research article rapid and efficient synthesis of...

Research ArticleRapid and Efficient Synthesis of 120596-Alkylenediphosphoric Acidsfrom Phosphorus Oxychloride

Dalila Meziane1 Abdelhamid Elias1 and Erwann Gueacutenin2

1Departement de Chimie Faculte des Sciences Universite Mouloud Mammeri BP 17 RP 15000 Tizi Ouzou Algeria2UFR SMBH Universite Paris 13 Sorbonne Paris Cite 74 rue Marcel Cachin 93017 Bobigny France

Correspondence should be addressed to Erwann Guenin gueninuniv-paris13fr

Received 2 November 2015 Revised 16 December 2015 Accepted 11 January 2016

Academic Editor Marijan Kocevar

Copyright copy 2016 Dalila Meziane et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The aim of this investigation was to develop an efficient rapid and selective method for the synthesis of 120596-alkylenediphosphoricacids (HO)

2(O)P-O-(CH

2)119899-O-P(O)(OH)

2from reaction of several diols with phosphorus oxychloride The reaction was

investigated using threemethodologies (i) presence of a base (ii) classical heating and (iii) use of microwave irradiation Influenceof reaction temperature and molar ratio of reagents as well as the nature of the solvent was studied using these three differentmethods

1 Introduction

Alkylphosphates also called phosphate esters have foundnumerous applications over the years mainly in variousindustrial processes such as flame retardants plasticizingagents lubricants surfactants reagents in solvent extractionof heavy metal ions and corrosion inhibitors [1ndash9]

Organic phosphates are generally synthesized from con-densation of alcohol with several phosphorus substancesP2O5 POCl

3 PCl3 PCl5 and H

3PO4[10ndash14] In general the

products are mixtures of mono- di- and triesters togetherwith some byproducts and unreacted alcohols [15] Thisphenomenon is of course enhanced when reacting diolsor polyols Nevertheless selective formation of monoesterscould be obtained by reacting excess of the phosphorusspecies but this involves more difficult purification steps

Among the different phosphorus reactants phospho-rus oxychloride appears as a good compromise to obtainmonoalkylphosphates as it is less reactive than phosphoruschloridesThe synthesis of alkylphosphoric acids through thereaction of phosphorus oxychloride with alcohols involvestwo stepsThe first step consists in a nucleophilic attack of thealcohol at the P center of POCl

3 in order to yield the forma-

tion of an intermediate compound phosphorodichloridate bya bimolecular mechanism (termed SN

2P) [16] The second

step is the hydrolysis of the phosphorodichloridate formedin the first step By a similar way the reaction of diols withPOCl

3may be represented as shown in Scheme 1 By the same

mechanism twomolecules of POCl3may react with the same

molecule of diol to form diphosphorotetrachloridate whichis then hydrolyzed in a second step thus forming the desiredalkylenediphosphoric acids (HO)

2(O)P-O-(CH

2)119899-O-P(O)-

(OH)2

In fact the reaction of a diol (as in case of an alcohol)with phosphorus oxychloride leads to a complex mixtureof mono(di)alkylphosphoric acids trialkylphosphate andpolyphosphoric acids The proportion of each compounddepends on the reaction conditions [17] The lack of selectiv-ity is a major inconvenience for this synthetic route since thecomposition is hardly controlled giving generally low yieldsof the desired product which is difficult to separate from thecrude mixture Another problem of this reaction mainly incase of alcohols or diolswith long hydrocarbon chains is theirlower reactivity compared to the alcohols with shorter alkylchain At classical conditions this low reactivity induces theneed of long reaction times and high temperatures (gt100∘C)[11 18]

In this paper we report reactions of phosphorus oxy-chloride with several diols with varying hydrocarbon chainlength In order to try to control the selectivity of the reaction

Hindawi Publishing CorporationJournal of ChemistryVolume 2016 Article ID 8046893 7 pageshttpdxdoiorg10115520168046893

2 Journal of Chemistry

minus

minusHO

minus

minusHO

minus

minusOH minusHCl

minusHCl

Step 1

Step 2H2O

Example of possible byproducts

lowastlowastlowastlowast

m

m

+ Ominus

minus

Ominus

HOCl

ClCl

ClCl

Cl

Cl

ClP

P

POO

O

H

ClCl

Cl

ClCl Cl Cl

P

PP

O

OOOO

HO

HO

OHP

OO

OO

HO HO OHOHP P

OO O O

HO

HO

OHP

O O

O

HO OHOHPPPP O

O O O O

OO

O

OO

O O O O

O O

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

oplus ⊖

Scheme 1 General route for the formation of 120596-alkylenediphosphoric acids from phosphorus oxychloride

to obtain monoalkyl diphosphoric esters and improve thesynthetic process we investigated three different approachesfor this reaction firstly the reactions were activated by classi-cal heating and then by the use of triethylamine at low tem-perature and finally the reactions were run under microwaveirradiation

