Research Article p -Sulfonic Acid Calix[4]arene as an ...downloads.hindawi.com/archive/2015/738202.pdf · 1.00 4.01 1.00 (ppm) 10 9 8 7 6 5 4 3 2 1 (a) 0 (ppm) 1.02 1.00 10 9 8 7

Research Articlep-Sulfonic Acid Calix[4]arene as an Efficient Catalyst forOne-Pot Synthesis of Pharmaceutically Significant CoumarinDerivatives under Solvent-Free Condition

Hamed Tashakkorian1 Moslem Mansour Lakouraj2 and Mona Rouhi2

1Cellular and Molecular Biology Research Center (CMBRC) Health Research InstituteBabol University of Medical Sciences Babol 47176 41367 Iran2Department of Organic Chemistry Faculty of Chemistry University of Mazandaran Babolsar 47416 95447 Iran

Correspondence should be addressed to Hamed Tashakkorian htashakkoriangmailcom

Received 12 October 2015 Accepted 26 November 2015

Academic Editor Benedetto Natalini

Copyright copy 2015 Hamed Tashakkorian et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

One-pot and efficient protocol for preparation of some potent pharmaceutically valuable coumarin derivatives under solvent-freecondition via direct coupling using biologically nontoxic organocatalyst calix[4]arene tetrasulfonic acid (CSA) was introducedCalix[4]arene sulfonic acid has been incorporated lately as a magnificent and recyclable organocatalyst for the synthesis of someorganic compounds Nontoxicity solvent-free conditions good-to-excellent yields for pharmaceutically significant structures andespecially ease of catalyst recovery make this procedure valuable and environmentally benign

1 Introduction

Finding novel synthetic procedures for a variety of attractivecompounds that can be considered as pharmaceutics hasbeen investigated over last decades The introduction of newmethodologies in recent years based on environmentallyfriendly conditions using efficient and reusable catalyst aswell as solvent-free procedures has gained significant atten-tions among the researchers Among the thoroughly inves-tigated organic structures coumarins and their derivativeswere highly regarded due to their vast applications in phar-maceutical industries Coumarins also recognized as ben-zopyrones have revealed characteristics of these potent het-erocyclic compounds and proved to feature significant bio-logical activities including antimicrobial antiviral antitumorand antioxidant properties For instancemonoamine oxidaseinhibitors (MAO) have antidiabetic activity [1] antiallergicactivity [2] anabolic antioxidant and hepatoprotective activ-ities [3 4] These valuable structures natural or syntheticones due to theirmentioned characteristics aremultipurposecompounds and play variety of roles in our lives On the otherhand they are being applied to agrochemical [5] food and

cosmetic industries as additives to serve as optical brighteners[6 7] anticoagulants [8] and laser dyes [9 10] and theyhave significant therapeutic roles in pharmaceuticals [11]and treatment of cancer [12] Experimental surveys exhibitthe noteworthy chemotherapeutics activities of these organicstructures and they hence have been employed as inhibitorsin growth of diverse human tumour cell lines [13]

Their known functionalized families have shown varietyof antioxidant [14 15] anti-HIV anticoagulant hypotensiveand spasmolytic activities [16ndash18] Besides some potentialantibiotic characteristics have been reported for coumarinderivatives such as chartesium coumermycin and novo-biocin [19]These valuable compounds also have proved theirefficiency as biologically active structures in the formulationof some medicines for a long time [20 21] As being naturalmolecules coumarins are among the phytochemical com-pounds that exist in high concentration in tonka beanapricots cherries cinnamonmullein strawberries and someother natural products However due to their valuable andimpressive characteristics which resulted in being employedin the wide range of products they became desirablemolecules for researchers to find the least harmful and

Hindawi Publishing CorporationInternational Journal of Medicinal ChemistryVolume 2015 Article ID 738202 8 pageshttpdxdoiorg1011552015738202

2 International Journal of Medicinal Chemistry

HO OHOH HO HO HOOH HO

H2SO4

80∘C 5hr

HO3S HO3S SO3H SO3H

Scheme 1 Sulfonation of calix[4]arene using Shinkai method

the most efficient preparative procedures In synthetic chem-istry some methods were considered as famous and pioneermethods for preparation of these organic compounds Thefirst reported procedure for preparation of coumarins wasPerkin reaction that was suggested in 1868 [22] HoweverPerkin reaction is efficient and suitable just for synthesisof simple coumarins but some alternative methods weredeveloped during the years including Pechmann [23] Kno-evenagel [24 25] Reformatsky [26] Kostanecki-Robinson[27] andWittig reactions [28 29] Although these categoriesof well known reactions give coumarins in acceptable yieldsusually they need severe conditions such as high tempera-tures dangerous solvents long reaction time and producingbyproducts Excess amounts of harsh acidic activating agentssuch as POCl

3 P2O5 and polyphosphoric acid besides quan-

titative amount of Lewis acids or sulfuric or sulfonic acids addto their usage drawbacks due to possible severe difficultiessuch as corrosion problem

So far different catalyses have been raised to overcomethe mentioned drawbacks in the last decade [30ndash32] Oneof the motivating macrocyclic structures with great capacityin different area and that attracted much interest especiallyin biochemistry is calixarene Among the interesting com-pounds derived from this scaffold sulfonate calixarene hasaroused much interest in biopharmaceutical applications[33] due to its promising capabilities in incapsulating cal-ixarenes increase not only solubility but also bioavailabilityof valuable pharmaceutical drugs such as nifedipine [3435] furosemide [36] niclosamide [37] carbamazepine [38]and topotecan for improving solubility in chemotherapy byhost-guest complexes [39] Surprisinglymedical experimentseither of in vivo studies or at the cellular level indicate that thecalixarenes have no activity in the Ames test [37] Moreoverno acute toxicity for the sulfonated calixarenes is reportedwhen specified amounts were injected in mice for in vivostudies Number of previous organized studies revealed thatthese multipurpose compounds are not cytotoxic [40] Cal-ixarenes have very favorable physicochemical properties thatare similar to other useful pharmaceutical excipients such ascyclodextrins [41] Besides the biocompatibility of sulfonatedcalixarenes investigation on catalytic activity of this motifin the synthesis of pharmaceutical compounds seems to beinteresting In this regard and in continuation of our recentstudies on the development of convenient effective andsafe protocol in organic and pharmaceutical synthesis [42ndash45] herein we represent calix[4]arene tetrasulfonic acid asan efficient and environmentally friendly organocatalyst forthe preparation of coumarin derivatives under solvent-freeconditions

