Staudinger’s phosphazene as an efficient esterifying reagent

Article abstract of DOI:10.1080/00397911.2016.1211705

A new application of Staudinger’s phosphazene as an efficient esterifying reagent is reported. Staudinger’s phosphazene formed in situ by the reaction of organic mono-azide with triphenylphosphine, which is trapped by carboxylic acid, to afford amide exclusively. In contrast, interestingly the same phosphazene behaves in a different way as an efficient esterifying reagent, affording ester under a solvent-free microwave-assisted protocol wherein alcohol is added as the another component in addition to the other reactants. This discovery adds yet another new application of Staudinger’s phosphazene to synthetic chemistry.

Full text of DOI:10.1080/00397911.2016.1211705

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Staudinger’s Phosphazene as an Efficient
Esterifying Reagent
Murugan Dinesh, Raja Ranganathan, Sivasubramaniyan Archana, Murugan
Sathishkumar, Mohamed Sulthan Roshan banu & Alagusundaram
Ponnuswamy
To cite this article: Murugan Dinesh, Raja Ranganathan, Sivasubramaniyan Archana, Murugan
Sathishkumar, Mohamed Sulthan Roshan banu & Alagusundaram Ponnuswamy (2016):
Staudinger’s Phosphazene as an Efficient Esterifying Reagent, Synthetic Communications, DOI:
10.1080/00397911.2016.1211705
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1211705
View supplementary material
Accepted author version posted online: 18
Jul 2016.
Published online: 18 Jul 2016.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [University of Exeter]
Date: 19 July 2016, At: 07:13

Staudinger’s Phosphazene as an Efficient Esterifying Reagent
Murugan Dinesh1, Raja Ranganathan1, Sivasubramaniyan Archana1, Murugan
Sathishkumar1, Mohamed Sulthan Roshan banu1, Alagusundaram Ponnuswamy1
1Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai, Tamilnadu, India
Corresponding author: Alagusundaram Ponnuswamy. E-mail address:
ramradkrish@yahoo.co.in
Abstract
A newer applicability of Staudinger’s phosphazene as an efficient esterifying reagent is
reported. Staudinger’s phosphazene formed insitu by the reaction of organic mono-azide
with triphenylphosphine is trapped by carboxylic acid to afford amide exclusively. In
contrary, interestingly the same phosphazene behaves in a different way as an efficient
esterifying reagent affording ester under a solvent-free microwave assisted protocol
wherein in addition to the above reactants, alcohol is added as the another component.
This discovery adds yet another new applicability of Staudinger’s phosphazene to
synthetic chemistry.
Graphical Abstract:
1

KEYWORDS: Mono azide; Staudinger’s Phosphazene; Modified Staudinger Reaction;
reagent; esterification.
INTRODUCTION
Extensive applications of Staudinger’s phosphazene in organic syntheses since its
discovery [1] are evident from its utility in the synthesis of potential organic
compounds such as amine,[2] imine,[3] carbodiimide,[4] amide,[5] thioamide,[6]
thiazolidone,[7] spirothiazolidones,[8] thiohydantoin,[9] isoquinolines.[10] Recently,
we have discovered that bis-phosphazene,[11] also known as bis-iminophosphorane
generated from Bis azide-Triphenylphosphine acts as an efficient esterifying
reagent.
A deeper look on the proposed mechanism[11] of esterification using Bis
azide/TPP clearly indicates that initially protonation of one of the nitrogens of the
bis-phosphazene takes place in presence of carboxylic acid. This protonation leads
to the formation of phosphonium ion (I) which is stabilized by the electron pair
donated by the nitrogen of the second phosphazene in an intramolecular manner
resulting in a cyclic phosphonium ion (II) (Scheme 1). This ion (II) eventually
seems to drive the coupling of the carboxylic acid and the alcohol to achieve the
esterification efficiently.
If the above proposed mechanism is true, then it is reasonable to question
why not a similar but acyclic phosphonium ion shall be generated insitu
2

(analogous to the cyclic phosphonium ion discussed vide scheme 1) by the
intermolecular participation of two individual phosphazenes (instead of Bis-
phosphazene discussed vide scheme 1) which can be prepared readily from mono-
azide and triphenylphosphine (Scheme 2). Moreover, the feasibility of such a
presumption seems to be favourable as the phosphazenes would be proximate to
each other under solvent-free condition.
If this expectation turns to be true then it would be more remarkable in the
sense that instead of bis azide-triphenylphosphine, one can expect the well-known
commercially available mono azide-triphenylphosphine combination itself to
behave as an efficient esterifying reagent via. the formation of the corresponding
mono-phosphazene. In view of this, we were prompted to proceed with the
reaction, the reactants being carboxylic acid, alcohol, triphenyl phosphine and
organic mono-azide (instead of bis-azide of the earlier study[11] ). To our delight,
the attempt was successful thus disclosing yet another unknown applicability of the
Staudinger’s phosphazene as an esterifying reagent. The findings of our attempt
are presented in the forthcoming pages.
RESULTS AND DISCUSSION
At the outset, to a mixture of triphenyl phosphine (1.0 mmol), carboxylic
acid (1.0 mmol) and phenyl ethanol (1.0 mmol), benzyl azide (1.0 mmol) was
added slowly in a drop wise manner (to avoid accumulation of azide) and the
mixture was irradiated at 140 °C in microwave (CEM DISCOVER, Benchmate
3

