 112.9, 113.6, 114.1, 126.4, 127.5, 128.3, 128.5, 129.2,

131.5, 131.6, 144.9, 159.4, 159.5, 170.8, 171.3, 171.8. Found: C, 69.76; H, 6.13; N, 4.59.


Diethyl N-(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycinate]

(4e).


1.20 (m, 3H, CH3), 1.23–1.28 (m, 3H, CH3), 3.73 (s, 3H, CH3), 3.75(3.78) (s, 3H, CH3), 3.80

(s, 3H, CH3), 4.07–4.30 (m, 4H, CH2), 4.78 (s, H, NH), 4.87 (s, H, CH), 6.09 (s, H, CH),

6.18–6.20 (d, J = 8.80 Hz, 2H, ArH), 6.60–6.62 (d, J = 8.40 Hz, 2H, ArH), 6.67–6.73 (d, J =

9.20 Hz, 4H, ArH), 6.83–6.88 (m, 2H, ArH), 6.99–7.01 (d, J = 8.80 Hz, 4H, ArH), 7.23–7.31

(m, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 14.2, 55.1, 55.2, 60.4, 61.3, 61.8, 64.7,

112.8, 113.0, 113.6, 114.2, 126.6, 128.2, 128.3, 129.1, 129.2, 130.8, 131.4, 131.6, 144.8,


C36H38N2O8: C, 68.99; H, 6.11; N, 4.47 %.

Diethyl N-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycinate] (4f).


38

1.17 (m, 3H, CH3), 1.19–1.27 (m, 3H, CH3), 3.73 (s, 3H, CH3), 3.79 (s, 3H, CH3), 4.01–4.32

(m, 4H, CH2), 4.82 (s, 1H, CH), 4.84 (s, H, NH), 6.10–6.12 (d, J = 7.60 Hz, 2H, ArH), 6.15 (s,

1H, CH), 6.67–6.71 (t, J = 8.80 Hz, 2H, ArH), 6.80–6.82 (d, J = 8.80 Hz, 2H, ArH), 6.95–

6.97 (d, J = 8.80 Hz, 2H, ArH), 7.21–7.24 (d, J = 8.80 Hz, 4H, ArH), 7.36–7.39 (d, J = 8.80

Hz, 2H, ArH), 7.93–7.95 (d, J = 8.00 Hz, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1,

62.0, 64.1, 123.1, 128.5, 128.8, 129.3, 130.1, 130.7, 132.8, 138.5, 141.5, 148.0, 169.0, 170.0.


3.4.2 Synthesis of compound 6g-l

A two-neck round bottom flask equipped with a magnetic bar was charged CH2Cl2 (10 mL),

aroyl chloride (1,8 mmol, 1.2 equiv.) and KCO3 (0.49 g, 3.6 mmol, 2.4 equiv.). To this

mixture, compound 4a-b, 4d-e (0.84 g, 1.5 mmol, 1 equiv.) was added. At room temperature

and stirred for 2 d. The reaction mixture was then washed with distilled water 3 times. The

organic layer was separated, dried with anhydrous MgSO4, removal of the solvent, and dried

in vacuo. The crude products were subjected to column chromatography (silica gel; ethyl

acetate/hexane, 1:2, v/v) to give compound 5.

Diethyl Nʹ-benzoyl-N-(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)N-bis(2-phenyl glycinate)

(5g).


1.19–1.25 (m, 6H, CH3), 3.78 (m, 3H, CH3), 4.17–4.26 (m, 4H, CH2), 6.15 (s, 1H, CH), 6.22

(s, 1H, CH), 6.51 (s, 4H, ArH), 6.57–6.59 (d, J = 8.80 Hz, 2H, ArH), 6.88–6.97 (m, 4H, ArH),

7.09–7.25 (m, 13H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 55.2, 61.5, 61.6, 64.5, 64.7,

113.1, 127.5, 127.8, 128.3, 128.4, 128.5, 128.6, 129.6, 130.3, 130.4, 130.5, 130.8, 133.8,

134.0, 135.6, 139.0, 139.7, 160.6, 170.2, 170.7,171.1. Found: C, 65.68; H, 4.88; N, 7.63. Calc.

39

for C26H28N2O4: C, 65.75; H, 4.69; N, 7.67 %.

Diethyl N-(4-methoxybenzoyl)-Nʹ-(4-nirobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenyl

glycinate) (5h).


1.19–1.25 (m, 6H, CH3), 3.78 (s, 3H, CH3), 4.18–4.30 (m, 4H, CH2), 6.21 (s, 2H, CH), 6.56

(s, 4H, ArH), 6.58–6.60 (d, J = 8.80 Hz, 2H, ArH), 6.88–6.94 (t, J = 7.80 Hz, 4H, ArH), 7.07–

7.25 (m, 6H, ArH), 7.29–7.31 (d, J = 8.80 Hz, 4H, ArH), 7.94–7.98 (d, J = 8.80 Hz, 2H, ArH).

13C NMR (CDCl3, 100 MHz): δ = 14.1, 14.4, 55.2, 61.5, 61.8, 64.3, 64.6, 112.9, 113.1, 123.0,

128.2, 128.4, 128.7, 129.3, 130.1, 130.2, 130.4, 130.7, 139.6, 139.7, 147.9, 160.8, 168.9,


5.87 %.

Diethyl N-benzoyl-Nʹ-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycinate) (5i).


1.24 (t, J = 7.20 Hz, 3H, CH3), 1.21–1.25 (t, J = 7.20 Hz, 3H, CH3), 4.18–4.26 (m, 4H, CH2),

6.20 (s, 1H, CH), 6.23 (s, 1H, CH), 6.54 (s, 2H, ArH), 6.88–6.93 (m, 4H, ArH), 7.01–7.26 (m,

15H, ArH), 7.89–7.91 (d, J = 8.40 Hz, 2H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 14.1,

61.5, 64.5, 123.1, 127.8, 128.4, 128.4, 128.7, 129.2, 129.6, 130.1, 130.3, 130.5, 130.9, 131.0,

133.1, 133.7, 135.5, 139.9,141.6, 147.8, 169.0, 169.8, 170.2, 171.2. Found: C, 69.90; H, 5.17;


Diethyl N-benzoyl-Nʹ-(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)

glycinate] (5j).


1.24 (m, 6H, CH3), 3.74 (s, 3H, CH3), 3.77 (s, 3H, CH3), 3.78 (s, 3H, CH3), 4.15–4.26 (m, 4H,

CH2), 6.13 (s, 1H, CH), 6.18 (s, 1H, CH), 6.51 (s, 4H, ArH), 6.57–6.69 (m, 4H, ArH), 6.77–

6.89 (m, 4H, ArH), 7.07–7.29 (m, 9H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 14.2, 55.2,

61.4, 61.5, 63.8, 64.0, 64.1, 64.3, 113.0, 113.7, 125.8, 125.9, 126.0, 127.6, 127.7, 128.6,

128.7, 129.6, 130.6, 130.7, 130.8, 130.9, 131.5, 131.6, 135.6, 139.0, 139.1, 139.6, 139.8,

159.6, 159.7, 160.6, 170.4, 170.5, 170.6, 171.0, 171.1. Found: C, 70.57; H, 5.80; N, 3.74.