2 Experimental

21 Materials and Instruments The fine chemicals includingp-tert-butylphenol formaldehyde solution (37) diphenylether ethylacetate methanol and sodium hydroxide werepurchased from Merck (Schuchardt Germany) Ethyl ace-toacetate resorcinol bisphenols salicylic acid 25-dihy-droxy salicylic acid phosphorus oxychloride and silicagelwere obtained from Fluka (Switzerland) Parent tert-butyl-calixarene was synthesized according to Gutsche procedurepublished in [51] Then it was detertiobutylated and sul-fonated simultaneously by Shinkai method using concen-trated sulfuric acid (Scheme 1) [52] After further purificationdescribed in the literature the obtained product was appliedas a proficient acidic organocatalysis (Figures 1 and 2)Melting points were determined with an Electrothermal 9100Melting Point Apparatus IR and 1H NMR spectra wererecorded respectively on Bruker FTIR Spectrometer andBruker Avance III 400MHz NMR Spectrometer GC-MSanalyseswere carried out on ShimadzuGC 17Agas chromato-graph coupled with MS-QP 5000 Shimadzu Mass Spectrom-eter (Tokyo Japan) Elemental analyses were performed byCHN Rapid Heraeus Elemental Analyzer (Wellesley MA)

22 General Procedure for Preparation of Coumarins Aspecified amount of the catalyst CSA (45mg 006mmol)was added to the mixture of ethyl acetoacetate (130mg1mmol) and phenol derivatives (1mmol)Then theThe flaskwas placed in an oil bath and temperature was adjusted to90∘C After completion of the reaction which was moni-tored by TLC it was cooled down to room temperatureand then poured onto the crushed ice After half an hourreaction mixture was extracted with chloroform three times(3 times 25mL) Subsequently the combined organic phasewas washed with saturated aqueous sodium bicarbonatebrine solution and water respectively Then organic solutionwas dried using magnesium sulfate and the crude productwas obtained using rotary evaporator For further purifi-cation flash column chromatography was performed usingpetroleum etherethylacetate 90 10 (Figure 3)

23 Coumarin Derivatives Characterization

4-Methyl-2H-chromen-2-one (1a) This compound wasobtained (24mg 15) and characterized according to thedescribed procedure from Ethyl acetoacetate (130mg1mmol) and resorcinol (110mg 1mmol)

IR (120592maxcmminus1) 1064 1238 1543 1705 3020

International Journal of Medicinal Chemistry 3

0

100 100401

(ppm)12345678910

(a)

0(ppm)

102 100

12345678910

(b)

Figure 1 1H NMR spectra of calix[4]arene sulfonic acid in (a) DMSO-d6 and (b) D2O

SO3H

SO3H

SO3H

HO3S OHOH

HOOH

200 180 160 140 120 100 80 60 40 20(ppm)

0

151

3413

580

128

0412

644

567

8

304

014

98

Figure 2 13CNMR spectrum of calix[4]arene sulfonic acid in D2O

1H NMR (400MHz CDCl3) (120575 ppm) 120575 242 (d 3H)

632 (q 1H) 715ndash742 (m 3H) 748 (d 119869 = 60Hz 1H)13CNMR (100MHz CDCl

3) (120575 ppm) 191 116 1179 122

1241 1246 1326 153 1545 1616 ESI-MS 119898119911 160 AnalCalcd for C

10H8O2 C 7500H 500 Found C 7523 H 518

7-Hydroxy-4-methyl-2H-chromen-2-one (2a) This com-poundwas prepared (167mg 95) and characterized accord-ing to the described procedure from Ethyl acetoacetate(130mg 1mmol) and resorcinol (110mg 1mmol)

IR (120592maxcmminus1) 1060 1227 1590 1680 3150

1H NMR (400MHz CDCl3) (120575 ppm) 235 (d 3H) 611

(q 1H) 669 (d 119869 = 24Hz 1H) 678 (dd 119869 = 88Hz 1H)756 (d 119869 = 88Hz 1H) 1052 (s 1H)13C NMR (100MHz CDCl

3) (120575 ppm) 1856 10262

11070 11247 11329 12705 15397 15528 16074 1616

OHOH

HOOH

H

H

H H

O

O

O O

R

HO

R Solvent-free protocol

CH3

CH3

SO3

SO3

SO3

O3S

C2H5O

Figure 3 Schematic preparation of coumarin

ESI-MS119898119911 176 Anal Calcd for C10H8O3 C 6818 H 454

Found C 6845 H 476

6-Hydroxy-4-methyl-2H-chromen-2-one (3a) This com-pound was obtained (132mg 75) and identified accordingto the described procedure from Ethyl acetoacetate (130mg1mmol) and hydroquinone (110mg 1mmol)

IR (120592maxcmminus1) 1055 1225 1565 1693 3010 3412

1HNMR (400MHz CDCl3) (120575 ppm) 242 (d 3H) 633

(q 1H) 673 (d 119869 = 84Hz 1H) 681 (d 119869 = 84Hz 1H) 728(s 1H)


13C NMR (100MHz CDCl3) (120575 ppm) 1838 10940

11440 11750 12065 12154 14710 15393 15510 15970 ESI-MS 119898119911 176 Anal Calcd for C

10H8O3 C 6818 H 454

Found C 6836 H 488

47-Dimethyl-2H-chromen-2-one (4a) This compound wasprepared (87mg 50) and identified according to the men-tioned procedure from Ethyl acetoacetate (130mg 1mmol)and m-cresol (108mg 1mmol)

IR (120592maxcmminus1) 1070 1146 1212 1248 1378 1579 1636

1704 2920 29701H NMR (400MHz CDCl

3) 120575 (ppm) 210 (s 3H) 231

(d 3H) 417 (s 1H) 671ndash729 (m 3H)13CNMR (100MHz CDCl

3) 120575 (ppm) 1804 2417 11070


11H10O2 C 7586 H 574

Found C 7552 H 549

7-Methoxy-4-methyl-2H-chromen-2-one (5a) This com-pound was obtained (171mg 90) and charectarized accord-ing to the mentioned procedure from Ethyl acetoacetate(130mg 1mmol) and m-methoxy phenol (124mg 1mmol)

