MSc project report on self assembly

1. Project Report
On
Synthesis and Post-synthetic Modification of
Discrete Molecular Architectures
Submitted by:
Sohan Hazra
School of Chemical Sciences,
National Institute of Science Education and Research,
Bhubaneswar, Odisha.
Under the guidance of:
Prof. Partha Sarathi Mukherjee
Department of Inorganic and Physical Chemistry,
Indian Institute of Science,
Bangalore-560012.

2. Table of Contents
 Certificate
 Acknowledgement
 Abstract
 Aim of project
 Introduction
 Experimental section
 Result and discussion
 Characterization techniques
 NMR
 IR
 Mass spectrometry
 Conclusion
 References

3. Certificate:
This is to certify that Mr. Sohan Hazra worked on the project titled as ‘Synthesis and post
synthetic modification of discrete molecular architectures’ in the Department of Inorganic
and Physical Chemistry, Indian Institute Of Science, Bangalore under my guidance and he has
completed it satisfactorily.
Signature:
Dr. Partha Sarathi Mukherjee
Department of Inorganic and Physical Chemistry
Indian Institute of Science,
Bangalore-560012

4. Acknowledgement:
I express my sincere gratitude to Dr. Partha Sarathi Mukhejee, Professor, IPC, IISc for giving me the
wonderful opportunity to work in his laboratory.
I express my deepest sense of heartfelt gratitude to Mr. Aniket Chowdhury whose constant guidance in
every aspect of my lab work and report has made it possible for me to complete this project. I would
also like to thank all the lab members without whose support and encouragement this study would never
have been accomplished.
I also thank my parents who have offered me solid support that helped me work efficiently. Lastly, I
thank the Almighty for everything.

5. Synthesis and post synthetic modification of discrete molecular architectures
Abstract
A new PtII
2 organometallic building block (8) with 90o
geometry is synthesized by ‘Sonogashira
coupling reaction’. The self-assembly of the acceptor with two new pyridyl donors (6), (7) in acetone
give rise to two new molecular squares which are characterized by multinuclear NMR (1
H,31
P), IR
and ESI-MS spectrometric analysis. The Molecular Square (1) is treated with metal anchoring moiety
in order to generate a post synthetically modified macrocycle functionalized with metal binding sites.
A model macrocycle was also prepared to compare the difference between the responses of all three
macrocycles in the presence of different analytes.
Aim of the project:
Our aim in this project is to synthesize discrete molecular architectures by self-assembly, which also
contain highly reactive functional groups like the aldehyde group. After synthesis and characterization
of the self-assembled discrete molecules we will try to functionalize them to generate post synthetically
modified molecular architectures. The macrocycle will be functionalized with metal chelating groups
which will enable them to show different responses in presence of various metal ions. The original and
modified macrocycles are expected to show bright luminescence generated from Platinum-ethynyl
linkage. Therefore their different response can easily be monitored. Also luminescent model
compounds will be prepared to study the advantage of post-synthetic modification of macrocycles in
detail. The original macrocycle and the post-synthetically modified macrocycle will be characterized
by multinuclear NMR, IR and Mass spectrometry.
Introduction:
From the quaternary structure of proteins to the DNA double-helix formation by complementary base
pairing, weak bond interactions play a pivotal role as nature’s tool in every aspect of life force in this
universe. Inspired by this fascinating discovery, scientists have long been engaged in utilizing the weak
bond interaction, giving birth to new fields like self-sorting, coordination driven metal-ligand self-
assembly and many more. By carefully selecting metal center and its counter ligands, different
geometrical architectures can be accomplished ranging from 2D squares, triangles and rectangles to
3D prisms, spheres and many more. All these architectures if functionalized may form structures
having the potential of not only fine tuning its geometry but also to have rational applications.
Recently there have been several reports where different systems like MOFs1, Metal Organic
Nanocages2 and Conjugated Micro porous Polymers3 have been investigated for the scope of post
synthetic modifications. Recently, Prof Stangs group and Prof Hai Bo Yang’s group have reported
post-synthetic functionalization of molecular rhomboids4 and hexagons5. From our group, previously,
several reports have been made on synthesis and sensing studies of 2D and 3D discrete molecular

6. architectures6. Therefore we have chosen to synthesize two new molecular squares containing easily
functionalizable groups and to investigate their scope for post synthetic modification.
Scheme 1: Self-assembly of molecular squares by new organometallic Pt acceptor (8) and two new
pyridyl donors (6) and (7)
CHCl3: MeOH
60o
C, 24 hr
Macrocycle 1
Macrocycle 2
Macrocycle 1 Macrocycle 1 psm

