1H-1,3-benzazaphospholes: The organometallic route and a new three-step synthesis with reductive ring closure

Article abstract of DOI:10.1055/s-1999-3394

Primary and N-secondary 2-phosphanylanilines were synthesized via metallation of 2-bromoanilines, coupling with CIP(NMe₂)₂, alcoholysis and reduction with LiAlH₄, and subsequently reacted with formimidoester hydrochloride to give 1,3-benzazaphospholes. For 1H-1,3-benzazaphospholes, a shorter alternative three-step synthesis was developed, based on N-acylation of 2-bromoaniline, NiCl₂-catalyzed arylation of triethyl phosphite and a new reductive cyclization of amidophosphonic acid ester with excess LiAlH₄.

Full text of DOI:10.1055/s-1999-3394

264
PAPER
1H-1,3-Benzazaphospholes: The Organometallic Route and a New Three-Step
Synthesis with Reductive Ring Closure
Raj K. Bansal,a Neelima Gupta,a,b Joachim Heinicke,b* George N. Nikonov,c Farida Saguitova,b,c Dinesh C. Sharma a,b
a
Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
Fax +91(141)652784
b
Institut fŸr Anorganische Chemie, UniversitŠt Greifswald, 17487 Greifswald, Germany
Fax +49(3834)864319; E-mail: heinicke@rz.uni-greifswald.de
A.E. Arbuzov Institute of Organic and Physical Chemistry, ul. Arbuzova 8, Kazan 420083, Russia
c
Fax +7(8432)752253; E-mail: nikonov@glass.ksu.ras.ru
Received 2 July 1998; revised 7 August 1998
not interfere with the further reaction of 2 with formimi-
Abstract: Primary and N-secondary 2-phosphanylanilines were
doester hydrochloride affording the non-basic 1H-1,3-
synthesized via metallation of 2-bromoanilines, coupling with
benzazaphosphole 3, which can easily be purified.
ClP(NMe2)2, alcoholysis and reduction with LiAlH4, and subse-
quently reacted with formimidoester hydrochloride to give 1,3-
benzazaphospholes. For 1H-1,3-benzazaphospholes, a shorter alter-
native three-step synthesis was developed, based on N-acylation of
2-bromoaniline, NiCl2-catalyzed arylation of triethyl phosphite and
a new reductive cyclization of amidophosphonic acid ester with ex-
cess LiAlH4.
Scheme 1
Key words: C,N-dilithium reagent, phosphanylaniline, amido-
arylphosphonate, reductive cyclization, 1,3-benzazaphosphole
For N-substituted derivatives, the following reaction se-
quence was established. 2-Bromo-N-acylanilides 4, ob-
tained from 1,were reduced with LiAlH4 to give N-alkyl-
2-bromoanilines 5. The latter were dilithiated and reacted
The complex chemistry of phospholes and phosphole an-
with ClP(NMe2)2 to give 6 which were converted to 7 with
ethanol. Then 7 was reduced to 8 with LiAlH4 and the lat-
ter underwent cyclocondensation with formimidoester hy-
drochloride affording the N-alkyl-1,3-benzazaphospholes
9 (Scheme 2). Shortcomings of these procedures were low
yields in the substitution of the tri- or dilithium com-
pounds if the reactions were carried out on a larger scale.
ions has found considerable interest in recent years.1,2 Lit-
tle is known, however, about metal derivatives or
complexes of related 1,3-azaphospholes3 or annulated
azaphospholes.4Ð7 The early papers presented an interest-
ing ambident reactivity of the ÒNÓ-lithiated and the first
stable RP=C(Li)-X species, but since then no further work
on these compounds has been reported.8 One of the rea-
sons may be the cumbersome synthetic access of aza-
phospholes8 and benzazaphospholes4,5 by multi-step
procedures. We describe here in more detail the organo-
metallic route5 and a new and shorter way to prepare 1H-
1,3-benzazaphospholes.