2 Results and Discussion

21 Method 1 Conventional Thermal Activation Using con-ventional heating the reactions were carried out according toa slightlymodified procedurewith respect to the one reportedfor similar products [18] A large excess of POCl

3versus diol

was used (119877 = 4) and refluxed with the diol for several hoursin toluene The evolution of the reaction was followed byNMR the 31P 1H spectrum showed the appearance of a newpeak around 5-6 ppm which corresponds to the monoalkylphosphorodichloridate intermediates (POCl

3signal appears

around 45 ppm (Figure 1(a))) During the hydrolysis step wenoted some progressive decrease of the peak area at 6 ppmin favor of a new one around 0 ppm corresponding to thedesired productsThe other peaks observed with a little con-tribution correspond to byproducts due to a partial hydro-lysis of POCl

3and formation of anhydride (Figure 1(b)) The

desired product was then isolated by means of precipitation

from methanolethyl acetate (14) The final product corre-sponds to themonoesterified phosphoric acids However it isworthmentioning that underwhatever conditions used it wasnever obtained in pure form The maximum purity (calcu-lated by 31P NMR) that corresponds to optimized conditionswas 95The remaining 5 impurities were attributed to theformation of at least one dialkyl phosphoric acid Attempts torealize the reaction with a decreased or stoechiometric ratioof POCl

3Diol (119877 = 2 or 119877 = 3) were unsuccessful it resulted

in product mixtures only which were quite difficult to sepa-rate or even to identify Using the optimized conditions pureproducts were obtained yields ranging from 65 to 85depending on the diols nature (Table 1) Although appreciableyields and purity are obtained this method presents somedrawback such as length of reaction (several hours) and needof high reaction temperatures and excess of POCl

3

22 Method 2 Activation by a Base (NEt3) Due to the lownucleophilicity of diols their reaction with POCl

3is slow

In the literature bases are frequently used to activate thereaction of hydroxyl compounds with phosphorus oxychlo-ride [17] In this study we tested the activating role oftriethylamine (NEt

3) in the reaction of diols with POCl

3

NEt3has a double character nucleophilic and basic so it

can readily react with POCl3to form an activated product

Journal of Chemistry 3

6057

POCl

3

10 0 minus10 minus20

OOPP

O On( )

ClClCl Cl

(a)

15 10 5 0 minus5 minus10 minus15

OOPP

O O

HOHO OHOHn( )

(b)

Figure 1 31P NMR spectra of the reaction mixtures obtained during the two-step synthesis (a) Step 1 (b) step 2 (Method 1)

Et Et Et

Et

EtEt

Et

EtEt

Cl

Cl

ClClClCl

Cl

ClCl

Cl

ClClCl

ClCl

P

P P

P

PP

O

OOOO

OH

O O+ +

+

+

+ Ominus

Ominus

minus

Nminus

Nminus

N

minus

minusHO

HOHO

minus

minusOH

Et3HNCl

NEt3POCl3

Et3HNCl

n( )

n( )n

( )

n( )

oplus ⊖

oplus⊖oplus ⊖

oplus ⊖

Scheme 2 General route to the formation of 120596-alkylenediphosphoric acids from phosphorus oxychloride using triethylamine

(Scheme 2) This positively charged intermediate is morereactive than the POCl

3 It is then easily attacked by the

hydroxyl group of the diols The reaction is even exothermicand was conducted at low temperature (minus15∘C) implyingsome handling caution In this reaction the amine plays asecond role which consists in the fixation of the formed HCland provides the corresponding chlorhydrate (NEt

3 HCl)

The precipitation of the chlorhydrate in an adequate solventdisplaces the reaction-equilibrium towards the formation ofthe phosphonic ester (Scheme 2)

The reactions of POCl3with diols according to this

pathway were followed by NMR The 31P 1H NMR spectrashowed the formation of different intermediates but at the

end of the process the major product showed a signalaround 5-6 ppm (Figure 2(a)) After a hydrolysis step theseintermediates mainly afford the desired product and othernonidentified byproducts probably resulting from polyester-ification In this procedure an excess of POCl

3was also

necessary to lessen double or even triple attack of the diolson the same POCl

3molecule allowing for the formation of

di- or trialkylphosphates compounds Nevertheless use of 4equivalents of POCl

3did not completely avoid the formation

of these byproducts since the desired product was neverobtained in pure form (maximum purity obtained was 90)One must also note that an increase in POCl

3did not result

in any increase of purity either


Table 1 Reaction conditions and results of the synthesized productswith the different methods

Yield 120578 ()

Diols rarr C6

C9

C12

Method 1119879 = 110

∘C 119877 = 4 119905119903= 8ndash10 h

solvent toluene70a 65a 85a

Method 2119879 = minus15

∘C rarr 20∘C 119877 = 4 1198771015840 = 4119905119903= 2 h

solvents THF (C12) or diethyl ether

(C6and C

9)

