Hafnium (IV) bis(perfluorooctanesulfonyl)imide complex

catalyzed direct amidomethylation for the synthesis of

1-(arylamido)-methyl-2-naphthols in fluorous medium

Mei Hong, Chun Cai *, Wen Bin Yi

School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China

Received 1 July 2010

Available online 22 December 2010

Abstract

Hafnium (IV) bis(perfluorooctanesulfonyl)imide complex is found to be an efficient catalyst for the multicomponent

condensation of b-naphthol, aromatic aldehydes and urea or amides in perfluorodecalin to afford the corresponding substituted

amidomethyl naphthols in good yields. The remarkable features of this new procedure are high yields, shorter reaction times,

reusability of catalyst and simple work-up procedures.

# 2010 Chun Cai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Keywords: Hafnium (IV) bis(perfluorooctanesulfonyl)imide complex; Perfluorodecalin; Substituted amidomethyl naphthol; Multicomponet

reaction

Aminonaphthols have been reported to exhibit a variety of pharmacological activities, including antihypertensive,

adrenoceptor blocking, and Ca2+ channel blocking activities [1]. It is noteworthy that 1-(arylamido)methyl-2-

naphthols can be converted to important biologically active derivatives by amide hydrolysis. The preparation of 1-

(arylamido)methyl-2-naphthols can be carried out by condensation of aryl aldehydes, 2-naphthol and amides or urea in

the presence of Lewis or Brfsted acid catalysts such as Ce(SO4)2 [2], iodine [3], p-TSA [4], FeCl3–SiO2 [5], Brfsted

acidic ionic liquid ([TEBSA][HSO4]) [6], P2O5 [7].

Very recently, we reported a simple and convenient method for synthesis of dibenzoxanthenes by the condensation of

aldehydes with b-naphthol in the presence of scandium bis(perfluorooctanesulfonyl)imide (Sc(NPf2)3) as a catalyst [8].

The reaction proceeds through the in situ formation of ortho-quinone methide intermediate by the nucleophilic addition

of b-naphthol to aldehyde, which is further attacked by second molecule of b-naphthol followed by cyclodehydration to

give the benzoxanthenes. To expand this type of tandem process that would permit the condensation of the in situ

generated ortho-quninone methide with nucleophiles other than phenols, we utilized urea or amides to react with methide

to produce novel compounds. Here the ortho-quninone methide intermediates are trapped by urea or amides. The reaction

of b-naphthol, aromatic aldehyde and urea or amides in perfluorodecalin at 110 8C catalyzed by catalytic amount of

hafnium (IV) bis(perfluorooctanesulfonyl)imide complex (Hf(NPf2)4) was examined (Scheme 1).

www.elsevier.com/locate/cclet

Available online at www.sciencedirect.com

Chinese Chemical Letters 22 (2011) 322–325

* Corresponding author.

E-mail address: c.cai@mail.njust.edu.cn (C. Cai).

1001-8417/$ – see front matter # 2010 Chun Cai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

doi:10.1016/j.cclet.2010.10.046

1. Results and discussion

Initially we chose benzaldehyde and acetamide as the reactants and examined the reaction with several

catalysts in perfluorodecalin (C10F18, cis- and trans-mixture) at 110 8C, and the results are listed in Table 1. It was

found that metal bis(perfluorooctanesulfonyl)imide complexes showed best catalytic activity among these

catalysts. Most excitingly, when Hf(NPf2)4 was used, the reaction proceeded very smoothly and gave the product

in 87% yield (Table 1, entry 9). Moreover, we found that the yields were obviously affected by the amount of

Hf(NPf2)4 loaded. When 0.5 mol%, 1 mol% and 1.5 mol% of Hf(NPf2)4 were used, the yields were 77%, 87% and

88%, respectively (Table 1, entries 9–11). Therefore, 1 mol% of Hf(NPf2)4 was sufficient and excessive amount of

catalyst did not increase the yields significantly. The catalytic activity of the recycled Hf(NPf2)4 was also

examined. Hf(NPf2)4 could be reused five times for the reaction without noticeable loss of activity (Table 1, entry

9). No product was detected in the absence of catalyst (Table 1, entry 1). The above results showed that Hf(NPf2)4

was essential in the reaction.