40


Diethyl N-(4-methoxybenzoyl)-Nʹ-(4-nirobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxy

phenyl)glycinate] (5k).


1.18–1.25 (m, 6H, CH3), 3.74 (m, 3H, CH3), 3.75 (m, 3H, CH3), 3.77 (m, 3H, CH3), 4.15–

4.29 (m, 4H, CH2), 6.12 (s, 1H, CH), 6.23 (s, 1H, CH), 6.57–6.70 (m, 10H, ArH), 6.77–6.84

(m, 4H, ArH), 7.10–7.12 (d, J = 8.80 Hz, 2H, ArH), 7.30–7.32 (d, J = 8.80 Hz, 2H, ArH),

7.96–7.98 (d, J = 8.80 Hz, 2H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 14.2, 55.2, 61.5, 64.9,

113.0, 127.4, 127.5, 128.3, 128.4, 128.5, 130.3, 130.4, 130.9, 134.0, 139.6, 139.7, 160.7,


5.42 %

Diethyl Nʹ-benzoyl-N-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)

glycinate] (5l).


1.26 (m, 6H, CH3), 4.17–4.27 (m, 4H, CH2), 3.75 (3.77) (s, 3H, CH3), 3.78 (s, 3H, CH3),

6.12(6.13) (s, 1H, CH), 6.19(6.20) (s, 1H, CH), 6.55 (s, 2H, ArH), 6.62–6.64 (6.64–6.66) (d, J

= 6.40 Hz, 2H, ArH), 6.89–6.71 (d, J = 8.80 Hz, 2H, ArH); 6.79–6.85 (m, 4H, ArH); 7.00–

7.05 (m, 2H, ArH); 7.09–7.12 (m, 2H, ArH); 7.20–7.29 (m, 2H, ArH); 7.89–7.91 (d, J = 8.80

Hz, 2H, ArH); 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 55.2, 55.3, 61.5, 61.7, 63.6, 63.7, 63.9,

64.1, 113.7, 113.9, 123.1, 127.7, 128.4, 129.3, 131.4, 131.5, 131.6, 135.6, 137.9, 138.1, 139.8,

141.7, 147.9, 159.6, 159.8, 168.9, 170.1, 170.3, 171.2. Found: C, 67.54; H, 5.42; N, 5.63.


3.4.3 Synthesis of compound 6g-l

41

A two-neck round bottom flask equipped with a magnetic bar was charged with the

compound 5 (1 mmol, 1 equiv.), ethanol (5 mL) and water (10 mL). To this mixture,

Potassium hydroxide (4.2 mmol, 4.2 equiv.) was added. The mixture was heated to 80 ℃,

stirred for 3–1 h. The aqueous solution was acidified with HCl (10%) to pH 2. The acidic

solution was extracted with ethyl acetate 3 times, The combined extracts were washed

successively with H2O, 1% Na2CO3, and H2O. The organic layer was separated, dried with

anhydrous MgSO4, and removal of the solvent, gave compounds 6g-l.

N-Benzoyl-Nʹ-(4-methoxybenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycine) (6g).

White power, yield: 95.0 %. Mp: 190–193 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 3.72

(3.73) (s, 3H, CH3), 5.85 (5.86) (s, 1H, CH), 5.92 (5.94) (s, 1H, CH), 6.53 (s, 2H, ArH), 6.57

(s, 2H, ArH), 6.62–6.64 (d, J = 9.2, 2H, ArH), 6.93–7.29 (m, 17H, ArH). 13

C NMR

(DMSO-D6, 100 MHz): δ = 55.7, 65.1, 65.3, 65.4, 65.5, 113.5, 127.9, 128.2, 128.5, 129.9,

130.1, 130.3, 130.5, 130.6, 130.7, 134.5, 134.6, 134.7, 136.0, 139.5, 139.6, 140.2, 160.5,


72.30; H, 4.92; N, 4.56 %.

N-(4-Methoxybenzoyl)-Nʹ-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis(2-phenylglycine)

(6h).

Colorless solid, yield: 68.5 %. Mp: 219–222 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 3.69 (s,

3H, CH3), 5.86 (s, 1H, CH), 5.98 (s, 1H, CH), 6.55 (s, 4H, ArH), 6.92–6.94 (d, J = 7.2 MHz,

2H, ArH), 6.95–6.97 (d, J = 8.8 MHz, 2H, ArH), 6.98–7.00 (d, J = 7.6 MHz, 2H, ArH), 6.98–

7.00 (d, J = 7.2 MHz, 2H, ArH), 7.05–7.17 (m, 5H, ArH), 7.19–7.23 (d, J = 7.2 MHz, 1H,

ArH), 7.31–7.33 (d, J = 8.8 MHz, 2H, ArH), 7.97–7.99 (d, J = 8.8 MHz, 2H, ArH). 13

C NMR

(DMSO-D6, 100 MHz): δ = 55.6, 66.0, 66.3, 113.3, 123.6, 127.9, 128.3, 128.5, 128.7, 129.5,

130.2, 130.5, 130.6, 130.8, 133.9, 134.7, 142.6, 147.8, 160.6, 168.7, 169.7, 171.3, 171.5.


N-Benzoyl-N'-(4-nitrobenzoyl)-N,N'-(1,4-phenylene)bis(2-phenylglycine) (6i).


2H, CH), 5.98 (s, 2H, CH), 6.57 (s, 4H, ArH), 6.93–7.23 (m, 15H, ArH), 7.26–7.28 (d, J =8.8,

42

2H, ArH), 7.94–7.96 (d, J =8.8, 2H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 64.8, 64.9,

123.7, 128.1, 128.3, 128.4, 128.6, 128.8, 129.5, 130.5, 130.6, 133.9, 134.4, 136.1, 138.4,


C36H26N4O10: C, 64.09; H, 3.88; N, 8.31 %.

N-Benzoyl-Nʹ-(4-methoxybenzoyl)-N,N'-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycine]

(6j).

Colorless power, yield: 62.9 %. Mp: 207–209 ℃; 1H NMR (DMSO-D6, 400 MHz): δ = 3.68

(s, 3H, CH3), 3.69 (s, 3H, CH3), 3.72 (s, 3H, CH3), 5.83 (s, 1H, CH), 5.91 (s, 1H, CH), 6.53 (s,

2H, ArH), 6.56 (s, 2H, ArH), 6.60–6.67 (m, 6H, ArH), 6.83–6.85 (d, J = 8.8, 2H, ArH), 6.88–

6.90 (d, J = 8.8, 2H, ArH), 6.98–7.01 (d, J = 8.8, 2H, ArH), 7.06–7.13 (m, 4H, ArH), 7.22–

7.28 (q, J = 7.2, 1H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 55.5, 55.7, 64.4, 64.7, 113.4,

113,8, 126.5, 127.9, 128.1, 128.6, 129.9, 130.3, 130.5, 130.9, 131.9, 132.0, 136.1, 139.4,


C, 69.43; H, 5.08; N, 4.15 %.

N-Benzoyl-Nʹ-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxyphenyl)glycine]

(6k) .

