appendix-b - inflibnetshodhganga.inflibnet.ac.in/bitstream/10603/8203/14/14_appendix b.pdf · the...

Appendix-B

Novel Combination of Sodium Borohydride and Reusable

Polyaniline Salt Catalyst for Rapid and Efficient Reductive

Amination of Carbonyl Compounds

Appendix-B: reductive amination!..

168

B.1 Introduction

Reductive amination of aldehydes and ketones is one of the most useful

methods to prepare amines, which are useful in biological and chemical systems

as solvents, in the synthesis of intermediates for pharmaceuticals and

agrochemicals, in polymers, dyes and raw materials for resins, textile additives,

disinfectants, rubber stabilizers, corrosion inhibitors, and in the manufacturing of

detergents and plastics [1,2]. The methylamine derivatives of anthracene and

naphthalene have various applications, including anticancer inhibitory effects [3-6],

Fluorescent sensors [7-12] Fluorescent pH indicators [13-14], and pH-controllable

supramolecular switches [15].

Reductive amination of carbonyl compounds with the use of NaBH4 was

carried out by microwave method [16], in micellar media [17], ionic liquids [18],

titanium (IV) isopropoxide [19], NaBH4 along with catalysts such as various acids

[20] boric acid/p-toulenesulfonic acid/ benzoic acid [21], boric acid [22], acetic acid

[23], trifluoroacetic acid [24], silica-phosphoric acid [25] iodine [26], indium chloride

[27], guanidine-hydrochloride [28], 12-Tungstophosphoricacid [29] etc. However,

the reductive amination of anthraldehyde and naphthaldehyde was carried out by

two steps, i.e. condensation of anthraldehyde / naphthaldehyde with appropriate

amines to generate imines, which are then reduced to the corresponding anthryl /

naphthyl methylamines by NaBH4 [12,30]. Also in most cases, reaction proceeded

for a longer time. Despite several methods present in the literature for reductive

amination, simple, efficient, high yielding and environmentally benign approaches

for reductive amination is still needed.

Very recently, we are establishing conducting polymer salt as polymer

based acid catalyst in organic transformations [31-33] and in some reactions this

catalyst does not show catalytic activity. In order to find the suitability of this

catalyst in academic work and viability in industry, it is essential to carry out

particular organic reaction with this catalyst. The choice of PANI catalyst is due to

its number of intrinsic redox states, stability, and ease of synthesis, cheaper,

handling, versatility, simple workup procedure, mildness and recyclability.


169

The structure of polyaniline is known as a Para-linked phenylene

amineimine. The base form of polyaniline can, in principle, be described by the

following general formula (Figure1).

HN NH N

nx 1-x

Figure1: Structure of polyaniline base

In the generalized base form (1!x) measures the function of oxidized units.

When (1!x) = 0, the polymer has no such oxidized groups and is commonly known

as a leucoemeraldine base. The fully oxidized form, (1!x) = 1 is referred to as a

pernigraniline base. The half-oxidized polymer, where the number of reduced units

and oxidized units are equal, i.e. (1!x) = 0.5, is of special importance and is

termed as the emeraldine oxidation state or the emeraldine base. Partially oxidized

emeraldine base is shown to be an alternating copolymer of reduced and oxidized

repeat units. The value of x varies from 0 to 1, but the percentage of carbon,

hydrogen and nitrogen will be almost the same. Taking these points into

consideration, the following formula of polyaniline base (Figure 2) and polyaniline

salt (Figure 3) is considered for simplicity.

NH

n

Figure 2: Simplified structure of polyaniline base

NH

nyH A

where H+A! is the acid group and y is the number of acid group per aniline unit. Figure 3: Simplified structure of polyaniline salt


170

In this work, a simple, fast and efficient method is successfully developed

for reductive amination of anthraldehydes and naphthaldehydes to amines in single

step for the first time by the use of novel combination of NaBH4 and various PANI

as a polymer-based solid acid catalyst. In order to establish the versatility of the

polymer-based catalyst, we also extended the reductive amination reaction for

benzaldehyde, !," – unsaturated aldehydes, heterocyclic aldehydes and ketones.

We obtained the products immediately after mixing the reactants in excellent yield

with NaBH4/PANI-HBF4 when compared to the earlier reports.

B. 2. Results and discussion

Initially, anthraldehyde was reacted with butylamine using NaBH4 in DCM-

CH3OH (3:1) mixture at r.t. for 2 h and obtained anthryl methyl butyl amine, imine

and alcohol mixture as products. In order to prepare amine in better yield without

side products, we catalyzed the reaction with emeraldine form of PANI salt (PANI-

HBF4) powder containing HBF4 as lewis acid dopant prepared by emulsion

polymerization pathway and obtained the product immediately with 96% yield.