The original synthesis of 1H-1,3-benzazaphospholes was
based on cyclocondensations of various carbonic acid de-
rivatives with 2-phosphanylanilines. The latter were pre-
pared by photoinitiated MichaelisÐBecker reaction of
sodium diethyl phosphite with 2-iodoaniline in liquid am-
monia and subsequent reduction with LiAlH4.9 For further
Scheme 2
studies of benzazaphospholes, we explored a preliminary
reported organometallic route5 with respect to a more gen-
A further disadvantage is the easy replacement of bromine
eral use in the synthesis of 2-phosphanylanilines. 2-Bro-
by hydrogen during the reduction of 4 with LiAlH4 which
moaniline (1) was reacted successively with three
therefore requires careful control of the reaction condi-
equivalents of butyllithium, phosphorous acid bis(dimeth-
tions. To overcome these problems, we investigated a
ylamide) chloride and ethyl alcohol in a one-pot reaction.
primary PÐC coupling by NiCl2-catalyzed arylation of tri-
After removal of volatile components (bath temperatutre
ethyl phosphite with 2-bromoaniline (1) and the N-acyl
100¡C/0.01 Torr), the resulting mixture was reduced with
excess LiAlH4 to give 2-phosphanylaniline 2 in a total
derivatives 4. Metal-catalyzed arylations of phosphites
were described by Tavs10 and reported to be useful for aryl
yield of 30% (Scheme 1). Small impurities of secondary
halides activated by electron-withdrawing substituents.10Ð12
phosphanes could not be removed by distillation but did
Synthesis 1999, No. 2, 264Ð269 ISSN 0039-7881 © Thieme Stuttgart á New York

PAPER
1H-1,3-Benzazaphospholes
265
Later, bromobenzene13 and even 4-bromoanisole14 were steric shielding, is partly attacked by 10% sulfuric acid
used in this reaction. Our attempts to react 2-bromoaniline and forms diastereoselectively the water adduct 11c. The
2
3
(1) with triethyl phosphite in the presence of NiCl2 did not two bond coupling constants JPH = 19.8 Hz and JHH
=
lead to PÐC bond formation. At high temperature (180Ð 3.9 Hz of the hydrogen in position 2 are consistent with an
220¡C), we observed the formation of HP(O)(OEt)2, E-configuration with 2-H and oxygen at phosphorus on
HP(O)(OEt)(NHC6H4Br) and smaller amounts of a di- the same side15. Compound 11c was separated from 8c
1
amide and other products (31P NMR: d = 7.6, dp, JPH
=
=
and smaller amounts of E/Z-2-tert-butyldihydro-1,3-ben-
zazaphosphole by distillation and subsequent recrystalli-
692 Hz, 3JPH = 9.1 Hz; d = 4.6, dt, 1JPH = 646 Hz, 3JPH
7.9 Hz; d = 2.7, d, 1JPH = 659 Hz). However, the reaction zation or by repeated recrystallization from hexane.
of the N-acylated derivatives 4bÐd with triethyl phosphite
in the presence of NiCl2 proceeded smoothly and fur-
nished high yields of N-acyl-2-aminobenzenephosphonic
acid ester 10bÐd. The reaction of 4b with triisopropyl
phosphite gave similar results, whereas in the case of 4c
thermal decomposition (gas evolution) and formation of
the respective phosphonic acid was observed. The 2-bro-
moformanilide 4a reacted in a different way and under-
went, at 180Ð200¡C, a vigorous condensation affording
Hexane, Et2O, THF and toluene were dried under argon with sodi-
um/benzophenone and freshly distilled from the ketyl solutions be-
fore use. All reactions except the N-acylations of 2-bromoaniline
(1) were carried out under an atmosphere of purified argon using
an insoluble brown polymer. The reduction of 10bÐd with
standard Schlenk techniques. Melting points were uncorrected.