Yellow solid, yield: 93.2 %. Mp: 107–109 ℃; 1H NMR (DMSO-D6, 400 MHz): δ = 3.66

(3.67) (s, 3H, CH3), 3.69 (s, 3H, CH3), 5.80 (5.85) (s, 1H, CH), 5.91 (5.94) (s, 1H, CH), 6.54

(s, 2H, ArH), 6.61–6.63 (d, J = 8.8, 2H, ArH), 6.65–6.68 (d, J = 8.8, 2H, ArH), 6.71–6.73 (d,

J = 8.4, 2H, ArH), 6.81–6.90 (m, 3H, ArH), 6.98–7.20 (m, 6H, ArH), 7.26–7.28 (t, J = 8.4,

2H, ArH), 7.94–7.96 (t, J = 8.4, 2H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 55.5, 64.1,

64.3, 64.6, 113.7, 113.9, 114.3, 123. 6, 125.7, 126.4, 128.0, 128.5, 129,4, 129.7, 130.6, 130.7,

131.2, 131.9, 132.0, 136.1, 138.3, 140.0, 142.7, 147.7, 159.4, 159.5, 168.7, 170.2, 171.6,

171.7. Found: C, 66.63; H, 4.30; N, 6.27. Calcd for. C38H31N3O10: C, 66.18; H, 4.53; N,

6.09 %.

N-(4-Methoxybenzoyl)-Nʹ-(4-nitrobenzoyl)-N,Nʹ-(1,4-phenylene)bis[2-(4-methoxy

phenyl)glycine] (6l).

Yellow solid, yield: 98.0 %. Mp: 205–208 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 3.65 (s,

43

3H, CH3), 3.67 (s, 6H, CH3), 5.79 (s, 1H, CH), 5.95 (s, 1H, CH), 6.53–6.61 (m, 4H, ArH),

6.65–6.67 (d, J = 8.8, 2H, ArH), 6.88–6.91 (d, J = 8.8, 2H, ArH), 6.96–6.99 (d, J = 8.8, 2H,


C NMR (DMSO

-D6, 100 MHz): δ = 55.5, 55.6, 64.3, 64.8, 113.2, 113.6, 113.9, 123.5, 125.9, 126.7, 127.8,

129.6, 130.2, 130.4, 130.7, 130.9, 131.9, 132.1, 138.2, 140.7, 142.6, 147.8, 159.3, 159.5,

160,6, 168.6, 169.5, 171.6, 171.7. Found: C, 64.97; H, 4.33; N, 5.64. Calcd for. C39H33N3O11:

C, 65.09; H, 4.62; N, 5.84 %.

3.4.4 General procedure for the preparation of compounds 8.

A two-neck round bottom flask equipped with a magnetic bar was charged the compound 6

(0.1 mmol, 1 equiv.) and toluene (7 mL). Under atmosphere of nitrogen, at 0–5℃, to this

mixture, DIC (0.22 mmol, 2.2 equiv.) dissolved in toluene (3 mL) was dripped, and stirred for

1.5–2 h. Then DMAD (0.22 mmol, 2.2 equiv.) dissolved in toluene (3 mL) was added, stirred

for 1 d at 80–100 ℃. The reaction mixture was then washed with distilled water 3 times. The

organic layer was separated, dried with anhydrous MgSO4, removal of the solvent, and dried

in vacuo. The crude products were subjected to column chromatography (ethyl acetate–

dichloromethane, 1:4, v/v), gave the pure bipyrrole compounds 8g-l.

Tetramethyl 2,5,2ʹ-triphenyl-5ʹ-(4-methoxyphenyl)-1,1ʹ-(1,4-phenylene)bis(1H-pyrrole-3,

4-dicarboxylate) (8g).


3H, CH3), 3.68 (s, 6H, CH3), 3.69 (s, 3H, CH3), 3.81 (s, 3H, CH3), 6.55 (s, 4H, ArH), 6.66–

6.68 (d, J = 8.8, 2H, ArH), 6.92–6.94 (d, J = 8.8, 2H, ArH), 7.99–7.01 (m, 4H, ArH)，7.12–

7.16 (t, J = 7.2, 6H, ArH), 7.21–7.23 (d, J = 8.8, 3H, ArH). 13

C NMR (CDCl3, 100 MHz): δ =

51.8, 51.9, 55.2, 113.3, 114.8, 115.1, 115.2, 122.0, 127.8, 128.2, 128.8, 129.0, 129.1, 129.9,

44

130.7, 132.0, 136.3, 136.5, 136.6, 136.7, 159.4, 165.3. Found: C, 72.45; H, 5.20; N, 3.52.


Tetramethyl 2,2ʹ-phenyl-5-(4-methoxyphenyl)-5ʹ-(4-nitrophenyl)-1,1ʹ-(1,4-phenylene)bis

(1H-pyrrole-3,4-dicarboxylate) (8h).

Yellow–green solid, yield: 17.6 %. Mp: 106–109 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.66

(s, 3H, CH3), 3.69 (s, 6H, CH3), 3.71 (s, 3H, CH3), 3.81 (s, 3H, CH3), 6.56–6.58 (d, J = 9.2,

2H, ArH), 6.62–6.65 (d, J = 8.8, 2H, ArH), 6.66–6.68 (d, J = 8.8, 2H, ArH), 6.93–6.95 (d, J =

8.8, 2H, ArH), 6.97–7.02 (m, 4H, ArH), 7.12–7.28 (m, 8H, ArH), 7.97–8.00 (d, J = 9.2, 2H,

ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 52.1, 52.2, 55.2, 113.3, 121.8, 123.0, 127.8,

128.0, 128.4, 128.6, 128.8, 129.2, 129.6, 129.9, 130.5, 130.7, 131.5, 132.0, 135.7, 137.1,


5.13 %.

Tetramethyl 2,5,2ʹ-triphenyl-5ʹ-(4-nitroxyphenyl)-1,1ʹ-(1,4-phenylene)bis(1H-pyrrole-3,

4-dicarboxylate) (8i).


6H, CH3), 3.68 (s, 3H, CH3), 3.71 (s, 3H, CH3), 6.55–6.57 (d, J = 8.8 Hz, 2H, ArH), 6.63–

6.65 (d, J = 8.8 Hz, 2H, ArH), 6.97–6.99 (d, J = 7.6 Hz, 2H, ArH), 7.01–7.02 (t, J = 7.6 Hz,

4H, ArH), 7.12–7.16 (t, J = 7.6 Hz, 6H, ArH), 7.14–7.16 (t, J = 8.8 Hz, 2H, ArH), 7.23–7.27

(m, 3H, ArH), 7.96–6.99 (t, J = 8.8 Hz, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9,

52.0, 52.1, 115.3, 116.0, 116.3, 123.0, 127.8, 128.0, 128.4, 128.6, 128.8, 129.2, 129.6, 129.8,

130.5, 130.7, 131.5, 133.7, 135.8, 136.5, 136.7, 137.1, 137.6, 147.1, 164.7, 164.9, 165.1.


Tetramethyl 2,5,2ʹ-tri(4-methoxyphenyl)-5ʹ-phenyl-1,1ʹ-(1,4-phenylene)bis(1H-pyrrole

-3,4-dicarboxylate) (8j).

