novel heterogeneously catalysed selective, solventless monotetrahydropyranylation of different...

Catalysis Communications 5 (2004) 463–468

www.elsevier.com/locate/catcom

Novel heterogeneously catalysed selective, solventlessmonotetrahydropyranylation of different symmetrical 1,n-diols

and various alcohols using ZrO2-pillared clay

Vasundhara Singh a,*, Varinder Sapehiyia a, Goverdhan Lal Kad b

a School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147004, Indiab Department of Chemistry, Punjab University, Chandigarh 160014, India

Received 5 March 2004; accepted 24 May 2004

Available online 26 June 2004

Abstract

ZrO2-pillared clay (Zr-PILC) a mild recyclable solid Lewis acid catalyst prepared by a short and simple novel method by us, has

been used for the selective, monotetrahydropyranylation under solvent-free condition both by heating and microwave irradiation of

1,n-symmetrical diols and simple alcohols with good selectivity and conversion in high yields for the first time.

HO� ðCH2Þn �OHþDHP !Zr-PILC

MWHO� ðCH2Þn �OTHP

A comparative study with previously reported methods and other acid catalysts has been done to demonstrate the efficacy of the

present developed methodology.

� 2004 Elsevier B.V. All rights reserved.

Keywords: ZrO2-pillared clay; THP; 1,n-Symmetrical diols; MW

1. Introduction

The prevalence of alcohol functionality in multi-

functional intermediates of drugs, pharmaceuticals and

other natural products makes the selective protection of

these groups an important functional group transfor-

mation in organic synthesis. The versatility of the 3,4-

dihydro-2H-pyran (DHP) as a hydroxy group protector

has been proven in peptide, nucleotide, carbohydrate

and steroid chemistry [1]. The increasing number ofenvironmental problems has led to a search for more

friendly forms of catalysis. As a result, the development

of green and clean methodologies has recently gained

importance.

Very few methods for the selective monoprotection of

different 1,n-symmetrical diols as tetrahydropyranyle-

* Corresponding author. Tel.: +91-175-239-3303; fax: +91-175-236-

4498.

E-mail address: [email protected] (V. Singh).

1566-7367/$ - see front matter � 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.catcom.2004.05.013

thers [2], an important challenge in organic chemistry

are known which give high selectivity and conversion.Nishinguchi et al. [3] used metallic sulfate supported on

silica gel or cation exchange resins [4], while Sarma et al.

[5] describes microwave-mediated selective monotetra-

pyranylation of symmetrical diols catalysed by iodine in

THF as solvent. The use of flammable solvents is not

recommended under domestic microwave irradiation

due to fire hazard. All these procedure developed so far

require longer reaction time, tedious separation and useof different solvents. A comparative study with previ-

ously reported methods has been done to demonstrate

the efficacy of the present developed methodology.

In continuation with our work [6], on use of hetero-

geneous acid catalysts and ultrasound and microwave

technology to promote reactions, we herein, introduce a

novel protocol for the selective, efficient monoetherifi-

cation of different 1,n-diols and other various alcoholsand phenols under solventless conditions using recycla-

ble ZrO2-pillared clay (Zr-PILC) catalyst both by

mail to: [email protected]

464 V. Singh et al. / Catalysis Communications 5 (2004) 463–468

heating and microwave activation. The effect of tem-

perature and solvent on the selectivity, reaction time and

conversion ratio has been studied. The scope of the re-

action for various chain lengths of diols has been studied

and optimum reaction conditions are reported.The use of insoluble inorganic solid acid heteroge-

neous catalysts in place of homogeneous catalysts has

the advantages of easy recovery, recyclability, increased

yields and selectivity. We have recently reported [7] a

novel method using ultrasound for intercalation and

microwave heating for rapid aging together for the

preparation of Zr-PILC in 30 min referred to as PIL-

MNT-MW10-US20 with microporous solid structurehaving good thermal stability and structural rigidity,

porosity, enhanced surface area and good catalytic

properties. The interlayer spacing of d0 0 1 ¼ 22:1 �A and

surface area of 224.2 m2/g has been achieved by this

method. The limited use of these catalysts is due to the

long and tedious method of preparation reported in

literature and also, the fine tuning of physicochemical

properties of Zr-PILC largely depends on the method ofpreparation [8]. The catalytic activity has been checked

for the monoacylation of 1,n-symmetrical diols. It is

proposed that since the acidity is confined to the inter-

layer space in the catalyst, with relatively large channels

and it provides a precisely defined, but flexible, micro-

environment as selective acid catalysts. This catalyst is

non-corrosive and non-toxic in nature easy to handle

and can be recovered by simple filtration from the re-action mixture and recycled.

