Chitosan: highly efficient, green, and reusable biopolymer catalyst for the synthesis of alkylaminophenols via Petasis borono–Mannich reaction

Accepted Manuscript Chitosan: Highly efficient, green and reusable biopolymer catalyst for the synthesis of alkylaminophenols via Petasis borono-Mannich reaction Sirigi Reddy Sudharsan Reddy, Bhoomireddy Rajendra Prasad Reddy, Peddiahgari Vasu Govardhana Reddy PII: DOI: Reference:

S0040-4039(15)01134-X http://dx.doi.org/10.1016/j.tetlet.2015.07.004 TETL 46493

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Tetrahedron Letters

Received Date: Revised Date: Accepted Date:

17 May 2015 26 June 2015 1 July 2015

Please cite this article as: Reddy, S.R.S., Reddy, B.R.P., Reddy, P.V.G., Chitosan: Highly efficient, green and reusable biopolymer catalyst for the synthesis of alkylaminophenols via Petasis borono-Mannich reaction, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.07.004

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Chitosan: Highly efficient, green and reusable Leave this area blank for abstract info. biopolymer catalyst for the synthesis of alkylaminophenols via Petasis borono-Mannich reaction Sirigireddy Sudharsan Reddy, Bhoomireddy Rajendra Prasad Reddy and Peddiahgari Vasu Govardhana Reddy* Petasis borono-Mannich reaction was applied to synthesis of alkylaminophenols from o-hydroxy aldehydes, secondary amines and various boronicacids in presence of chitosan as a heterogeneous green catalyst.

Tetrahedron Letters

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Tetrahedron Letters j o ur n al h om e p a g e : w w w . e l s e v i er . c o m

Chitosan: Highly efficient, green and reusable biopolymer catalyst for the synthesis of alkylaminophenols via Petasis borono-Mannich reaction Sirigi Reddy Sudharsan Reddy, Bhoomireddy Rajendra Prasad Reddy and Peddiahgari Vasu Govardhana Reddy∗ *Department of Chemistry, Yogi Vemana University, Kadapa-516003, Andhra Pradesh, India. AR TIC LE IN F O

A B S TR A C T

Article history: Received Received in revised form Accepted Available online

We screened the catalytic efficacy of different functionalized polymeric catalysts such as nafion® 117, PEG-OSO 3H, tween® 80, poly styrene -SO3 H and chitosan for the preparation of alkylaminophenols through Petasis borono-Mannich reaction by one-pot three component condensation of o-hydroxy aldehydes, secondary amines and various boronic acids. It was observed that the reaction was completed in a short period of time and the yield was optimum by virtue of chitosan heterogeneous catalyst. Furthermore, the catalyst can be recovered by simple filtration and reused up to ten cycles. Smooth loss of catalytic activity was observed from 6th cycle of reuse.

Keywords: Nafion® 117 PEG-OSO3 H Tween® 80 Poly styrene -SO3H Chitosan Petasis borono-Mannich reaction.

1. Introduction Petasis borono-Mannich (PBM) reaction is a one-step multi component process, involving an organoboronic acid, an amine, and a carbonyl derivative, which can produce novel multifunctional molecules, including geometrically pure allylamines,1a αaminoacids,1b,1c anti-β-amino alcohols,1d,1e α-arylglycines,1f 1g aminophenol derivatives, indolyl-N-substituted glycines,1h 2hydroxymorpholines,1i α-hydrazino carboxylic acids,1j α-(4-N,Ndialkylamino-2-alkyloxy phenyl) carboxylic acids1k,1l and aromatic tertiary amines.1m Among these, the PBM reaction has been the focus of attention in the last decade because of some features of the organoboron compounds such as (i) compatibility with many functional groups allowing the facile synthesis of multifunctional molecules without the excessive use of protective groups, (ii) availability of reagents in a large variety of structural configurations, (iii) possibility of using water and alcohols as the reaction medium, and (iv) low toxicity and environmental friendliness..2 This PBM reaction proceeds through condensation of amine and aldehyde to give the corresponding iminium species followed by intramolecular transfer of the organyl ligand from the activated ate complex of organoboronic acid yielding alkylaminophenols.3 The presence of a hydroxyl group or other coordinating group is essential to form a boronate, which results in the new carbon-carbon bond after reaction with the in situ prepared imine.4 In the last few decades, many improved procedures with new catalysts such as CuBr + bpy, 5a BF3.OEt2,5b InBr3,5c Yb(OTf) 3 + Pd (TFA) 25d and 4Å MS.5e have been reported for PBM reaction. In some cases, hexafluoroisopropanol,6a microwave irradiation6b and solid phase synthesis6c, 6d were employed in this reaction. However, these procedures required either a long reaction time or microwave activation. The development of environmental friendly protocol for