excess LiAlH4 (2.5 equivalents) in Et2O at 0Ð10¡C pro-
vided small amounts of the expected N-secondary 2-phos-
phanylanilines 8bÐd. The main products, however, were
1H-1,3-benzazaphospholes 3bÐd (Scheme 3) which thus
are available now in a three-step procedure. The key
step in the formation of the heterocycles is probably a
base-catalyzed cyclocondensation of a primarily formed
o-phosphanylanilide in competition with its reduction to
8bÐd. This is supported by the failure of attempts to pre-
pare o-phosphanylacetanilide using a smaller amount of
LiAlH4 (1.5 equiv) which, instead, gave mainly a mixture
of unreacted 10b and 8b. Furthermore, the high excess of
the reducing agent should favor the reduction of the amide
function relative to the condensation unless it also cata-
lyzes the condensation. It seems reasonable that interme-
diately formed phosphides undergo instantaneous ring
closure to ÒNÓ-metallated benzazaphospholes. The l3-
P=C compounds resist an extensive reduction by the reac-
tive hydride underlining the high stabilization of the p-ex-
cess heteroaromatic 1,3-benzazaphospholate system.
Only small amounts of 2,3-dihydro-1,3-benzazaphosp-
holes were observed (R = Me and t-Bu) which increased
if the reduction was carried out at room temperature.
NMR data were recorded on a multinuclear FT-NMR spectrometer
ARX300 (Bruker) at 300.1 (1H), 75.5 (13C), and 121.5 MHz (31P)
with reference to TMS and H3PO4 (85%), respectively. CDCl3 was
used as solvent unless otherwise indicated. Mass spectra (EI, 70eV)
were measured on a single focussing sector-field mass spectrometer
AMD40 (Intectra).
2-Bromoanilides 4a,16 4b,17 4d18 and the aniline derivative 5a16
were prepared according to known procedures.
2-Bromoanilides 4bÐd; General Procedure16Ð18
To a solution of 1 (29.0 g, 169 mmol) and Et3N (23.5 mL) in Et2O
(300 mL) was added dropwise an equimolar amount of the respec-
tive carboxylic acid chloride at 0Ð5¡C with stirring. After 2d the
mixture was filtered and the precipitate thoroughly washed with
Et2O. Evaporation of the solvent in vacuo furnished the crude
amides which were sufficiently pure for direct use.
The new compound 4c was obtained by using pivaloyl chloride;
yield: 84%: mp 56Ð58¡C. NMR data of 4bÐd are given for compar-
ison with respective phosphorus compounds.
4b
1H NMR (CH-COSY): d = 2.44 (s, 3 H, CH3), 6.97 (ÒtÓd, 3J = 7.8
Hz, 4J = 1.4 Hz, 1 H, H-4), 7.31 (ÒtÓd, 3J = 7.8 Hz, 4J = 1.4 Hz, 1 H,
H-5), 7.53 (dd, 3J = 8.0 Hz, 4J = 1.4 Hz, 1 H, H-3), 8.34 (br d, 3J =
8.1 Hz, 1 H, H-6), 7.60 (br, 1 H, NH).
13C NMR: d = 24.8 (CH3), 113.2 (Cp-2), 121.9 (C-6), 125.1 (C-4),
128.3 (C-5), 132.1 (C-3), 135.6 (Cq-1).
4c
3
4
1H NMR: d = 1.35 (s, 9 H, CH3), 6.95 (ÒtÓd, J = 7.5 Hz, J =
1.6 Hz, 1 H, H-4), 7.29 (ÒtÓd, 3J = 7.9 Hz, 4J = 1.3 Hz, 1 H, H-5),
7.52 (dd, 3J = 8.1 Hz, 4J = 1.6 Hz, 1 H, H-3), 8.39 (dd, 3J = 8.2 Hz,
4J = 1.6 Hz, 1 H, H-6), 8.00 (br, 1 H, NH).
4d
Scheme 3
3
4
1H NMR: d = 7.01 (ddd, J = 8.1, 7.4 Hz, J = 1.6 Hz, 1 H, H-4),
7.35 (m, 3J = 8.4, 7.4 Hz, 4J = 1.4 Hz, J = 0.3 Hz, 1 H, H-5), 7.48Ð
7.60 (m, 4 H, H-3 and C6H5), 7.94 (dm, J = ca. 8 Hz, J = ca.