IR (120592maxcmminus1) 1068 1284 1510 1725 2927 3070

1HNMR (400MHz DMSO) 120575 (ppm) 240 (d 3H) 386(s 3H) 621 (q 1H) 695 (d 1H) 698 (q 1H) 768 (d 119869 =84Hz 1H)13CNMR (100MHz DMSO) 120575 (ppm) 1860 5637 10117


11H10O3 C 6947 H 526

Found C 6976 H 548

7-Amino-4-methyl-2H-chromen-2-one (6a) This compoundwas prepared (147mg 84) and identified according tothe described procedure from Ethyl acetoacetate (130mg1mmol) and m-hydroxy aniline (109mg 1mmol)

IR (120592maxcmminus1) 1052 1238 1570 1688 3012 3312 3468


(q 1H) 663 (s 1H) 665 (d 119869 = 87Hz 1H) 750 (d 119869 =87Hz 1H)13C NMR (100MHz CDCl

3) (120575 ppm) 1940 10157

10940 11158 11457 12346 15317 15441 15463 16154 ESI-MS119898119911 175 Anal Calcd for C

10H9O2N C 6857 H 514 N

802 Found C 6879 H 536 N 821

78-Dihydroxy-4-methyl-2H-chromen-2-one (7a) This com-pound was obtained (169mg 88) and identified accordingto the described procedure from Ethyl acetoacetate (130mg1mmol) and pyrogallol (126mg 1mmol)

IR (120592maxcmminus1) 629 807 1006 1064 1186 1337 1480 1524

1653 2925 32171H NMR (400MHz DMSO) 120575 (ppm) 235 (d 3H) 612

(q 1H) 680 (d 119869 = 84Hz 1H) 708 (d 119869 = 88Hz 1H) 967(s 1H) 1004 (s 1H)13C NMR (100MHz DMSO) 120575 (ppm) 1872 11064


10H8O4 C 6250 H 417

Found C 6286 H 431

57-Dimethoxy-4-methyl-2h-chromen-2-one (8a) This com-pound was obtained (209mg 95) and characterized

according to the mentioned procedure from Ethyl acetoac-etate (130mg 1mmol) and 35-methoxy phenol (154mg1mmol)

IR (120592maxcmminus1) 1130 1353 1460 1616 1733 2939 2992

30241HNMR (400MHz DMSO) 120575 (ppm) 246 (d 3H) 383

(s 3H) 384 (s 3H) 598 (q 119869 = 12Hz 1H) 646 (d 119869 =24Hz 1H) 654 (d 119869 = 24Hz 1H)13CNMR(100MHzDMSO)120575 (ppm) 2405 5631 5665

9401 9599 10435 11108 15463 15679 15943 16015 16314ESI-MS 119898119911 220 Anal Calcd for C

12H12O4 C 6445 H

545 Found C 6422 H 529

4-Methyl-2H-benzo[h]chromen-2-one (9a) This compoundwas prepared (1932mg 92) and identified according tothe mentioned procedure from Ethyl acetoacetate (130mg1mmol) and 120572-naphthol (144mg 1mmol)

IR (120592maxcmminus1) 1044 1275 1572 1750 2922 3012

1HNMR (400MHz DMSO) 120575 (ppm) 253 (d 3H) 650(q 1H) 768ndash774 (m 2H) 778 (d 119869 = 88Hz 1H) 787 (d119869 = 88Hz 1H) 802ndash806 (m 1H) 834ndash837 (m 1H)13C NMR (100MHz DMSO) 120575 (ppm) 1914 11434

11558 12174 12210 12266 12444 12786 12844 1291213483 15013 15470 16013 ESI-MS 119898119911 210 Anal Calcdfor C14H10O2 C 8000 H 476 Found C 8032 H 494

4-Methyl-2H-benzo[f]chromen-2-one (10a) This compoundwas obtained (63mg 30) and identified according tothe described procedure from Ethyl acetoacetate (130mg1mmol) and 120573-naphtol (144mg 1mmol)

IR (120592maxcmminus1) 1044 1215 1514 1630 3052

1H NMR (400MHz CDCl3) 120575 (ppm) 245 (d 3H) 632

(q 1H) 732ndash760 (m 4H) 79 (d 119869 = 90Hz 1H) 854 (d119869 = 90Hz 1H)13C NMR (100MHz CDCl

3) 120575 (ppm) 2440 10947

11570 11776 12360 12635 12653 12891 12984 1345815140 15496 16070 ESI-MS 119898119911 210 Anal Calcd forC14H10O2 C 8000 H 476 Found C 8045 H 489

468-Trimethyl-2h-chromen-2-one (11a) Reaction of Ethylacetoacetate (130mg 1mmol) and 24-xylenol (122mg1mmol) according to the described procedure did not yieldthe mentioned product

3 Result and Discussion

Due to environmental concerns in the last decade a varietyof catalysts has been introduced in organic synthesis amongthem are organocatalysts which have shown recyclabilityand nontoxicity as well as efficiency in producing key prod-ucts One of the most interesting supramolecular organicstructures that have played so many roles in different areasespecially in chemistry is calixarene and its derivatives

In the recent years calix[4]arene tetrasulfonic acid asan organic catalyst has shown considerable capability inorganic reactions and has been used as a novel efficientacidic organocatalyst in esterification [53 54] Mannich typereaction [55 56] and synthesis of xanthones dixanthones[57] and bis(indolyl)methanes [58] In this paperwe aimed to


Table 1 Coumarins prepared from tetrasulfonic acid calixarene via Pechmann reaction

Substrate Product Time (h) Yield () M P (found) M P (obtained)1 1a 24 15 79ndash81 [46] 78-792 2a 25 95 182ndash184 [47] 183ndash1853 3a 4 75 241-242 [46] 240ndash2424 4a 25 50 130-131 [48] 1328 5a 2 90 158ndash160 [47] 158-1596 6a 25 84 220ndash224 [49] 222ndash2247 7a 25 88 234-235 [47] 232ndash2348 8a 15 95 mdash 173ndash1759 9a 4 92 153ndash155 [47] 151ndash15410 10a 10 30 182-183 [50] 180-18111 11a 24 mdash mdash mdashM P melting point

R

OH

(solvent-free)

O

R+

O O

H3C OC2H5

Catalyst (006 mmol)