In order to make the reaction more accessible, we then explored different co-solvent systems using a common

organic solvent (Table 2). The results indicated that different co-solvents affected the efficiency of the reaction.

Dichloromethane, chloroform, toluene and methanol afforded low yields (Table 2, entries 2–5). When 1,2-

M. Hong et al. / Chinese Chemical Letters 22 (2011) 322–325 323[()TD$FIG]

OH

OH

NHCORAr

ArCHO + RCONH2 +Hf(NPf2)4

C10F18, 110 oC

1 23

Scheme 1. Synthesis of 1-(arylamido)methyl-2-naphthols.

Table 2

Co-solvent and temperature effects on the reaction of benzaldehyde, b-naphthol and acetamide catalyzed by Hf(NPf2)4a.

Entry Co-solvent Temperature Yield (%)b Entry Co-solvent Temperature Yield (%)b

1 ClCH2CH2Cl Reflux 77 6 CH3CH2OH Reflux 65

2 CH2Cl2 Reflux 36 7 None 110 8C 87

3 CHCl3 Reflux 49 8 None RT –

4 Toluene Reflux 57 9 None 90 8C 78

5 CH3OH Reflux 31

a Reaction conditions: Benzaldehyde (1 mmol), b-naphthol (1 mmol), acetamide (1.2 mmol), Hf(NPf2)4 (0.01 mmol), perfluorodecalin (1.5 mL),

co-solvent (2 mL), 6 h.b Isolated yield.

Table 1

Catalyst effect on the condensation reaction of benzaldehyde, b-naphthol and acetamidea.

Entry Catalyst Catalyst (mol%) Yield (%)b Entry Catalyst Catalyst (mol%) Yield (%)b

1 None – – 7 Yb(NPf2)3 1 73

2 YbCl3 1 47 8 Sn(NPf2)4 1 75

3 HfCl4 1 41 9 Hf(NPf2)4 1 87, 85, 85, 84, 83c

4 Yb(OTf)3 1 65 10 Hf(NPf2)4 0.5 77

5 Yb(OPf)3 1 69 11 Hf(NPf2)4 1.5 88

6 HNPf2 1 61

a Reaction conditions: Benzaldehyde (1 mmol), b-naphthol (1 mmol), acetamide (1.2 mmol), perfluorodecalin (1.5 mL), 110 8C, 6 h.b Isolated yield.c Catalyst was reused five times.

dichloroethane was used, the yield increased to 77% (Table 2, entry 1). Especially, the reaction was carried out

under only perfluorodecalin as the sole solvent condition to give better yield than using any co-solvents here. The

reaction condition was further optimized by conducting the reaction at temperatures ranging from room

temperature to 110 8C (Table 2, entries 7–9). The yield of product was increased with increasing the temperature.

So the best condition was that the reaction was catalyzed by 1 mol% of Hf(NPf2)4 in C10F18 at 110 8C (Table 3).

Under these optimal conditions, various amidomethyl naphthols were synthesized in high yields by the

reaction of different aromatic aldehydes with b-naphthol and urea or amides including acetamide and benzamide

[9]. In all cases, amidomethyl naphthols were the sole products and no by-product or isomer was observed.

Aromatic aldehydes with substituents bearing either electron-donating or electron-withdrawing groups reacted

successfully and gave the products in high yields. It was shown that the aromatic aldehydes with electron-

withdrawing groups reacted faster than the aromatic aldehydes with electron-donating groups as expected. Urea

or different amides, such as acetamide and benzamide worked equally. The reactions with thiourea were

considered, but no corresponding products were produced.

To further expand the scope of amino containing substrates, we employed aniline, p-nitroaniline and p-

methylphenyl sulphonylamide instead of acetamide to react with b-naphthol and benzaldehyde in the presence of

Hf(NPf2)4. However, we observed only high yield Schiff base type products when we used aniline and p-nitroaniline.

And trace Schiff base product was obtained when we used p-methylphenyl sulphonylamide.

In addition, using a-naphthol instead of b-naphthol, the reaction gave a mixture of the regioisomers 4 and 5 with the

total yield of 63% in 10 h (Scheme 2).

M. Hong et al. / Chinese Chemical Letters 22 (2011) 322–325324

Table 3

Synthesis of amidomethyl naphthols in the presence of Hf(NPf2)4a.