1.3 Hz, 2 H, H-o), 8.47 (br, 1 H, NH), 8.55 (dd, J = 8.3 Hz, J =
1.6 Hz, 1 H, H-6).
3
4
The separation of 3b and 3d from the phosphanylanilines
8b or 8d and impurities like dihydro-1,3-benzazaphos-
pholes was accomplished by extraction of the latter with
dilute cold sulfuric acid. The 1H-benzazaphospholes re-
main in the solvent (diethyl ether) phase. They are not ba-
sic since the lone electron pair at nitrogen takes part in the
aromatic delocalization. The somewhat more basic 2-tert-
butyl-1,3-benzazaphosphole (3c), although with highest
3
4
2-Phosphanylaniline (2)
A 1.55 M hexane solution of BuLi (70 mL of a total of 100 mL,
155 mmol) were added dropwise at Ð40¡C to a solution of 1 (8.2 g,
48 mmol) in Et2O (50 mL). Then the residual amount of BuLi
(30 mL) was added rapidly and the mixture stirred for 3 h at r.t. Af-
Synthesis 1999, No. 2, 264–269 ISSN 0039-7881 © Thieme Stuttgart · New York

266
R. K. Bansal et al.
PAPER
ter cooling to Ð40¡C, ClP(NMe2)2 (24.0 g, 155 mmol) was added
dropwise. The suspension was stirred overnight, filtered and the
precipitate thoroughly washed with Et2O. Removal of the solvent
from the filtrate gave an oil which exhibited in 31P NMR three main
signals in the CPN2 (d = 94.9, 99.7, 102.7) and PN3 regions (d =
122.6, 122.9, 123.0) and a smaller amount of a PÐP compound [d =
73.2, 21.9 (br), JPP = 253 Hz]. Excess absolute EtOH (17 mL) was
added and the mixture heated for 3 h at 60¡C. Then, all volatile
compounds were removed in vacuo (0.01Torr). Et2O (100 mL) was
added and the resulting suspension was poured in small portions to
LiAlH4 tablets (3.0 g, 79 mmol) stirred in Et2O (100 mL). Stirring
was continued for 2 d at r.t. to complete the reduction. Then, in or-
der to hydrolyze phosphides, amides and excess hydride, degassed
H2O was added dropwise at 5Ð10¡C until evolution of H2 ceased.
The precipitate was removed by filtration, the filtrate was dried
(Na2SO4) and the solvent evaporated. Distillation of the residue at
110Ð118¡C/1 Torr gave 1.8 g (ca. 30%) of 2 contaminated with a
small amount of two other anilines. Typical NMR signals: 1H
NMR: d = 3.38 (d, 1JPH = 199 Hz, PH2); 31P NMR: d = Ð152.7 (cf.
Ref.4).
cous oil; bp 122Ð127¡C/0.01 Torr. (The first fraction, 9 g of an oil
of bp 90Ð122¡C/0.01 Torr, consisted also mainly of 6a.)
31P NMR (40.5 MHz, no solvent): d = 97.6 (br, CPN2), 117.5 (br,
NPN2).
C15H31N5P2 calcd
(343.4) found
N
20.39
20.30
P
18.04
18.15
2-(Me2N)2PC6H4N(Et)P(NMe2)2 (6b)
A solution of 5b (11.6 g, 57.85 mmol) in Et2O (100 mL) was di-
lithiated (80 mL BuLi, 1.45 M, 116 mmol) and reacted at Ð40¡C
with ClP(NMe2)2 (17.9 g, 116 mmol) as described above; yield:
11.0 g (55%); bp 110Ð115¡C/0.001 Torr.
3
1H NMR (C6D6): d = 0.99, 1.04 (2 t, CH3, B/A), 2.40 (d, JPH
=
9.3 Hz, PNMe2, B), 2.48 (d, 3JPH = 8.9 Hz, PNMe2, B), 2.52 (d, 3JPH
= 9 Hz, 12 H, PNMe2, A), 2.59 (d, 3JPH = 8.4 Hz, 12 H, PNMe2, A),
3.39 (m, NCH2
, B), 3.53 (m, NCH , A), 7.10Ð7.25 (m, 3 H, H-4 to
2
6), 7.82 (m, 1 H, H-3); intensity A:B = ca. 2:1.
31P NMR (C6D6): d = 98.4 (CPN2), 117.7 (NPN2), 4JPP = 19.4 Hz.