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the PBM reaction is necessary. Therefore, Yadav et al.7a reported the use of ionic liquid to accelerate the PBM reaction. Recently, Candeias et al.7b also reported that water is a suitable medium for the reaction, but the procedure needed longer reaction time of 24 h. Therefore development of new methodologies should take into consideration for reducing the reaction time, minimum metal contamination of products, simple reaction conditions, and easy isolation of products and renewability of catalyst which are highly desirable for the PBM reaction. Recently, the trends in Science and Technology shown greater emphasis on eco-friendly and sustainable resources and processes. In this regard, direct utilization of natural materials for catalytic applications is a very attractive strategy. In particular, bio polymers are attractive catalysts to explore the various organic transformations. Among biopolymers, chitosan is attaining a privileged position in various bio-innovation programs. Chitosan is derived from chitin,8a the second most abundant polysaccharide on earth after cellulose. Chitin is composed of N-acetyl-D-glucosamine monomers connected through β (1→4) linkages. Owing to the presence of readily functionalizable amino groups and hydroxyl groups in chitosan makes it useful as a chelating agent. It can activate the nucleophilic as well as electrophilic components of the reactions by hydrogen bonding and presence of lone pairs respectively. Recently, chitosan was used in aldol and Knoevenagel condensation reactions,8b Strecker reaction,8b synthesis of quinoline derivatives,8d 1, 2, 3-triazole derivatives,8e C-N bond cross coupling,8f organocatalysis reactions,8g one pot synthesis of pyridine derivatives8h and green synthesis of heterocycles.8i Inspired by these achievements, we surmised that alkylaminophenols can be synthesized from o-hydroxy aldehydes, secondary amines and various boronic acids via PBM reaction in the presence of environmentally benign, easily separable, recyclable and

——— *Corresponding Author. Tel:+91-8562-225410, e-mail: [email protected] (P. V. G. Reddy)

highly effective catalyst system chitosan, further the reaction conditions like optimization of catalyst and solvent were carried out and listed in Tables 1 and 2.

2. Results and Discussion Initially, we optimized the catalytic efficacy of different functionalized polymeric catalysts such as nafion® 117, PEGOSO3H, tween® 80, poly styrene -SO3 H and chitosan (Table 1, entry a-e) applied for one-pot three component PBM reaction of salicylaldehyde (1a) (1 mmol), 4-chloro phenyl boronic acid (2a) (1.2 mmol) and morpholine (3a) (1.1 mmol) in 1, 4-dioxane at 80˚C as a model reaction (Table 1). Among them chitosan showed best catalytic activity towards PBM reaction when compared to other polymeric catalysts. We have tested the PBM reaction with 15 mg weight of the chitosan to obtain 70% yield of the product in 150 min (Table 1, entry e). By increasing the loading of the chitosan from 20 mg to 25 mg, improved in yield and reaction rate up to 80 % in 90 min and 95 % in 40 min (Table 1, entry f and g) respectively. It is remarkable to note that no improvement was observed in the case of reaction rate and yield by increasing the amount of chitosan beyond 25 mg (Table 1, entry h). Based on these results, 25 mg of the chitosan is sufficient for PBM reaction.