The selectivity, conversion, yields and reaction time

for the formation of mono and dietherification products

is reported for a model compound 1,4-butanediol under

various reaction conditions and shown in Table 1. It is

clear from the results that the method (entry 5) of sol-

ventless conditions by microwave irradiation using

Zr-PILC gave the best results with respect to yield,conversion and selectivity with the advantage of mani-

fold reduction in reaction times. The selectivity of the

method (entry 4) when the reaction mixture was heated

at 65 �C without solvent is also good, however the

Table 1

Selective monoetherification of 1,4-diol catalysed by Zr-PILC under differen

Entry Mode of activation Solvent Time (min

1 r.t CH2Cl2 270

2 D CH2Cl2 40

3 r.t – 210

4 D – 25

5 MW – 3

aThe reactions were monitored by Nucon 57651 GC (FID detector) using C

270 �C, detector temperature 280 �C, oven temperature, program 70 �C (1 m

times: 1,4-butanediol 14.27 min, monoether of 1,4-diol 16.5 min, diether of 1,

and lR.

reaction time taken is much longer. It is observed that in

(entries 1 and 3) some unidentified side products

observed by GC analysis were formed. The catalyst has

been recycled five times with no loss of activity and

selectivity of the products formed.

2. Experimental

2.1. Monotetrahydropyranylation of 1,n-symmetrical

diols

In a typical reaction, butane-1,4-diol (270 mg, 1mmol) was mixed with DHP (252 mg, 1 mmol) in a 50

ml borosil beaker containing 250 mg activated Zr-pil-

lared clay. The reaction mixture in the beaker covered

with a watch glass was then irradiated in a domestic

microwave oven at power level 350 W for 3 min. The

reaction was monitored by GC analysis and TLC to

study the ratio of products formed, yields and percent-

age conversion. On complete conversion, the productformed was dissolved in CH2Cl2, followed by mere fil-

tration to remove the catalyst. Purification by column

chromatography (Pet.ether:ether, 8:2) gave the monoe-

ther 452 mg (86%) and diether 86 mg (11%). 1HNMR

(CCl4): For monoether, d 1.3–1.9 (10H, m), 2.55 (1H, s,

D2O-exchangeable), 3.36 (t, 2H, –CH2–O–, J ¼ 7 Hz),

3.52 (t, 2H, –CH2OH, J ¼ 7 Hz), 3.79 (t, 2H, cyclic –

CH2–O–, J ¼ 7 Hz), 4.56 (1H, s). For diether, d 1.3–1.9(10H, m), 3.3l (t, 4H, –CH2–O–, J ¼ 7 Hz), 3.85 (t, 4H,

cyclic –CH2–O–, J ¼ 7 Hz), 4.51 (1H, s), no change in

spectra on adding D2O.

The reaction with other diols has been optimized by

varying the ratio of diol, DHP and catalyst taken besides

the time and power level of microwave irradiation and

results are reported in Table 2. The selectivity in the range

of 80–95% ofmonoether with nearly 90% conversionwithrespect to starting material is achieved. The reactions

have been monitored by GC analysis and products

characterized by IR and NMR analysis. All the reactions

were repeated three times for reproducibility of results.

t reaction conditions

) Conversion (%)a Product ratio (%)a

Mono: Diether

92 70 15

95 79 15

90 70 17

95 80 15

98 87 11

arbowax-20M column, N2 as carrier gas at 20 psi, injector temperature

in), 10 �C/min, 145 �C (0 min), 10 �C/min, 250 �C (8 min), retention

4-diol 19.21 min. DHP 1.5 min. Final products characterized by 1NMR

Table 3

Comparison of Zr-PILC with KSF, bH-HPZ and Montmorillonite-K10 clay for solvent less, selective monoetheriflcation of 1,4-butanediol under

microwave irradiation

Entry Catalyst Conversion (%) Product ratio (%)

Mono: Diether

1 KSF 60 33 27

2 Mont.-K10 68 39 29

3 Zr-PILC 98 87 11

4 bH-HPZ 70 35 35

All above reactions were carried out in microwave using 1,4-butanediol as model reaction in similar conditions. 1 equiv. DHP and 1 equiv. 1,4-

butanediol were irradiated in microwave oven at 350 W for 3 min, using 250 mg of catalyst viz. KSF, Mont.-K10, Zr-PILC in entries 1, 2 and 3,

respectively.