1H-1,3-Benzazaphosphole (3a)
N-Methylaminobenzenephosphonous Acid Diethyl Ester (7a)
Compound 6a (49.0 g, 142.7 mmol) was added rapidly to absolute
EtOH (45 mL, 1.24 mol) resulting in a moderate reaction and evo-
lution of Me2NH. The temperature was slowly raised to 70¡C and
kept there for 3 h. Then the solution was heated for 15 min to 110Ð
140¡C and distilled in vacuum to give 24.7 g (76%) colorless liquid
7a; bp 90Ð92¡C/0.01 Torr.
To a solution of 2 (1.8 g, 14.4 mmol) in absolute MeOH (5 mL) was
added a solution of formimidomethylester hydrochloride (1.7 g,
17.8 mmol) in MeOH. The mixture was allowed to stand overnight,
NH4Cl formed and was separated and the solvent removed. The
crude 1H-1,3-benzazaphosphole was recrystallized from hexane af-
fording 1.2 g (62%) of nearly colorless solid; mp 101Ð103¡C (Lit.4
mp 102Ð103 ¡C).
1H NMR (C6D6): d = 7.02 (ÒtÓm, 3J = ca. 7Ð8 Hz, 1 H, H-5), 7.09
(dm, 1 H, H-7), 7.18 (ÒtÓm, 1 H, H-6), 7.97 (dd, JHH = 4.7 Hz, 2JPH
= 38.2, 4J = 1 Hz, 1 H, H-2), 8.20 (ddd, 3J = 7.8 Hz, 3JPH = 3.6, 4J =
1 Hz, 1 H, H-4), (NH appeared at >10).
31P NMR (CDCl3): d = 166.1.
C11H18NO2P calcd
(227.2) found
N
6.16
5.97
P
13.63
13.45
N-Methyl-2-phosphanylaniline (8a)
31P NMR (C6D6): d = 82.6.
A solution of 7a (24.0 g, 105.6 mmol) was added dropwise at
0Ð5¡C to a suspension of LiAlH4 (5.5 g, 1.447 mol) in Et2O
(100 mL), stirred overnight at r.t. and refluxed for 2 h. The mixture
was hydrolyzed with H2O at 5Ð10¡C until the H2 evolution was
slow, the suspension filtered and the filtrate dried (Na2SO4). Distil-
lation furnished 8.6 g (57%) of 8a; 66Ð71¡C/0.1 Torr.
1H NMR (100 MHz, CDCl3): d = 2.83 (br, 3 H, CH3), 3.48 (d, 1JPH
= 200 Hz, 2 H, PH2), 3.92 (br, 1 H, NH), 6.50Ð6.75 (m, 2 H, H-6,4),
7.15Ð7.55 (n, 2 H, H-5,3).
2-Bromo-N-ethylaniline (5b)
To a suspension of LiAlH4 tablets (13 g, 342 mmol) in Et2O
(200 mL) was added dropwise a solution of 4b (68.0 g,
317.7 mmol) in Et2O (100 mL) at 0Ð10 ¡C. The mixture was stirred
at r. t. and the progress of the reduction controlled by NMR spec-
troscopy. (Usually, about 3 d are necessary to achieve good yields.
Reflux or prolonged reaction time caused partial replacement of Br
by H) Then the mixture was hydrolyzed by dropwise addition of
H2O until the H2 evolution ceased. The precipitate was separated
and thoroughly washed with Et2O and the organic solution dried
(Na2SO4). Et2O was stripped off to give 5b (46.2 g, 73%); bp 50Ð
56¡C/0.01 Torr.
1H NMR: d = 1.30 (t, 3J = 7.1 Hz, 3 H, CH3), 3.18, 3.19 (q, 3J = 7.1
Hz, 2 H, NCH2), 4.19 (br, 1 H, NH), 6.54 (ÒtÓd, 3J = 7.5, 7.7 Hz, 4J
= 1.4 Hz, 1 H, H-4), 6.61 (dd, 3J = 8.1 Hz, 4J = 1.4 Hz, 1 H, H-6),
7.16 (ÒtÓd, 3J = 7.6, 8.1 Hz, 4J = ca. 1 Hz, 1 H, H-5), 7.40 (dd, 3J =
7.9 Hz, 4J = 1.4 Hz, 1 H, H-3).
31P NMR (C6D6): d = Ð150.0.