Colorless crystal, yield: 52.0 %. Mp: 305–306 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.68 (s,

3H, CH3), 3.69 (s, 6H, CH3), 3.70 (s, 3H, CH3),3.79 (s, 3H, CH3), 3.80 (s, 6H, CH3), 6.57 (s,

4H, ArH), 6.66–6.68 (d, J = 8.8 MHz, 4H, ArH), 6.67–6.69 (d, J = 9.2 MHz, 2H, ArH), 6.92–

6.94 (d, J = 8.8 MHz, 4H, ArH), 6.93–6.95 (d, J = 9.2 MHz, 2H, ArH), 7.00–7.02 (d, J = 7.2

45

MHz, 2H, ArH), 7.11–7.15 (t, J = 7.2 MHz, 2H, ArH), 7.19–7.23 (t, J = 7.2 MHz, 1H, ArH).

13C NMR (CDCl3, 100 MHz): δ = 51.8, 55.1, 113.2, 114.8, 114.9, 115.2, 121.9, 122.0, 127.7,

128.2, 129.0, 129.1, 129.9, 132.0, 136.3, 136.5, 159.4, 159.5, 165.4, 165.5. Found: C, 70.52;

H, 5.39; N, 3.37.02. Calcd for. C49H42N2O11: C, 70.49; H, 5.07; N, 3.36 %. Crystal data:

C49H38N2O22, M = 830.85, colorless, triclinic; Z = 1, Dcalc = 1.134 g/cm3; a = 9.6928 (3) Å, b

= 10.4101 (3) Å, c = 13.1847 (3) Å, α = 73.0512(16)o, β = 72.9722(15)

o, γ = 85.1563(18)

o, V

= 1216.80(6) Å3, space group P1 (#1), R1 (I > 2.00 σ(I))= 0.0702, R (All) = 0.0844, wR2 =

0.2182, GOF ≈ 1.0.

Tetramethyl 2,5,2ʹ-tri(4-methoxyphenyl)-5ʹ-(4-nitrophenyl)-1,1ʹ-(1,4-phenylene)bis(1H

-pyrrole-3,4-dicarboxylates) (8k).

Yellow solid, yield: 34.4.0 %. Mp: 247–250 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.69 (s, 6H,

CH3), 3.705 (s, 3H, CH3), 3.709 (s, 3H, CH3), 3.802 (s, 6H, CH3), 3.809 (s, 3H, CH3), 6.59–

6.61 (d, J = 8.8, 2H, ArH), 6.64–6.66 (d, J = 8.8, 2H, ArH), 6.67–6.69 (d, J = 8.8, 4H, ArH),

6.69–6.71 (d, J = 8.8,2H, ArH), 6.92–6.94 (d, J = 8.8, 2H, ArH), 6.93–6.96 (d, J = 8.8, 4H,


C NMR (CDCl3,

100 MHz): δ = 51.8, 52.0, 52.1, 55.2, 113.2, 113.4, 115.7, 116.4, 121.2, 121.9, 122.9, 128.4,

128.8, 129.6, 131.6, 131.9, 132.1, 133.4, 135.7, 136.4, 136.5, 137.2, 137.6, 147.3, 159.6,


66.89; H, 4.70; N, 4.78 %.

Tetramethyl 2,2ʹ-tri(4-methoxyphenyl)-5-phenyl-5ʹ-(4-nitrophenyl)-1,1ʹ-1,4-phenylene)

bis(1H-pyrrole-3,4-dicarboxylate) (8l).

Yellow solid, yield: 60.0 %. Mp: 165–167 ℃. 1H NMR (CDCl3, 400 MHz): δ = 3.66 (s, 3H,

CH3), 3.69 (s, 3H, CH3), 3.70 (s, 6H, CH3), 3.79 (s, 3H, CH3), 3.81 (s, 3H, CH3), 6.57–6.60

(d, J = 8.8, 2H, ArH), 6.64–6.69 (m, 6H, ArH), 6.91–6.93 (d, J = 8.8, 2H, ArH), 6.94–6.96 (d,

J = 8.8, 2H, ArH), 7.01–7.03 (d, J = 7.2, 2H, ArH), 7.10–7.29 (m, 5H, ArH), 7.97–7.99 (d, J

= 8.8, 2H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 52.1, 55.2, 113.2, 113.4, 115.0,

115.3, 115.7, 121.2, 121.7, 123.0, 127.8, 128.4, 128.9, 129.6, 129.9, 130.7, 131.5, 131.9,

132.0, 135.8, 136.5, 137.1, 147.2, 159.6, 159.8, 164.8, 165.1, 165.4. Found: C, 67.23; H, 4.53;


46

4. Synthesis of Polysubstituted Tetramethyl

1,1ʹ-(Propane-1,3-diyl)bis(1H-pyrrole-3,4-dicarboxylates)

47

4.1 Synthesis of N,Nʹ-Diacyl-N,Nʹ-(propane-1,3-diyl)bis(2-arylglycine)

The N-alkylation of a primary alkylamines to N,N-disubstituted alkylamines is an

important transformation in organic synthesis. For instance, the preparation of

N,N-disubstituted amines can be performed with base and an alkyl halide. The synthetic route

for preparation of diethyl N,N′-(propane-1,3-diyl)bis(2-arylglycinate) (3c-d) is depicted in

Scheme 4.1. N,N′-alkylation of propane-1,3-diamine with ethyl 2-bromo-2-phenylacetate (2a)

or ethyl 2-bromo-2-(4-methoxyphenyl)acetate (2b) in THF gave the corresponding

compounds (3c-d) (see Scheme 4.1).

Scheme 4.1. the N,N′-alkylation of propane-1,3-diamine

According to typical methods, Diethyl N,N′-diacyl-N,N′-(propane-1,3-diyl)bis(2-aryl

glycinate) (5m-r) were synthesized by the acylation of diethyl N,N′-(propane-1,3-diyl)bis(2-

arylglycinate) using the corresponding acyl chloride (see Scheme 4.2).

Scheme 4.2. The N,N′-acylation of diethyl N,N′-(1,3-propanediyl)bis(2-arylglycinate)

N,N′-Diacyl-N,N′-(propane-1,3-diyl)bis(2-arylglycinate) was hydrolyzed to give N,N′-di

acyl-N,N′-(1,3-propanediyl)bis(2-arylglycine) (6m-r) (see Scheme 4.3).

4.2 Synthesis of Polysubstituted Tetramethyl 1,1ʹ-(Propane-1,3-diyl)bis

(pyrrole-3,4-dicarboxylates)

We used a standard method to synthesize bimünchnones 7m-r from the N, Nʹ-diacyl- N,N′-

48

(propane-1,3-diyl)bis(2-arylglycine) 6m-r. The bimünchnones 7m-r were not isolated, but

instead generated in situ by cyclodehydration with DIPC in dry toluene. Thus, a mixture of

the bimünchnones 7m-r and DMAD in dry toluene was heated at 80–100 ℃ for 24 h to

yield the desired substituted bipyrroles 8m-r (see Scheme 4.4).

Scheme 4.3. Hydrolytic reaction of N,N′-diacyl-N,N′-(propane-1,3-dily)bis(2-arylglycine)

Scheme 4.4. The cyclodehydration and cycloaddition-extrusion reaction of

N,N′-diacyl-N,N′-(propane-1,3-diyl)bis(2-arylglycine)


In generally, N,Nʹ-dialkyl-1,3-propanediamines 3c-d were prepared with difficulty. Primary

alkylamine are generally higher basic than primary arylamine. Therefore, alkylation of

primary alkylamines are difficult to control and often give mixtures of products. Because

ammonia and primary amines have similar reactivity, these reactions do not stop cleanly after

a single alkylation has occurred. the initially formed monoalkylated substance often

undergoes further reaction to yield a mixture of products.