Table 2

Monotetrahydropyranylation of different 1,n-symmetrical diols by Zr-PILC under microwave irradiation in dry media

S.no. Diols Reaction conditions Total conversion (%) Power level (W) Product ratio (%)a

DHP (equiv) MWI time (min) Mono: Diether

1 HO(CH2)2OH 1 2 100 350 78 22

2 HO(CH2)3OH 1 3 99 350 84 15

3 HO(CH2)4OH 1 3 98 350 87 11

4 HO(CH2)5OH 1.1 5 95 420 85 10

5 HO(CH2)6OH 1.1 5 90 420 82 8

6 HO(CH2)7OH 1.2 5 93 420 85 8

7 HO(CH2)8OH 1.2 5 89 490 80 9

8 HO(CH2)10OH 1.2 6 84 560 77 7

The characterization has been done of the pure products by IR and 1H NMR.a Spectral data is given at the Appendix A.

Table 4

Solventless Zr-PILC catalysed tetrahydropyranylation of various 1�, 2�, 3�, allylic, and benzylic alcohols under microwave irradiation

S.no. Alcohol DHP (equiv.) MW time (min) Power level (Watt) Yield (%)

1 CH3CH2CH2OH 1.1 4 210 100

2 CH3(CH2)3OH 1.1 4 350 100

3 CH3(CH2)4OH 1.1 5 490 100

4 CH3(CH2)5OH 1.2 5 490 100

5 CH3(CH2)7OH 1.2 7 490 92

6 CH3CHOHCH3 1.1 4 210 95

7 CH3(CH2)2CHOHCH3 1.1 5 420 98

8 CH3(CH2)CHOHCH3 1.1 5 350 97

9 (CH3)3COH 1 5 350 94

10 (CH3)2C@CHCH2CH2C(CH3)(OH)CH@CH2 1.3 8 630 70

11 HCCCH2OH 1 5 350 99

12 (CH3)2C@CHCH2CH2C(CH3)@CHCH2OH 1.3 8 560 97

13 (CH3)2C@CHCH2CH2CH(CH3)CH2CH2OH 1.3 5 420 89

14 H2C@CH–CH2OH 1.1 5 420 97

15 C6H5CH2OH 1.2 5 350 84

16 C6H11OH 1.1 5 420 97

17 C6H5OH 1.1 5 470 70

V. Singh et al. / Catalysis Communications 5 (2004) 463–468 465

2.2. Comparison of Zr-PILC with KSF, bH-HPZ and

Montmorillonite-K10 Clay for solvent less, selective

monoetherification of 1,4-butanediol under microwave

irradiation

Commercially available Montmorillonite-K10 clay,

KSF clay and b zeolite (Hþ-form of HPZ), were also

tried for monoetherification of 1,4-butanediol, but gave

very poor selectivity as shown in Table 3. In each re-

action, 1 equiv. of DHP and 1 equiv. of 1,4-butanediol

were irradiated in microwave oven at 350 W for 3 min

using 250 mg of catalyst viz. KSF, Mont.-K1O, Zr-

PILC in entries 1, 2 and 3, respectively. The results are

summarized in Table 3.


2.3. Tetrahydropyranylation of 1�, 2�, 3�, allylic, cyclicand aromatic alcohols

Various other classes of reagents used as heteroge-

neous catalysts for etherification of different alcohols areacidic ion-exchange resin [9], sulphuric acid absorbed on

silica gel [10], H-MCM-41 mesoporous molecular sieves

[11], HSZ zeolite [12] and several other reagents [13]. Zr-

PILC is also effective for various types of alcohols such

as 1�, 2�, 3�, allylic, cyclic and aromatic systems as given

in Table 4.

2.4. General details

1H NMR was recorded in CDCl3 on a 300 MHz

Bruker instrument using TMS as the internal standard

reference. IR spectra were recorded on a Perkin–Elmer

337 spectrometer. Microwave irradiation carried out in

a domestic microwave oven, BPL BMO 700T, India.

The Zr-PILC composite was prepared by pillaring of

Naþ-Montmorillonite clay sample provided by Kuni-mine Co. Ltd., Japan. ZrOCl2 � 8H2O was purchased

from S.D. Fine Chemicals, India. DHP and different

diols were purchased from Sigma–Aldrich Chemical

Co., USA.