65b 62b 75b

Method 3119879Max = 85

∘C 119877 = 2 119905119903= 2min

119882 = 100W solvent acetonitrile65 68 72

119905119903 reaction time (step 1) 119877 molar ratio POCl3diol 1198771015840 molar ratio triethy-

laminediol C6 hexane-16-diol C9 nonane-19-diol and C12 dodecane-112-diolabProducts were not obtained in pure form (maximum purity a 95 b90)

During the reaction an excess of NEt3was also needed

in order to scavenge the totality of the formed HCl and thusavoid the formation of chloroalkanes as byproducts Use oflowmolar ratios (2-3 equivalents) of POCl

3andor NEt

3gave

quite complex mixtures Only small quantities of the desiredproduct were formed and isolated in this case Differentsolvents were evaluated for the reaction (dichloromethanetetrahydrofuran and diethyl ether) The best results wereobtained with diethyl ether in case of C

6and C

9diols while

in case of C12

the best results were obtained with THF Thesuccess of the reactions with these solvents is probably dueto the precipitation of the chlorhydrate salt (NEt

3 HCl)

When dichloromethane in which triethylammonium salt isknown to be partially soluble was used only low quantity ofproductwas extractedUsing the optimized conditions yieldslie in the range 62ndash75 These are comparable to thoseobtained with the first method yet the products exhibit lesspurity (reaching its maximum at 90) However this secondmethod presents two advantages as compared to thermalactivation that is a decrease of the reaction time (2 h versus10 h) and the absence of any heating since everything worksat ambient temperature as compared to the usual 110∘C Themajor inconvenience of this procedure lies in the need ofreagents POCl

3(119877 = 4) and amine (1198771015840 = 4) in excess

23 Method 3 Activation by Microwave Irradiation Micro-wave offers a number of advantages over conventional heat-ing such as fast-and-homogeneous noncontact heating [19]Moreover use of microwaves offers drastically reduced pro-cessing time That could in fact account for its spreadingduring the last three decades in several areas of chemistry[20] In particular this methodology had a positive impacton phosphorus chemistry as well as on several organophos-phorus reactions that has benefited from the use of micro-waves [21 22] We thus apply it to the synthesis of 120596-alkyl-enediphosphoric acids The reaction was conducted in open

vessel by controlling power delivery during the reactionUnder microwave irradiation the final and intermediateproducts emerging from the reaction of diols with POCl

3

were identical to those which were formed using conven-tional heating These products essentially consist in thediphosphorotetrachloridate formed in the first step (Scheme2) and the alkylenediphosphoric acids (HO)

2(O)P-O(CH

2)119899-

O-P(O)-(OH)2obtained after the hydrolysis step (Figure 3)

The results are satisfactory (65ndash72) and comparableto those obtained with the previous methods (1 and 2)(Table 1) However this time the purity was better as no tracesof di- or polyalkylphosphate were observed Another assetof this methodology was that the amount of phosphorusoxychloride was reduced by a factor 2 from 4 to 2 equivand the reaction time of the diphosphorotetrachloridateformation was shortened to 2 minutes instead of more than8 hours when using thermal heatingThis method comparedto method 2 has also the advantage of being catalyst-free

Polar solvents like acetonitrile seem to be useful forthe reaction under microwave irradiation When toluenewas used only traces of products are detected even undermuch harsher conditions (119875 = 150W 119905 = 30min and119877 = 4) This is due to the nonpolar nature of toluene asonly polar molecules selectively absorb microwaves whilenonpolar molecules are known to be inert to microwavedielectric losses [20 23] Indeed the heat generated by thereactants rotating molecules when submitted to microwaveirradiation dissipated in this solvent through convectionmechanisms Using the conditions cited above the resultingtemperature (119879max = 40∘C) is too low to activate the reactionTests carried out without solvent generated a rapid anduncontrollable increase of the temperature in the reactionmixture especially when no excess of POCl

3(119877 = 2) was

used Yields in solvent-free conditions did not exceed 50even under the use of a large excess of the reagent (119877 = 4)

The optimal conditions and the corresponding yields forthe 3 methodologies are summarized in Table 1

3 Experimental Section

31 Reagents and Solvents Phosphorus oxychloride (99)triethylamine (gt99) and diols hexane-16-diol (99)nonane-19-diol (98) and dodecane-112-diol (99) werepurchased from Sigma-Aldrich Diols were used withoutfurther purification Phosphorus oxychloride and triethy-lamine were distilled before use All solvents were pur-chased from Carlo Erba-SDS and also distilled before useDichloromethane acetonitrile and ethyl acetate were dis-tilled over P

2O5Methanol ethanol diethyl ether and toluene

were distilled over sodium The THF was likewise distilledover sodium in presence of benzophenone

