3.1 INTRODUCTION: 3.2 LITERATURE SURVEY: 3.3...

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Development and Application of New Methodologies for Synthesis of Bioactive Molecules176

3.1 INTRODUCTION:

3.2 LITERATURE SURVEY:

3.3 OBJECTIVE OF THE WORK:

3.4 DESIGN AND DEVELOPMENT:

3.5 EXPERIMENTAL:

3.6 RESULT AND DISCUSSION:

3.6.1 Mechanism:

3.7 APPLICATION:

3.8 SUMMERY AND CONCLUSION:

3.9 REFERENCES:

3.10 SPECTRA:

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3.1 INTRODUCTION:

The first synthetic dye discovered by Perkin, an English scientist working under

Hoffman, a German professor and even today the geographical focus of dye

production lies in Germany (BASF, Dystar), England (Avecia) and Switzerland

(Clariant, Ciba Specialties). Far Eastern countries, such as Japan, Korea and Taiwan,

as well as countries such as India, Brazil and Mexico also produce dyes.1

Dyes may be classified according to their chemical structure or by their usage or

application method. The former approach is adopted by practicing dye chemists, who

use terms such as azo dyes, anthraquinone dyes, triphenylmethane dyes and

phthalocyanine dyes. The later approach is used predominantly by the dye users, the

dye technologists, who speak of reactive dyes for cotton and dispersed dyes for

polyester. Very often, both terminologies are used, for example, an azo dispersed dye

for polyester and a phthalocyanine reactive dye for cotton.1

Triphenylmethane derivatives are hydrocarbons with the formula (R1-Ar-R2)3CH,

where R1 and R2 indicate different substituents, including hydrogen, halogen, alkyl

and alkoxy groups.1 The most important substituent is the amino group which is

present in diaminotriphenylmethane (DTM) compounds. Important dyes belonging to

this class include the well-known Leucomalachite Green and Crystal Violet, which are

some of the oldest synthetic dyes (Figure 1).1-2

Figure 1: Two examples of diaminotriphenylmethane (DTM) compounds

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The leuco forms of triarylmethane dyes are extensively used in biological

applications. They show photo toxicity toward tumor cells3 and also demonstrate

antifungal4a-c antitubercular5 anti-infective, and antimicrobial activity.6 Additionally,

they have been used for sterilization of trypanosome cruizi-infected blood,7a-b in

biotechnology process control,8-9 in dye-assisted laser inactivation of enzymes,10 in

wastewater treatment plants,11 and in the photo chemotherapy of neoplastic

diseases.12-14 In analytical chemistry, they are used as indicators in calorimetric and

titrimetric determinations,15 in detection of various heavy metals,16 and for the

detection of iodide17 and carboxylic acids.18 Diaminotriphenylmethane (DTM) dyes

are the most important group of triarylmethane dyes and were selected for the present

study due to their brilliance, high pictorial strength, and wide variety of applications.

Such as pressure-sensitive heat-sensitive materials, high-speed photo duplicating

copying paper, light-sensitive paper, ultrasonic recording paper, electrochemical heat-

sensitive recording paper, inks, crayons, typewriter ribbons, and photoimaging

systems.19 analysis of biological fluids, and wastewater treatment.20

Furthermore, they have particular structural properties in solid and solution phases.

This group includes a broad range of dyes such as Cresol Red, Bromocresol Green,

Light Green SF Yellowish, Victoria Blue BO, Ethyl Green, Brilliant Green,

Diaminotriphenylmethane, Fast Green FCF, Green S, Fuchsine Acid, Chlorophenol

Red, Crystal Violet Lactone, Fuchsine, Pararosaniline, Water Blue, Thymolphthalein,

Bromocresol Purple, and Aurin. (Figure 2) These compounds are usually soluble in

non-polar organic solvents and are insoluble in water.

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Figure 2

Because of the wide range of applications of DTMs, the development of new and

more efficient synthetic methods for their preparation is of great importance.