acetonitrile, toluene and tetrahydrofuran (THF) as solvents at 80˚C and reflux conditions for a period of 60 min, 90 min and 3 h produced 85 %, 76 % and 80 % (Table 2, entry e-g) yields respectively. A moderate yield of 53 % (Table 2, entry h) observed with 1, 2-dichloroethane (DCE) as solvent at reflux condition for 12 h. A low yield of 22 %, 27 %, 20 % and 21 % (Table 2, entry i-l) were obtained when we used dimethyl sulfoxide (DMSO), ethanol, dimethylformamide (DMF) and dimethyl acetamide (DMA) at 80˚C for 12 h. We also performed the reaction with water at 80˚C for 24 h produced 55 % of yield (Table 2, entry n). Based on the above results we concluded that 1, 4-dioxane is the most excellent solvent media in the case of chitosan catalyzed PBM reaction. Table 2: Effect of the solvent on the PBM reactiona

Entry a b c d e f g h i j k l n

Table 1: Comparison of the catalytic efficacy of chitosan with other functionalized polymeric catalysts (4a)a

Entry

Catalyst

Catalyst Load (mg)

Time

Yieldb (%)

a b c d

Nafion® 117 PEG-OSO3H Tween® 80 Poly styrene SO3H Chitosan Chitosan Chitosan Chitosan

25 25 25 25

10 h 12 h 10 h 10 h

65 70 68 73

15 20 25 30

150 min 90 min 40 min 40 min

70 80 95 95

e f g h

-

Reaction of salicylaldehyde (1a) (1 mmol), 4-chloro phenylboronic acid (2a) (1.2 mmol) and morpholine (3a) (1.1 mmol) in presence of different polymeric catalysts in 1, 4-dioxane at 80 ˚C. b Isolated yield

R

HO B Ar HO

CHO

1 R1

H N

R1

H N

= R2

O

H N

o

80 C

R1

R2

Yieldb (%) 85 80 95 65 85 76 80 53 22 27 20 21 55

Reaction of salicylaldehyde (1a) (1 mmol), 4-chloro phenylboronic acid (2a) (1.2 mmol) and morpholine (3a) (1.1 mmol) in presence of chitosan (25 mg) in different solvents at various temparatures. b Isolated yield

N

R2

4 (a-s)

H N HO O HO

R=H and CH3

Temperature (˚C) RT 50 80 100 80 80 reflux reflux 80 80 80 80 80

Ar

1, 4-Dioxane R

3 H N

1,4-Dioxane 1,4-Dioxane 1,4-Dioxane 1,4-Dioxane Acetonitrile Toluene THF DCE DMSO Ethanol DMF DMA Water

Time (min) 24 h 4h 40 40 60 90 3h 12 h 12 h 12 h 12 h 12 h 24 h

OH

Chitosan

2

Solvent

a

a

OH

Catalyst load (mg) 25 25 25 25 25 25 25 25 25 25 25 25 25

NH2 O

HO O HO

O NH 2

Chitosan

HO O

NH 2 O O

HO n

Scheme 1: Chitosan catalyzed PBM reaction Further, we also screened the PBM reaction by employing salicylaldehyde (1a), 4-chloro phenylboronic acid (2a) and morpholine (3a) in various solvents and chitosan as a catalyst at different temperatures as shown in the Table 2. First we performed the reaction in 1, 4-dioxane (5 mL) by loading chitosan (25 mg) at ambient temperature for 24 h to obtain the 85% of alkylaminophenol (Table 2, entry a). To reduce the reaction time, we performed the reaction at various temperatures such as 50˚C and 80˚C with same amount of catalyst yielding the alkylaminophenol in 80 % and 95 % (Table 2, entry b and c) for 4 h and 40 min respectively. Further increasing the temperature to 100˚C led to decrease in yield of 65 % (Table 2, entry d). When the same reaction was carried out in

Fig.1 The recyclability of chitosan in ten cycles for the PBM reaction of salicylaldehyde (1a), 4- chloro phenylboronic acid (2a) and morpholine (3a). Having identified the optimal reaction conditions, we sought to evaluate the scope and efficiency of the reaction. For this purpose, a broad range of structurally varied o-hydroxy aldehydes, secondary amines and aryl boronic acids were chosen to perform the PBM reaction to yield the corresponding alkylaminophenols (4a-s) and the results were displayed in Table 3. With regard to the various boronic acids bearing both electron donating and withdrawing substituents can be efficiently converted into alkylaminophenols in high yields as