model, single-mode design with inbuilt IR sensor) to afford the corresponding
ester[12-17] in good yield. ( Caution! As azides are potentially explosive, all the
reactions should be carried out behind a blast shield with personal protective
equipment. In particular, the sequence of addition of the reactants should be
strictly followed to avoid the accumulation of organic azides. This has been
achieved in the present investigation by the slow drop wise addition of the benzyl
azide to the reaction mixture containing triphenylphosphine during which the azide
group is instantaneous converted to phosphazene and hence no difficulty was
encountered). The synthesis of a library of esters has been accomplished by the
optimised protocol (Table 1).
A plausible mechanism for the esterification is sketched below (Scheme 4). As already
discussed vide supra, apparently the reaction proceeds via the reactive acylic
phosphonium ion formed insitu which would have been trapped either by the carboxylate
anion (Route A) or the alcohol (Route B) leading to the formation of the
acyloxyphosphonium ion or alkoxy phosphonium ion respectively. Then these
intermediates would have afforded the ester in good yield by dealkylation or deacylation.
As the reaction is very rapid and completes in 10 minutes under the solvent free
condition, the intermediates could not be isolated. However, as a supporting evidence for
the above sketched plausible mechanism, the byproduct viz. triphenylphosphine oxide
has been isolated as white solid.
4

Having understood that both Bis phosphazene of our earlier report[11] and mono
phosphazene of the present study behave as good esterifying reagents, it is pertinent to
mention here the resemblance of their skeletal feature with that of the commercially
available esterifying reagents like DCC and DEAD (Figure 1).
It is pertinent to mention here that phosphazene unlike DCC and DEAD, is an aza ylide
with more of phosphonium ion character and thus acts efficiently as an esterifying
reagent even at neutral condition. Also it could be realized that the mechanisms involved
during the esterification using these commercial reagents are parallel to what has been
discussed in the present investigation. Thus, our earlier study[11] and the present report
add two more new reagents to the list of prevailing esterifying reagents.
Though many methods are available for activation of carboxylic acid during
esterification, some of their disadvantages are (i) these methods often use organic
solvents and/or reagents which results in hazardous/corrosive by-produts (ii) some of the
reagents are expensive (iii) the work-up of the reaction is tedious(iv) some reactions need
catalyst, scavenger or additive.(v) the reaction is time consuming. However, our present
methodology involving Staudinger’s Phospazene is advantageous than many other
existing reagents as it is devoid of all the above said disadvantages.
5

EXPERIMENTAL
General
All chemicals, reagents and solvents were of commercially high purity grade purchased
from Avra Synthesis Pvt. Ltd. and Merck Ltd. India. Silica gel (60–120 mesh) was used
1
for column chromatographic isolation and purification of the compounds synthesized. H
NMR (300 MHz) and 13C NMR (75 MHz) spectra were recorded in CDCl3 on Bruker
(Avance) (300 MHz) spectrometer and the chemical shifts are reported in δ values in
parts per million (ppm) relative to tetramethylsilane, with coupling constant (J) values in
Hertz. Microwave irradiation (CEM DISCOVER, Benchmate model, single-mode design
with inbuilt IR sensor)
Procedure And Characterization
General Procedure For The Synthesis Of Alkyl Esters Under Microwave
Irradiation (5a-P)
To a mixture of triphenylphosphine (1.0 mmol), benzyl azide (1.0 mmol) was
added slowly in a phenylethanol (1.0 mmol) and carboxylic acid (1.0 mmol) (drop
wise manner (to avoid accumulation of azide) and the mixture was place to
microwave at 140°C for 10 minutes. (Caution! As azides are potentially explosive,
all the reactions should be carried out behind a blast shield with personal protective
equipment. In particular, the sequence of addition of the reactants should be
strictly followed to avoid the accumulation of organic azides. This has been
achieved in the present investigation by the slow drop wise addition of the benzyl
azide to the reaction mixture containing triphenylphosphine during which the azide
6