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3.2 LITERATURE SURVEY:

A wide range of approaches are available for the preparation of the aforementioned

compounds. Dyes has great influence in the field of chemistry as diagnostic agents,

colour forming agents, indicator in titration reaction, in paint and pigment industries

and high tech application as in solar cells.

1) Ceric (IV) Ammonium Nitrate Catalyzed Synthesis of 4,4′-

Diaminotriarylmethane

Bardajee, G. R and et. Al. have been reported, one step synthesis of 4,4′-

dimethylaminotriarylmethanes in the presence of ceric(IV) ammonium nitrate as a

Lewis acid catalyst. The entitled compounds were prepared by the tandem regio-

selective electrophilic aromatic substitution reaction of N, N-dimethylaniline with aryl

aldehydes to form corresponding diaminotriarylmethane compounds. The synthetic

scheme is given in Scheme 3.121

Scheme 3.1: CAN catalysed synthesis of 4,4’-dimethylaminotriarylmethanes.

2) Synthesis using Montomorillonate K-10 22

Synthesis of triarylmethanes via Baeyer condensation dimethylaniline catalysed by of

aromatic aldehydes with N,N-dimethylenediamine catalysed by montmorillonite k-10.

Scheme 3.2

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3) Microwave mediated synthesis23

Guzman and et al have been reported a microwave mediated synthesis of DTM.

Scheme 3.3

4) Antimony chloride mediated synthesis of DTM24

A solvent-free one-step synthesis of various 4,4′-diaminotriarylmethane derivatives in

the presence of antimony trichloride as catalyst is described.

Scheme 3.4

5) Acid catalysed synthesis of DTM25

George et al have been reported the synthesis of DTM, is the reaction of arylaldehydes

with N,N-dimethylaniline in the presence of an acid such as sulfuric acid, HCl, p-

TSA.

Scheme 3.5

6) Bi(NO3)3•5H2O mediated synthesis of DTM26

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Recently, a synthesis of a variety of diaminotriarylmethane derivatives were

synthesized by the tandem Regio-selective electrophilic aromatic substitution reaction

of N,N-dimethylaniline with aryl aldehydes to form the corresponding

diaminotriarylmethane compounds.

Scheme 3.6

7) By using ZrOCl2•8H2O27

Solvent-free synthetic technique of diaminotriarylmethanes was reached by treating

N,N-dimethylaniline with some arylaldehydes over zirconium(IV) oxide chloride

(ZrOCl2•8H2O).

Scheme 3.7

Although different methods for the preparation of the aforementioned compounds

have been described, most of them however, suffer from drawbacks such as the use of

corrosive acids or toxic or hazardous chemicals, excess of solvents and harsh reaction

conditions, long reaction times which will result in generation of waste streams,

complicated workup procedures, byproducts and isomeric mixtures and consequently,

low yields. Therefore, there is still a need to search for a better catalyst with regards to

toxicity, selectivity, availability and operational simplicity for the synthesis of

triarylmethane compounds.

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3.3 OBJECTIVE OF THE WORK:

Iodine and iodine reagents have attracted increasing interest during the last decade

because of their selective, mild, and environmentally friendly properties as oxidizing

agents in organic synthesis. Investigation from our laboratories have revealed a series

of new paradigm for iodine reagent mediated reactions under mild conditions.28

Sodium dichloroiodate (I) {NaICl2} is nothing but a iodine reagent (non hypervalent

iodine compound) have recently attracted rising attention because of their selective,

mild, and environmentally friendly properties as oxidizing agents in organic

synthesis.39 So in this perspective, we develop a first novel synthetic utility of NaICl2

for synthesis of triaryl alkane compounds by aromatic C-C coupling, while the

developed method also useful for the preparation of diarylmethane compounds.

Sodium dichloroiodate is commercially available iodine reagent in a 50% water

solution and reported for the iodination of the aromatic ring at 40–70OC for 72 h.29

more recently we used this for the transformation of alcohol to aldehyde30a and

aldehyde to corresponding nitriles.30b While working on this reagent, we found that it

can be used for the regioselective carbon-carbon bond forming reaction. Relevant of

this methodology stems from the fact that all the aforementioned transformations are

quite fundamental in nature and can be easily applied to a multitude of synthetic

strategies.