90∘C

CH3

Scheme 2 General procedure for preparation of coumarin derivatives with a variety of phenols using calix[4]arene sulfonic acid

report a green recognized procedure for the one-pot con-struction of coumarin derivatives using nonhazardous andrecyclable organocatalyst calix[4]arene sulfonic acid undersolvent-free condition To survey the applicability of the cata-lyst for synthesis of pharmaceutically interesting compoundsa variety of coumarins were prepared via direct coupling ofphenols and ethylacetoacetate ester in the presence of a cat-alytic amount (006mmol) of the organocatalyst (Scheme 2)

The product structures and their corresponding meltingpoints are shown in Table 1 As can be seen the resultsclearly indicated good-to-high yields for coumarin deriva-tives except three compounds which were obtained in smallquantities To produce coumarin derivatives mechanism ofthe reaction proceeds similarly to previously prepared xan-thone derivatives through direct in situ cyclization of inter-mediates [57] Exploring the outcome of the cyclization reac-tion between phenols and Ethyl acetoacetate as well as overallyields pointed out that some functional groups on phenolicsubstrate accelerate the ring closure and promote the productyields obviously

As can be deduced from Table 1 enhancing the electrondensity will cause higher yields Yields were promoted bythe presence of electron releasing groups such as aminohydroxyl and methoxy groups (5andash9a) As was expectedphenols with electron donating groups such as hydroxyand methoxy activate the phenolic moieties to react fasterwith Ethyl acetoacetate and consequently the products wereobtained in higher yields and shorter times

To find the best condition and optimize the reaction con-ditions especially from the environmental point of view per-forming some experiments for possible modification on thereaction was necessary So we studied the reaction param-eters including solvent amount of catalyst and reaction

temperature Reaction of resorcinol and Ethyl acetoacetate(2a) was considered as a typical reaction and the reactionparameters were changed and the yields were monitoredconsequently At first reaction medium was investigatedusing polar and nonpolar solvents such as tetrahydrofuran(THF) dichloromethane (DCM) n-hexane acetonitrile andsolvent-free condition Temperature and amount of catalystwere unchanged through the reactions The result indicatedthat solvent-free condition gave the higher amount of theproduct in shorter periods (Table 2) However in additionto higher yields employing solvent-free protocol reduces theenvironmental pollutions and hazardous organic solvents Toreach the optimum catalytic activity of the catalyst the dif-ferent amounts of the catalyst were evaluated with some try-outs So according to Table 2 some experiments were doneand the minimum amount of the catalyst with the acceptableresult was considered as the most favorable amount of thecatalyst Determination of the optimum reaction tempera-ture which is critical for energy consumption issues wasconducted with some experiments in the range of 25 to120∘CResults indicate that higher temperatures are needed toprovide sufficient energy for nucleophilic attack by phenolicrings and consequently ring closure Temperatures above90∘C have shown excellent results in the least time (Table 2)

To explore the potential applicability of this notableorganocatalyst in catalytic organic reactions especially inproducing fine chemicals as well as to cover industrial con-cern in reducing the chemical pollutants in an environmentreusability of the catalyst has been practiced and the resultswere acceptable Hence after each reaction catalyst wasrecovered by washing the precipitate with specified amountsof deionized water to dissolve the organocatalyst Then onfiltration aqueous solution of catalyst was evaporated dried


Table 2 Optimization of the reaction medium for the synthesis of 4-methyl-2H-chromen-2-one (1)a

Entry Catalyst (mg) Solvent Temp (∘C) Time (h) Yield ()b

1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2

80 12 304 25 n-Hexane 80 12 205 25 Solvent-free 80 3 786 15 Solvent-free 80 5 507 25 Solvent-free 80 3 788 45 Solvent-free 80 3 889 60 Solvent-free 80 25 9010 45 Solvent-free rt 24 3011 45 Solvent-free 50 10 6012 45 Solvent-free 80 3 8813 45 Solvent-free 90 25 9514 45 Solvent-free 120 25 96aReaction condition resorcinol (1mmol) with Ethyl acetoacetate (1mmol) p-sulfonic acid calix[4]arenebIsolated yield

First

Second

Third

Fourth

20 40 60 80 1000Yield ()

Figure 4 Efficiency of the calixarene sulfonic acid (CSA) in thesynthesis of coumarins

and adjusted for in further successive reactions The resultsshowed that the recycled catalyst was still as efficient as thefresh one even after four runs of usage and decreases inproduct yields are negligible Figure 4

4 Conclusions

In this research potential applicability of p-sulfonic acidcalix[4]arene (CSA) as a catalyst in the synthesis of phar-maceutically significant coumarin derivatives was evaluatedEfficient catalytic activity as well as recyclability makes CSAan exciting organocatalyst for researchers who are searchingfor more environmentally friendly catalysts with less harmfulandmore proficient capabilities Moreover herein the earlierstrategies in the synthesis of coumarin derivatives weredeveloped using CSA as a catalyst in one-pot and solvent-free procedure In this study we demonstrated especial andvaluable organocatalyst for the synthesis of coumarins

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The partial assistance by Research Council of Babol Univer-sity of Medical Sciences as well as Mazandaran University isgratefully acknowledged

References

[1] R Sharma and V J Arya ldquoA review on fruits having anti-diabetic potentialrdquo Journal of Chemical and PharmaceuticalResearch vol 3 no 2 pp 204ndash212 2011

[2] R D H Murrey D Medez and S A Brown The NaturalCoumarins Occurrences Chemistry and Biochemistry JohnWiley Interscience New York NY USA 1982

[3] KM Paramjeet S H Dipak andD J Arti ldquoComparative studyof microwave and conventional synthesis and pharmacologicalactivity of coumarins a reviewrdquo Journal of Chemical andPharmaceutical Research vol 4 no 1 pp 822ndash850 2012

[4] L A Singer and N P Kong ldquoVinyl radicals Stereoselectivity inhydrogen atom transfer to equilibrated isomeric vinyl radicalsrdquoJournal of American Chemical Society vol 88 no 22 pp 5213ndash5219 1966

[5] B G Lake ldquoCoumarin metabolism toxicity and carcinogenic-ity relevance for human risk assessmentrdquo Food and ChemicalToxicology vol 37 no 4 pp 423ndash453 1999

[6] H M Cakmak S Kahraman F Bayansal and S CetinkayaldquoA novel study on ZnO nanostructures coumarin effectrdquoPhilosophical Magazine Letters vol 92 no 6 pp 288ndash294 2012

[7] M Zahradnik The Production and Application of FluorescentBrightening Agents John Wiley amp Sons New York NY USA1992