7. Experimental Section:
 Synthesis of 4-(9H-carbazol-9-yl)benzaldehyde (2):
9H-carbazole (2.5 gm, 14.95 mmol) was taken in a clean and oven dried double-neck round bottom
flask. To the carbazole, 4-bromobenzaldehyde (4.2 gm, 22.42 mmol), CuI (7 gm, 44.85 mmol) and
potassium carbonate (680 mg, 3.57 mmol) were added. The mixture was dispersed in dry 1, 2-
dichlorobenzene under nitrogen atmosphere and degassed. Then 18-crown-6 ether (500 mg, 4 mmol)
was added and the reaction mixture was refluxed at 1400
C for 48 hr. Then the solvent was evaporated
and the reaction mixture was cooled and quenched with saturated solution of ammonium carbonate.
The resulting red solid was extracted with DCM (30 mLx3) and treated with Na2SO4. The organic part
was dried to obtain crude brown product which was purified by column chromatography using silica
gel (60-120 mesh) and DCM: Hexane (1:1) as eluent to afford pure white product (3.51 gm, 88.20%
yield). 1
H NMR (CDCl3, 400 MHz): - 10.12 (s, 1H), 8.14 (m, 4H), 7.80 (d, 2H), 7.51 (d, 2H), 7.45(m,
2H), 7.33 (m, 2H).
 Synthesis of 4-(3,6-dibromo-9H-carbazol-9-yl)benzaldehyde (3):
To an oven dried clean 100 mL round bottom flask 2 (500 mg, 1.84 mmol) was dissolved in 20 mL
DMF. NBS (689 mg, 3.87 mmol) was added to the solution and the reaction mixture was stirred at
room temperature for 24 hr. The crude was added to crushed ice and stirred for 30 min. The resulting
white precipitate was extracted with DCM three times (50 mL × 3). The organic layer was treated
with Na2SO4 and evaporation of DCM gave white solid product (706 mg, yield 88.72%). 1
H NMR
(CDCl3, 400 MHz): - 10.13 (s, 1H), 8.14 (d, 2H), 8.19 (d, 2H), 7.74 (d, 2H), 7.55 (m, 2H), 7.43 (m,
2H).
 Synthesis of 4-(3,6-bis((trimethylsilyl)ethynyl)-9H-carbazol-9-yl)benzaldehyde (4):
To an oven dried 100 mL Schlenk flask were suspended 3 (700 mg, 1.63 mmol), CuI (20 mg, 5 mol%),
Pd (PPh3)2Cl2 (58 mg, 3mol%), PPh3 (85 mg, 20 mol%) in 30 mL freshly distilled triethylamine and
the mixture was heated to 400
C for 15 min. Trimethylsilylacetylene (0.5 mL, 3.58 mmol) was added to
the suspension and the reaction mixture was refluxed for 24 hr. The solvent was evaporated and the
crude was purified using column chromatography (silica gel 60-120 mesh) and DCM: Hexane (1:4) as
eluent to afford white solid (630 mg, 93%). 1
H NMR (CDCl3, 400MHz): - 10.11 (s, 1H), 8.23 (s, 2H),
8.13 (d, 2H), 7.73 (d, 2H), 7.55 (m, 2H), 7.36 (m, 2H).
 Synthesis of 4-(3,6-diethynyl)-9H-carbazol-9-yl)benzaldehyde (5):
Compound 4 (600mg, 1.29 mmol) and potassium carbonate (411mg, 2.97 mol) were dissolved in a
mixture of DCM: MeOH (20mL: 15mL) in a 100 mL round bottom flask and stirred at room
temperature for 24 hr. The solvent was evaporated and the crude was purified using column
chromatography (silica gel, 60-120 mesh) and DCM: Hexane (1:4) used as eluent to afford white
product (300 mg, yield 75 %). 1
H NMR (CDCl3, 400MHz): - 10.15 (s, 1H), 8.27 (s, 2H), 8.15 (d, 2H),
7.75 (d, 2H), 7.59 (m, 2H), 7.40 (m, 2H).