group is instantaneous converted to iminophosphorane and hence no difficulty was
encountered). After the completion of the reaction (as monitored by TLC), the
mixture was poured onto crushed ice. Then the reaction mixture was extracted
with dichloromethane and the organic layer was dried over anhydrous Na2SO4.
The solvent was removed and the residue was purified by column chromatography
using silica gel as the adsorbent and petroleum ether: ethyl acetate (98:2) as the
mobile phase to afford the corresponding carboxylic esters (5a-p) as colourless oily
liquids. Yield (73-85%).
Phenethyl Benzoate (5a)[11]
Yield: 80 %; 1H NMR (300 MHz, CDCl3) δ 8.02 (dd, J = 8.3, 1.1 Hz, 2H), 7.54 (d, J =
7.6 Hz, 2H), 7.43 (t, J = 7.7 Hz, 3H), 7.32 (d, J = 6.8 Hz, 3H), 7.29 – 7.23 (m, 2H), 4.53
(t, J = 7.0 Hz, 3H), 3.08 (t, J = 7.0 Hz, 3H ). 13C NMR (75 MHz, CDCl3) δ 166.5, 137.8,
132.8, 130.2, 129.5, 128.9, 128.5, 128.3, 126.5, 65.4, 35.2.
CONCLUSIONS
In conclusion, herein we report a novel hitherto unknown applicability of
Staudinger‘s Phosphazene as an efficient new reagent for esterification under
neutral and solvent-free condition.
FUNDING
The authors thank IRHPA, DST for providing 300MHz NMR instrument for recording
the NMR spectra for the compounds synthesized. One of the author thanks UGC and
DST for the financial support.
7

SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website
REFERENCES
1.
2.
3.
4.
5.
Staudinger, H.; Meyer, J. Helv. Chim. Acta. 1919, 2, 635
Peterson, T.; Streamland, T.; Awad, A. Molecules. 2014, 19, 2434.
Shah, S.; Protasiewicz, J. D. Coord. Chem. Rev. 2000, 210,181.
Wang, X.; Yin, J.; Shi, L.; Zhang, G.; Song, B. Eur. J. Med. Chem. 2014, 77, 65.
Sathishkumar, M.; Shanmugavelan, P.; Nagarajan, S.; Maheswari, M.; Dinesh, M.;
Ponnuswamy, A. Tetrahedron Lett. 2011, 52, 2830.
6. Nagarajan, S.; Shanmugavelan, P.; Sathishkumar, M.; Priyadharshini, N.; Sudakar,
P.; Ponnuswamy, A. Synth Commun. 2013, 43, 668.
7. Shanmugavelan, P.; Sathishkumar, M.; Nagarajan, S.; Ranganathan, R. J.
Heterocyclic Chem. 2014, 51, 1004.
8. Shanmugavelan, P.; Nagarajan, S.; Sathishkumar, M.; Ponnuswamy, A. Helv.
Chim. Acta. 2012, 95, 922.
9. Gosling, S.; El Amri, C.; Tatibouët, A. Synthesis. 2014, 46, 1079.
10. Yang, Y.; Shou, W.; Chen, Z.; Hong, D.; Wang, Y.; Able, T. J. Org. Chem. 2008,
8, 7500.
11. Dinesh, M.; Archana, S.; Ranganathan, R.; Sathishkumar, M.; Ponnuswamy, A.
Tetrahedron Lett. 2015, 56, 6975.
12. Chakraborti, A. K.; Singh, B.; Chankeshwara, S. V.; Patel, A. R. J. Org. Chem.
2009, 74, 5967.
8

13. Huang, X.; Li, X.; Zou, M.; Song, S.; Tang, C.; Yuan, Y.; Jiao, N. J. Am. Chem.
Soc. 2014, 136 , 14858.
14. But, T. Y. S.; Lu, J.; Toy, P. H. J. Am. Chem. Soc. 2010, 3, 1115–1117.
15. Zhang, C.; Feng, P.; Jiao, N. J. Am. Chem. Soc. 2013, 135, 15257−15262.
16. Tian, J.;. Gao, W.C.; Zhou, D.M.; Zhang, C. Org. Lett. 2012, 14, 3020–3023.
17. Kim, D.; Park, W.; Lee, C.; Jun, C. J. Org. Chem. 2014, 79, 12191−12196.
18. Liu, X. H.; Wu, J.; Shang, Z. C. Synth. Commun. 2012, 42 759
19. Sarova, D.; Kapoor, A.; Narang, R.; Judge, V.; Narasimhan, B. Med. Chem. Res.
2010, 20 769
9

Table 1. Scope of Staudinger’s phosphazene as esterifying reagent
Reaction conditions: To a mixture of triphenylphosphine (1.0 mmol), 2-phenylethanol
(1.0 mmol) and carboxylic acid (1.0 mmol), benzyl azide (1.0 mmol) was added slowly in
a drop wise manner (to avoid accumulation of azide) and the mixture was irradiated
(CEM DISCOVER, Benchmate model, single-mode design with inbuilt IR sensor) with
microwave at 140 °C for 10 minutes.
10

Scheme 1. Proposed mechanism for the esterification using bis –azide /TPP [11]
11

Scheme 2. Presumption leading to the present investigation
12

Scheme 3. Staudinger‘s phosphazene as an esterfying reagent
13

Scheme 4. Plausible mechanism of the Staudinger phosphazene
14

Fig. 1. Phosphazene resembles the partial structures of the esterifying reagent
15