3. Results and discussion

3.1. Plausible mechanism

The plausible mechanism of the reaction may be due

to effective and efficient reaction of the alcohol with the

polyoxyzirconium cations in the interlayer spacing of

the pillared clay catalyst which reacts with the dihyd-

ropyran to form the intermediate oxonium ion which

HO OHn

Zr-PILC

H

HO On

ZrOHO O O

H

n

OH OTHPnZrO2

Scheme 1. Diagrammatic representa

subsequently deprotonates to give the tetrahydropyr-

anylated product and regenerates the catalyst with high

conversion in short duration of time. The acceleration of

the reaction is also due to the large surface area and

more number of acidic sites provided by the catalyst dueto desegregation of the clay structure. The reason for

high selectivity to form monoetherification product is

likely due to steric effect as the reaction takes place in

the restricted interlayer spacing of the catalyst and rapid

diffusing out of the mono-protected product which gets

desorbed faster than the diol, after it is formed. This is

supported by experimental results in comparison with

other catalysts where the acidity is confined to the sur-face only and hence gives poor selectivity Scheme 1.

3.2. A comparison with reported procedure is as given in

Table 5

A comparative study with the reported methods for

the monoetherification of 1,n-diols is done to show the

efficiency of the catalyst and reported in Table 5 withthe added advantage of using the Zr-PILC as a recy-

clable catalyst, can be used at commercial scale due to

ease of separation and under solventless conditions.

4. Conclusion

In conclusion, a highly selective, solventless, simpleand eco-friendly methodology for the monotetrahydro-

pyranylation of different symmetrical 1,n-diols and

various other alcohols using a recyclable Zr-PILC as an

efficient catalyst, accelerated by microwave irradiaton,

has been developed by us. The commercial scale up of

this reaction is possible in neat DHP and diol mixture

using this catalyst also by heating to get the desired

HO On

H

ZrO2

H++

O

O+

2

tion of plausible mechanism.

Table 5

Comparison of monotetrahydropyranylation of different symmetrical 1,n-diols by Zr-PILC with literature reported methods

S.no. Substrate Catalyst Conditions Yield (%) References

Solvent Temperature (�C)or power level

Time (min) Mono: Diether

1. 1,2-Ethanediol I2 THF 67 2.5 78 18 [5]

Al2(SO4)3–SiO2 Hexane 25 150 94 5 [3]

Zr-PILC Solventless 350 W 2.5 78 22

2. 1,3-Propanediol I2 THF 67 2.5 77 17 [5]

Al2(SO4)3–SiO2 Hexane 25 120 91 3 [3]


3. 1,4-Butanediol I2 THF 67 2.5 75 16 [5]

Al2(SO4)3–SiO2 Hexane 25 90 96 4 [3]


4. 1,5-Pentanediol – – – – – –

Al2(SO4)3–SiO2 Hexane 25 150 78 8 [3]


5. 1,6-Hexanediol I2 THF 67 2.67 76 16 [5]

Al2(SO4)3–SiO2 Hexane 45 85 74 10 [3]


6. 1,8-Octanediol – – – – – –

Al2(SO4)3–SiO2 Hexane 65 90 76 9 [3]


7. 1,10-Decanediol – – – – – –

Al2(SO4)3–SiO2 Hexane 78 150 76 10 [3]


V. Singh et al. / Catalysis Communications 5 (2004) 463–468 467

products with good conversion, selectivity and highyield.

Acknowledgements

The authors are grateful to Department of Science

and Technology (DST), New Delhi, for the financial

support provided. We thank Kunimine Co. Ltd., Japanfor supplying MNT samples and RSIC/CIL/USIC,

Punjab University, Chandigarh, for taking 1H NMR

(Mr. Avtar Singh) and IR spectra.

Appendix A. Spectral data

1,2-Ethanediol:

(a) Monoether: mmax(neat)/cm�1 3400 (OH); 1H NMR

(CDCl3) d 1.45–1.71 (m, 6H), 2.01 (s, 1H) D2O ex-

changeable, 3.56 (t, 2H, –CH2–O–, J ¼ 7 Hz), 3.61(t, 2H, –CH2OH, J ¼ 6 Hz), 3.71 (t, 2H, cyclic –

CH2–O–, J ¼ 7 Hz), 4.51 (s, 1H).

(b) Diether: 1HNMR (CDCl3) d 1.41–1.75 (m, 12H),

3.51 (t, 4H, –CH2–O–, J ¼ 7 Hz), )3.67 (t, 4H, cy-

clic –CH2–O–, J ¼ 7 Hz), 4.61 (s, 2H).