8.  Scheme 2: Schematic representation of the synthesis of 4-(3, 6-bis (pyridin-4-ylethynyl)-9H-
carbazol-9-yl) benzaldehyde (6) from 9H-carbazole:
 Synthesis of 4-(3, 6-bis (pyridin-4-ylethynyl)-9H-carbazol-9-yl) benzaldehyde (6):
To an oven dried 100 mL Schlenk flask were suspended 5 (200 mg, 0.63 mmol), 4-bromopyridine
hydrochloride (368 mg, 1.88 mmol), CuI (4 mg, 5 mol %), Pd (PPh3)2Cl2 (20 mg, 3mol %), PPh3 (16
mg, 20 mol %) in 30 mL freshly distilled triethylamine and the mixture was heated to reflux for 24 hr.
The solvent was evaporated and the crude was purified using column chromatography (neutral
alumina) and DCM: Hexane (1:4) used as eluent to afford white solid (170 mg, 54%). 1
H NMR (CDCl3,
400MHz): - 10.15 (s, 1H), 8.63 (d, 4H), 8.37 (s, 2H), 7.78 (d, 2H), 7.65 (m, 2H), 7.42 (m, 6H).

9.  Synthesis of 9-hexadecyl-3,6-bis(pyridin-4-ylethynyl)-9H-carbazole (7):
The synthesis was performed in the same procedure as for compound 6. The starting material was
prepared by using Hexadecylbromide instead of 4-bromobenzaldehyde. 1
H NMR (CDCl3, 400MHz):
- 8.59 (d, 4H), 8.28 (d, 2H), 7.65 (d, 2H), 7.39 (m, 6H), 4.26 (m, 2H), 1.83 (m, 3H), 1.31 (m, 28H).
 Synthesis of carbazole based Pt acceptor(8):
This synthesis was done following the procedure already reported from our group7
. For the starting
material 9-phenylcarbazole was chosen instead of 9H-carbazole. 1
H NMR (CDCl3, 400MHz):  7.95
(s, 4H), 7.61 (m, 2H), 7.50 (d, 2H), 7.28 (m, 4H).
 Synthesis of Macrocycles (1, 2):
All the macrocycles are prepared following the same procedure. To the solution of acceptor (2 mL) in
a 10 mL drying vial was added a solution of the donor in acetone (2 mL). The reaction mixture was
heated at 500
C for 24hr. The solvent was reduced and cold ether (3 mL) was added to form precipitate.
The solid was washed with ether several times and dried to obtain final product.
 Synthesis of Macrocycles (1):
The platinum acceptor (13 mg, 0.0105 mmol) was treated with ligand 6 (5 mg, 0.01057 mmol) to obtain
macrocycle 1 (isolated yield 78%).
 Synthesis of Macrocycle (2):
The platinum acceptor (13 mg, 0.0105 mmol) was treated with ligand 6 (5.93 mg, 0.01057 mmol) to
obtain macrocycle 2 (isolated yield 73%).
 Synthesis of Macrocycles (1 psm):
The macrocycle 1 (10 mg, 0.0028 mmol) was dissolved in 10 mL CHCl3: MeOH (7:3) mixture. To
the solution 2-hydroxybenzohydrazide (1mg) was added and heated at 600
C for 24 hr. The solvent was
reduced and cold ether (4 mL) was added to give yellow precipitate. The solid was washed several
times with cold ether to afford macrocycle psm1 (60 % yield)
Result and discussion:
Conversion of 1 to 2 was a typical ‘Ullman reaction’. The carbazole nitrogen acted as nucleophile
and replaced the bromine of the 4-bromobenzaldehyde in presence of CuI as catalyst to form the
desired product. The crown ether acted as the phase transfer catalyst for CuI and potassium carbonate
used as base which helped in catalyzing the adduct formation by removing the 9H proton of the
carbazole moiety. Dichlorobenzene acted as high boiling solvent, which was necessary because high
temperature was required to drive pass the energy barrier of the reaction. The yield of the reaction
was high and the product was characterized by 1
H NMR (CDCl3, 400 MHz).