Tetrahedron Letters Table 3: Chitosan catalysed synthesis of alkylaminophenolsa Entry Aldehyde Boronic acid (1 a-b) (2 a-m)

Amine (3 a-c)

4 Product (4 a-s) OH

OH

a CHO

OH

3a

2a

Cl

b CHO

3a

2b

OCH3

B(OH )2

OH

c CHO

S

OCH 3 OCH3

1a

CHO OCH3

1a

2e

B(OH) 2 O

CHO

2f OH CHO

N

3a

2g OH

h

B(OH) 2

CHO

2h

90

50

89

45

93

45

90

50

86

43

91

4f

OCH3 N

3a

4g O OH

H N O

1a

O

O OH

O

OCH3

1a

40

4e O OH

H N

B(OH) 2

OCH3

N

O

1a

g

O

3a H N

OH

90

4d

O OH

H N

(HO)2 B

44

N

3a

2d

87

OCH3

O

OH

f

OCH3

H N

CHO

45

4c

O OH

B(OH)2

d

92

N

3a

OH

40

4b

O OH

O

2c

e

OCH3

H N

S

1a

95

N

O

1a

40

4a

O OH

H N

B(OH)2

Yieldb (%)

N

O

1a

Cl

H N

B(OH)2

Time (min)

N

3a

4h

O OH

i

B(OH )2

H N

OH S

H3CO

CHO

1b

S

2c

O

H3CO N

3a

4i

O OH

OH

j H3CO

H N

B(OH)2

H3CO N

CHO

1b

OCH3

O OCH3

2b

3a

4j O

B(OH)2

OH

k

H3CO

H N

CHO OCH 3

1b

OCH3

B(OH) 2

H3CO

CHO

2h B(OH)2

OH CHO

OH

n

B(OH)2

H N

88

OH H3CO N

3a

4l

O OH

N

3a

40

95

45

91

40

95

45

90

50

93

50

89

50

87

CH3

4m O OH

H N

CH3

45

4k O

O

2i

1a

90

N

H N

CH3

m

O

45

OCH3

3a

O

1b

OCH3

H3CO

2d

OH

l

OH

CHO

2i

1a

B(OH)2

OH

o

CHO

N

H N

OH

2j

CH3 B(OH) 2

OH

2k OH

B(OH)2

q

4o O OH

NO2

O

NO2

1a

CH3

N

3a H N

CHO

CH3

4n

O

1a

p

3b

N

3a

4p O OH

H N

CHO

2l

1a

N

3c

B(OH) 2 H N

OH

r

CHO

H3CO

OCH3 OCH3

1a

2m

OH

4q

OCH3 OCH3 OCH3

O

3a

N

4r O

B(OH) 2

s

CHO

1a a

H N

OH

H3CO

OH

OCH3 OCH3

2m

OCH3 OCH3 OCH3

3b

N

4s

Reaction of o-hydroxy aldehydes (1 a-b) (1 mmol), secondary amines (2 a-c) (1.1 mmol) and various boronic acids (3 a-h) (1.2 mmol) in presence of chitosan (25 mg) in 1, 4-dioxane (5 mL) at 80˚C. Isolated yield

b

shown in the Table 3. All the products were characterized by IR, (1H & 13C) NMR spectra and elemental analyses. The resulting alkylaminophenols were obtained as racemates and these are evidenced by 1: 1 ratio peaks in chiral HPLC. In addition, we tested the efficiency of the catalyst in terms of the reusability in the PBM reaction. After completion of the reaction, the catalyst was simply filtered, washed with ethyl acetate and dried at 80oC. Catalyst recycling experiments were carried out with repeated use for further ten more consecutive reactions between salicylaldehyde, morpholine and 4-chloro phenylboronic acid to

yield the alkylaminophenol. Smooth loss of catalytic activity was observed from 6th cycle of reuse as showed in the Fig 1. These results led us to tentatively assign a mechanism for the process. The free hydroxyl and amino groups distributed on the surface of chitosan in high concentration activates the carbonyl group of the salicylaldehyde through hydrogen bonding for nucleophilic attack of amines to produce the corresponding iminiumion intermediate (IM-1). Coordination between the oxygen anion of phenolate and the boron atom of boronic acid leads to the formation of a tetra coordinate borate intermediate. Subsequently,

Tetrahedron Letters the aryl carbanion moiety of boronic acid favourably attacks the iminium ion forming the stable intermediate (IM-2) which upon hydrolysis furnished the desired product by the loss of H3BO 3 molecule. Here chitosan plays a key role in the formation of iminium ion intermediate (IM-1) (Scheme 2).