32 Instruments NMR spectra were recorded with a VAR-IAN Unity Inova 500MHz (13C 1259 1H 5006MHz) or aVARIAN Gemini 200MHz (31P 809MHz) spectrometer inCD3OD Chemical shifts are reported in parts per million

(ppm) on the 120575 scale The residual solvent peak (CD3OH)

was used as a reference for 1H NMR (331 ppm) and 13C


5094

10 0 minus10

(ppm)

OOPP

O O

ClClCl Cln( )

4421

(a)

5561

4147

minus0000

minus2734

minus2960

10 0

(ppm)

OOPP

O O

HOHO OHOHn( )

(b)

Figure 2 31P NMR spectra of the reaction mixtures obtained during the two-step synthesis (a) Before the hydrolysis (step 1) (b) Duringhydrolysis step 2 (Method 2)

5 0 minus5 minus10 minus15

OOPP

O O

ClClCl Cl

0943

0000

minus0679

minus13027

n( )

(a)

10 5 0 minus5 minus10 minus15

OOPP

O O

HOHO OHOH

0905

0000

n( )

(b)

Figure 3 31P NMR spectra of 112-Bis[(dihydroxyphosphinyl)oxy]dodecane obtained with method 3 (a) Crude mixture obtained duringstep 1 (b) Crude mixture obtained after hydrolysis step 2 and before purification

NMR (490 ppm) 31P NMR spectra were recorded usingphosphoric acid (85) as the external reference Data arereported as follows s = singlet d = doublet t = tripletq = quartet dt = doublet of triplet and m = multipletCoupling constants are given in Hz The FTIR spectra wererecorded using a Nicolet FTIR 380 spectrophotometer andmeasured in wavenumbers (cmminus1) The mass spectra wererun on a MALDI-TOF mass spectrometer (Biflex IV BrukerDaltonique) with 25-dihydroxybenzoic acid as matrix

All melting points are recorded using a Stuart SMP3melting point apparatus and are uncorrected

All experiments under microwave irradiations were runin open vessel using a CEM-Discover microwave apparatus

33 General Procedure for the Conventional Heating Synthesis(Method 1) The following procedure was adapted fromsynthesis reported for similar compounds [18] Phosphorusoxychloride (3066 g 200mmol) and the diol (59 801 1011 g(resp for 119899 = 6 9 or 12) 50mmol) were added underargon successively to a round bottom flask containing 120mLof toluene The mixture was refluxed for 8 to 10 h undermagnetic stirring The solution was then concentrated with arotary evaporator and the viscous residue was coevaporatedtwice with 100mL of toluene

In the second step the obtained residue was hydrolyzedby 100mL of cold water Distilled water was added care-fully to the residue previously cooled (5ndash10∘C) Then the


solution was warmed down to 90∘C and stirred for 2 to 3hours During the hydrolysis a white precipitate appearedand was isolated after water filtration The obtained whitesolid was dissolved in 100mL of ethanol which was thenevaporated This operation was repeated twice in order toremove the remaining HCl The residue was finally dissolvedin methanolethyl acetate (14) (vv) and the solution was leftto precipitate overnight (in a freezer for compounds I andII at rt for compound III) The white powder was filteredwashed with diethyl ether and dried in desiccators

34 General Procedure for the Synthesis Using Triethylamine(Method 2) In a 150mL tricol flask equipped with a refluxcondenser a thermometer and an addition funnel a solutionof phosphorus oxychloride (92 g 60mmol) was mixed with30mL of solvent (diethyl ether dichloromethane or tetrahy-drofuran (THF)) A solution of diol (15mmol) and triethy-lamine (608 g 60mmol) was then introduced dropwise Thereaction being very exothermic the flask was placed in amix-ture of liquid nitrogen and ethanol to keep the temperatureat approximately minus15∘C during the reagent addition Aftercompletion of the addition the mixture was stirred at roomtemperature (20∘C) for 2 hours 20mL of distilled water wasthen added to the reaction mixture and left under magneticstirring at room temperature overnight The mixture wasthen concentrated with a rotary evaporator before 20mLof cold water was finally added to the viscous residue andthe yellow organic layer removed from the aqueous phaseThe desired product was isolated by recrystallization frommethanolethyl acetate (14) (vv)

35 General Procedure for the Synthesis under MicrowaveIrradiation (Method 3) Phosphorus oxychloride (336 g22mmol) was placed in a 100mL flask equipped with areflux condenser and closed by a calcium chloride tube witha diol (10mmol) and acetonitrile (15mL) as solvent Themixture was then irradiated at 100W for 2min under vig-orous stirring The mixture initially heterogeneous becamehomogenous within a few seconds of irradiation At the endof the irradiation process the mixture is poured into a flaskcontaining 30mL of cold distilled water The hydrolysis andthe purification procedures are similar to those described inmethod 1