10. Compound 3 was prepared by simple bromination reaction at room temperature in presence of NBS
as the bromine source. The bromination reaction took place at the most active para position to the
carbazole nitrogen. Precise amount of NBS was added to avoid further bromination which undergoes
radical mechanism pathway. The purification of the product was by extraction with organic solvent
as the byproduct succinic acid was soluble in water. The product was characterized by 1
H NMR
(CDCl3, 400 MHz)
The silylation of 3 gave the desired compound 4. The ‘Sonogashira reaction’ was performed under
inert atmosphere and dry solvent was necessary to avoid spoiling of the catalyst due to oxidation of
the Palladium by water. Excess amount of TMSA was required to make sure that no monosilyl
product had formed. The reaction was monitored by TLC and upon total consumption of the starting
material the reaction was stopped. The solvent was removed and the crude was purified by column
chromatography to afford pure white product. The product was verified by 1
H NMR (CDCl3, 400
MHz).
The desired pyridyl donor was synthesized by the same reaction method as mentioned in the previous
procedure. Excess amount of 4-bromopyridine hydrochloride was added to avoid formation of mono
pyridyl linker. The reaction was comparatively slow and took longer time to finish as monitored by
TLC. The solvent was dried after the reaction was finished and the crude was purified by using
neutral alumina as the stationary phase. DCM: Hexane mixture (20%) was used initially as the eluent
and the polarity was increased up to DCM (100%) gradually. THF was added in small portions to the
DCM (2%) and finally the product came at THF: DCM (10%) mixture. The final product was yellow
in color and was characterized by 1
H NMR (CDCl3, 400MHz).
The other pyridyl donor was prepared using the same procedure as mentioned above. The only
difference was that Hexadecylbromide was used in place of 4-bromobenzaldehyde. The product was
purified by column chromatography and using the same stationary and mobile phase to afford yellow
colored product, verified by 1
H NMR (CDCl3, 400MHz).
The macrocycle 1 was obtained by treating equivalent amount of compound 6 with 8 in acetone at
elevated temperature. The NMR was taken in a solvent mixture of CDCl3: MeOD, and MeOH was
used as the solvent in ESI-MS spectrometry. The assembly was characterized by 1
H NMR, 31
P NMR,
IR and ESI-MS spectrometry. The 31
P NMR of macrocycle 1 exhibited sharp singlet at 16.03 ppm
which has shifted up field from the starting acceptor by 4 ppm. The characteristic satellite peaks
corresponded to 195
Pt-P coupling present in the compound. The formation of (2+2) macrocycle was
supported by ESI-MS spectrometric analysis where multiply charged molecular ions corresponding
to the macrocycle was observed. The molecular ion peaks of macrocycle 1 are m/z = 1687.52 (M-
2NO3)2+
, 1104.35 (M-3NO3)3+
, 812.76 (M-4NO3)4+
.
The macrocycle 2 was prepared in the same procedure as mentioned earlier and was characterized by
similar spectroscopic analysis. NMR was taken in a solvent mixture of CDCl3: MeOD, and MeOH
was used as the eluent in ESI-MS spectrometry. The 31
P NMR showed sharp singlet at 15.34 ppm
which is a 5 ppm up field shift from the acceptor. Also the peaks corresponding to the 195
Pt-P
coupling were also present. The molecular ion peaks of macrocycle 2 are m/z = 1780.7254 (M-
2NO3)2+
, 1184.50(M-3NO3)3+
, 872.88(M-4NO3)4+
.
The product obtained by post synthetic modification of the macrocycle was also verified by the
similar characterization techniques. The NMR was taken in a solvent mixture of CDCl3: MeOD, and
MeOH was used as the solvent in ESI-MS spectrometry. The 1
H NMR showed the absence of the
aldehyde peak at 10.33 ppm. Although a minimum change in the 31
P NMR was observed the ESI-MS

11. spectrometry data unambiguously proved the formation of the macrocycle 1 psm. The molecular ion
peaks are m/z = 1794.54 (M-2NO3-PEt3+2MeOH) 2+
, 1660.49 (M-2NO3-3PEt3+MeOH) 2+
.
Characterization Techniques:
NMR Spectra:
Macrocycle 1:
1H NMR Spectra: 31P NMR Spectra:
Macrocycle 2:
1H NMR Spectra: 31P NMR Spectra:

12. Macrocycle 1 psm:
1H NMR Spectra: 31P NMR Spectra:
IR Spectra:
Macrocycle 1: Macrocycle 1 psm:

13. Mass Spectra:
Macrocycle 1:
Macrocycle 2:

14. Macrocycle 1 psm:
Conclusion:
During the one month project, three self-assembled discrete molecular architectures were successfully
synthesized and characterized by 1
H-NMR, 31
P-NMR, IR and ESI-MS spectrometry. During the project,
standard practical experimental techniques were used and sophisticated instruments were handled. The next
step of the project will be to study the response of the macrocycle in the presence of different analytes.
References:
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