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3.4 DESIGN AND DEVELOPMENT:



corrosive acids or toxic or hazardous chemicals, as well as the inconvenience in

handling the reagents. Considering these restrictions, excess of solvents and harsh

reaction conditions, which will result in generation of waste streams, complicated

workup procedures, byproducts and isomeric mixtures and consequently, low yields.

Therefore, there is still a need to search for a better catalyst with regards to toxicity,

selectivity, availability and operational simplicity for the synthesis of triarylmethane

compounds.

In this contribution, we describe a new route for the preparation of DTM derivatives.

In addition, as our group has been working extensively on the development of novel

methodologies under mild conditions using iodine reagents. We observed that in the

presence of aqueous sodium dichloroiodate solution, N,N-dimethylaniline and

aromatic or aliphatic aldehydes, converted into either 4,4’-arylmethylene-bis-(N,N-

dimethylaniline) or 4,4’-alkylmethylene-bis-(N,N-dimethylaniline) (Scheme 3.9).

Scheme 3.9 Reaction of aryl and alkyl aldehydes with N,N-dimethylaniline in presence of NaICl2

Here, a first synthetic utility of NaICl2 (sodium dichloroiodate) for preparation of

triarylmethanes and diarylalkanes is described. In the presence of aqueous solution of

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NaICl2, the reaction of arenes with aromatic aldehydes gives corresponding

triarylmethane regioselectivly, in moderate to good yields. The method also useful for

the synthesis of diarylalkane derivatives by using aliphatic aldehydes.

3.5 EXPERIMENTAL:

General Experimental Procedure for synthesis of Triarymethanes using Iodine

Reagent:

Arylaldehydes (1 equiv), N, N-dimethylaniline (2 equiv) and aqueous NaICl2 (2 M, 10

ml, 0.5 equiv) was reflux in round bottom flask for 3-6 h. After completion of reaction

(TLC), the reaction mixture was quenched in water (10 mL) and further diluted with

dichloromethane (30 mL). The organic layer was separated and washed successively

with 10% aqueous solution of Na2S2O3 (2 x 20 mL), 10% aqueous solution of

NaHCO3 (2 x 15 mL), and finally with H2O (2 x 20 mL). Then organic layer was dried

over anhydrous Na2SO4 and concentrated under reduced pressure to give crude

product. Pure DTM as a green solid was obtained after silica gel column

chromatography (EtOAc: hexane, 1: 9).

Synthesis of Leucomalachite green:

Table 1, entry 1: 4,4’-(phenylmethylene)bis(N,N-dimethyleaniline)

Benzaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.23g, (2 equiv) and aqueous was

treated by general procedure with NaICl2 0.104g, (2 M, 10 ml, 0.5 equiv) in round

bottom flask for 4h to gave the product with 75% yield (0.225 g); M.P. 92-93OC; 1H

NMR (CDCl3): δ 2.93 (s, 12H), 5.40 (s, 1H ), 6.66-7.25 (m, 13H,); IR (KBr, cm-1):

3075, 1611, 1532, 1459, 1347; 13C NMR (CDCl3): 148.91, 145.41, 132.81, 129.98,

129.86, 129.32, 128.02, 112.54, 112.41, 55.04, 40.79, 40.65

Table 1, entry 2: 4,4’-(4-fluorophenyl)methylene)bis(N,N-dimethylaniline)

4-fluro-benzaldehyde 0.1g,(1 equiv), N, N-dimethylaniline 0.19g, (2 equiv) and

aqueous was treated by general procedure with NaICl2 0.104g, (2 M, 10 ml, 0.5 equiv)

in round bottom flask for 5h to gave the product with 70% yield (0.195 g); M.P.100-

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101OC 1H NMR (CCl4, 60 MHz): 2.84(s, 12H), 5.21(s,1H), 6.41-7.33 (m, 12H); IR

(KBr, cm-1): 3075, 1611, 1532, 1459, 860

Table 1, entry 3: 4,4’-(4-chlorophenyl)methylene)bis(N,N-dimethylaniline)

