One-Pot Alkoxylation of Phenols with Urea and1,2-Glycols
Hsing-Yo Lin()and Shenghong A.Dai*()
Department of Chemical Engineering,National Chung-Hsing University,Taichung,Taiwan,R.O.C.
A one-pot epoxide-free alkoxylation process has been developed for phenolic compounds.The pro-cess involves heating phenols and urea in1,2-glycols at170-190°C using Na2CO3/ZnO as co-catalysts under atmospheric conditions.During the cour of this new alkoxylation reaction,a five-membered ring cyclic carbonate intermediate,ethylene carbonate(EC)or propylene carbonate(PPC),was produced in-transit as the key intermediate and was subquently consumed by phenols to form alkoxylated ether al-cohols as final products in excellent yields.For instance,phenol,bisphenol A(BPA),hydroquinone and resorcinol were converted into their respective mono-alkoxylated ether alcohols on each of their phenolic groups in80-95%isolated yields.In propoxylation of phenols,this approach shows great product lec-tivity favoring production of high condary alcohols over primary alcohols in isomeric ratios of nearing 95/5.Since ammonia(NH3)and carbon dioxide(CO2)evolving from the reaction can be re-combined in theory into urea for re-u,the overall net-alkoxylation by this approach can be regarded as a simple con-densat
ion reaction of phenols with1,2-glycols giving off water as its by-product.This one-pot process is simple,safe and environmentally friendlier than the conventional alkoxylated process bad on ethyl-ene oxide(EO)or propylene oxide(PO).Moreover,this process is particularly well-suited for making short chain-length alkoxyether alcohols of phenols.
Keywords:Alkoxylation;Ethoxylation;Propoxylation;Urea;Green process.
1.INTRODUCTION
Development of an environmentally friendly process for practical industrial chemical transformations is an im-portant consideration nowadays.Society demands it;gov-ernments encourage it,and sustainability of the chemical industry hinges upon it.The basic approach in designing green chemical process is to avoid using hazardous re-agents and halogen-derived chemicals in the overall syn-thetic scheme.In addition,recycling of by-products from the reaction to eliminate wastes and pollutants should also be emphasized.1,2Herein,we report an efficient one-pot alkoxylation of phenols with urea and1,2-glycols that meets the general green chemistry principles.
喜欢你的这么些年The most commonly ud alkoxylating agents such as ethylene oxide(EO)and propylene oxide(PO)are versatile industrial chemicals.For instance,long-chained polyal-koxyether polyols,major
derivatives of alkoxylated prod-ucts of EO and PO,are widely ud in the synthes of poly-urethanes and polyesters.3,4Making of hydrophilic poly-alkoxyethers especially from polymerization of EO are well known for their utilities in the synthes of cleaners,detergents,surfactants,and waterborne polymeric interme-diates.5Typically,the alkoxylation reaction is achieved by introducing EO or PO into an enclod pressure reactor containing an initiator at about120-150°C in the prence of a ba catalyst such as NaOH or KOH.Depending upon the amount of epoxides added to the reactor,different chain-lengths of the alkoxylated products can be obtained. However,there is always a possibility of an un-controlled chain-reaction due to rapid exothermic reactions releasing the strained ring energy of the epoxides.Thus,low boiling, volatile EO or PO in pressurized conditions does po a po-tential dangerous situation.
Since the u of EO and PO has inherent danger of rapid exothermic reaction,finding alternative raw materi-als for alkoxylation under atmospheric condition is highly desirable.Ethylene carbonate(EC)and propylene carbon-ate(PPC)are the potential good candidates for filling this gap.First of all,EC and PPC are high boiling liquids with little ring-strain.6Alkoxylation with EC/PPC has been in-vestigated previously.7In fact,short-alkoxylated products of phenols have been obtained by using EC or PPC.For in-
Journal of the Chine Chemical Society,2010,57,167-173167
*Corresponding author.E-mail:
成长教育电影
hu.edu.tw
stance,bis-hydroxyethyl ether of bisphenol A(BHE-BPA, 3ba),a raw material ud in polyesters,was prepared sim-ply by heating BPA and EC at about160°C in the prence of a ba.7
Recent literature8indicated that,EC and PPC can be synthesized from urea and1,2-glycols,but there has not been any report of alkoxylation accomplished by using urea-1,2-glycol mixtures directly.Recently,we reported the first application of this technology in polycarbonate re-cycling,9and it appears to us that this one-pot process has great potential for the general alkoxylation of phenols. Herein,we report the chemistry involved in this convenient one-pot high yield synthesis using urea-glycol mixtures as the raw materials.