IR (film): n = 2280 (s, PH2), 3400 cmÐ1 (br, NH).
C7H10NP
(139.1)
calcd
P
22.26
21.90
found
N-Ethyl-2-phosphanylaniline (8b)
EtOH (16 mL) was added to 6b (16.04 g, 50 mmol) at 40Ð50¡C
whereupon evolution of Me2NH was observed. The mixture was
heated for 3 h at 60Ð70¡C, and the volatiles were removed in vacu-
um (120¡C/0.01 Torr). The residue (7b) was dissolved in Et2O
(30 mL) and added dropwise to LiAlH4 (3 g, 78.9 mmol) in Et2O
(200 mL) at 0Ð10¡C. Workup as above yielded 4.0 g (52%) of col-
orless 8b; bp 42Ð45¡C/0.001 Torr.
1H NMR (C6D6): d = 0.88 (t, 3J = 7.2 Hz, 3 H, CH3), 2.77 (m, 3J =
7.2 Hz, 2 H, NCH2), 3.39 (d, 1JPH = 198 Hz, 2 H, PH2) 3.70 (br, NH),
6.44 (d, 3J = 8.1 Hz, 1 H, H-6), 6.63 (ÒtÓ, 3J = ca. 7Ð8 Hz, 1 H, H-
4), 7.21 (m, 3J = ca. 8 Hz, 1 H, H-5), 7.52 (ddd, 1 H, H-3).
2-(Me2N)2PC6H4N(Me)P(NMe2)2 (6a)
PCl3 (11.6 mL, 133.3 mmol) was added dropwise with stirring to
P(NMe2)3 (48.5 mL, 266.7 mmol) at 60¡C, kept 1 h at this temper-
ature and then stirred for 4 h at r.t. affording ClP(NMe2)2. Mean-
while, 5a (37.2 g, 200 mmol) was dissolved in Et2O (300 mL) and
dilithiated at Ð50¡C by the addition (the first half dropwise) of a so-
lution of BuLi in hexane (370 mL, 1.08 M, 400 mmol). The mixture
was stirred for 2 h at r. t. After cooling to Ð65¡C, ClP(NMe2)2 was
added dropwise. The resulting suspension was stirred overnight, the
precipitation separated by filtration and the solvent removed in vac-
uum. The residue was distilled to give 49.9 g (72%) of 6a as a vis-
31P NMR (C6D6): d = Ð154.8.
Synthesis 1999, No. 2, 264–269 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
1H-1,3-Benzazaphospholes
267
1-Ethyl-1,3-benzazaphosphole (9b)
C15H24NO4P calcd
(313.3) found
C
57.50
57.95
H
7.72
7.55
N
4.47
4.11
A
solution of formimidomethylester hydrochloride (3.5 g,
36.6 mmol) in anhyd MeOH (15 mL) was added to a solution of 8b
(3.5 g, 23 mmol) in anhyd MeOH (10 mL). The mixture was al-
lowed to react for 2 d at r.t., the NH4Cl was separated and the filtrate
distilled to give 3.2 g (86%) of 1-ethyl-1,3-benzazaphosphole; bp
60Ð65¡C/0.001 Torr; mp 34Ð35¡C (after distillation).
1H NMR (C6D6): d = 0.78 (t, 3J = 7.2 Hz, 3 H, CH3), 3.40 (q, 3J =
7.2 Hz, 2 H, NCH2), 7.07 (m, 3J = ca. 7, 8 Hz, 4JPH ca. 2 Hz, 4J =
1 Hz, 1 H, 5-H), 7.12 (br d, 3J = ca. 8 Hz, 1 H, 7-H), 7.21 (ddÒtÓ, 3J
= 6.8, 8.5 Hz, 4J = 5JPH = 1.1 Hz, 1 H, 6-H), 8.02 (d, 2JPH = 38.1, 1
H, 2-H), 8.14 (ddm, 3J = 7.5 Hz, 3JPH = 3.9 Hz, J ≤ 1 Hz, 1 H, 4-H).