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Supporting information Supplementary data of all 1H and 13C NMR spectra associated with article can be found in the online version at

References 1.

Scheme 2: Plausible mechanism for chitosan catalyzed PBM reaction.

3. Conclusions In summary, we have developed the application of chitosan as a green and reusable heterogeneous catalyst for the preparation of alkylaminophenols via PBM reaction and the results were obtained as good to excellent yields (86-95 %) in a shorter reaction time. The complete conversion of the starting material to desired product, non requirement of column chromatography purification, recoverability and reusability of the catalyst up to ten cycles are the salient features of this method. To the best of our knowledge, so far “chitosan catalyzed three component PBM reaction” has not yet been reported in the literature. Furthermore, studies are under progress on the synthesis of chiral alkylaminophenols by our newly synthesized chiral Brønsted acids such as camphor derived thioureas for the same racemates.

2. 3. 4.

5.

General procedure for the synthesis of 2-((4-chlorophenyl) (morpholino) methyl) phenol (4a): To a stirred mixture of salicylaldehyde (122 mg, 1mmol) and morpholine (96 mg, 1.1 mmol) in 1, 4-dioxane (5 mL) were added 4chloro phenylboronic acid (187 mg, 1.2 mmol) and chitosan (25 mg) at room temperature. The resulting reaction mixture was allowed to stir at 80˚C for 40 min. After complete conversion as indicated by TLC, the reaction mixture was cooled to room temperature and the catalyst was recovered by simple filtration after being washed with ethyl acetate. The filtrate was diluted with water (15 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with 0.1 N HCl to remove excess of morpholine, 0.1 N NaOH solution to remove the excess of boronic acid followed by brine solution and dried over anhydrous sodium sulphate and evaporated under reduced pressure to afford pure 2-((4chlorophenyl) (morpholino) methyl) phenol as a color less solid (4a) in 95 % (288 mg) yield. This procedure is followed to the other reactions, which are enlisted in Table 3.

Acknowledgements The authors are thankful to the Board of Research in Nuclear Sciences (BRNS), Mumbai, India for providing the financial support (NO. 2012/37C/33/BRNS). We also acknowledge the support of University Grants Commission (UGC), New Delhi for providing Junior Research Fellowship (JRF) to S.S.Reddy.

6.

7.

8.