4-chloro-benzaldehyde 0.1g,(1 equiv), N, N-dimethylaniline 0.17g, (2 equiv) and


in round bottom flask for 5h to gave the product with 68% yield (0.175 g); M.P.256-

257OC; 1H NMR (CCl4, 60 MHz): 2.90 (s, 12H), 5.31 (s,1H), 6.53-7.42 (m, 12H); IR

(KBr, cm-1): 3074, 1615, 1531, 1462, 863

Table 1, entry 4: 4,4’-(4-nitrophenyl)methylene)bis(N,N-dimethylaniline)

4-nitro-benzaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.16g, (2 equiv) and


in round bottom flask for 3h to gave the product with 78% yield (0.192 g); M.P. 178-

179OC; 1H NMR (CCl4, 60 MHz): 2.86(s, 12H), 5.49(s,1H), 6.81(d, 1H), 8.00-

8.49(m, 11H); IR (KBr, cm-1): 3076, 1611, 1532, 1459, 1355, 860

Table 1, entry 5: 4,4’-(4-methylphenyl)methylene)bis(N,N-dimethylaniline)

4-methyl-benzaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.20g, (2 equiv) and


in round bottom flask for 6h to gave the product with 65% yield (0.185 g); 1H NMR

(CCl4, 60 MHz): 2.35 (s, 3H), 2.92(s, 12H), 5.48 (s,1H), 6.64(d, 4H), 7.05-7.15(m,

8H); IR (KBr, cm-1): 3070, 2960, 1609, 1530, 1455, 1350, 855

Table 1, entry 6: 4,4’-(4-methoxyphenyl)methylene)bis(N,N-dimethylaniline)

4-methoxy-benzaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.17g, (2 equiv) and



105OC; 1H NMR (CCl4, 60 MHz): 2.90(s, 12H), 3.71(s, 3H), 5.49(s,1H), 6.62 (d,

4H),7.13(d, 4H), 7.52(d, 4H) 12H); IR (KBr, cm-1): 3410, 3075, 2931, 1611, 1532,

1459, 1317, 1270, 817

Table 1, entry 7: 4,4’-(pyridine-2-ylmethylene)bis(N,N-dimethylaniline)

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Pyridine-2-aldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.22g, (2 equiv) and



171OC; 1H NMR (CCl4, 60 MHz)): 2.94(s, 12H), 5.38(s,1H), 6.61(d, 6H), 7.04(d,

5H), 8.04(d,1H); IR (KBr, cm-1): 3075, 1611, 1532, 1459

Table 1, entry 8: 4,4’-(thiophen-2-ylmethylene)bis(N,N-dimethylaniline)

Thiophen-2-aldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.21g, (2 equiv) and



84OC; 1H NMR (CCl4, 60 MHz): 2.90(s, 12H), 5.50(s, 1H), 6.58-7.25 (m, 11H); IR

(KBr, cm-1): 3073, 1611, 1534, 1460, 1341,1200

Table 1, entry 9: 4,4’-(furan-2-ylmethylene)bis(N,N-dimethylaniline)

Furan-2-aldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.44g, (2 equiv) and aqueous

was treated by general procedure with NaICl2 0.11g, (2 M, 10 ml, 0.5 equiv) in round

bottom flask for 6h to gave the product with 75% yield (0.248 g); 1H NMR (CCl4, 60

MHz): 3.06 (s, 12H), 5.57(s, 1H), 6.08-7.58 (m, 11H); IR (KBr, cm-1): 3081, 1625,

1542, 1470, 1346,1210

Table 1, entry 10: 4,4’-(cyclohexylphenylmethylene)bis(N,N-dimethyleaniline)

Cyclohexaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.37g, (2 equiv) and aqueous


bottom flask for 4h to gave the product with 40% yield (0.119 g); M.P. 150-152OC; 1H NMR (CDCl3): 1.27-1.52(m, 10H), 2.35(m, 1H), 2.95(s, 12H), 4.19(d, 1H),

6.61(d, 4H), 7.25(d, 4H); IR (KBr, cm-1): 3061, 2926, 1611, 1532, 1440, 1347; 13C