2-Benzamidobenzenephosphonic Acid Diethyl Ester (10d)
A mixture of 4d (27.5 g, 99.6 mmol) and anhyd NiCl2 (0.1 g) was
heated up to 165¡C in a distillation apparatus while triethylphos-
phite (18.2 mL, 114 mmol) was added dropwise. Then the temper-
ature was raised to 180¡C for 20 min. The residue was distilled in a
short-path distillation device affording 27.4 g (83%) of a syrupy liq-
uid; bp 178Ð182¡C/0.001 Torr.
1H NMR: d = 1.31 (t, 3J = 7.1 Hz, 6 H, 2 CH2CH3), 4.12 (m, 4 H, 2
OCH2CH3), 7.15 (dd ÒtÓ, 3J = 7.5 Hz, 4JPH= 3.1 Hz, 4J = 1 Hz, 1 H,
H-5), ca. 7.50 (m, 3 H, H-4, C6H5), 7.62 (ddd, 3J = 7.8 Hz, 3JPH = ca.
15 Hz, 4J = 1.6 Hz, 1 H, H-6), 7.58 (m, 1 H, C6H5), 8.15 (m, 2 H,
C6H5), 8.61 (ÒtÓ br, 3J = 7.6 Hz, 4JPH = ca. 7.6 Hz, 1 H, H-3), 11.58
(br, 1 H, NH).
13C NMR (C6D6): d = 14.5 (s, CH3), 44.6 (d, J = 2.3 Hz, NCH2),
3
112.6 (s, C-7), 120.2 (d, 3J = 11.7 Hz, C-5), 124.6 (d, 4J = 2.8 Hz,
4
2
C-6), 130.0 (d, J = 21.4 Hz, C-4), 142.2 (d, J = 5.8 Hz, C-7a),
143.4 (d, 1J = 41.1 Hz, C-3a), 160.3 (d, 1J = 53.3 Hz, C-2).
31P NMR (C6D6): d = 75.4.
13C NMR: d = 15.7 (d, 3J = 6.5 Hz, CH3), 62.2 (d, 2J = 5.0 Hz, CH2),
113.4 (d, 1J = 179.6 Hz, C-1), 120.4 (d, 3J = 11.0 Hz, C-3), 122.6 (d,
3J = 13.3 Hz, C-5), 127.0 (s, 2C-m), 128.2 (s, 2C-o), 131.4 (s, C-p),
132.0 (d, 2J = 5.7 Hz, C-6), 133.6 (d, 4J = 1.8 Hz, C-4), 134.0 (s, C-
i), 142.6 (d, 2J = 7.7 Hz, C-2), 164.9 (s, CO).
2-Acetamidobenzenephosphonic Acid Diethyl Ester (10b)
A mixture of 4b (30.0 g, 140 mmol) and anhyd NiCl2 (0.1 g) was
heated up to 170¡C in a distillation apparatus. Triethyl phosphite
(28.2 mL, 148 mmol) was added dropwise maintaining the temper-
ature at 170Ð180¡C. After the addition, the mixture was heated for
10 min up to 190¡C during which time 9.4 g of EtBr was collected.
Distillation of the residue at 110Ð120¡C/0.01 Torr afforded 30.6 g
(81%) of 10b as viscous oil.
31P NMR: d = 20.0 .
C17H20NO4P calcd
(333.3) found
C
61.26
61.11
H
6.05
6.20
N
4.20
4.33
1H NMR (CH-COSY): d = 1.33 (t, 3J = 7.1 Hz, 6 H, 2 OCH2CH3),
2.21 (s, 3 H, CH3), 4.08 (m, 4 H, 2 OCH2CH3), 7.13 (ÒtÓdd, 3J = 7.5,
7.7 Hz, 4JPH= 3.1 Hz, 4J = 1 Hz, 1 H, H-5), 7.53 (m, 3J = 7.5, 8.5 Hz,
2-Acetamidobenzenephosphonic Acid Diisopropyl Ester
A mixture of 4b (31.7 g, 149 mmol) and anhyd NiCl2 (0.1 g) was
reacted with triisopropyl phosphite (37.0 mL, 150 mmol) as de-
scribed for 10b during which process 13.5 g of isopropyl bromide
was distilled out. Distillation of the residue afforded 36.4 g (82%)
of 2-acetamidobenzenephosphonic acid diisopropyl ester as a vis-
cous oil; bp 108Ð118¡C/0.01 Torr.
