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Acta Chim. Slov. 2007, 54, 642–646
Short communication
Zirconyl(IV) Chloride – Catalyzed Multicomponent
Reaction of ß-Naphthols: An Expeditious Synthesis
of Amidoalkyl Naphthols
Rahul R. Nagawade and Devanand B. Shinde*
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad – 431004 (M.S.), India.
* Corresponding author: Tel. 91-240-2400431; E-mail: devanandshinde@yahoo.com
Received: 06-07-2006
Abstract
Zirconyl(IV) chloride is found to be an efficient catalyst for the multicomponent condensation reaction of ß-naphthol, aromatic aldehydes and urea or amide to afford the corresponding amidoalkyl naphthols in good yields. The remarkable features of this new procedure are high conversions, shorter reaction times, cleaner reaction profiles and simple experimental and work-up procedures.
Keywords: Zirconyl(IV) chloride, multicomponent reaction, condensation, ß-naphthol, aryl aldehyde, urea.
1. Introduction
Multicomponent reactions (MCRs) have attracted considerable attention since they are performed without need to isolate the any intermediate during their processes; this reduces time and saves both energy and raw mate-rials.1 They have merits over two-component reactions in several aspects including the simplicity of a one-pot procedure, possible structural variations and building up complex molecules. Biginelli,2 Ugi,3 Passerini4 and Man-nich5 are some examples of MCRs. Neverthless, development and discovery of new MCRs is still in demand.
In this context, ortho-quinone methides (O-QMs) have been used in many tandem processes,6 but only limited work on their reaction with nucleophiles has appeared in the literature.7 Very recently, a simple and convinient method for the synthesis of dibenzoxanthenes by the condensation of aldehydes with ß-naphthol in the presence of p-toluene sulfonic acid (p-TSA) as a catalyst has been re-ported.8 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 ureas and amides to produce novel amidoalkyl naphthol compounds using zirconyl(IV) chloride as a catalyst.
Zirconyl(IV) chloride is moisture stable, readily available and inexpensive oxy- salt of zirconium, and until now has not been explored in synthetic organic chem-
istry as a mild and versatile Lewis acid catalyst. Compared to conventional Lewis acids, particularly zirconyl(IV) chloride has advantages of low catalyst loading, moisture stability and catalyst recycling. In our attempt to explore the role of zirconyl(IV) chloride as an mild and efficient Lewis acid catalyst, we demonstrated the use of zirconyl-(IV) chloride as a catalyst for the synthesis of 1,5-benzo-diazepines,9 benzimidazoles10 and bis(indolyl)methanes.11
In continuation of our work on zirconyl(IV) chloride, in this paper we have demonstrated the use of zirconyl(IV) chloride as a mild and efficient catalyst for the synthesis of amidoalkyl naphthols by multicomponent reaction of ß-naphthol, aromatic aldehydes and urea or amide.
2. Results and Discussion
Herein, we wish to disclose a novel protocol for the rapid synthesis of a variety of biologically important ami-doalkyl naphthols using a catalytic amount of zirconyl-(IV) chloride under extremely mild conditions (Scheme 1). Firstly, 4-chlorobenzaldehyde and urea was chosen as a model for the reaction with ß-naphthol. 4-Chlorobenzal-dehyde was treated with equimolar amount of ß-naphthol and urea in the presence of 10 mol % ZrOCl2 · 8H2O at room temperature in various solvents to afford amidoalkyl naphthols (Table 1, entries 1–8). We found that 1,2-di-chloroethane was the best choice.
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Scheme 1
Table 1: Solvent effect on the reaction of 4-chlorobenzaldehyde, ß-naphthol and urea, catalyzed by ZrOCl2.
Solvent	Time (hr.)	Yield (%)a
ClCH CH Cl	11	86
CH3CN	14	47
MeOH	14	71
EtOH	15	62
CHCl	13	77
CH2Cl2	13	81
DMF	14	20
1,4-Dioxane	15	73
a isolated yields
Having established the reaction conditions, various amidoalkyl naphthols were synthesized in excellent yields by the reaction of different aromatic aldehydes with ß-naphthol and urea and several representative examples are summarized in Table 2. In all cases, amidoalkyl naphthols were the sole products and no by-product was observed. Similar results were obtained under the same conditions when N-methyl urea was used in place of urea (Table 2, entry 7). The reaction of aromatic aldehydes with ß-naph-thol and different amides including acetamide and benza-mide in 1,2-dichloroethane under similar reaction conditions also provided the corresponding amidoalkyl naph-thols in high yields (Table 2, entry 8 and 9).