NMR (CDCl3): 14.83, 133.90, 128.66, 128.54, 113.13, 112.99, 54.03, 41.61,

41.05, 32.35, 29.79, 25.57

Table 1, entry 11: 4,4’-(3-methylbutane-1,1-diyl)bis(N,N-dimethyleaniline)

3-methylbutanal 0.1g, (1 equiv), N, N-dimethylaniline 0.49g, (2 equiv) and aqueous


bottom flask for 2h to gave the product with 60% yield (0.216 g); M.P. liquid

>250OC;1H NMR (CDCl3): 0.97 (t, 6H), 1.45(m, 1H), 1.89(t, 2H), 2.80(s, 12H),

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3.95(d, 1H), 6.69(d, 4H), 7.15(d, 4H); IR (KBr, cm-1): 3070, 2915, 1465, 1375, 800;

13C NMR (CDCl3): 149.05, 148.86, 134.76, 130.62, 129.50, 129.40, 128.40,

128.31, 113.26, 113.13, 46.85, 45.51, 43.30, 41.19, 41.06, 41.00, 40.93, 39.96,

29.77, 25.57, 22.81

Table 1, entry 12: 4,4’-(propane-1,1-diyl)bis(N,Ndimethyleaniline)

Propanaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.41g, (2 equiv) and aqueous


bottom flask for 2h to gave the product with 65% yield (0.316 g); B.P. 51-52OC;1H

NMR (CDCl3): 0.90(t, 3H), 1.95(m, 2H), 2.80(s, 12H), 3.90(t, 1H), 6.68(d, 4H),

7.15(d, 4H); IR (KBr, cm-1): 3070, 2980, 1462, 1370, 802; 13CNMR(CDCl3):

149.04, 130.33, 129.46, 129.35, 113.10, 112.96, 49.04, 41.14, 41, 40.88, 40.72 ,

39.88, 12.04

Table 1, entry 13: (E)-4,4’-(3-phenylprop-2-ene-1,1-diyl)bis(N,Ndimethyleaniline)

Cinnamaldehyde 0.1g, (1 equiv), N, N-dimethylaniline 0.28g, (2 equiv) and aqueous


bottom flask for 5h to gave the product with 30% yield (0.071 g); 1H NMR (CDCl3):

2.95(s, 12H), 4.80(d, 1H), 6.60 (d, 1H), 6.80(d, 1H), 7.10(m, 8H), 7.21-7.60(m, 5H);

IR (KBr, cm-1): 3065, 2924, 1611, 1470, 1532, 801; 13CNMR,(CDCl3): 144.09,

136.34, 134.74, 130.08, 129.92, 128.48, 127.08, 116.78, 113.09, 52.79, 40.78

3.6 RESULT AND DISCUSSION:

From our investigations it was observed that N,N-dimethylaniline reacts smoothly

with arylaldehydes and heterocyclic aldehydes in the presence of NaICl2 to produce

the corresponding DTMs (Scheme 3.10) in good to excellent yields. At first we

focused on the reaction of benzaldehyde and N,N-dimethylaniline as a model reaction

under various reaction conditions (with solvent, solvent-free). Various protic and

aprotic solvents (Table no.2) were examined: The best results were obtained under

solvent-free conditions. It was also observed that under similar reaction conditions but

at room temperature slower reaction rate was observed.

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The general route for the synthesis of these compounds as shown below.

Scheme 3.10

Then, to explore the possibility of other reagents (Table no. 1) for conversion of

aldehydes into corresponding DTM, we also carried out the reaction with other iodine

reagents including ICl, DIB, and Iodine. Unlike the situation with sodium

dichloroiodate (Table no. 1, entry 4), no good yield was obtained. Hence from this

observation it was concluded that the sodium dichloroiodate was a best reagent for

this reaction.

Table 1: Reagent Studya

Entry Reagent Solvent Time (h)

Yieldb (%)

1 I2 CHCl3 8 50

2 ICl CHCl3 7 60

3 DIB CHCl3 12 25

4 NaICl2 CHCl3 6 75

aBenzaldehyde (1 equiv.) and N,N-dimethylaniline (2 equiv.) with different

iodine reagents, b isolated yield.