36 (16-Bis[(dihydroxyphosphinyl)oxy]hexane) (CompoundI) mp= 96∘C 31P 1HNMR 120575 02 1HNMR 120575 397 (dt 4H3119869H-H = 3119869P-H = 65Hz POCH

2) 168 (m 4H POCH

2CH2)

145 (m 4H POCH2CH2CH2) 13C 1HNMR120575 677 (d 2119869P-C

= 58Hz POCH2) 314 (d 3119869P-C = 58Hz POCH

2CH2) 263

(POCH2CH2CH2) Elementary Analysis C

6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217

37 19-Bis[(dihydroxyphosphinyl)oxy]nonane (CompoundII) mp = 109∘C 31P 1H NMR 120575 06 1H NMR 120575 396(dt 4H 3119869H-H = 3119869P-H = 67Hz POCH

2) 167 (m 4H

POCH2CH2) 141 (m 4H POCH

2CH2CH2) 132 (m 8H

POCH2CH2CH2CH2CH2) 13C 1H NMR 120575 679 (d 2119869P-C

= 58 Hz POCH2) 316 (d 3119869P-C = 58Hz POCH

2CH2) 303

(POCH2CH2CH2CH2) 306 (POCH

2CH2CH2CH2CH2)

267 (POCH2CH2CH2) Elementary Analysis C

9H22O8P2

calcld C 338 H 69 O 400 P 193 found C 332 H 72 O399 P 197

38 112-Bis[(dihydroxyphosphinyl)oxy]dodecane (CompoundIII) mp = 114∘C 31P 1H NMR 120575 09 1H NMR 120575396 (dt 4H 3119869H-H = 3119869P-H = 67Hz POCH

2) 166

(m 4H POCH2CH2) 140 (m 4H POCH

2CH2CH2)

132 (m 12H POCH2CH2CH2CH2CH2CH2) 13C 1H

NMR 120575 679 (d 2119869P-C = 58Hz POCH2) 316 (d 3119869P-C

= 59Hz POCH2CH2) 304 (POCH

2CH2CH2CH2) 307

(POCH2CH2CH2CH2CH2CH2) 263 (POCH

2CH2CH2) IR

(KBr) (cmminus1) 2919 2852 1474 (C-H) 2360 (PO-H) 12341095 1038 (P=O) and (C-O) 1012 937 (P-O) Mz (MH+)36325 calcld 36313 Elementary Analysis C

12H28O8P2cal-

cld C 398 H 78 O 353 P 171 found C 397 H 80 O 350P 169

4 Conclusion

In this work we evaluated three different methodologies toobtain various 120596-alkylenediphosphoric acids from conden-sation of phosphorus oxychloride onto diols with varyingchain length Three methodologies were studied (i) theconventional heating of both reactants in organic solvent(ii) the reaction under basic activation at low temperatureand (iii) the use of short microwave heating After opti-mization all methodologies permit obtaining the desiredalkylenediphosphoric acids (HO)

2(O)P-O-(CH

2)119899-O-P(O)-

(OH)2as main product but only the microwave assisted one

allows for the obtaining of pure products without presenceof any traces of polyalkylation byproducts Moreover thislatermethodology permits drastically decreasing the reactiontime without using excess of either reactant or any catalyst Itthus appears as an interesting way of synthesizing selectivelymonoalkylphosphate In addition due to relatively friendlyconditions it could be further applied to more sensiblesubstrates

Conflict of Interests

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

References

[1] D W Johnson and J E Hils ldquoPhosphate esters thiophosphateesters and metal thiophosphates as lubricant additivesrdquo Lubri-cants vol 1 no 4 pp 132ndash148 2013

[2] M A Hegazy A S El-Tabei A H Bedair andM A Sadeq ldquoAninvestigation of three novel nonionic surfactants as corrosioninhibitor for carbon steel in 05M H

2SO4rdquo Corrosion Science

vol 54 no 1 pp 219ndash230 2012[3] D Ciceri L R Mason D J E Harvie J M Perera and G

W Stevens ldquoExtraction kinetics of Fe(III) by di-(2-ethylhexyl)phosphoric acid using a Y-Y shaped microfluidic devicerdquoChemical Engineering Research and Design vol 92 no 3 pp571ndash580 2014


[4] R Murugavel A Choudhury M G Walawalkar R Pothirajaand C N R Rao ldquoMetal complexes of organophosphate estersand open-framework metal phosphates synthesis structuretransformations and applicationsrdquo Chemical Reviews vol 108no 9 pp 3549ndash3655 2008

[5] C Shi DDuan Y Jia andY Jing ldquoA highly efficient solvent sys-tem containing ionic liquid in tributyl phosphate for lithium ionextractionrdquo Journal of Molecular Liquids vol 200 part B pp191ndash195 2014