Then the reaction of different anthraldehydes with amines (aliphatic primary and

secondary amines, aromatic amines) was carried out using NaBH4/PANI-HBF4

system in DCM-CH3OH (3:1) at room temperature. The reaction went immediately

(within a minute) and gave anthryl methyl amines (Scheme 1) in excellent yields

(95-96%) (Table 1, entries 1-6). HBF4 acid dopant present on PANI-HBF4 salt play

a role in the reductive amination reaction, wherein, polyaniline salt acts as polymer

supported acid catalyst. First, H+ ion of HBF4-PANI attack carbonyl group which

interact with amine to form imine by losing water molecule. Again H+ ion attack

imine, forms immonium ion and then hydride ion from NaBH4 attack on carbon

atom of the immonium ion and forms the reduced amine.

CHO

H NR1

R2R

NR2

R1

RDCM-MeOHr.t., Immediate

NaBH4/PANI-HBF4

Scheme 1: Reductive amination of anthraldehydes with NaBH4

catalyzed by PANI


171

R= -H, -CH3

R1= -butyl, -phenyl, - anisyl, -9-ethyl-9H-carbazol-3-yl

R2 = -H

R1, R2=-CH2-CH2-CH2-CH2-CH2-

We have applied this method successfully for the reductive amination of

naphthaldehyde with butylamine, aniline and piperdine (Scheme 2), which gave the

corresponding amines in excellent yields immediately [Table 1, entries 7-9].

CHONR2

R1

NR1R2

HNaBH4/PANI-HBF4

DCM-MeOHr.t., Immediate

Scheme 2: Reductive amination of naphthaldehydes with NaBH4

catalyzed by PANI R1= -butyl, -phenyl

R2 = -H


In order to check the versatility of the reductive amination of NaBH4/PANI-

HBF4 system, benzaldehyde was reacted with series of amines (Scheme 3), the

reactions went smoothly to afford the corresponding amines in quantitative yields

[Table 1, entries 10-12]. Further, we extended this reaction for heterocyclic

aldehydes such as furfuraldehyde, thiophene-2-carboxaldehyde and pyridine-2-

carboxaldehyde with butyl amine (Scheme 3), which gave the corresponding

amines in high yields [Table 1, entries 13-15].

RDCM-MeOHr.t., Immediate

NR2

R1

NR1R2

HNaBH4/PANI-HBF4

R-CHO

Scheme 3: Reductive amination of benzaldehyde and heterocyclic aldehydes

with NaBH4 catalyzed by PANI


172

R = -aryl, -heterocyclic

R1= -butyl, -phenyl,

R2 = -H


To explore the scope of this system [NaBH4-PANI] in the reaction of !, " –

unsaturated aldehydes, we carried out the reaction of crotonaldehyde and

cinnamaldehyde with aniline (Scheme 4) and obtained the corresponding amines

in quantitative yields [Table 1, entries 16, 17] with the double bond intact.

NH2 HN R3

R3CHO


NaBH4/PANI-HBF4

Scheme 4: Reductive amination of !, " – unsaturated aldehydes with NaBH4

catalyzed by PANI

R3 = -C6H5, -CH3

We also examined this method for reductive amination of ketone by

carrying out the reaction of cyclohexanone with aliphatic and aromatic amines.

This method yielded the corresponding cyclohexylamine derivatives (Scheme 5) in

high yields [Table 1, entries 18-20].

O

NR1R2

H

NR2 R1


NaBH4/PANI-HBF4

Scheme 5: Reductive amination of cyclohexanone with NaBH4 catalyzed by

PANI

R1=-butyl, -phenyl

R2 = -H



173

Table 1: Reductive amination of carbonyl compounds with NaBH4 catalyzed

by PANI-HBF4

CHO

NH2

HN

CHO NH2

HN

CHO HN

N

CHO

N

HN N

CHO NH2

HN

CHO NH2

O

HN O

Carbonylcompound Amine ProductIsolatedYield(%)

1

2

3

4

5

6

96

96

95

96

96

96

H2N

S.No


174

CHO

NH2

HN

CHO NH2

CHO HN

N

CHO

NH2

HN

CHO NH2HN

CHO HN

N

S CHO NH2S

HN

O CHO NH2 O

HN

HN

NNH2

NCHOHN

7

8

9

10

11

12

13

14

15

94

95

95

98

98

96

94

95

90


175

NH2

CHONH2 NH

O

NH2

HN

O NH2 HN

O HN

HN

CHO

N

16

17

18

19

20

97

98

90

90

90

Very recently Alinezhad et al. [25] have reported an efficient reductive

amination. In this work, they reported reductive amination of aldehydes and

ketones using sodium borohydride-silica phosphoric acid in THF solvent and the

reaction took place from 2 to 31 min. In our method, we obtained the product

immediately after mixing the reactants with NaBH4-PANI. For example, in our

reaction with benzaldehyde and aniline, product was obtained immediately (95%

yield) against 10 min (93% yield). Similarly, the reaction with cinnamaldehyde and

aniline, we obtained the product immediately (98% yield) against 5 min (90% yield)

of the reported one. The above observations indicate that the present method is

more efficient than the reported ones.