In all cases, aromatic aldehydes with substituents carrying 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 would be expected. To demonstrate the scope and limitations of the procedure, the reaction of ortho-substituted aromatic aldehydes such as 2-chlorobenzaldehyde, and the het-eroaromatic aldehyde furfural were studied and the results are summarized in Table 2. Aliphatic aldehyde like propi-onaldehyde was also examined, but the yields were low as compared to aromatic aldehyde (Table 2, entry 11). On the other hand, the reactions with thiourea were considered, but no corresponding products were produced. Also, amines such as ethylamine and aniline were utilized and no aminoalkyl naphthol was obtained.
3. Conclusions
A novel and highly efficient methodology for the synthesis of amidoalkyl naphthols by multicomponent condensation reaction of aromatic aldehyde, ß-naph-thol, and ureas or amides, catalyzed by zirconyl(IV) chloride is reported. This method offers several significant advantages: such as, high conversions, easy handling, cleaner reaction profile and shorter reaction times, which makes it a useful and attractive process for the rapid synthesis of substituted amidoalkyl naph-thols.
4. Experimental
1H NMR and 13C NMR spectra were recorded on a Varian Gemini 200 MHz spectrometer. Chemical shifts are reported in ? units (ppm) relative to TMS as internal standard. Electron spray ionization mass spectra (ES-MS) were recorded on a Water-Micromass Quattro-II spectrometer. IR spectra were recorded on a Varian spectrometer. All reagents used were of AR grade and were used without further purification. Column chromatography employed silica gel of 60–120 mesh.
4. 1. General Procedure
A mixture of aromatic aldehyde (1 mmol), ß-naph-thol (1 mmol), urea or amide (1.1 mmol) and ZrOCl2 ? 8H2O (0.1 mmol) in 1,2-dichloroethane (2 mL) was stirred at room temperature for the appropriate time (Table 2). The progress of the reaction was monitored by TLC (solvent system: MeOH: CHCl3, 1 : 9). After completion of the reaction, as indicated by TLC, the reaction mixture was filtered and the precipitate washed well with diethyl ether and then with water. The crude compounds were purified by silica gel column chromatography (60–120 mesh size silica gel) eluting with chloroform, followed by 2% methanol in chloroform to afford the desired compound in pure form. All the synthesized compounds were characterized by 1H NMR, 13C NMR, mass spectrometry (ES-MS) and elemental analysis.
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Acta Chim. Slov. 2007, 54, 642–646
Table 2: ZrOCl2 – Promoted synthesis of amidoalkyl naphthol derivatives.
Entry            Aldehyde
Urea or amide
Product            Time (h)           Yield (%)
H2NCONH2
11
86
H2NCONH2
14
83
H2NCONH2
15
80
H2NCONH2
10
87
H2NCONH2
17
57
H2NCONH2
25
63
Çh
H NCONHCH
09
88
O M
H2NCOPh
11
79
o,n
H9NCOCH,
CHO                    2                   3
MO
09
84
10
H2NCONH2
25
25
1
2
3
4
5
6
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[(4-Chlorophenyl)-(2-hydroxy naphthelene-l-yl)-met hyl]-urea (Table 2, entry 1): IR (neat): 3456, 3360, 3200, 2240, 1632, 1580, 1513, 1430, 1370, 1238, 816 cm"1, :H NMR (200 MHz, DMSO-d6): 8 10.32 (s, IH), 7.95-7.75 (m, 3H, Ar-H), 7.50-7.10 (m, 7H, Ar-H), 6.80 (s, 2H), 5.80 (s, 2H), 13C NMR (50 MHz, DMSO-d6): 8 159.3, 153.6, 144.3, 132.8, 131.1, 130.0, 129.4, 129.1, 128.9, 128.6, 128.4, 127.4, 123.3, 120.4, 119.2, 48.4, Mass (ES/MS): m/z 325 (M-H, 100%); Anal. calcd. for C18H15C1N202: C 66.16, H 4.63, N 8.57; found: C 66.32, H 4.59, N 8.62.