1,3-Propanediol:


(CDCl3) d 1.38–1.79 (m, 8H), 2.31 (s, 1H) D2O ex-

changeable, 3.35 (t, 2H, –CH2–O–, J ¼ 7 Hz), 3.57(t, 2H, –CH2OH, J ¼ 6 Hz), 3.85 (t, 2H, cyclic –

CH2–O–, J ¼ 7 Hz), 4.59 (s, 1H).

(b) Diether: 1H NMR (CDCl3) d 1.31–1.71 (m, 14H),

3.37 (t, 4H, –CH2–O–, J ¼ 7 Hz), 3.70 (t, 4H, cyclic

–CH2–O–, J ¼ 7 Hz), 4.51 (s, 2H).

1,4-Butanediol:


(CDCl3) d 1.3–1.9 (10H, m), 2.55 (1H, s, D2O-ex-changeable), 3.36 (t, 2H, –CH2–O–, J ¼ 7 Hz),

3.52 (t, 2H, –CH2OH, J ¼ 7 Hz), 3.79 (t, 2H, cyclic

–CH2–O–, J ¼ 7 Hz) 4.56 (1H, s).

(b) Diether: 1H NMR (CDCl3) d 1.3–1.9 (10H, m), 3.31

(t, 4H, –CH2–O–, J ¼ 7Hz), 3.85 (t, 4H, cyclic –

CH2–O–, J ¼ 7 Hz), 4.51 (1H, s) no change in spec-

tra on adding D2O.

1,5-Pentanediol:(a) Monoether: mmax(neat)/cm

�1 3400 (OH); 1H NMR

(CDCl3) d 1.25–1.91 (m, 12H), 2.65 (s, 1H) D2O ex-

changeable, 3.30 (t, 2H, –CH2–O–, J ¼ 7 Hz), 3.51

(t, 2H, –CH2OH, J ¼ 7 Hz), 3.81 (t, 2H, cyclic –

CH2–O–, J ¼ 7 Hz), 4.65 (s, 1H).


3.31 (t, 4H, –CH2–O–, J ¼ 7 Hz ), 3.85 (t, 4H, cyclic

–CH2–O–, J ¼ 7 Hz), 4.51 (s, 2H).1,6-Hexanediol:


(CDCl3) d 1.10–1.95 (m, 14H), 3.65 (s, 1H within


the triplet of –CH2–) D2O exchangeable, 3.29 (t, 2H,

–CH2–O–, J ¼ 7 Hz), 3.65 (m due to –CH2OH),

3.91 (t, 2H, cyclic –CH2–O–, J ¼ 7 Hz), 4.59 (s, 1H).


3.41 (t, 4H, –CH2–O–, J ¼ 7 Hz), 3.89 (t, 4H, cyclic–CH2–O–, J ¼ 7 Hz), 4.51 (1H, s) no change in

spectra on adding D2O.

1,7-Heptanediol:


(CDCl3) d 1.15–1.91 (m, 16H), 2.85 (s, 1H) D2O ex-

changeable, 3.21 (t, 2H, –CH2–O–, J ¼ 7 Hz), 3.57


CH2–O–, J ¼ 7 Hz), 4.55 (s, 1H).(b) Diether: 1H NMR (CDCl3) d 1.21–1.91 (m, 22H),


–CH2–O–, J ¼ 7 Hz), 4.65 (s, 2H).

1,8-Octanediol:


(CDCl3) d 1.11–1.95 (m, 18H), 3.35 (s, 1H with in

triplet of –CH2–), D2O exchangeable, 3.35 (m due

to insertion of –OH peak), 3.59 (t, 2H, –CH2OH,J ¼ 6Hz), 3.91 (t, 2H, cyclic –CH2–O–, J ¼ 7 Hz),

4.49 (s, 1H).


3.39 (t, 4H, –CH2–O–, J ¼ 7 Hz), )3.75 (t, 4H, cy-

clic –CH2–O–, J ¼ 7 Hz), 4.51 (s, 2H).

1,10-Decanediol:


(CDCl3) d 1.11–1.99 (m, 22H), 2.55 (s, 1H) D2O ex-changeable, 3.31 (t, 2H, –CH2–O–, J ¼ 7 Hz), 3.53


CH2–O–, J ¼ 7 Hz), 4.55 (s, 1H).



–CH2–O–, J ¼ 7 Hz), 4.51 (s, 2H).

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novel heterogeneously catalysed selective, solventless monotetrahydropyranylation of different...

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