176

B.3. Recyclability of Catalyst PANI-HBF4

In order to verify the recyclability of the PANI-HBF4 catalyst, we carried out

reductive amination reaction using anthraldehyde and n-butyl amine as a model

substrate. The catalyst was filtered from the reaction mixture, washed with water

and then by DCM. Catalyst was dried and reused for five cycles. The reaction

proceeded smoothly with a yield of 96-90% (Table 2). This result indicates that the

activity of the catalyst was not affected on recycling.

Table 2 Results of recyclability of PANI-HBF4 catalyst in reductive amination

of anthraldehyde with butylamine

___________________________________________________________________

Run Anthraldehyde (mg) Butyl amine (mL) Catalyst (mg) Isolated Yield (%) 1 1000 0.53 50 96 2 740 0.40 37 95 3 680 0.36 34 95 4 600 0.32 30 93 5 500 0.27 25 91 6 320 0.17 16 90

B.4. Catalytic Activity of PANI salts

In order to establish the use of PANI as catalyst in reductive amination

reaction, Various PANI salts containing mineral acids such as sulphuric acid

(PANI-H2SO4), hydrochloric acid (PANI-HCl); solid organic acid such as p-toulene

sufonic acid (PANI-PTSA), !-Naphthalene sulphonic acid (PANI-NSA) and liquid

organic acids such as acetic acid (PANI-AA) have been prepared by chemical

polymerization method and the amount of dopants and number of dopant unit per

aniline unit are reported in Table 3. These PANI salts are tried out as catalyst in

the reductive amination of anthradehyde and butylamine, which resulted in

anthrylmethylbutylamine in excellent yields (93-96 %; see Table 3). These results


177

indicate that PANI containing any protonic acid group prepared by

emulsion/aqueous polymerization pathway can acts as catalyst in the reductive

amination reactions.

Table 3 The amount of acid dopant and nuber of dopant unit per aniline unit

of PANI salts and yield of anthryl methyl butyl amine obtained using PANI

salts in the reductive amination of anthraldehyde and butyl amine.

PANI-PTSA 33.3 0.24 95

PANI-NSA 34.1 0.23 95

PANI-H2SO4 17.4 0.20 94

PANI-HCl 13.3 0.38 93

PANI-AA 20.2 0.38 95

PANI

Amount of aciddopant present onpolyaniline salt

(wt %)

Number of dopantunit per anilineaniline unit

Isolated yieldof anthrylmethylbutylamine (%) a

a anthraldehyde (1 mmol), n-butyl amine (1.1 mmol) , DCM-MeOH mixture (4mL), PANI salt catalyst (5 wt % with respect to anthraldehyde) and NaBH4 (1.1 mmol)

B.4. Conclusion

In conclusion, an efficient method has been developed for direct reductive

amination of carbonyl compounds with amines using sodiumborohydride catalyzed

by PANI. The advantages of this method are: simple reaction, rapid formation of

product, versatility, use of little amount of easily synthesizable, stable, handlable,

inexpensive, eco-friendly, stable and mild reusable catalyst. This methodology

may open up new direction for the synthesis of various organic compounds.

B.5. Typical Experimental Procedure for the Reductive Amination

In a typical experiment, anthraldehyde (206 mg, 1 mmol) and n-butyl amine (0.11

mL, 1.1 mmol) were dissolved in 4 mL of dichloromethane and methanol (DCM-

MeOH) mixture (3:1). To this reaction mixture, PANI-HBF4 catalyst (5 wt % with

respect to anthraldehyde) and NaBH4 (41 mg, 1.1 mmol) were added, stirred at


178

room temperature, immediately checked the TLC and showed the formation of

product. The reaction mixture was quenched with aq. NH4Cl solution (2 mL),

filtered the solution and washed with 10 mL of DCM. The catalyst was recovered.

The organic layer was separated, dried in Na2SO4 and concentrated the solution to

get the product. The crude product was purified by silica gel column

chromatography (eluent: hexane). The above experimental procedure was adopted

for the preparation of amines reported in the present study. The authenticity of the

products was confirmed from their 1H NMR and mass spectral data.