[(2-Hydroxy naphthalen-l-yl)-phenyl-methyl]-urea (Table 2, entry 2): :H NMR (200 MHz, DMSO-d6): 8 10.28 (s, IH), 7.85-7.15 (m, 12H), 6.90 (s, 2H), 5.70 (s, 2H); 13C NMR (50 MHz, DMSO-d6): 8 159.3, 153.6, 144.3, 132.8, 131.1, 130.0, 129.4, 129.1, 128.9,
128.6,  128.4, 127.4, 123.3, 120.4, 119.2, 48.4; Mass (ES/MS): m/z 291 (M-H, 100%); Anal. calcd. for C18H16N202: C 73.96, H 5.52, N 9.58; found: C 74.51, H 5.57, N 9.62.
[(4-Methoxyphenyl)-(2-hydroxy naphthalen-l-yl)-met hyl]-urea (Table 2, entry 3): :H NMR (200 MHz, DM-SO-d6): 8 10.30 (s, IH), 7.60-7.05 (m, 8H), 6.80 (d, 2H), 6.70 (bs, 2H), 5.70 (s, 2H); 13C NMR (50 MHz, DMSO-d6): 8 162.7, 153.5, 142.8, 135.1, 133.5, 129.3, 128.8, 128.3, 126.3, 123.2, 122.3, 118.9, 115.4, 114.8, 51; Mass (ES/MS): m/z 321 (M-H, 100%); Analysis calcd. for C19H18N203: C 70.79, H 5.63, N 8.69; found C 70.43, H 5.61, N 8.75.
[(3-Nitrophenyl)-(2-hydroxy naphthalen-l-yl)-methyl] -urea (Table 2, entry 4): :H NMR (200 MHz, DMSO-d6): 8 10.27 (s, IH), 8.05-7.95 (m, 2H), 7.55-6.85 (m, 8H), 6.75 (bs, 2H), 5.80 (s, 2H); 13C NMR (50 MHz, DM-SO-d6): 8 162.5, 153.3, 148.7, 143.5, 133.3, 132.4, 130.2,
128.7,  128.2, 126.2, 124.4, 123.6, 123.1, 119.1, 118.6, 115.7, 50.2; Mass (ES/MS): m/z 336 (M-H, 100%); Analysis calcd. for C18H15N304: C 64.09, H 4.48, N 12.46; found C 64.37, H 4.53, N 12.52.
[(Furan-2-yl)-(2-hydroxy naphthalen-l-yl)-methyl]-urea (Table 2, entry 5): :H NMR (200 MHz, DMSO-d6): 8 10.27 (s, IH), 7.70-7.05 (m, 7H), 6.75 (s, 2H), 6.40 (bs, IH), 6.25 (m, IH), 6.10 (m, IH), 5.75 (bs, IH); 13C NMR (50 MHz, DMSO-d6): 8 162.9, 153.7, 152.7, 142.3, 133.6, 129.1, 128.6, 126.5, 123.4, 122.6, 118.7, 115.6, 110.8, 106.9, 46.1; Mass (ES/MS): m/z 281 (M-H, 100%); Analysis calcd. for C16H14N203: C 68.08, H 5.00, N 9.92; found C 67.89, H 5.06, N 9.85.
[(2-Chlorophenyl)-(2-hydroxy naphthalen-l-yl)-met hyl]-urea (Table 2, entry 6): :H NMR (200 MHz, DM-SO-d6): 8 10.35 (s, IH), 7.60-7.45 (m, 2H), 7.30-6.95 (m, 8H), 6.75 (s, 2H), 5.85 (s, 2H); 13C NMR (50 MHz, DM-
SO-d6): 8 163.2, 154,143.9, 134.3, 134.1, 130.1, 129.9, 129.2, 128.8, 127.9, 126.8, 123.2, 119.4, 115.8, 42.3; Mass (ES/MS): m/z 325 (M-H, 100%); Analysis calcd. for C18H15C1N202: C 66.16, H 4.63, N 8.57; found C 66.02, H 4.69, N 8.51.