[8] S Weigt N Huebler R Strecker T Braunbeck and T HBroschard ldquoDevelopmental effects of coumarin and the antico-agulant coumarin derivative warfarin on zebrafish (Danio rerio)


embryosrdquo Reproductive Toxicology vol 33 no 2 pp 133ndash1412012

[9] M Camur M Bulut M Kandaz and O Guney ldquoEffects ofcoumarin substituents on the photophysical properties of newlysynthesised phthalocyanine derivativesrdquo Supramolecular Chem-istry vol 21 no 7 pp 624ndash631 2009

[10] J Chen W Liu J Ma et al ldquoSynthesis and properties offluorescence dyes tetracyclic pyrazolo [34-b] pyridine-basedcoumarin chromophores with intramolecular charge transfercharacterrdquo The Journal of Organic Chemistry vol 77 no 7 pp3475ndash3482 2012

[11] K Rohini and P S Srikumar ldquoTherapeutic role of coumarinsand coumarin-related compoundsrdquo Journal ofThermodynamicsamp Catalysis vol 5 no 2 article 130 2014

[12] A Lacy and R OrsquoKennedy ldquoStudies on coumarins and couma-rin-related compounds to determine their therapeutic role inthe treatment of cancerrdquoCurrent Pharmaceutical Design vol 10no 30 pp 3797ndash3811 2004

[13] X-W Yang B Xu F-X Ran R-Q Wang J Wu and J-R CuildquoInhibitory effects of 11 coumarin compounds against growthof human bladder carcinoma cell line E-J in vitrordquo Journal ofChinese Integrative Medicine vol 5 no 1 pp 56ndash60 2007

[14] N Hamdi F Bouabdallah A Romerosa and R BenhassenldquoExpedious synthesis for120572120573-unsaturated coumarin derivativesusing boran chelates a novel class of potential antibacterial andantioxidant agentsrdquo Comptes Rendus Chimie vol 13 no 10 pp1261ndash1268 2010

[15] A A H Kadhum A A Al-Amiery A Y Musa and A BMohamad ldquoThe antioxidant activity of new coumarin deriva-tivesrdquo International Journal of Molecular Sciences vol 12 no 9pp 5747ndash5761 2011

[16] G Smitha R Sanjeeva and G Smitha ldquoZrCl4minuscatalyzed

Pechmann reaction synthesis of coumarins under solventminusfreeconditionsrdquo Synthetic Communications vol 34 no 21 pp 3997ndash4003 2004

[17] A Kotali I S Lafazanis and P A Harris ldquoSynthesis of 67-diacylcoumarins via the transformation of a hydroxy into acarbonyl grouprdquo Synthetic Communications vol 38 no 22 pp3996ndash4006 2008

[18] I P Kostova I I Manolov I N Nicolova and N D DanchevldquoNew metal complexes of 4-methyl-7-hydroxycoumarinsodium salt and their pharmacological activityrdquo II Farmaco vol56 no 9 pp 707ndash713 2001

[19] R OrsquoKennedy and R D Thornes Coumarins Biology Applica-tions and Mode of Action John Wiley amp Sons Chichester UK1997

[20] Z M Nofal M I El-Zahar and S S Abd El-Karim ldquoNovelcoumarin derivatives with expected biological activityrdquoMolecu-les vol 5 no 2 pp 99ndash113 2000

[21] S S Sahoo S Shukla S Nandy and H B Sahoo ldquoSynthesisof novel coumarin derivatives and its biological evaluationsrdquoEuropean Journal of Experimental Biology vol 2 no 4 pp 899ndash908 2012

[22] WH Perkin ldquoXXIIImdashOn the hydride of aceto-salicylrdquo Journalof Chemical Society vol 21 pp 181ndash186 1868

[23] V H Pechmann and C Duisberg ldquoNeue Bildungsweise derCumarine Synthese des Daphnetinsrdquo Chemische Berichte vol17 no 1 pp 929ndash936 1884

[24] G Jones ldquoThe Knoevenagel condensationrdquo in Organic Reac-tions vol 15 pp 204ndash206 John Wiley amp Sons 1967

[25] G Brufola F Fringuelli O Piermatti and F Pizzo ldquoSimpleand efficient one-pot preparation of 3-substituted coumarins inwaterrdquo Heterocycles vol 43 no 6 pp 1257ndash1266 1996

[26] R L Shirner ldquoThe reformatsky reactionrdquo Organic Reactionsvol 1 pp 15ndash18 1942

[27] D N Shah and N M Shah ldquoThe Kostanecki-Robinson acy-lation of 5-hydroxy-6-acetyl-4-methylcoumarinrdquo Journal of theAmerican Chemical Society vol 77 no 6 pp 1699ndash1700 1955

[28] N S Narasimhan R S Mali and M V Barve ldquoSyntheticapplication of lithiation peactions part XIII Synthesis of 3-phenylcoumarins and their benzo derivativesrdquo Synthesis vol1979 no 11 pp 906ndash909 1979

[29] I Yavari RHekmat-Shoar andA Zonouzi ldquoAnewand efficientroute to 4-carboxymethylcoumarins mediated by vinyltriph-enylphosphonium saltrdquo Tetrahedron Letters vol 39 no 16 pp2391ndash2392 1998

[30] F N Miros G Huang Y Zhao N Sakai and S MatileldquoCoumarin synthesis on 120587-acidic surfacesrdquo SupramolecularChemistry vol 27 no 5-6 pp 303ndash309 2015

[31] A Rahmatpour and S Mohammadian ldquoPolystyrene-supportedTiCl4as a novel efficient and reusable polymeric Lewis acid

catalyst for the chemoselective synthesis and deprotection of11-diacetates under eco-friendly conditionsrdquo Comptes RendusChimie vol 16 no 10 pp 912ndash919 2013

[32] J Albadi F Shirini J Abasi N Armand and TMotaharizadehldquoA green efficient and recyclable poly (4-vinylpyridine)-supported copper iodide catalyst for the synthesis of coumarinderivatives under solvent-free conditionsrdquo Comptes RendusChimie vol 16 no 5 pp 407ndash411 2013

[33] R A P Castanheiro A M S Silva N A N Campos M S JNascimento and M M M Pinto ldquoAntitumor activity of someprenylated xanthonesrdquo Pharmaceuticals vol 2 no 2 pp 33ndash432009

[34] W Yang andMM DeVilliers ldquoThe solubilization of the poorlywater soluble drug nifedipine by water soluble 4-sulphoniccalix[n]arenesrdquo European Journal of Pharmaceutics and Bio-pharmaceutics vol 58 no 3 pp 629ndash636 2004