(a) Petasis, N. A.; Akritopoulou, I. Tetrahedron Lett. 1993, 34, 583-586; (b) Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc. 1997, 119, 445-446; (c) Grigg, R.; Sridharan, V.; Thayaparan, A. Tetrahedron Lett. 2003, 44, 90179019; (d) Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc. 1998, 120, 11798-11799; (e) Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. J. Org. Chem. 2002, 67, 3718-3723; (f) Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetrahedron 1997, 53, 16463-16470; (g) Petasis, N. A.; Boral, S. Tetrahedron Lett. 2001, 42, 539-542; (h) Jiang. B.; Yang, C. G.; Gu, X. H. Tetrahedron Lett. 2001, 42, 2545-2547; (i) Berree, F.; Debache, A.; Marsac, Y.; Carboni, B. Tetrahedron Lett. 2001, 42, 3591-3594; (j) Portlock, D. E.; Naskar, D.; West, L.; Li, M. Tetrahedron Lett. 2002, 43, 6845-6847; (k) Naskar, D.; Roy, A.; Seibel, W. L. Tetrahedron Lett. 2003, 44, 8861-8863; (l) Naskar, D.; Roy, A.; Seibel, W. L.; Portlock, D. E. Tetrahedron Lett. 2003, 44, 5819-5821; (m) Wang, J.; Li, P.; Shen, Q.; Song, G. Tetrahedron Lett. 2014, 55, 3888-3891. Petasis, N. A. Aust. J. Chem. 2007, 60, 795-798. Southwood, T. J.; Curry, M. C.; Hutton, C. A. Tetrahedron 2006, 62, 236-242. (a) Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. Org. Lett. 2000, 2, 3173-3176; (b) Schlienger, N.; Bryce, M. R.; Hansen, T. K. Tetrahedron 2000, 56, 10023-10030; (c) Kaiser, P. F.; Churches, Q. I.; Hutton, C. A. Aust. J. Chem. 2007, 60, 799-810; (d) Wang, Q.; Finn, M. G. Org. Lett. 2000, 2, 4063-4065. (a) Frauenlob, R.; Garci, C.; Buttler, S.; Bergin, E. Appl. Organometal. Chem. 2014, 28, 432-435; (b) Stas, S.; Tehrani, K. A. Tetrahedron 2007, 63, 8921-8931; (c) Li, Y.; Xu, M. H. Org. Lett. 2012, 14, 2062-2065; (d) Beisel, T.; Manolikakes, G. Org. Lett. 2013, 15, 6046-6049; (e) Shi, X.; Hebrult, D.; Humora, M.; Kiesman, W. F.; Peng, H.; Talreja, T.; Wang, Z.; Xin, Z. J. Org. Chem. 2012, 77, 1154-1160. (a) Nanda, K. K.; Trotter, B. W. Tetrahedron Lett. 2005, 46, 2025-2028; (b) Follmann, M.; Gaul, F.; Schafer, T.; Kopec, S.; Hamley, P. Synlett. 2005, 1009-1011; (c) Klopfenstein, S. R.; Chen, J. J.; Golebiowski, A.; Li, M.; Peng, S. X.; Shao, X. Tetrahedron Lett. 2000, 41, 48354839; (d) Golbiowski, A.; Klopfenstein, S. R.; Chen, J. J.; Shao, X. Tetrahedron Lett. 2000, 41, 4841-4844. (a) Yadav, J. S.; Subba Reddy, B. V.; Naga Lakshmi, P. J. Mol. Catal. A: Chem. 2007, 274, 101-104; (b) Candeias, N. R.; Veiros, L. F.; Afonso, C. A. M.; Gois, P. M. P. Eur. J. Org. Chem. 2009, 1859-1863. (a) Hajji, S.; Younes, I.; Ghorbel-Bellaaj, O.; Hajji, R.; Rinaudo, M.; Nasri, M.; Jellouli, K. Int. J. Biol. Macromol. 2014, 65, 298-306; (b) Rajender Reddy, K.; Rajgopal, K.; Uma Maheswari, C.; Lakshmi Kantam, M. New. J. Chem. 2006, 30, 1549-1552; (c) Dekamin, M. G.; Azimoshan, M.; Ramezani, L. Green Chem. 2013, 15, 811-820; (d) Subba Reddy, B. V.; Venkateswarlu, A.; Niranjan Reddy, G.; Rami Reddy, Y. V. Tetrahedron Lett. 2013, 54, 57675770; (e) Anil Kumar, B. S. P.; Harsha Vardhan Reddy, K.; Karnakar, K.; Satish, G.; Nageswar, Y. V. D. Tetrahedron Lett. 2015, 56, 1968-1972; (f) Bodhak, C.; Kundu, A.; Pramanik, A. Tetrahedron Lett. 2015, 56, 419424; (g) Mahe, O.; Briere, J. F.; Dez, I. Eur. J. Org. Chem. 2015, 2559-2578; (h) Siddiqui Zeba, N. Tetrahedron Lett.

2015, 56, 1919-1924; (i) Sahu, P. K.; Sahu, P. K.; Gupta, S. K.; Agarwal, D. D. Ind. Eng. Chem. Res. 2014, 53, 2085-2091.

Tetrahedron Letters Highlights • First time we reported the chitosan catalyzed Petasis Borono-Mannich reaction. • Short reaction time, high conversions and recyclability of the catalyst. • The plausible mechanism of chitosan catalyzed PBM reaction is proposed. • Synthesis of chiral alkylaminophenols for the same racemates is under progress.

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