[6] C Shi Y Jia C Zhang H Liu and Y Jing ldquoExtraction oflithium from salt lake brine using room temperature ionic liquidin tributyl phosphaterdquo Fusion Engineering and Design vol 90pp 1ndash6 2015

[7] S Raatz and P Klapper ldquoUsing interfacial tension measure-ments to analyze the mechanism of zinc extraction withD2EHPArdquo Hydrometallurgy vol 134-135 pp 19ndash25 2013

[8] A Cheraghi M S Ardakani E Keshavarz Alamdari DHaghshenas Fatmesari D Darvishi and S K SadrnezhaadldquoThermodynamics of vanadium (V) solvent extraction bymixture of D2EHPA and TBPrdquo International Journal of MineralProcessing vol 138 pp 49ndash54 2015

[9] D Das V A Juvekar V H Rupawate K Ramprasad and RBhattacharya ldquoEffect of the nature of organophosphorous acidmoiety on co-extraction of U(VI) and mineral acid from aque-ous solutions using D

2EHPA PC88A and Cyanex 272rdquo Hydro-

metallurgy vol 152 pp 129ndash138 2015[10] J M Kuiper R Hulst and J B F N Engberts ldquoA selective and

mild synthetic route to dialkyl phosphatesrdquo Synthesis no 5 pp695ndash698 2003

[11] A Wagenaar L A M Rupert J B F N Engberts and DHoekstra ldquoSynthesis and vesicle formation of identical- andmixed-chain di-n-alkyl phosphate amphiphilesrdquoThe Journal ofOrganic Chemistry vol 54 no 11 pp 2638ndash2642 1989

[12] Q Taotao W Xuechuan and R Longfang ldquoStudy on produc-tion of lanonol phosphates by a sustained-releasemethodrdquo Jour-nal of Surfactants and Detergents vol 10 no 1 pp 9ndash12 2007

[13] A Elias M A Didi D Villemin T Semaoune and S OuattasldquoSynthesis of mono-and dialkylphosphates by the reactions ofhydroxycompounds with the phosphorus pentaoxide undermicrowave irradiationrdquo Phosphorus Sulfur and Silicon and theRelated Elements vol 179 no 12 pp 2599ndash2607 2004

[14] C Dueymes C Pirat and R Pascal ldquoFacile synthesis of simplemono-alkyl phosphates from phosphoric acid and alcoholsrdquoTetrahedron Letters vol 49 no 36 pp 5300ndash5301 2008

[15] D Miller E-M Wiener A Turowski C Thunig and HHoffmann ldquoOW emulsions for cosmetics products stabilizedby alkyl phosphatesmdashrheology and storage testsrdquo Colloids andSurfaces A Physicochemical and Engineering Aspects vol 152no 1-2 pp 155ndash160 1999

[16] R F Hudson Structure and Mechanism in Organ-PhosphorusChemistry Academic Press London UK 1965

[17] A Russo C Tonelli and E Barchiesi ldquoNew developments inthe synthesis and characterization of phosphate esters of linear(per)fluoropolyether monofunctional and difunctional macro-monomersrdquo Journal of Polymer Science Part A Polymer Chem-istry vol 43 no 20 pp 4790ndash4804 2005

[18] Q Lu R P Ubillas Y Zhou et al ldquoSynthetic analogues ofirlbacholine a novel antifungal plant metabolite isolated fromIrlbachia Alatardquo Journal of Natural Products vol 62 no 6 pp824ndash828 1999

[19] L Perreux and A Loupy ldquoA tentative rationalization of micro-wave effects in organic synthesis according to the reaction

medium and mechanistic considerationsrdquo Tetrahedron vol 57no 45 pp 9199ndash9223 2001

[20] C O Kappe ldquoControlledmicrowave heating inmodern organicsynthesisrdquo Angewandte ChemiemdashInternational Edition vol 43no 46 pp 6250ndash6284 2004

[21] E Guenin and D Meziane ldquoMicrowave assisted phosphorusorganic chemistry a reviewrdquo Current Organic Chemistry vol15 no 19 pp 3465ndash3485 2011

[22] G Keglevich A Grun E Balint N Z Kiss and E JablonkaildquoMicrowave-assisted organophosphorus synthesisrdquo CurrentOrganic Chemistry vol 17 no 5 pp 545ndash554 2013

[23] M R Rosana Y Tao A E Stiegman and G B Dudley ldquoOnthe rational design of microwave-actuated organic reactionsrdquoChemical Science vol 3 no 4 pp 1240ndash1244 2012