[35] WYangD POttoW Liebenberg andMM deVilliers ldquoEffectof para-sulfonato-calix[n]arenes on the solubility chemical sta-bility and bioavailability of a water insoluble drug nifedipinerdquoCurrent Drug Discovery Technologies vol 5 no 2 pp 129ndash1392008

[36] W Yang and M M de Villiers ldquoAqueous solubilization offurosemide by supramolecular complexation with 4-sulphoniccalix[n]arenesrdquo Journal of Pharmacy and Pharmacology vol 56no 6 pp 703ndash708 2004

[37] W Yang and M M de Villiers ldquoEffect of 4-sulphonato-calix[n]arenes and cyclodextrins on the solubilization ofniclosamide a poorly water soluble anthelminticrdquo The AAPSJournal vol 7 no 1 pp E241ndashE248 2005

[38] J G Panchal R V Patel and S K Menon ldquoPreparation andphysicochemical characterization of carbamazepine (CBMZ)para-sulfonated calix[n]arene inclusion complexesrdquo Journal ofInclusion Phenomena and Macrocyclic Chemistry vol 67 no 1-2 pp 201ndash208 2010

[39] G-S Wang H-Y Zhang F Ding and Y Liu ldquoPrepara-tion and characterization of inclusion complexes of topotecanwith sulfonatocalixarenerdquo Journal of Inclusion Phenomena andMacrocyclic Chemistry vol 69 no 1-2 pp 85ndash89 2011

[40] M-H Paclet C F Rousseau C Yannick F Morel and AW Coleman ldquoAn absence of non-specific immune response


towards para-sulphonato-calix[n] arenesrdquo Journal of InclusionPhenomena andMacrocyclic Chemistry vol 55 no 3-4 pp 353ndash357 2006

[41] W Yang R Manek W M Kolling et al ldquoPhysicochemicalcharacterization of hydrated 4-sulphonato-calix [n] arenesthermal structural and sorption propertiesrdquo SupramolecularChemistry vol 17 no 6 pp 485ndash496 2005

[42] M M Lakouraj M Tajbakhsh H Tashakkorian and KGhodrati ldquoFast and efficient oxidation of sulfides to sulfoneswith NN1015840-dibenzyl-NNN1015840N1015840-tetramethyl diammonium per-manganaterdquo Phosphorus Sulfur and Silicon and the RelatedElements vol 182 no 2 pp 485ndash490 2007

[43] M M Lakouraj M Tajbakhsh and H Tashakkorian ldquoMont-morillonite K10 catalyzed selective oxidation of sulfides to sul-foxides using hydrogen peroxiderdquo Letters in Organic Chemistryvol 4 no 1 pp 75ndash79 2007

[44] M M Lakouraj M Tajbakhsh and H Tashakkorian ldquoIonexchange resin catalyzed selective oxidation of sulfides to sul-foxides using hydrogen peroxiderdquoMonatshefte fur Chemie vol138 no 1 pp 83ndash88 2007

[45] S M Baghbanian N Rezaei and H Tashakkorian ldquoNanozeo-lite clinoptilolite as a highly efficient heterogeneous catalyst forthe synthesis of various 2-amino-4H-chromene derivatives inaqueousmediardquoGreen Chemistry vol 15 no 12 pp 3446ndash34582013

[46] R L Atkins and D E Bliss ldquoSubstituted coumarins andazacoumarins Synthesis and fluorescent propertiesrdquo Journal ofOrganic Chemistry vol 43 no 10 pp 1975ndash1980 1978

[47] A S R Anjaeyulu L R Row C S Krishna and C SrinivasululdquoSynthesis of benzochromenes and related compounds I5-6and 7-8 benzochromanones and benzocoumarinesrdquo CurrentScience vol 37 pp 513ndash515 1968

[48] X M Dong J-F Revol and D G Gray ldquoEffect of microcrystal-lite preparation conditions on the formation of colloid crystalsof celluloserdquo Cellulose vol 5 no 1 pp 19ndash32 1998

[49] W Keim W Korth and P Wasserscheid WO 016 902 (toBP Chemicals limited UK Akzo Nobel NV Elementis UKLimited) chem abstr no 132 238691 2000

[50] J Gui X Cong D Liu X Zhang Z Hu and Z Sun ldquoNovelBroslashnsted acidic ionic liquid as efficient and reusable catalystsystem for esterificationrdquo Catalysis Communications vol 5 no9 pp 473ndash477 2004

[51] CDGutscheCalixarenes Revisited edited by J F StoddartTheRoyal Society of Chemistry Cambridge UK 1998

[52] S Shinkai K Araki T Tsubaki T Some and O Manabe ldquoNewsyntheses of calixarene-p-sulphonates and p-nitrocalixarenesrdquoJournal of the Chemical Society Perkin Transactions 1 vol 1 pp2297ndash2299 1987

[53] S A Fernandes R Natalino P A R Gazolla M J da Silva andG N Jham ldquop-Sulfonic acid calix[n]arenes as homogeneousand recyclable organocatalysts for esterification reactionsrdquoTetrahedron Letters vol 53 no 13 pp 1630ndash1633 2012

[54] R Natalino E V V Varejao M J da Silva A L Cardoso and SA Fernandes ldquop-Sulfonic acid calix[n]arenes the most activeand water tolerant organocatalysts in esterification reactionsrdquoCatalysis Science amp Technology vol 4 no 5 pp 1369ndash1375 2014

[55] D L da Silva S A Fernandes A A Sabino and A de Fatimaldquop-Sulfonic acid calixarenes as efficient and reusable organocat-alysts for the synthesis of 34-dihydropyrimidin-2(1H)-ones-thionesrdquo Tetrahedron Letters vol 52 no 48 pp 6328ndash63302011

[56] S Shimizu N Shimada and Y Sasaki ldquoMannich-type reactionsin water using anionic water-soluble calixarenes as recoverableand reusable catalystsrdquo Green Chemistry vol 8 no 7 pp 608ndash614 2006

[57] M M Lakouraj H Tashakkorian and M Rouhi ldquoOne-potsynthesis of xanthones and dixanthones using calix [4] arenesulfonic acid under solvent free conditionrdquo Chemical ScienceTransactions vol 2 no 3 pp 739ndash748 2013