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Afterward, in solvent study, it was observed that, in chloroform reaction gave good

yield (Table 2 entry 4). But lower yields were observed in case of acetone, methanol

and dichloromethane (Table 2, entries 1-3). It was noteworthy that, when reaction

was carried out under solvent free condition, it gave good yield as compare the results

obtained from other solvents (Table 2, entry 6). And finally from this study it was

concluded that benzaldehyde (1equiv.) and N, N-dimethylamine (2 equiv) in solvent

free under reflux condition was good optimum condition.

Table 2: Solvent Studya

Entry Solvent Time (h)

Yieldb (%)

1 Acetone 12 20

2 Methanol 12 25

3 Dichloromethane 12 30

4 Chloroform 6 75

5 THF 12 30

6 Solvent free 4 85

aBenzaldehyde (1 equiv.) and N,N-dimethylaniline (2 equiv.) with different iodine reagents. bisolated

yield.

During reaction it was also, observed that N, N-dimethylaniline reacted with para-

formaldehyde at reflux temperature in presence of aqueous solution of sodium

dichloiodate and resulted in the formation of 4,4’-methylene-bis(N, N-

dimethylaniline) (Scheme 3.11) and thus provided an interesting rout for synthesis of

diphenylmethane compounds.

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Scheme 3.11 Reaction of Paraformaldehyde with N,N-dimethylaniline in presence of NaICl2

Next to evaluate scope of this method, these conditions were applied to variety of

aromatic and aliphatic aldehydes and the results are presented in Table 3. The results

clearly indicate that this method is suitable for electron withdrawing and donating

substituted aromatic substrates (Table 3, entries 2-6). In each case, good to excellent

yields of the desired 4,4’-arylmethylene-bis-(N,N-dimethylaniline) products were

isolated. Heterocyclic aromatic aldehyde compounds were also suitable for this

transformation (Table 3, entries 7- 9). A lowered reaction rate was observed in case

of aliphatic aldehydes (Table 3, entries 11, 12). Further investigations indicated that

α, β-unsaturated aldehydes are also suitable for this reaction (Table 3, entry 13)

without affecting the geometry of double bond.

Table 3: Reaction of N,N-dimethylaniline with aldehydes in presence of aqueous NaICl2 Scheme

3.12. a

Scheme 3.12

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Entry R-CHO Product Time

(h) Yieldb

(%)

1

4

75

2

5 70

3

5 68

4

3 78

5

6 65

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6

6 65

7

4 60

8

6 80

9

O

NCH3

CH3

N

CH3

H3C

6 75

10

4 40

11

2 60

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12 2 65

13

5 30

aReaction conditions: N,N’dimethylaniline (2 equiv), NaICl2 (0.5 equiv), aldehyde (1equiv). bIsolated

yields after column chromatography and structures were confirmed by comparison of IR and 1H NMR

with authentic materials.

So herein, we developed efficient and versatile methodology for synthesizing

diaminotriphenylmethanes as well as diamininodiphenylalkanes by using aqueous

sodium dichloroiodate reagent.

3.6.1 MECHANISM:

The plausible mechanism for this reaction can be proposed in (Figure 3), in which the

C-C coupling may be due to activation of the carbonyl group of the aldehyde by

NaICl2.

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Figure 3 . Plausible reaction mechanism

In this nucleophilic addition reaction, nucleophilic attack of N, N-dimethyleneamine

on electrophilic carbonyl carbon took place. Here the roll of NaICl2 is to increase the

electrophilicity of carbonyl group of aldehyde. Then, formation of intermediate 2, in

this chloride ion abstract a proton and ring get aromatized. In next step, the

intermediate 3 will again attacked by another mole of N, N-dimethylenediamine group.

And again by same way chloride ion pickup a proton, and another ring also get

aromatized, finally converted into Leucomalachite green compound.