2.RESULTS AND DISCUSSION
2.1.General One-Pot Ethoxylation Condition
The one-pot urea-ethylene glycol process for synthe-sis of ethoxylated ether alcohols was outlined in Scheme I (eq.1,R1=H).Phenols,urea and ethylene glycol were mixed and heated together in solution.In the ca of our model study with phenol,we found that mono-ethoxylation product,2-phenoxyethanol(3aa),was isolated in89% yields at160to180°C by using urea-ethylene glycol in the prence of catalysts(Na2CO3and ZnO).The reaction was monitored by IR,checking the disappearance of carbonyl absorptions at1711,1736,1774and1802cm-1.The reac-tion time took approximately4-6hours to complete.Dur-ing the cour of the reaction,ammonia evolved from the mixture rapidly,and some urea deposits could be found on the condenr which would account for portion of urea loss.Therefore,an excess of urea in30%molar excess was typically ud to compensate for this apparent loss in the solution.Similarly,in all our studies using bisphenols,high yields of bis-ethoxylated diols were isolated in greater than 80%isolated yield(Table1).
2.2.Mechanism:IR Monitoring,By-product Forma-
tions and Optimization
To monitor the reactions involved in this one-pot re-action,the changes of absorption spectra of the r
eaction mixture in FTIR was followed cloly,particularly paying attention to the carbonyl regions.The composition of the product mixture was also examined by1H NMR and HPLC to ascertain the product structures and their relative iso-meric ratios.As shown in Fig.1a,the absorption of iso-cyanic acid,H-N=C=O(2211cm-1),due to partial decom-position of urea could be detected at a very early stage when the temperature of the mixed solution reached100°C.Addition product of isocyanic acid with ethylene gly-col,carbamate7,was then obrved in the solution as indi-cated by the appearance of a1711cm-1carbamate absorp-tion.
Ethylene glycol could also directly react with urea to form carbamate7by substitution reaction which is shown
168J.Chin.Chem.Soc.,Vol.57,No.2,2010Lin and
Dai
Scheme I One-pot alkoxylation of phenols using1,2-glycols-urea catalyzed by Na2CO3and ZnO
(eq.1)Table1.Reaction combinations and yields for the alkoxylated products
Entry
Phenolic
compound
1,2-Glycol Product Isomer ratio a
Yield
(%)b 11a2a3aa–89 21a2b3ab c–(94/6e)92 31b2a3ba–88(83f) 41b2b3bb d92:1:0(95/5e)93 51c2a3ca–91(85f) 61c2b3cb d91:2:0(92/8e)93 71d2a3da–99 81d2b3db d91:1:0(91/9e)92 91e2a3ea–86(77f) a Isomer ratios of2°-2°,2°-1°and1°-1°isomeric propoxylated ether alcohols(by HPLC analys).
b Isolated yields of mono-alkoxylated product(s)for each phenol group.
c A mixture of two isomers,1-phenoxypropan-2-ol and2-phenoxypropan-1-ol.
d Mixtures of2°-2°,2°-1°and1°-1°isomeric alcohols.
e Isomeric ratios of(2°/1°)o
f all mono-propoxylated alcohols(by NMR analys).
f Isolated yields by re-crystallization.
in the Scheme II.Carbamates 7appeared to undergo an intra-molecular cyclization at a temperature greater than 150°C in formation of ethylene carbonate (EC).The for-mation of EC was evidenced by the appearance of absorp-tions at 1774and 1802cm -1in IR analysis.Potential by-product oxazolidone 8,which may result from intra-molec-ular dehydration of 7,was minimized by using ZnO as a co-catalyst as evidenced by showing little absorption at 1732in the final ethoxylated product.10,11
Reactions between phenols and the intermediate car-bonyl compounds em complicated becau
many parallel reactions are proceeding during the reaction.However,logical routes that phenol or its derivatives react with car-bonyl intermediates in formation of 2-phenoxyethanol,3aa ,are compiled in Scheme IIIa-b.In the ca of ethoxy-lation of BPA as the example,the formation of 4-type car-bonate alcohols are obrved in IR absorptions at 1736-1740cm -1as shown in Fig.1b by the first two hours of heat-ing.Monitoring of the product mixtures at this transition
period revealed that two methylene NMR peaks of the 4-type carbonate alcohols were obrved at 4.07and 4.43ppm,while two methylene NMR peaks of ethoxylated ethers of 3aa -like products appeared as two signals at 3.90and 4.07ppm (Fig.2a).After re-heating the product mix-tures at about 180°C for two additional hours,the IR ab-sorptions of carbonate alcohols disappeared completely through evolution of CO 2,and at the same time the 1H NMR spectrum becomes simplified into Fig.2b,indicating that ethoxylated ether alcohols became the ultimate prod-
One-Pot Alkoxylation of Phenols with Urea and 1,2-Glycols J.Chin.Chem.Soc.,Vol.57,No.2,2010
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169
Fig.1.Ethoxylation of BPA monitored by FTIR:(a)
气鸣乐器
120°C,2h;(b)170°C,4h;(c)180°C,6
h.