[58] S M Baghbanian Y Babajani H Tashakorian S Khaksar andM Farhang ldquoP-sulfonic acid calix[4]arene an efficient reusableorganocatalyst for the synthesis of bis(indolyl)methanes deriva-tives in water and under solvent-free conditionsrdquo ComptesRendus Chimie vol 16 no 2 pp 129ndash134 2013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


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Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


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Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


HO OHOH HO HO HOOH HO

H2SO4

80∘C 5hr

HO3S HO3S SO3H SO3H

Scheme 1 Sulfonation of calix[4]arene using Shinkai method

the most efficient preparative procedures In synthetic chem-istry some methods were considered as famous and pioneermethods for preparation of these organic compounds Thefirst reported procedure for preparation of coumarins wasPerkin reaction that was suggested in 1868 [22] HoweverPerkin reaction is efficient and suitable just for synthesisof simple coumarins but some alternative methods weredeveloped during the years including Pechmann [23] Kno-evenagel [24 25] Reformatsky [26] Kostanecki-Robinson[27] andWittig reactions [28 29] Although these categoriesof well known reactions give coumarins in acceptable yieldsusually they need severe conditions such as high tempera-tures dangerous solvents long reaction time and producingbyproducts Excess amounts of harsh acidic activating agentssuch as POCl

3 P2O5 and polyphosphoric acid besides quan-

titative amount of Lewis acids or sulfuric or sulfonic acids addto their usage drawbacks due to possible severe difficultiessuch as corrosion problem

So far different catalyses have been raised to overcomethe mentioned drawbacks in the last decade [30ndash32] Oneof the motivating macrocyclic structures with great capacityin different area and that attracted much interest especiallyin biochemistry is calixarene Among the interesting com-pounds derived from this scaffold sulfonate calixarene hasaroused much interest in biopharmaceutical applications[33] due to its promising capabilities in incapsulating cal-ixarenes increase not only solubility but also bioavailabilityof valuable pharmaceutical drugs such as nifedipine [3435] furosemide [36] niclosamide [37] carbamazepine [38]and topotecan for improving solubility in chemotherapy byhost-guest complexes [39] Surprisinglymedical experimentseither of in vivo studies or at the cellular level indicate that thecalixarenes have no activity in the Ames test [37] Moreoverno acute toxicity for the sulfonated calixarenes is reportedwhen specified amounts were injected in mice for in vivostudies Number of previous organized studies revealed thatthese multipurpose compounds are not cytotoxic [40] Cal-ixarenes have very favorable physicochemical properties thatare similar to other useful pharmaceutical excipients such ascyclodextrins [41] Besides the biocompatibility of sulfonatedcalixarenes investigation on catalytic activity of this motifin the synthesis of pharmaceutical compounds seems to beinteresting In this regard and in continuation of our recentstudies on the development of convenient effective andsafe protocol in organic and pharmaceutical synthesis [42ndash45] herein we represent calix[4]arene tetrasulfonic acid asan efficient and environmentally friendly organocatalyst forthe preparation of coumarin derivatives under solvent-freeconditions

2 Experimental

21 Materials and Instruments The fine chemicals includingp-tert-butylphenol formaldehyde solution (37) diphenylether ethylacetate methanol and sodium hydroxide werepurchased from Merck (Schuchardt Germany) Ethyl ace-toacetate resorcinol bisphenols salicylic acid 25-dihy-droxy salicylic acid phosphorus oxychloride and silicagelwere obtained from Fluka (Switzerland) Parent tert-butyl-calixarene was synthesized according to Gutsche procedurepublished in [51] Then it was detertiobutylated and sul-fonated simultaneously by Shinkai method using concen-trated sulfuric acid (Scheme 1) [52] After further purificationdescribed in the literature the obtained product was appliedas a proficient acidic organocatalysis (Figures 1 and 2)Melting points were determined with an Electrothermal 9100Melting Point Apparatus IR and 1H NMR spectra wererecorded respectively on Bruker FTIR Spectrometer andBruker Avance III 400MHz NMR Spectrometer GC-MSanalyseswere carried out on ShimadzuGC 17Agas chromato-graph coupled with MS-QP 5000 Shimadzu Mass Spectrom-eter (Tokyo Japan) Elemental analyses were performed byCHN Rapid Heraeus Elemental Analyzer (Wellesley MA)

22 General Procedure for Preparation of Coumarins Aspecified amount of the catalyst CSA (45mg 006mmol)was added to the mixture of ethyl acetoacetate (130mg1mmol) and phenol derivatives (1mmol)Then theThe flaskwas placed in an oil bath and temperature was adjusted to90∘C After completion of the reaction which was moni-tored by TLC it was cooled down to room temperatureand then poured onto the crushed ice After half an hourreaction mixture was extracted with chloroform three times(3 times 25mL) Subsequently the combined organic phasewas washed with saturated aqueous sodium bicarbonatebrine solution and water respectively Then organic solutionwas dried using magnesium sulfate and the crude productwas obtained using rotary evaporator For further purifi-cation flash column chromatography was performed usingpetroleum etherethylacetate 90 10 (Figure 3)

23 Coumarin Derivatives Characterization

4-Methyl-2H-chromen-2-one (1a) This compound wasobtained (24mg 15) and characterized according to thedescribed procedure from Ethyl acetoacetate (130mg1mmol) and resorcinol (110mg 1mmol)

IR (120592maxcmminus1) 1064 1238 1543 1705 3020


0

100 100401

(ppm)12345678910

(a)

0(ppm)

102 100

12345678910

(b)


SO3H

SO3H

SO3H

HO3S OHOH

HOOH

200 180 160 140 120 100 80 60 40 20(ppm)

0

151

3413

580

128

0412

644

567

8

304

014

98




3) (120575 ppm) 191 116 1179 122


10H8O2 C 7500H 500 Found C 7523 H 518


IR (120592maxcmminus1) 1060 1227 1590 1680 3150



3) (120575 ppm) 1856 10262

11070 11247 11329 12705 15397 15528 16074 1616

OHOH

HOOH

H

H

H H

O

O

O O

R

HO


CH3

CH3

SO3

SO3

SO3

O3S

C2H5O



Found C 6845 H 476


IR (120592maxcmminus1) 1055 1225 1565 1693 3010 3412


(q 1H) 673 (d 119869 = 84Hz 1H) 681 (d 119869 = 84Hz 1H) 728(s 1H)