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3.7 APPLICATION:

As discussed early in introduction, these type molecules have broad scope of

application like ink, it also Use in flexographic printing colours. Worldwide annual

sales of these dyes are approximately 1000 tones (Gessner & Mayer, 2000). Apart

from this application, these dyes are also have been used in medicinal field.

a) Synthesis of malachite green

This methodology can also be successfully used for the synthesis of malachite green.

Scheme 3.13

b) Synthesis of Michler’s base and Michler’s ketone

Here, we can be also applying for the synthesis of michler’s ketone. Michler base or

michler ketone is active ingredient in the synthesis of auramine. Worldwide annual

sales of these dyes are approximately 1000 tones (Gessner & Mayer, 2000). It is used

in flexographic printing colours.

Experimental: Step-1: Synthesis of Michler’s base (Spectra 14, 15)

Paraformaldehyde 0.1g,(1 equiv), N, N-dimethylaniline 0.49g,(2 equiv) and aqueous

was treated by general procedure with NaICl2 0.26g,(2 M, 0.5 equiv) in round bottom

flask for 8h to gave the solid product with 70% yield (0.195 g); M.P.90-91OC; 1H

NMR (CCl4, 60 MHz): 2.89(s, 12H), 3.81(s, 2H), 6.52-6.70 (d, 4H), 6.99-7.25 (d,

4H); IR (KBr, cm-1): 3350, 1601, 1513, 943, 792

Step-2: Synthesis of Michler’s Ketone (Spectra 16)

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Michler’s base 0.1g,(1 equiv), DIB 0.18g,(1.5 equiv) and sodium azide was added

catalytic in a 10ml of ACN:H2O system, at room temperature for an 1 h.50% yield

(0.0501g); M.P.172-174OC; 1H NMR (CCl4, 60 MHz): 2.85(s, 12H), 6.10-6.25 (d,

4H), 7.20-7.40 (d, 4H); IR (KBr, cm-1): 3080, 1610, 1700, 1535, 1462, 755

Scheme 3.14

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3.8 SUMMARY AND CONCLUSION:



corrosive acids or toxic or hazardous chemicals, excess of solvents and harsh reaction

conditions, long reaction times which will result in generation of waste streams,

complicated workup procedures, byproducts and isomeric mixtures and consequently,

low yields. Therefore, there is still a need to search for a better catalyst with regards to

toxicity, selectivity, availability and operational simplicity for the synthesis of

triarylmethane compounds.

In summary, it has been demonstrated that NaICl2 is a mild and efficient catalyst for

the one-pot reaction of N,N-dimethylaniline with a variety of aryl and heteroaryl

aldehydes under solvent-free conditions to give substituted triarylmethanes. Using

NaICl2 as catalyst, even electron-rich benzaldehydes gave the corresponding products

in good yields. Operational simplicity, high yields, and the ability to prepare a wide

range of products are the advantages of this protocol.

In conclusion, a new reaction system using NaICl2 for C-C coupling has been

developed, which is capable of converting various aldehydes into corresponding

triphenyl and diphenyl compounds. The developed method is mild and gives moderate

to good yields of product for both aliphatic and aromatic substrates.

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3.9 REFERENCES:

1. K. Venkataraman, The Chemistry of Synthetic Dyes, 1st edition (Academic

Press, New York, 1952)

2. H.A. Lubs, The Chemistry of Synthetic Dyes and Pigments, 1st edition

(Reinhold Publishing Corporation, New York, 1955

3. Kandela, I. K.; Bartlett, J. A.; Indig, G. L.; Photochem. Photobiol. Sci., 2002, 1,

309

4. a) Culp, S. J.; Beland, F. A.; J. Am. Coll. Toxicol. 1996, 15, 219 b) Alderman,

D. J.; J. Fish. Dis. 1985, 8, 289 c) Cho, B. P.; Yang, T.; Blankenship, L. R.;

Moody, J. D.; Churchwell, M.; Beland, F. A.; Culp, S. J.; Chem. Res. Toxicol.

2003, 16, 285

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2179

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nthesis of Bio

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Developm

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nthesis of Bio

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cules208

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Developm

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Table

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nthesis of Bio

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Developm

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