A mild one-pot deamination of aromatic amines bearing electron- withdrawing groups. Calcium hypophosphite as a dediazonation reagent in nonaqueous media

Article abstract of DOI:10.1016/S0040-4039(00)00883-2

Diazotization of the title amines with nitrogen dioxide in acetonitrile at -20°C, followed by treatment with calcium hypophosphite in the presence of methanol and catalytic amounts of iron(II) sulfate at room temperature results in the reductive removal of the amino group, giving the corresponding arenes in moderate to good yield. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00883-2

Tetrahedron Letters 41 (2000) 5567±5569
A mild one-pot deamination of aromatic amines bearing
electron-withdrawing groups. Calcium hypophosphite as a
dediazonation reagent in nonaqueous media
Hirokazu Mitsuhashi, Takehiko Kawakami and Hitomi Suzuki*
Department of Chemistry, School of Science, Kwansei Gakuin University, Uegahara, Nishinomiya 662-8501, Japan
Received 8 May 2000; revised 25 May 2000; accepted 26 May 2000
Abstract
ꢀ
Diazotization of the title amines with nitrogen dioxide in acetonitrile at ^20 C, followed by treatment
with calcium hypophosphite in the presence of methanol and catalytic amounts of iron(II) sulfate at room
temperature results in the reductive removal of the amino group, giving the corresponding arenes in moderate
to good yield. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: deamination; diazo compounds; phosphinous acids and derivatives; amines; arenes.
Reductive removal of a nitrogen substituent from organic molecules constitutes an important
process in organic synthesis. For primary aromatic amines, they are diazotized and subsequently
decomposed in the presence of an appropriate reducing agent. Many reagents have been proposed
1
for this purpose, among which hypophosphorous acid is most preferred in the laboratory.
Hypophosphorous acid is commercially available as 30% aqueous solution. It is produced
from calcium hypophosphite Ca(H PO ) , which in turn is manufactured by boiling white phos-
2
2 2
2
phorus in a slurry of lime. Despite being a cheap precursor to hypophosphorous acid, this salt
does not seem to have found use in organic transformation. We wish to report herein that calcium
hypophosphite can be used as a mild deamination reagent for less basic aromatic amines under
nonaqueous neutral conditions.
*
Corresponding author. E-mail: hsuzuki@kwansei.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00883-2

5
568
Recently, we have reported the diazotization of aromatic amines with liquid nitrogen dioxide in
3
nonaqueous media. This method proved to work especially well with less basic amines bearing
electron-withdrawing groups. When calcium hypophosphite was added to the diazotized solution
and stirred for a short time at room temperature, nitrogen was evolved and there resulted the
parent arenes in good to moderate yield (Table 1; entries 1±6). The reductive deamination was
facilitated in the presence of methanol and a transition metal catalyst. The best results were
obtained when the reaction was carried out using 4 equiv. of Ca(H PO ) and 0.2 equiv. of FeS-
2
2 2
.
O 7H O or Cu O in a 6:1-mixture of acetonitrile and methanol (Table 2; entries 1 and 3).
4
2
2
Table 1
Deamination of various aromatic amines with Ca(H PO )
a
2 2
2
Table 2
Optimization of the reductive deamination of 2,4,6-trichloroanilinea
When the reaction was carried out in the presence of methanol-O-d, the product was not
deuterated. In the presence of methanol-d , however, the product was partially deuterated,
4
showing the role of methanol as a competing hydrogen source for aryl radical intermediate.
In summary, calcium hypophosphite can be used as a cheap substitute for hypophosphorous
acid in the deamination of aromatic amines. This one-pot deamination method worked well with
electron-de®cient aromatic amines, but failed with electron-rich ones due to low eciency of
diazotization.

5
569
One-pot deamination of aromatic amines in nonaqueous media. Typical procedure: To a stirred
solution of 2,4,6-trichloroaniline (0.42 g, 2.1 mmol) in acetonitrile (30 ml) was introduced liquid
ꢀ
nitrogen dioxide (0.14 ml, 4.5 mmol) at ^20 C (Fume hood). When diazotization was complete,
.
dried Ca(H PO ) (0.73 g, 4.3 mmol), FeSO 7H O (0.06 g, 0.2 mmol) and methanol (5 ml) were
2
2 2
4
2
added successively, and the resulting suspension was stirred for 30 min at room temperature. The
mixture was diluted with water (30 ml) and the organic phase was extracted with ether (30 mlÂ3).
The combined extracts were washed with brine, dried over Na SO , and evaporated to leave a
2
4
yellow solid, which was puri®ed by chromatography on silica gel using hexane±EtOAc as the
ꢀ
4
ꢀ
eluant to a€ord 1,3,5-trichlorobenzene (0.32 g, 83%), mp 61±63 C (lit. 63.5 C).
References
1
. For a recent review, see: Engel, A. Houben-Weyl Methoden der Organischen Chemie, Vol. E16a/2; Georg Thieme:
Stuttgart, 1990; p. 1052.
2
. Hypophosphorous acid and its salts are commercially used for electrodeless plating of nickel on metallic parts of
electric workpieces.
3
4
. Suzuki, H.; Nonoyama, N. Tetrahedron Lett. 1998, 39, 4533.
. Holleman, A. F. Recl. Trav. Chim. Pays-Bas 1918, 37, 198.