Based on the above consideration, we investigated alkylation reactions of

propane-1,3-diylamine with compound 2a, 2b (see Table 4.1). When alkylation reactions of

1,3-propanediamine with compound 2a, 2b were performed in potassium carbonate/THF at

49

room temperature, compounds 3c, 3d were obtained in good yields (Table 4.1, entries 1 and

4). when alkylation reactions of propane-1,3-dilydiamine with compound 2a, 2b were carried

out in potassium carbonate/DCM or triethylamine at room temperature or 80 ℃ for 24 or

0.5 h, the result was unsatisfactory (Table 4.1, entries 2, 3 and 4, 5). We then selected

potassium carbonate/THF for the direct alkylation of propane-1,3-dilyamine.

Table 4.1. Synthetic conditions of diethyl N,N′-(propane-1,3-diyl)bis(2-arylglycinate)

Entry R Solvent Base tempt Time (h) Compd 3 Yield (%)

1 H THF K2CO3 r.t 24 3c 66.4

2 H DCM K2CO3 r.t 24 3c 20.0

3 H TEA TEA 80 0.5 3c 35.8

4 OCH3 THF K2CO3 r.t 24 3d 65.0

5 OCH3 DCM K2CO3 r.t 24 3d 18.0

6 OCH3 TEA TEA 80 0.5 3d 30.0

Compound 3c or 3d reacted with different aromatic acid chlorides in the presence of

K2CO3 gave the corresponding compounds 5m-r, The yield of compound 5 influenced by the

steric hindrance of the substituents R and R1 and acylation activity of acyl chlorides. The

results are summarized in Table 4.2. When R1 is H, yield of compound 5m was higher than

that of compound 5j (Table 4.2, entries 1 and 3), the results indicated that the steric hindrance

of the starting material had a profound effect on the overall isolated yield. When R is H, yield

of compound 5g was higher than compounds 5h and 5i (Table 4.2, entries 1, 2 and 3), the

results indicated that the steric hindrance of acyl chloride had a profound effect on the overall

isolated yield. When R is H, yield of compound 5h was lower than compound 5i (Table 4.2,

entries 2 and 3), the results indicated that the acylation activity of acyl chloride had a

profound effect on the overall isolated yield.

Table 4.3 shows that the hydrolysis reaction time of compound 5. For instance, the rate of

50

hydrolysis is high when the compound 5 possesses the methoxy group, (Table 4.3, entries 2,

Table 4.2. Sythesis of diethyl N,N′-diacyl-N,N′-(propane1,3-diyl)bis(2-arylglycinate)


1 H H 24 5m 87.9

2 H OCH3 24 5n 85.8

3 H NO2 24 5o 95.0

4 OCH3 H 48 5p 86.2

5 OCH3 OCH3 48 5q 92.6

6 OCH3 NO2 48 5r 90.7

Table 4.3. Synthesis of diethyl N,N′-diacyl-N,N′-(propane-1,3-diyl)bis(2-arylglycine)

Entry R R1 Time (h) / Hydrolysis Compound 6 Yield (%)

1 H H 2 6m 96.3

2 H OCH3 2 6n 96.0

3 H NO2 3 6o 97.0

4 OCH3 H 2 6p 98.0

5 OCH3 OCH3 2 6q 99.0

6 OCH3 NO2 3 6r 97.0

51

4, and 5). In contrast, the rate of hydrolysis is low, when the compound 5 possesses the nitro

group (Table 4.3, entries 3 and 6). This difference in rates may result from different solubility

of compound 5 in the aqueous alcohol.

We used DIPC dissolved in toluene as a dehydrating agent instead of acetic anhydride. In

this way, propane-1,3-dilybipyrroles were obtained via a one–pot method. We prepared

N,Nʹ-linked bimünchnone from compounds 8m-r with DIPC at 0–5 ℃ in dry toluene for 1.5

h, until the color of reaction mixture changed from colorless to orange–red, pale yellow or

purple. DMAD was then added to the mixture, and it caused the quick color change from

orange–red, pale yellow or violet color to fade. The mixture was subsequently stirred for 24 h

at 80 ℃ to give the desired substituted linked bipyrroles 8m-r. Table 4.4. illustrated when

bimünchnones having phenyl and 4-methoxyphenyl substituents were treated with DMAD

under the double 1,3–dipolar cycloaddition reaction, the corresponding bipyrroles 8m-r

were obtained in moderate yield (Table 4.4). However, bimünchnone 7o, 7r having powerful

electron–withdrowing groups produced 8o, 8r in low yield (Table 4.4, entries 3 and 6), due to

low reactivity of bimünchnone 7 with DMAD.

Table 4.4. The double 1,3–dipolar cycloaddition of bismünchnone 7 with DMAD

Entry R R1 Reaction Time (h) Compd 8 Y (%)

1 H H 24 8m 49.5

2 H OCH3 24 8n 44.6

3 H NO2 24 8o 69.0

4 OCH3 H 24 8p 72.4

5 OCH3 OCH3 24 8q 77.7

6 OCH3 NO2 24 8r 52.5

52

Products 8 was characterized spectroscopically. In the 1H NMR spectra of compounds

8m-r, the proton of methylene possessed N showed triplet at 3.10–3.30 ppm, and it is

noteworthy that in the 1H NMR spectrum of all bis-pyrrole esters (see Figure 4.1), the proton

of methyl possessed ester group (–COOCH3) showed resonances at 3.6–3.7 ppm, the single

peak of 8m (8q) is observed at 3.61ppm (3.62 ppm), the two single peak of 8n (8o, 8p, 8r)

are observed at 3.60 and 3.62 ppm (9o 3.62 and 3.63 ppm, 8p 3.60 and 3.62 ppm, 8r 3.62 and

3.64 ppm), the proton of possessed aryl group showed resonances at > 6ppm. 13

C NMR

spectra of compound 8m-r showed resonances at 51–52 ppm (a carbon of methyl of

COOCH3); 114–116 ppm (carbon of pyrrole with methoxycarbonyl group) and 164–165 ppm

(carbon of carbonyl group of COOCH3), both consistent with the presence of the heterocyclic

ring.

Fig 4.1. 1H NMR (CDCl3) spectra of compound 8n, 8k

53

The optical properties of compounds 8m-r were investigated. The UV/Vis spectra of the

obtained propane-1,3-dilybipyrrole derivatives 8m-r taken in CH3OH are shown in Figure

4.2. Compounds 8m, 8n (8p) and 8q showed similar broad absorptions band (200–355 nm),

maximum absorption peaks of 8m, 8n (8p) were observed in the UV region (210 and 265

nm); 8q showed maximum absorptions at 205, 230 and 265 nm. Compounds 8o and 8r

showed similar maximum absorptions at 205, 255, and 330 nm. Comparison of 8m, 8n (8p)

and 8q absorption band, the broad absorption band (200–440 nm) of 8o and 8r is further red–

shifted.