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minus

minusHO

minus

minusHO

minus

minusOH minusHCl

minusHCl

Step 1

Step 2H2O

Example of possible byproducts

lowastlowastlowastlowast

m

m

+ Ominus

minus

Ominus

HOCl

ClCl

ClCl

Cl

Cl

ClP

P

POO

O

H

ClCl

Cl

ClCl Cl Cl

P

PP

O

OOOO

HO

HO

OHP

OO

OO

HO HO OHOHP P

OO O O

HO

HO

OHP

O O

O

HO OHOHPPPP O

O O O O

OO

O

OO

O O O O

O O

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

n( )

oplus ⊖

Scheme 1 General route for the formation of 120596-alkylenediphosphoric acids from phosphorus oxychloride

to obtain monoalkyl diphosphoric esters and improve thesynthetic process we investigated three different approachesfor this reaction firstly the reactions were activated by classi-cal heating and then by the use of triethylamine at low tem-perature and finally the reactions were run under microwaveirradiation

2 Results and Discussion

21 Method 1 Conventional Thermal Activation Using con-ventional heating the reactions were carried out according toa slightlymodified procedurewith respect to the one reportedfor similar products [18] A large excess of POCl

3versus diol

was used (119877 = 4) and refluxed with the diol for several hoursin toluene The evolution of the reaction was followed byNMR the 31P 1H spectrum showed the appearance of a newpeak around 5-6 ppm which corresponds to the monoalkylphosphorodichloridate intermediates (POCl

3signal appears

around 45 ppm (Figure 1(a))) During the hydrolysis step wenoted some progressive decrease of the peak area at 6 ppmin favor of a new one around 0 ppm corresponding to thedesired productsThe other peaks observed with a little con-tribution correspond to byproducts due to a partial hydro-lysis of POCl

3and formation of anhydride (Figure 1(b)) The

desired product was then isolated by means of precipitation

from methanolethyl acetate (14) The final product corre-sponds to themonoesterified phosphoric acids However it isworthmentioning that underwhatever conditions used it wasnever obtained in pure form The maximum purity (calcu-lated by 31P NMR) that corresponds to optimized conditionswas 95The remaining 5 impurities were attributed to theformation of at least one dialkyl phosphoric acid Attempts torealize the reaction with a decreased or stoechiometric ratioof POCl

3Diol (119877 = 2 or 119877 = 3) were unsuccessful it resulted

in product mixtures only which were quite difficult to sepa-rate or even to identify Using the optimized conditions pureproducts were obtained yields ranging from 65 to 85depending on the diols nature (Table 1) Although appreciableyields and purity are obtained this method presents somedrawback such as length of reaction (several hours) and needof high reaction temperatures and excess of POCl

3

22 Method 2 Activation by a Base (NEt3) Due to the lownucleophilicity of diols their reaction with POCl

3is slow

In the literature bases are frequently used to activate thereaction of hydroxyl compounds with phosphorus oxychlo-ride [17] In this study we tested the activating role oftriethylamine (NEt

3) in the reaction of diols with POCl

3

NEt3has a double character nucleophilic and basic so it

can readily react with POCl3to form an activated product


6057

POCl

3


OOPP

O On( )

ClClCl Cl

(a)


OOPP

O O

HOHO OHOHn( )

(b)


Et Et Et

Et

EtEt

Et

EtEt

Cl

Cl

ClClClCl

Cl

ClCl

Cl

ClClCl

ClCl

P

P P

P

PP

O

OOOO

OH

O O+ +

+

+

+ Ominus

Ominus

minus

Nminus

Nminus

N

minus

minusHO

HOHO

minus

minusOH

Et3HNCl

NEt3POCl3

Et3HNCl

n( )

n( )n

( )

n( )

oplus ⊖

oplus⊖oplus ⊖

oplus ⊖





3 HCl)





3was also






3did not result




Yield 120578 ()

Diols rarr C6

C9

C12

Method 1119879 = 110

∘C 119877 = 4 119905119903= 8ndash10 h



∘C rarr 20∘C 119877 = 4 1198771015840 = 4119905119903= 2 h


(C6and C

9)

65b 62b 75b


∘C 119877 = 2 119905119903= 2min






3andor NEt

3gave


6and C

9diols while

in case of C12


3 HCl)





3


2(O)P-O(CH

2)119899-




3(119877 = 2) was











5094

10 0 minus10

(ppm)

OOPP

O O

ClClCl Cln( )

4421

(a)

5561

4147

minus0000

minus2734

minus2960

10 0

(ppm)

OOPP

O O

HOHO OHOHn( )

(b)



OOPP

O O

ClClCl Cl

0943

0000

minus0679

minus13027

n( )

(a)


OOPP

O O

HOHO OHOH

0905

0000

n( )

(b)












2) 168 (m 4H POCH

2CH2)



2CH2) 263


6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217


2) 167 (m 4H


2CH2CH2) 132 (m 8H



2CH2) 303


2CH2CH2CH2CH2)


9H22O8P2



2) 166


2CH2CH2)




2CH2CH2CH2) 307


2CH2CH2) IR


12H28O8P2cal-


4 Conclusion


2(O)P-O-(CH

2)119899-O-P(O)-





References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


6057

POCl

3


OOPP

O On( )