Entry Ar R Product Time (h) Yield (%)b

1 C6H5 CH3 3a 6 87

2 4-MeOC6H4 CH3 3b 8 79

3 4-Me2NC6H4 CH3 3c 8 75

4 4-ClC6H4 CH3 3d 4 93

5 4-BrC6H4 CH3 3e 4 92

6 4-NO2C6H4 CH3 3f 4 95

7 3- NO2C6H4 CH3 3g 4 94

8 2- ClC6H4 CH3 3h 4 85

9 2,4-Cl2C6H3 CH3 3i 4 91

10 C6H5 Ph 3j 6 90

11 4-MeOC6H4 Ph 3k 8 81

12 4-ClC6H4 Ph 3l 4 95

13 C6H5 NH2 3m 8 83

14 4-MeOC6H4 NH2 3n 10 76

15 4-ClC6H4 NH2 3o 6 89

a Reaction conditions: Aromatic aldehyde (1 mmol), b-naphthol (1 mmol), urea or amide (1.2 mmol), Hf(NPf2)4 (0.01 mmol), perfluorodecalin

(1.5 mL), 110 8C.b Isolated yield.

[()TD$FIG]

OH

PhCHO

OH

Ph

NHCOCH3 OH

Ph NHCOCH3

CH++ 3CONH2

Hf(NPf 2)4

C10F18 110, o h8C,+

4 5%59%41

Scheme 2. Reaction of a-naphthol, benzaldehyde and acetamide.

2. Conclusion

In conclusion, a novel and highly efficient methodology for the synthesis of substituted amidomethyl naphthols by

the straightforward three-component condensation in one pot using aromatic aldehyde, b-naphthol and urea or amides

in perfluorodecalin. The method offers several advantages including operational simplicity, short reaction times, high

yields of products and the use of non-toxic solvents.

Acknowledgments

We thank the project of ‘‘Excellence Initiative’’ and ‘‘Zijin Star’’ in NJUST for financial support.

References

[1] (a) K.F. Jim, W.D. Matthews, J. Pharmacol. Exp. Ther. 234 (1985) 161;

(b) K.S. Atwal, B.C.O. Reilly, E.P. Ruby, et al. J. Med. Chem. 30 (1987) 627;

(c) M. Grundke, H.M. Himmel, E. Wettwer, et al. J. Cardiovasc. Pharmacol. 18 (1991) 918.

[2] N.P. Selvam, P.T. Perumal, Tetrahedron Lett. 47 (2006) 7481.

[3] (a) R.R. Nagawade, D.B. Shinde, Mendeleev Commun. 17 (2007) 299;

(b) B. Das, K. Laxminarayana, B. Ravikanth, B.R. Rao, J. Mol. Catal. A: Chem. 261 (2007) 180.

[4] M.M. Khodaei, A.R. Khosropour, H. Moghanian, Synlett (2006) 916.

[5] H. Reza Shaterian, H. Yarahmadi, Tetrahedron Lett. 49 (2008) 1297.

[6] A.R. Hajipour, Y. Ghayeb, N. Sheikhan, et al. Tetrahedron Lett. 50 (2009) 5649.

[7] G.C. Nandi, S.R. Kumar, M.S. Singh, Tetrahedron Lett. 50 (2009) 7220.

[8] M. Hong, C. Cai, J. Fluorine Chem. 131 (2010) 111.

[9] General procedure for the synthesis of amidomethyl naphthols: To a mixture of aldehyde (1 mmol), b-naphthol (1 mmol) and urea or amide

(1.2 mmol) was added Hf(NPf2)4 (0.01 mmol, 1 mol%) in C10F18 (1.5 mL). The mixture was stirred at 110 8C for the time as shown in Table 3.

The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and 1,2-

dichloroethane (2 mL) was added, and the mixture was stirred for another 5 min. The fluorous layer on the bottom was separated for the next

cycle. The 1,2-dichloroethane layer was evaporated, and the remaining solid product was recrystallized from ethanol to afford pure amidomethyl

naphthol. All compounds were characterized by MS and 1H NMR and compared with the authentic samples.

M. Hong et al. / Chinese Chemical Letters 22 (2011) 322–325 325