The fluorescence spectra of obtained propane-1,3-dilybipyrroles 8m-r were also measured

in CHCl3, and shown in Fig 4.3. All of those compound showed blue fluorescence emissions

in CHCl3 when the phenyl C4 position was occupied by the electron-donating group ( such as

OCH3), and all exhibited stronger blue fluorescence. In each of the spectra, the fluorescence

maxima of bipyrroles 8n, 8p, 8q are red–shifted compared to bipyrrole 8m. The intense

fluorescence band of 8n (8p) at 392 nm is slightly red–shifted from that of 8m (379 nm), The

intense fluorescence band of 8q at 398 nm is slightly red–shifted from that of 8m (379 nm);

the fluorescence maxima of bipyrrole 8o, 8r are blue–shifted compared to bipyrrole 8m, The

intense fluorescence band of 8o at 344 nm is larger blue–shifted compared to 8m (379 nm),

The intense fluorescence band of 8r at 343 nm is drastically blue–shifted 8m (379 nm); and

the fluorescence of bipyrroles 8o and 8r are quenched efficiently through the introduction of

an electron-withdrawing substituent (NO2).

Fig. 4.2. UV–Vis absorption spectra of 8m-r in CH3OH (1×10-5

mol/L)

0

0.2

0.4

0.6

0.8

1

200 250 300 350 400 450 500

AB

S

UV-Vis wavelength (nm)

8m

8n

8o

8p

8q

8r

54

Fig. 4.3. Fluorescence spectra of 8m-r in CHCl3 ( 1×10-5

mol/L)

4.4 Experiment and Characterization

4.4.1 Synthesis of compounds 3c, d.

In a nitrogen atmosphere, to a stirred solution of propane-1,3-diamine (5 mmol) in THF (6

mL), a solution of 2 (10.5 mmol) in THF (4mL) was added slowly to at 0–5℃, and then,

stirring for 24 h at room temperature. The mixture was extracted in ethyl acetate (20 mL).

The solution was washed with distilled water 3 times, the organic layer was separated, dried

with anhydrous MgSO4, and concentrated in vacuo. The residual mixture was subjected to

column chromatography (hexane–ethyl acetate, 1.5:1 v/v; ethyl acetate), gave the

corresponding compound 3.

Diethyl N,N'-(propane-1,3-diyl)bis(2-phenylglycinate) (3c).

Colorless oil, yield: 73.4 %. 1H NMR (CDCl3, 400 MHz): δ = 1.16–1.20 (t, J = 7.20 Hz, 6H,

CH3), 1.67–174 (m, J = 7.20 Hz, 2H, CH2), 2.16 (s, 2H, NH), 2.55–2.68 (m, 4H, CH2), 4.09–

4.21 (m, 4H, CH2), 4.31 (s, 2H, CH), 7.26–7.34 (m, 10H, ArH). 13

C NMR (CDCl3, 100 MHz):

δ = 14.2, 30.0, 46.3, 61.1, 65.7, 127.4, 128.0, 128.7, 138.3, 173.1. Found: C, 68.77; H, 7.57;

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

200 250 300 350 400 450 500 550 600

Rel

ati

ve

inta

nsi

ty

Wavelength (nm)

8m

8n

8o

8p

8q

8r

55


Diethyl N,N'-(propane-1,3-diyl)bis{2-(4-methoxyphenyl)glycinate}(3d).

Colorless oil, yield: 64.9 %. 1H NMR (CDCl3, 400 MHz): δ = 1.16–1.20 (t, J = 7.20 Hz, 6H,

CH3), 1.66–172 (m, J = 7.20 Hz,2H, CH2), 1.77 (s, 2H, NH), 2.50–2.66 (m, 4H, CH2), 3.77 (s,

6H, CH3), 4.06–4.20 (m, 4H, CH2), 4.25 (s, 2H, CH), 6.82–6.84 (d, J = 8.40 Hz, 4H, ArH),

7.24–7.26 (d, J = 8.40 Hz, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.2, 30.0, 46.1, 55.3,

61.0, 65.0, 113.8, 127.9, 128.5, 130.5, 159.3, 173.3. Found: C, 64.92; H, 7.23; N, 6.15. Calcd

for. C25H34N2O6: C, 65.48; H, 7.47; N, 6.11 %.

4.4.3 Synthesis of compounds 5m-r

A two–neck round bottom flask equipped with a magnetic bar was charged CH2Cl2 (6 mL),

acyl chloride (4.8 mmol, 2.4 equiv.) and KCO3 (4.8mmol, 2.4 equiv.). To this mixture,

solution of 3c-d (2 mmol, 1equiv.) dissolved in CH2Cl2 (4 mL) was dropped slowly via a

addition funnel at 0–5 ℃. After the addition was complete, the reaction mixture was stirred

for 1 d at room temperature. The reaction mixture was then washed with distilled water 3

times. The organic layer was separated, dried with anhydrous MgSO4, removal of the solvent,

and dried in vacuo. The crude products were subjected to column chromatography (silica gel;

ethyl acetate/hexane, 1.5:1, v/v) to give the corresponding target compounds 5m-r.

Diethyl N,Nʹ-dibenzoyl-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycinate) (5m).

Colorless solid, yield: 87.9 %. Mp: 35–38 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.20–1.24 (t,

J = 7.20 Hz, 8H, CH3 and CH2), 4.18–4.26 (m, 4H, CH2), 5.20 (s, 2H, CH), 6.89–6.91 (d, J =

7.60 Hz, 4H, ArH), 7.07–7.26 (m, 16H, ArH). 13

C NMR (CDCl3, 100 MHz): δ= 14.1, 61.5,

64.5, 127.8, 128.3, 128.4, 128.5, 129.6, 130.2, 130.5, 133.9, 135.5, 139.2, 170.1, 171.1.


56

Diethyl N,Nʹ-di(4-methoxybenzoyl)-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycinate) (5n).


J = 7.20 Hz, 8H, CH3 and CH2), 2.91 (bs, 4H, CH2), 3.85(s, 6H, CH3), 4.14–4.27 (m, 2H,

CH2), 6.85–6.87 (d, J = 7.60 Hz, 4H, ArH), 7.24–7.32 (m, 14H, ArH). 13

C NMR (CDCl3, 100

MHz): δ = 14.2, 55.4, 61.4, 113.9, 128.3, 128.6, 128.8, 129.4, 134.5, 160.7, 170.1. Found: C,


Diethyl N,Nʹ-di(4-nitrobenzoyl)-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycinate) (5o).


J = 7.20 Hz, 8H, CH3 and CH2), 2.91 (bs, 4H, CH), 4.11 (s, 1H, CH), 6.93–7.52 (m, 14H,

ArH), 8.24 (s, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 62.0, 64.1, 123.1, 128.5,

128.8, 129.3, 130.1, 130.7, 132.8, 138.5, 141.5, 148.0, 169.0, 170.0. Found: C, 63.59; H, 5.32;


diethyl N,Nʹ-dibenzoyl-N,Nʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)glycinate] (5p).


J = 7.20 Hz, 8H, CH3 and CH2), 2.77–2.98 (d, J = 8.80 Hz, 4H, CH2), 3.80 (s, 6H, CH3),

4.13–4.22 (m, 4H, CH2), 6.68–6.86 (d, J = 8.40 Hz, 4H, ArH), 7.07–7.38 (m, 14H, ArH). 13

C

NMR (CDCl3, 100 MHz): δ = 14.2, 55.3, 61.4, 114.2, 126.4, 128.5, 129.6, 130.9, 136.3,


4.20 %.