13C NMR (100MHz CDCl3) (120575 ppm) 1838 10940


10H8O3 C 6818 H 454

Found C 6836 H 488


IR (120592maxcmminus1) 1070 1146 1212 1248 1378 1579 1636

1704 2920 29701H NMR (400MHz CDCl

3) 120575 (ppm) 210 (s 3H) 231


3) 120575 (ppm) 1804 2417 11070


11H10O2 C 7586 H 574

Found C 7552 H 549


IR (120592maxcmminus1) 1068 1284 1510 1725 2927 3070



11H10O3 C 6947 H 526

Found C 6976 H 548


IR (120592maxcmminus1) 1052 1238 1570 1688 3012 3312 3468



3) (120575 ppm) 1940 10157


10H9O2N C 6857 H 514 N

802 Found C 6879 H 536 N 821


IR (120592maxcmminus1) 629 807 1006 1064 1186 1337 1480 1524




10H8O4 C 6250 H 417

Found C 6286 H 431



IR (120592maxcmminus1) 1130 1353 1460 1616 1733 2939 2992




12H12O4 C 6445 H

545 Found C 6422 H 529


IR (120592maxcmminus1) 1044 1275 1572 1750 2922 3012




IR (120592maxcmminus1) 1044 1215 1514 1630 3052



3) 120575 (ppm) 2440 10947









R

OH

(solvent-free)

O

R+

O O

H3C OC2H5

Catalyst (006 mmol)

90∘C

CH3











1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2


First

Second

Third

Fourth

20 40 60 80 1000Yield ()



4 Conclusions




Acknowledgments


References










































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


0

100 100401

(ppm)12345678910

(a)

0(ppm)

102 100

12345678910

(b)


SO3H

SO3H

SO3H

HO3S OHOH

HOOH

200 180 160 140 120 100 80 60 40 20(ppm)

0

151

3413

580

128

0412

644

567

8

304

014

98




3) (120575 ppm) 191 116 1179 122


10H8O2 C 7500H 500 Found C 7523 H 518


IR (120592maxcmminus1) 1060 1227 1590 1680 3150



3) (120575 ppm) 1856 10262

11070 11247 11329 12705 15397 15528 16074 1616

OHOH

HOOH

H

H

H H

O

O

O O

R

HO


CH3

CH3

SO3

SO3

SO3

O3S

C2H5O



Found C 6845 H 476


IR (120592maxcmminus1) 1055 1225 1565 1693 3010 3412


(q 1H) 673 (d 119869 = 84Hz 1H) 681 (d 119869 = 84Hz 1H) 728(s 1H)


13C NMR (100MHz CDCl3) (120575 ppm) 1838 10940


10H8O3 C 6818 H 454

Found C 6836 H 488


IR (120592maxcmminus1) 1070 1146 1212 1248 1378 1579 1636

1704 2920 29701H NMR (400MHz CDCl

3) 120575 (ppm) 210 (s 3H) 231


3) 120575 (ppm) 1804 2417 11070


11H10O2 C 7586 H 574

Found C 7552 H 549


IR (120592maxcmminus1) 1068 1284 1510 1725 2927 3070



11H10O3 C 6947 H 526

Found C 6976 H 548


IR (120592maxcmminus1) 1052 1238 1570 1688 3012 3312 3468



3) (120575 ppm) 1940 10157


10H9O2N C 6857 H 514 N

802 Found C 6879 H 536 N 821


IR (120592maxcmminus1) 629 807 1006 1064 1186 1337 1480 1524




10H8O4 C 6250 H 417

Found C 6286 H 431



IR (120592maxcmminus1) 1130 1353 1460 1616 1733 2939 2992




12H12O4 C 6445 H

545 Found C 6422 H 529


IR (120592maxcmminus1) 1044 1275 1572 1750 2922 3012




IR (120592maxcmminus1) 1044 1215 1514 1630 3052



3) 120575 (ppm) 2440 10947









R

OH

(solvent-free)

O

R+

O O

H3C OC2H5

Catalyst (006 mmol)

90∘C

CH3











1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2


First

Second

Third

Fourth

20 40 60 80 1000Yield ()



4 Conclusions




Acknowledgments


References










































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


13C NMR (100MHz CDCl3) (120575 ppm) 1838 10940


10H8O3 C 6818 H 454

Found C 6836 H 488


IR (120592maxcmminus1) 1070 1146 1212 1248 1378 1579 1636

1704 2920 29701H NMR (400MHz CDCl

3) 120575 (ppm) 210 (s 3H) 231


3) 120575 (ppm) 1804 2417 11070


11H10O2 C 7586 H 574

Found C 7552 H 549


IR (120592maxcmminus1) 1068 1284 1510 1725 2927 3070



11H10O3 C 6947 H 526

Found C 6976 H 548


IR (120592maxcmminus1) 1052 1238 1570 1688 3012 3312 3468



3) (120575 ppm) 1940 10157


10H9O2N C 6857 H 514 N

802 Found C 6879 H 536 N 821


IR (120592maxcmminus1) 629 807 1006 1064 1186 1337 1480 1524




10H8O4 C 6250 H 417

Found C 6286 H 431



IR (120592maxcmminus1) 1130 1353 1460 1616 1733 2939 2992




12H12O4 C 6445 H

545 Found C 6422 H 529


IR (120592maxcmminus1) 1044 1275 1572 1750 2922 3012




IR (120592maxcmminus1) 1044 1215 1514 1630 3052



3) 120575 (ppm) 2440 10947









R

OH

(solvent-free)

O

R+

O O

H3C OC2H5

Catalyst (006 mmol)

90∘C

CH3











1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2


First

Second

Third

Fourth

20 40 60 80 1000Yield ()



4 Conclusions




Acknowledgments


References










































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




R

OH

(solvent-free)

O

R+

O O

H3C OC2H5

Catalyst (006 mmol)

90∘C

CH3











1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2


First

Second

Third

Fourth

20 40 60 80 1000Yield ()



4 Conclusions




Acknowledgments


References










































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




1 25 THF 80 5 602 25 CH

3CN 80 5 67

3 25 CH2Cl2


First

Second

Third

Fourth

20 40 60 80 1000Yield ()



4 Conclusions




Acknowledgments


References










































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of






























Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

Documents

Research Article p -Sulfonic Acid Calix[4]arene as an ...downloads.hindawi.com/archive/2015/738202.pdf · 1.00 4.01 1.00 (ppm) 10 9 8 7 6 5 4 3 2 1 (a) 0 (ppm) 1.02 1.00 10 9 8 7