An improved preparation of O-(Diphenylphosphinyl)hydroxylamine

Full text of DOI:10.1080/00304948.2011.613701

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Organic Preparations and Procedures
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An Improved Preparation of O-
(
Diphenylphosphinyl)hydroxylamine
a a
Sébastien Laulhé & Michael H. Nantz
a
Department of Chemistry , University of Louisville , Louisville, KY,
0208, USA
4
Published online: 06 Oct 2011.
To cite this article: Sébastien Laulhé & Michael H. Nantz (2011) An Improved Preparation of O-
(Diphenylphosphinyl)hydroxylamine, Organic Preparations and Procedures International: The New
Journal for Organic Synthesis, 43:5, 475-476, DOI: 10.1080/00304948.2011.613701
To link to this article: http://dx.doi.org/10.1080/00304948.2011.613701
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Organic Preparations and Procedures International, 43:475–476, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.613701
OPPI BRIEFS
An Improved Preparation
of O-(Diphenylphosphinyl)hydroxylamine
S e´ bastien Laulh e´ and Michael H. Nantz
Department of Chemistry, University of Louisville, Louisville, KY 40208, USA
O-(Diphenylphosphinyl)hydroxylamine (DPPH) is a versatile electrophilic amination
reagent that has been used widely for the amination of stable carbanions, Grignard reagents
1
–4
and π-electron-rich nitrogen heterocycles. More recently, Armstrong et al. have used
5
DPPH for the aziridination of enones. Compared to other hydroxylamine derivatives that
typically are stored as hydrochloride salts, this activated phosphinyl reagent exhibits good
◦
stability and can be stored indefinitely at 0 C.
DPPH is prepared in a single step from hydroxylamine hydrochloride and
6
diphenylphosphinic chloride (1). However, the general and most used procedure, de-
1
veloped by Colvin et al., is not reliable. Yields ranging from 42% to a maximum of 70%
have been reported using this method.7,8 In our hands, we found Colvin’s method to be sen-
sitive to reaction scale, with multigram attempts generally delivering DPPH in ca. 30–60%
9
yield. Our interest in aminooxy chemistry led us to develop a reproducible, higher yield
synthesis of DPPH. We report herein a convenient procedure for the preparation of DPPH
on multigram scale.
10
Adaptationof Schotten-Baumannconditions using a two-phase solvent system helped
minimize hydrolysis of starting chloride 1 prior to its reaction with hydroxylamine and
afforded DPPH in 78% yield on a 10-gram scale. The yield of DPPH formed using these
conditions did not vary significantly when the reaction scale was decreased (e. g., 4-gram
scale gave an 84% yield of DPPH). Product purity, generally compromised by the presence
31
of Ph2P(O)OH prior to base treatment, was readily assessed using P NMR (CDCl3):
DPPH, δ 37.5; Ph2P(O)OH δ 28.3.
Experimental Section
To a stirred solution (mechanical stirring) of hydroxylamine hydrochloride (6.46 g, 93.0
◦
mmol) in water (20 mL) at −10 C was added a solution of sodium hydroxide (3.55 g,
Submitted May 20, 2011.
Address correspondence to Michael H. Nantz, Department of Chemistry, University of Louisville,
Louisville, KY 40208, USA. E-mail: michael.nantz@louisville.edu
475

476
Laulh e´ and Nantz
O
O
i, ii
P Cl
P ONH2
1
DPPH
Figure
Conditions: i. HONH
2
·HCl (2.2 equiv.), NaOH (2.1 equiv.), 4.5:1 Et
2 2
O:H
O, −15 ◦ to −0 C,
◦
◦
2
5 min; ii. 0.25 M NaOH, 0 C, 30 min.
8
8.7 mmol) in water (20 mL). Diethyl ether (180 mL) was then added and the biphasic
◦
mixture was further cooled using an ice-methanol bath (ca. −15 C). Diphenylphosphinic
chloride (10.0 g, 42.3 mmol) was added rapidly via syringe, and the reaction mixture was
◦
stirred vigorously for 10 min, and then warmed to 0 C and stirred an additional 15 min.
The resultant white slurry was filtered and the retentate was washed successively with cold
water (60 mL) and Et2O (70 mL). The resultant amorphous paste was dried under vacuum to
◦
afford a white powder that then was treated with aq. NaOH (0.25 M, 120 mL) at 0 C for 30
min. The slurry was filtered and the resultant amorphous solid was washed with cold water
(
>
40 mL), and was dried under vacuum 10 h to afford the title compound (7.68 g, 78%) with
31
97% purity by P nmr. Recrystallization of an analytical sample from methanol delivered
◦
6,7
◦
DPPH in crystalline form, mp. 140–141 C, lit. (uncrystallized sample) 130 C (dec); all
spectral data were in agreement with published values: H NMR (400 MHz, CDCl3):
1
31
δ 7.87–7.82 (4H, m), 7.57–7.53 (2H, m), 7.49–7.47 (4H, m), 5.84 (2H, br) ppm; P NMR
162 MHz, CDCl3): δ 37.5 ppm.
(
References
1
2
3
4
5
. E. W. Colvin, G. W. Kirby and A. C. Wilson, Tetrahedron Lett., 23, 3835 (1982).
. W. Kl o¨ tzer, J. Stadlwieser and J. Raneburger, Org. Synth., 64, 96 (1986).
. J. B. Macaulay and A. G. Fallis, J. Am. Chem. Soc., 112, 1136 (1990).
. H. Schmidhammer, D. Obendorf, G.-F. Pirkner and T. Sams, J. Org. Chem., 56, 3457 (1991).
. A. Armstrong, C. A. Baxter, S. G. Lamont, A. R. Pape and R. Wincewicz, Org. Lett., 9, 351
(2007).
6
7
8
9
. M. J. P. Harger, J. Chem. Soc., Perkin Trans. I, 3284 (1981).
. A. Armstrong, R. D. Pullin, C. R. Jenner and J. N. Scutt, J. Org. Chem., 75, 3499 (2010).
. G. R. Cook, R. Kargbo, and B. Maity, Org. Lett., 7, 2767 (2005).
. S. Biswas, X. Huang, W. R. Badger, and M. H. Nantz, Tetrahedron Lett., 51, 1727 (2010).
1
0. T. W. Bell, S. Anugu, P. Bailey, V. J. Catalano, K. Dey, M. G. B. Drew, N. H. Duffy, Q. Jin, M. F.
Samala, A. Sodoma, W. H. Welch, D. Schols and K. Vermeire, J. Med. Chem., 49, 1291 (2006).