[(3-Nitrophenyl)-(2-hydroxy naphthalen-l-yl)-met hyl]-3-methyl-urea (Table 2, entry 7): :H NMR (200 MHz, DMSO-d6): 8 10.30 (s, IH), 8.10-7.98 (m, 2H), 7.60-6.90 (m, 8H), 6.55 (m, IH), 5.75 (bs, 2H), 2.90 (d, 3H); 13C NMR (50 MHz, DMSO-d6): 8 157.8, 153.5, 148.9, 143.9, 133.8, 132.9, 130.7, 129.2, 128.7, 126.8, 124.9, 124.1, 123.6, 119.5, 119.1, 116.2, 50.8, 28.9; Mass (ES/MS): m/z 350 (M-H, 100%); Analysis calcd. for C19H17N304: C 64.95, H 4.88, N 11.96; found C 65.20, H 4.92, N 12.01.
N-[(2-Hydroxy-naphthalen-l-yl)-(3-nitro-phenyl)-methyl]-benzamide (Table 2, entry 8): :H NMR (200 MHz, DMSO-d6): 8 10.30 (s, IH), 8.10-7.85 (m, 4H), 7.65-6.95 (m, 11H), 6.55 (bs, IH), 6.15 (bs, IH); 13C NMR (50 MHz, DMSO-d6): 8 167.9, 153.5, 148.9, 143.7,
134.4,  134.2, 133.5, 132.2, 130.2, 128.9, 128.8, 128.3,
127.5,  126.3, 123.5, 123.2, 122.5, 118.9, 118.6, 115.4, 48.7; Mass (ES/MS): m/z 397 (M-H, 100%); Analysis Calcd. for C24H18N204: C 72.35, H 4.55, N 7.03; found C 72.65, H 4.61, N 7.08.
N-[(3-Nitro-phenyl)-(2-hydroxy-naphthalen-l-yl)-methyl]-acetamide (Table 2, entry 9): :H NMR (200 MHz, DMSO-d6): 8 10.30 (s, IH), 8.10-7.85 (m, 2H), 7.65-6.95 (m, 8H), 6.60 (bs, IH), 5.95 (bs, IH), 2.10 (s, 3H); 13C NMR (50 MHz, DMSO-d6): 8 171.1, 152.5, 147.8, 142.7, 133.4, 132.5, 129.2, 127.8, 127.3, 125.3, 122.5, 122.2, 121.5, 117.9, 117.5, 114.4, 46.9, 22.6; Mass (ES/MS): m/z 335 (M-H, 100%), Analysis calcd. for C19H16N204: C 67.85, H 4.79, N 8.33; found C 67.42, H 4.84, N 8.41.
[l-(2-Hydroxy-naphthalen-l-yl)-propyl]-urea (Table 2, entry 10): :H NMR (200 MHz, DMSO-d6): 8 10.35 (s, IH), 7.65-6.95 (m, 6H), 6.45 (bs, IH), 5.65 (bs, 2H), 4.85 (m, IH), 1.75 (m, 2H), 1.05 (t, 3H); 13C NMR (50 MHz, DMSO-d6): 8 160.5, 151.5, 131.3, 126.8, 126.1, 124.5, 121.8, 120.7, 116.4, 113.2, 43.6, 28.10, 16.2; Mass (ES/MS): m/z 243 (M-H, 100%); Analysis calcd. for C14H16N202: C 68.83, H 6.60, N 11.47; found C 69.11, H 6.64, N 11.53.
5. Acknowledgements
The authors are thankful to The Head, Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, 431004 – (M. S.), India for providing laboratory facility.
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Povzetek
Cirkonijev(IV) oksidklorid je uporabljen kot u~inkovit katalizator za ve~komponentno reakcijo kondenzacije ß-naftola, aromatskih aldehidov in uree/amida pri pripravi ustreznih amidoalkilnaftolov z visokimi izkoristki. Pomembne prednosti novega postopka so: visoka stopnja pretvorbe, kratki reakcijski ~asi, ~iste reakcijske poti, nezahtevni eksperimentalni pogoji in enostavna izolacija produktov.
Nagawade and Shinde:   Zirconyl(IV) Chloride – Catalyzed Multicomponent Reaction ...