Scheme II Decomposition of urea and formation of
cyclic
carbonate
Scheme III Reactions occurred between phenols and
carbonyl
compounds
Fig.2.1H NMR spectra.Ethoxylation of BPA:(a)170
°C,4h;(b)180°C,6h.
uct.Thus,in the one-pot process,EC converted from cy-clization of4-and7plays the key role in alkoxylation.
2.3.Product Selectivity in Propoxylation with Urea
and1,2-Propylene Glycol
One-pot propoxylations of phenols were similarly ac-complished at160-185°C just by replacing ethylene glycol with1,2-propylene glycol to react with urea.Although the reaction pathway and mechanism are basically the same in both cas,the products are more complex in propoxyla-tion.This is mainly becau propylene carbonate(PPC)is an asymmetrical compound,and two isomeric propoxy-lated products for each phenol group were expected.Due to the steric hindrance of the methyl group in propylene car-bonate,phenol appears to react preferentially at the less-hindered carbon of the PPC to form isomeric2°-alcohol5 as the major propoxylated isomer of phenol(Scheme IV). The isomeric molar ratio between condary(2°)and pri-mary(1°)propoxylated ether alcohols after propoxylation of phenol could be conveniently estimated in the product mixture by checking the relative areas of methyl groups of propoxylated ethers in1H NMR signals located12at~1.24 and1.18ppm corresponding to the condary and the pri-mary isomers respectively(e Table1).
In the ca of reactions involving BPA,the lectivity of isomeric2°diol components in the final products was found to be as high as95%under sodium carbonate cata-lyzed reaction at170-185°C for4hours.As indicated in Fig.3a,the methyl peaks of all2°diols at~1.25ppm are dominant as compared with tho of1°diols at1.18ppm. This high lectivity of propoxylated ether products has never been obrved previously in either PO(85%)or PPC (90%)propoxylation.13,14This lectivity
has also been confirmed by HPLC analysis in showing2°-2°bis-pro-poxylated diol being predominant component(92%)with 2°-1°(1%)and1°-1°(<1%)diols as the minor products.In short,one-pot urea-propylene glycol propoxylation offered a very unique route to high condary ether alcohols of phenols especially with sodium carbonate as the ba-cata-lyst.
2.4.Catalysts Ud in Urea-Glycol Alkoxylation
During the cour of our yield optimization study, bas other than sodium carbonate,such as cesium carbon-ate and potassium carbonate,were examined as possible catalyst alternatives.Under the identical conditions de-scribed earlier,IR monitoring reveals that the major prod-ucts obtained from cesium and potassium carbonates are still mono-alkoxylated ether alcohols.However,two nota-ble differences have been obrved.First,the yields of mono-ethoxylated products for each phenol groups in po-tassium or cesium carbonate mediated reactions were found to be lower than tho run with sodium carbonate.In other words,higher ethoxylated products were found in the prod-ucts in greater proportions,which could be readily quanti-fied from the areas of extra NMR absorptions correspond-ing to the cond extended ether ethylene protons located at3.5ppm and3.8ppm.For instance,11%of higher eth-oxylated products were prent in a reaction in K2CO3cata-lyzed reaction of phenol.Second,in the ca of propoxyla-tion,lectivity of condary alcohols in propoxylation mixt
ures became substantially reduced when potassium or cesium carbonate was ud.As an example,the lectivity
170J.Chin.Chem.Soc.,Vol.57,No.2,2010Lin and
Dai成长的路
Scheme IV Isomeric products in propoxylated ether
alcohols
Fig.3.Propoxylated ether diols of BPA prepared un-
der different conditions by one-pot propoxyla-
tion.Propoxylation conditions:(a)initially at
100°C and then slowly raid to185°C in4
hours,2°/1°=95/5;(b)initially at160°C and
龟兔then quickly raid to185°C in3hours,2°/1°=
89/11.