Diethyl N,Nʹ-di(4-methoxybenzoyl)-N,Nʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)

glycinate] (5q).


J = 7.20 Hz, 8H, CH3 and CH2), 2.83 (s, 4H, CH2), 3.80 (s, 6H, CH3), 3.82 (s, 6H, CH3),

4.13–4.24 (m, 4H, CH2), 5.46 (s, 2H, CH), 6.85–6.87 (d, J = 8.40 Hz, 8H, ArH), 7.23–7.25 (d,

J = 8.40 Hz, 8H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.2, 55.3, 61.4, 113.8, 114.2,


C41H46N2O10: C, 67.75; H, 6.38; N, 3.85 %.

Diethyl N,Nʹ-di(4-nitrobenzoyl)-N,Nʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)glycin

57

-ate] (5r).

Colorless solid, yield: 90.7 %. Mp: 66–69 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.07–1.28

(m, 8H, CH3 and CH2), 2,45–2.83 (m, 4H, CH3), 3.81 (s, 6H, CH3), 4.23 (s, 2H, CH2), 6.77–

7.20 (m, 6H, ArH), 7.38–7.42 (d, J = 8.80 Hz, 2H, ArH), 7.45–7.47 (d, J = 8.40 Hz, 4H, ArH),

8.20–8.23 (d, J = 8.40 Hz, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 14.1, 55.3, 61.8, 63.9,

113.9, 123.0, 124.8, 129.4, 130.9, 131.4, 138.7, 141.5, 148.1, 159.9, 168.8, 170.1. Found: C,


4.4.4 Synthesis of compounds 6m-r

A two–neck round bottom flask equipped with a magnetic bar was charged compounds

5m–r (1mmol, 1equiv.), ethanol (5 mL) and water (10 mL). To this mixture, Potassium

hydroxide (4.2 mmol, 4.2 equiv.) was added. The mixture was heated to reflux for 6 h. The

aqueous solution was acidified with HCl (10%) to pH 2. The acidic solution was extracted

with ethyl acetate 3 times, The combined extracts were washed successively with H2O, 1 %

Na2CO3, and H2O. The organic layer was separated, dried with anhydrous MgSO4, removal

of the solvent, and compounds 6m–r were obtained.

N,Nʹ-Dibenzoyl-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycine) (6m).

White power, yield: 99.0 %. Mp: 85–88 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 1.02–1.24

(m, 2H, CH2), 4.18–4.26 (m, 4H, CH2), 5.20 (s, 2H, CH), 6.48 (s, 4H, ArH), 6.89–6.91 (d, J =

7.60 Hz, 4H, ArH), 7.07–7.26 (m, 16H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.5,

61.5, 64.5, 127.8, 128.3, 128.4, 128.5, 129.6, 130.2, 130.5, 133.9, 135.5, 139.2, 170.1, 171.1.


N,Nʹ-Di(4-methoxybenzoyl)-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycine) (6n).

58

Colorless solid, yield: 98.1 %. Mp: 102–105 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 1.02–

1.25 (m, 2H, CH2), 2.91 (bs, 4H, CH2), 3.87(s, 6H, CH3), 5.17 (m, 2H, CH), 6.85–6.87 (d, J =

7.60 Hz, 4H, ArH), 7.24–7.32 (m, 14H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.5,

55.4, 61.4, 113.9, 128.3, 128.6, 128.8, 129.4, 134.5, 160.7, 170.1. Found: C, 68.65; H, 5.39;


N,Nʹ-Di(4-nitrobenzoyl)-N,Nʹ-(propane-1,3-diyl)bis(2-phenylglycine) (6o).

White power, yield: 99.0 %. Mp: 105–108 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 1.03–

1.24 (m, 2H, CH2), 2.21 (m, 4H, CH2), 5.19 (s, 2H, CH), 6.93–7.52 (m, 14H, ArH), 8.17–8.26

(d, J = 8.80 Hz, 4H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.6, 62.0, 64.1, 123.1,

128.5, 128.8, 129.3, 130.1, 130.7, 132.8, 138.5, 141.5, 148.0, 169.0, 171.2. Found: C, 61.94;

H, 4.54; N, 8.68. Calcd for. C33H28N4O10: C, 61.87; H, 4.41; N, 8.75 %.

N,Nʹ-Dibenzoyl-N,Nʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)glycine] (6p).


1.32 (m, 2H, CH2), 2.47–3.13 (m, 4H, CH2), 3.73 (s, 6H, CH3), 5.19 (s, 2H, CH), 6.88–7.42

(m, 18H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.6, 21.2, 55.6, 62.0, 114.2, 114,6,

126.4, 129.0, 129.9, 131.3, 136.8, 159.5, 171.2. Found: C, 68.63; H, 5.50; N, 4.47. Calcd for.

C35H34N2O8: C, 68.84; H, 5.61; N, 4.59 %.

N,Nʹ-Di(4-methoxybenzoyl)-N,Nʹ-(-propane-1,3diyl)bis[2-(4-methoxyphenyl)glycine]

(6q).


1.37 (m, 2H, CH2), 2.41–2.68 (m, 4H, CH2), 3.74 (s, 6H, CH3), 3.76 (s, 6H, CH3), 5.17 (s, 2H,

ArH), 6.89–7.13 (m, 18H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.6, 21.2, 55.6, 55.7,

62.0, 113.9, 114.2, 127.2, 128.6, 128.8, 129.4, 130.9, 131.2, 159.5, 160.5, 171.6. Found: C,


N,Nʹ-Di(4-nitrobenzoyl)-N,Nʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)glycine] (6r).

Yellow solid, yield: 97.1 %. Mp: 110–113 ℃. 1H NMR (DMSO-D6, 400 MHz): δ = 1.03–

1.24 (m, 2H, CH2), 3.16–3.28 (m, 4H, CH2), 3.78 (s, 6H, CH3), 5.21 (s, 2H, CH), 6.64–6.66

(d, J = 8.80 Hz, 4H, ArH), 6.77–6.80 (d, J = 8.80 Hz, 4H, ArH), 7.28–7.30 (d, J = 8.00 Hz,

59

4H, ArH), 7.96–7.98 (d, J = 8.00 Hz, 4H, ArH). 13

C NMR (DMSO-D6, 100 MHz): δ = 14.6,

55.3, 61.8, 63.9, 113.9, 123.0, 124.8, 129.4, 130.9, 131.4, 138.7, 141.5, 148.1, 159.9, 168.8,

170.1. Found: C, 60.17; H, 4.33; N, 7.74. Calcd for. C35H32N4O12: C, 60.00; H, 4.60; N,

8.00 %.

4.4.5 The preparation of compounds 8m–r

A two–neck round bottom flask equipped with a magnetic bar was charged the compounds

6m–r (0.2 mmol, 1 equiv.) and toluene (8 mL). Under atmosphere of nitrogen, at 0–5 ℃, to

this mixture, DIC (0.44 mmol, 2.2 equiv.) dissolved in toluene (2 mL) was dropped, and

stirring for 1.5 h. Then DMAD (0.44 mmol, 2.2 equiv.) dissolved in toluene (5 mL) was

added, when DMAD was added, heated to 80–100 ℃ with an oil bath, stirred for 1d. The

reaction mixture was then washed with distilled water 3 times. The organic layer was

separated, dried with anhydrous MgSO4, removal of the solvent, and dried in vacuo. The

crude products were subjected to column chromatographyand (ethyl acetate–dichloromethane,

1:4, v/v), gave the pure bipyrrole compounds 8m–r.

Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis(2,5-diphenyl-1H-pyrrole-3,4-dicarboxylate) (8m).

Colorless crystal, yield: 49.5 %. Mp: 119–121 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.06–

1.12 (m, 2H, CH2), 3.16–3.20 (t, J = 7.6 Hz, 4H, CH2), 3.61 (s, 12H, CH3), 7.02–7.09 (d, J =

7.6 Hz, 8H, ArH), 7.33–7.42 (m, 12H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 51.9, 115.2,

127.8, 128.3, 128.6, 129.0, 129.4, 129.8, 130.7, 136.5, 165.3. Found: C, 72.43; H, 5.43; N,


Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis[2-phenyl-5-(4-methoxyphenyl)-1H-pyrrole-3,4-di

carboxylate] (8n).


60

(m, 2H, CH2), 3.16–3.20 (t, J = 8.0 Hz, 4H, CH2), 3.60 (s, 6H, CH3), 3.62 (s, 6H, CH3), 3.87

(s, 6H, CH3), 6.87–6.89 (d, J = 8.8 Hz, 4H, ArH), 7.00–7.02 (d, J = 8.8 Hz, 4H, ArH), 7.06–

7.08 (d, J = 7.6 Hz, 4H, ArH), 7.30–7.42 (m, 6H, ArH). 13


31.6, 41.6, 51.6, 55.3, 113.9, 114.5, 114.6, 122.3, 128.5, 128.8, 130.2, 130.4, 131.5, 135.7,


70.12; H, 5.49; N, 3.63 %.

Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis[2-phenyl-5-(4-nitrophenyl)-1H-pyrrole-3,4-di

carboxylate] (8o).

Yellow solid, yield: 69 %. Mp: 199–201 ℃. 1H NMR (CDCl3, 400 MHz): δ = 0.96–1.45 (m,

2H, CH2), 3.23–3.27 (t, J = 7.2, 4H, CH2), 3.62 (s, 6H, CH3), 3.63 (s, 6H, CH3), 7.12–7.14 (t,

J = 8.8, 4H, ArH), 7.24–7.26 (d, J = 8.8, 4H, ArH), 7.37–7.47(m, 6H, ArH), 8.19–8.21 (d, J =

8.8, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 31.4, 41.8, 51.9, 53.5, 115.7, 116.0, 123.7,

128.7, 129.4, 129.6, 130.1, 131.2, 133.4, 136.7, 136.8, 147.8, 152.2, 164.3, 164.8. Found: C,


Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis[2-phenyl-5-(4-methoxyphenyl)-1H-pyrrole-3,4-di

carboxylate] (8p).


(m, 2H, CH2), 3.16–3.20 (t, J = 8.0 Hz, 4H, CH2), 3.60 (s, 6H, CH3), 3.62 (s, 6H, CH3), 3.87

(s, 6H, CH3), 6.87–6.89 (d, J = 8.8 Hz, 4H, ArH), 7.00–7.02 (d, J = 8.8 Hz, 4H, ArH), 7.06–

7.08 (d, J = 7.6 Hz, 4H, ArH), 7.30–7.42 (m, 6H, ArH). 13


31.6, 41.6, 51.6, 55.3, 113.9, 114.5, 114.6, 122.3, 128.5, 128.8, 130.2, 130.4, 131.5, 135.7,


70.12; H, 5.49; N, 3.63 %.

Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis[2,5-di(4-methoxyphenyl)-1H-pyrrole-3,4-di

carboxylate] (8q).

Colorless crystal, yield: 77.7 %. Mp: 261–262 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.11–

1.19 (m, 2H, CH2), 3.16–3.20 (t, J = 8.0, 4H, CH2), 3.62 (s, 12H, CH3), 3.87 (s, 12H, CH3),

6.87–6.89 (d, J = 8.8, 8H, ArH), 8.19–8.21 (d, J = 8.8, 4H, ArH). 13

C NMR (CDCl3, 100

61

MHz): δ = 31.7, 41.5, 51.6, 55.3, 113.9, 114.4, 122.4, 131.5, 135.7, 159.9, 165.4. Found: C,


Tetramethyl 1,1ʹ-(propane-1,3-diyl)bis[2-(4-methoxyphenyl)-5-(4-nitrophenyl)-1H-

pyrrole-3,4-dicarboxylate] (8r).

Yellow solid, yield: 52.5 %. Mp: 98–101 ℃. 1H NMR (CDCl3, 400 MHz): δ = 1.01–1.09 (d,

J = 8.0, 2H, ArH), 3.22–3.26 (d, J = 8.0, 4H, ArH), 3.62 (s, 6H, CH3), 3.64 (s, 6H, CH3), 3.89

(s, 6H, CH3), 6.92–6.94 (d, J = 8.8, 4H, ArH), 7.07–7.09 (d, J = 8.8, 4H, ArH), 7.23–7.25 (d,

J = 8.8, 4H, ArH), 8.19–8.21 (d, J = 8.0, 4H, ArH). 13

C NMR (CDCl3, 100 MHz): δ = 31.5,

41.8, 51.9, 55.4, 113.9, 114.1, 115.6, 115.7, 121.5, 123.6, 131.2, 131.5, 133.1, 136.7, 136.9,


62.79; H, 4.68; N, 6.51 %.

62

5. Conclusion

In conclusion, according to the typical methods, eighteen novel N,Nʹ-diacyl-bis(2-aryl

glycinate) compounds and the corresponding N,Nʹ-diacyl-bis(2-arylglycine) compounds were

synthesized, and eighteen N,Nʹ-linked-bimünchnones were prepared. Sixteen novel

N,Nʹ-linked-bipyrroles were obtained by double [3+2] cycloaddition-extrusion reactions of

N,Nʹ-linked-bimünchnones and DMAD. This is a novel synthetic route for the synthesis of

fully substituted bipyrroles.

The optical properties of these N,Nʹ-linked-bipyrrole compounds were investigated. Eight

N,Nʹ-linked-bipyrroles have strong blue fluorescence. These new N,Nʹ-linked-bipyrroles could

find widespread applications in materials science and pharmaceutical chemistry.

The synthetic procedures have the advantages of mild reaction conditions, convenient

handling as well as a wide substrate scope, which make this method useful for the synthesis

of potentially biologically active fully substituted bipyrrole derivatives, bipyrrolines,

biimidazoles, biimidazolines, and other heterocycles.

63

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32. 13

C NMR ( 100 MHz) of compound 3c and compound 3e were measured with D6-DMSO at 120℃.

33. 13

C NMR (100 MHz) of compound 5c was fail to measure with CDCl3, D6-DMSO at 120℃.

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College of Life and Materials Systems Engineering Graduate ... · Synthesis of fully substituted 1,1ʹ-linked-bipyrrole Tetramethyl substituted 1,1ʹ- ethylene-bipyrrole, 1,1ʹ-ethylene-bis(2,5-dimethyl-1H-pyrrole)