ClClCl Cl

(a)


OOPP

O O

HOHO OHOHn( )

(b)


Et Et Et

Et

EtEt

Et

EtEt

Cl

Cl

ClClClCl

Cl

ClCl

Cl

ClClCl

ClCl

P

P P

P

PP

O

OOOO

OH

O O+ +

+

+

+ Ominus

Ominus

minus

Nminus

Nminus

N

minus

minusHO

HOHO

minus

minusOH

Et3HNCl

NEt3POCl3

Et3HNCl

n( )

n( )n

( )

n( )

oplus ⊖

oplus⊖oplus ⊖

oplus ⊖





3 HCl)





3was also






3did not result




Yield 120578 ()

Diols rarr C6

C9

C12

Method 1119879 = 110

∘C 119877 = 4 119905119903= 8ndash10 h



∘C rarr 20∘C 119877 = 4 1198771015840 = 4119905119903= 2 h


(C6and C

9)

65b 62b 75b


∘C 119877 = 2 119905119903= 2min






3andor NEt

3gave


6and C

9diols while

in case of C12


3 HCl)





3


2(O)P-O(CH

2)119899-




3(119877 = 2) was











5094

10 0 minus10

(ppm)

OOPP

O O

ClClCl Cln( )

4421

(a)

5561

4147

minus0000

minus2734

minus2960

10 0

(ppm)

OOPP

O O

HOHO OHOHn( )

(b)



OOPP

O O

ClClCl Cl

0943

0000

minus0679

minus13027

n( )

(a)


OOPP

O O

HOHO OHOH

0905

0000

n( )

(b)












2) 168 (m 4H POCH

2CH2)



2CH2) 263


6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217


2) 167 (m 4H


2CH2CH2) 132 (m 8H



2CH2) 303


2CH2CH2CH2CH2)


9H22O8P2



2) 166


2CH2CH2)




2CH2CH2CH2) 307


2CH2CH2) IR


12H28O8P2cal-


4 Conclusion


2(O)P-O-(CH

2)119899-O-P(O)-





References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



Yield 120578 ()

Diols rarr C6

C9

C12

Method 1119879 = 110

∘C 119877 = 4 119905119903= 8ndash10 h



∘C rarr 20∘C 119877 = 4 1198771015840 = 4119905119903= 2 h


(C6and C

9)

65b 62b 75b


∘C 119877 = 2 119905119903= 2min






3andor NEt

3gave


6and C

9diols while

in case of C12


3 HCl)





3


2(O)P-O(CH

2)119899-




3(119877 = 2) was











5094

10 0 minus10

(ppm)

OOPP

O O

ClClCl Cln( )

4421

(a)

5561

4147

minus0000

minus2734

minus2960

10 0

(ppm)

OOPP

O O

HOHO OHOHn( )

(b)



OOPP

O O

ClClCl Cl

0943

0000

minus0679

minus13027

n( )

(a)


OOPP

O O

HOHO OHOH

0905

0000

n( )

(b)












2) 168 (m 4H POCH

2CH2)



2CH2) 263


6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217


2) 167 (m 4H


2CH2CH2) 132 (m 8H



2CH2) 303


2CH2CH2CH2CH2)


9H22O8P2



2) 166


2CH2CH2)




2CH2CH2CH2) 307


2CH2CH2) IR


12H28O8P2cal-


4 Conclusion


2(O)P-O-(CH

2)119899-O-P(O)-





References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


5094

10 0 minus10

(ppm)

OOPP

O O

ClClCl Cln( )

4421

(a)

5561

4147

minus0000

minus2734

minus2960

10 0

(ppm)

OOPP

O O

HOHO OHOHn( )

(b)



OOPP

O O

ClClCl Cl

0943

0000

minus0679

minus13027

n( )

(a)


OOPP

O O

HOHO OHOH

0905

0000

n( )

(b)












2) 168 (m 4H POCH

2CH2)



2CH2) 263


6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217


2) 167 (m 4H


2CH2CH2) 132 (m 8H



2CH2) 303


2CH2CH2CH2CH2)


9H22O8P2



2) 166


2CH2CH2)




2CH2CH2CH2) 307


2CH2CH2) IR


12H28O8P2cal-


4 Conclusion


2(O)P-O-(CH

2)119899-O-P(O)-





References







































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of






2) 168 (m 4H POCH

2CH2)



2CH2) 263


6H16O8P2calcld

C 259 H 58 O 460 P 223 found C 262 H 57 O 464P 217


2) 167 (m 4H


2CH2CH2) 132 (m 8H



2CH2) 303


2CH2CH2CH2CH2)


9H22O8P2



2) 166


2CH2CH2)




2CH2CH2CH2) 307


2CH2CH2) IR


12H28O8P2cal-


4 Conclusion


2(O)P-O-(CH

2)119899-O-P(O)-





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

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