of isomeric products with2°alcohols of BPA was down to about70%in Cs2CO3(Fig.4a and4b,1.15-1.30ppm).In the ca of potassium carbonate catalyzed propoxylation, formation of primary isomeric alcohols also were found to increa to about44%.Thus,the yield and the isomer lec-tivity of mono-alkoxylated product for each phenol group become reduced when strong bas were applied.
2.5.Higher Alkoxylation of Phenols with EG/PG-
Urea Alkoxylation
In traditional EO/PO alkoxylation,long-chained al-koxylated ether alcohols in molecular weights of veral thousands could readily be achieved by prolonged reaction with excess EO/PO addition.However,a similar type of oligomerization ems more difficult to accomplish in a urea-glycol one-pot approach.The major hindrance is due to the complication when excess of solid urea is ud in the reaction solution.For instance,while using three-molar ex-cess of urea per phenol group and K2CO3as catalyst in eth-oxylation,the resulting products had an average extension of only2.3repeating units of ethoxyether for each phenol (calculated from1H NMR,3.5-4.1ppm)(Fig.5).In the most elaborated conditions,the repeating units could be ex-tended to about3.0ethylene oxide units per phenol group with a4-fold molar excess of urea to phenol in one-pot urea-ethylene glycol approach.In the ca of propoxyla-tion with urea-propylene glycol catalyzed with K2CO3,the extension of propylene oxide units was even less efficient. Highest propoxylation extension was found to be about2 units under4mole excess of urea.Therefore,it is reason-able to conclude that the prent one-pot process is more suited for short alkoxylation extensions of phenols.
2.6.Competitive Reaction between in EG/PG-Urea
Alkoxylation高空作业安全培训
A competitive reaction between EC vs.PPC was run to alkoxylate phenol simultaneously from equal moles of excess EG/PG solution mixture.The relative mole ratios among the key reactants in the competitive alkoxylation are t at3.0/3.0/1.5/1.0for EG/PG/urea/phenol respectively in the comparative reaction.This controlled reaction cata-lyzed by Na2CO3-ZnO at175°C was designed to differen-tiate the rate of ethoxylation/propoxylation under the one-pot condition.From the IR monitoring of reaction mixture, it appears that the formation of EC(1802,1774cm-1)and PPC(1791cm-1)were both obrved during the cour re-action.The1H NMR analysis of the isolated alkoxylated products by the area ratios of propoxylated regions at1.28 (methyl group)and6.90-7.33ppm of the aromatic region concluded a calculated70/30(R=2.33/1)ratio in favor of ethoxylation.This ratio indicates that EG has a significant rate advantage over PG in performing the alkoxylation if run simultaneously in the mixture.It implies that steric-hindrance of methyl group in PG and PPC does have a re-tarding rate impact on both the cyclization(ring closure to PPC)and the alkoxylation(ring opening)rates as com-pared to tho of EG.
2.7.Green Chemistry Implication
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If NH3and CO2relead from the process were recap-tured and recycled back to urea15,16as indicated in Scheme I,eq.2,the overall alkoxylation of one-pot urea-glycol pro-cess can be regarded as a simple condensation reaction of phenol with1,2-glycols yielding alkoxylated alcohol giv-ing off water as the only by-product(Scheme I,eq.3).This overall ethoxylation in theory has a calculated atom-utili-zation efficiency of88.5%for phenol and89.8%for BPA respectively.17Thus,urea can be regarded as a recyclable carrier while the1,2-glycols become the only consumed re-agents in the whole process.In the ca of propoxylation, the atom-utilization efficiencies for phenol and BPA are calculated to be89.4%and90.5%respectively.
One-Pot Alkoxylation of Phenols with Urea and1,2-Glycols J.Chin.Chem.Soc.,Vol.57,No.2,2010
171 Fig.4.Propoxylated ether diols of BPA:catalyzed by
(a)Na2CO3;(b)Cs2CO3
.
Fig.5.Higher ethoxylation of BPA:BPA/urea/EG=
1/8/10,catalyzed by K2CO3.