1-(anthracen-9-ylmethyl) piperidine (3): Paleyellow solid, mp=1330C, TLC Rf =

0.2 (5 % ethyl acetate/hexane), IR (KBr): 3446, 3045, 2935, 2850, 2756, 1619,

1440, 1335, 1150, 1100, 892, 729 cm-1 ; 1H NMR (200 MHz, CDCl3): ! = 8.43 (d, J

= 9.4 Hz, 2H), 8.34 (s, 1H), 7.92 (dd, J = 7.03 Hz, 2H), 7.42 (m, J = 3.12 Hz, 4H),

4.35 (s, 2H), 3.45 (s , 2H), 2.54 (t, J = 4.38 Hz, 4H ), 1.48 (m, J = 7.03 Hz, 4H ); 13C

NMR (200 MHz, CDCl3): ! = 131.3, 130.4, 128.8, 127.1, 125.3, 124.7, 55.1, 54.7,

26.1, 24.5; MS (ESI): m/z = 276 (M+H+); HRMS (ESI): m/z, (M+H+) calculated for

C20H22N: 276.1752; found 276.1744.

N-(anthracen-9-ylmethyl)-9-ethyl-9H-carbazol-3-amine (4): Yellow solid,

mp=2160C, TLC Rf = 0.25 (5 % ethyl acetate/hexanes); IR (KBr): 3387, 3048,

2964, 2865, 1627, 1576, 1492, 1468, 1230, 1085, 791, 732cm-1; 1H NMR (200

MHz, CDCl3): ! = 8.42 (s, 1H), 8.30 (d, J = 8.31 Hz, 2H), 7.99 (q, J = 6.99 Hz, 3H),

7.58 (S, 1H), 7.44 (m, J = 7.93 Hz, 4H), 7.37 (dd, J = 7.93 Hz, 1H) 7.31 (d, J=8.12

1H), 7.14 (m, J = 8.69 Hz, 2H), 6.88 (dd, J = 8.69 Hz, 1H), 5.27 (s, 2H), 4.28 (q, J =

6.99 Hz, 2H), 1.40 (t, J = 7.18 Hz, 3H); 13C NMR (200 MHz, CDCl3): ! = 131.7,

130.3, 128.6, 127.5, 126.o, 125.0, 124.7, 124.1, 120.1, 117.8, 108.7, 107.9, 95.8,

42.4, 37.1, 13.6; MS (ESI): m/z = 401 (M+H+). HRMS (ESI): m/z, (M+H+) calculated

for C29H25N2: 401.2017; found 401.2013.

N-((10-methylanthracen-9-yl)methyl)aniline (5): Pale yellow solid, mp=1750C,

TLC Rf = 0.35 (5 % ethyl acetate/hexanes); IR (KBr): 3402, 3044, 2872, 1600,

1502, 1311, 749, 691cm-1; 1H NMR (200 MHz, CDCl3): ! = 8.29 (m, J = 3.21 Hz,

4H), 7.46 (m, J = 2.64 Hz, 4H), 7.22 (m, J = 3.40 Hz, 2H), 6.74 (m, J = 6.6 Hz, 3H),

5.10 (s, 2H), 3.45 (s, 1H), 3.13 (s, 3H); 13C NMR (200 MHz, CDCl3): ! = 148.4,

130.1, 129.8, 129.3, 125.8, 125.3, 125.0, 124.7, 117.5, 112.5, 40.8, 14.3; MS


179

(ESI): m/z = 298 (M+H+); HRMS (ESI): m/z, (M+H+) calculated for C22H19N:

298.1027; found 298.1019.

4-methoxy-N-(10-methylanthracen-9yl)methyl)aniline (6): Yellow solid, mp:

1480C, TLC Rf =0.3 (5 % ethyl acetate/hexanes); IR (KBr): 3396, 2963, 1615,

1510, 1261, 1094, 1023, 867, 800, 746, 700cm-1; 1H NMR (200 MHz, CDCl3): ! =

8.28 (m, J = 3.39 Hz, 4H), 7.45 (m, J = 3.71 Hz, 4H), 6.76 (m, J = 9.06 Hz, 4H),

5.08 (s, 2H), 3.77 (s, 3H), 3.13 (s, 3H); 13C NMR (200 MHz, CDCl3): ! = 152.1,

142.7, 131.1, 129.8, 129.7, 125.6, 125.1, 124.7, 124.5, 114.8, 113.5, 55.6, 41.6,

14.1; MS (ESI): m/z = 328 (M+H+); HRMS (ESI): m/z, (M+H+) calculated for

C23H22NO: 328.1701; found 328.1691.

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