3
3
4
4J = 1 Hz, 1 H, H-4), 7.57 (ddd, J = 7.7 Hz, JPH = 14.5 Hz, J =
1.5 Hz, 1 H, H-6), 8.61 (ÒtÓ br, 3J = 8.5 Hz, 4JPH = ca 8 Hz, 1 H, H-
3), 10.65 (br, 1 H, NH).
13C NMR: d = 15.9 (d, 3J = 6.2 Hz, CH3), 24.9 (s, CH3), 62.3 (d, 2J
= 4.9 Hz, CH2), 113.1 (d, 1J = 179.3 Hz, Cq-1), 120.4 (d, 3J = 11.7
Hz, C-3), 122.6 (d, 3J = 13.3 Hz, C-5), 132.1 (d, 2J = 5.8 Hz, C-6),
133.7 (d, 4J = 2.1 Hz, C-4), 142.5 (d, 2J = 7.9 Hz, Cq-2), 168.5 (s,
CO).
3
3
1H NMR: d = 1.26 [d, J = 6.2 Hz, 6 H, CH(CH3)2], 1.39 [d, J =
6.2 Hz, 6 H, CH(CH3)2], 2.21 (s, 3 H, CH3), 4.67 (m, 2 H, CH), 7.11
(ddÒtÓ, 3J = 7.5 Hz, 4JPH = 3 Hz, 4J = 0.9 Hz, 1 H, H-5), 7.50 (ÒtÓ, 3J
= 7.8 Hz, 4J = 1 Hz, 1 H, H-4), 7.58 (ddd, 3J = 7.7 Hz, 3JPH = 14.5
Hz, 4J = 1.5 Hz, 1 H, H-6), 8.59 (ÒtÓ br, 3J = 7.5 Hz, 4JPH = 7.5, 1 H,
H-3), 10.74 (br, 1 H, NH).
31P NMR: d = 19.8 .
C12H18NO4P calcd
(271.3) found
C
53.14
52.6
H
6.69
6.60
N
5.16
5.40
13C NMR: d = 23.3 [d, 3J = 4.9 Hz, CH(CH3)2], 23.6 [d, 3J = 3.9 Hz,
CH(CH3)2)], 24.8 (s, CH3), 71.2 (d, 2J = 5.4 Hz, OCH), 114.6 (d, 1J
3
3
= 179.6 Hz, C-1), 120.9 (d, J = 11.6 Hz, C-3), 122.4 (d, J =
13.5 Hz, C-5), 132.2 (d, 2J = 5.6 Hz, C-6), 133.3 (d, 4J = 1.6 Hz, C-
4), 142.1 (d, 2J = 7.9 Hz, C-2), 168.3 (s, CO).
2-Trimethylacetamidobenzenephosphonic Acid Diethyl Ester
(10c)
Triethyl phosphite (12.7 mL, 79.4 mmol) was added dropwise to a
mixture of 4c (17.8 g, 69.5 mmol) and anhyd NiCl2 (0.1 g) while
heating to 180Ð190¡C in a distillation apparatus. After complete ad-
dition, heating (up to 200¡C) was continued for 20 min to give 5.5 g
of condensed EtBr. The remaining mixture was distilled in vacuum
to yield 19.8 g (91%) of 10c as a viscous oil; bp 112Ð115¡C/
0.01 Torr.
31P NMR: d = 17.7.
C14H22NO4P calcd
(299.3) found
C
56.18
55.44
H
7.41
7.20
N
4.68
4.70
2-Methyl-1H-1,3-benzazaphosphole (3b) and 2-Phosphanyl-N-
ethylaniline (8b)
1H NMR: d = 1.33 (br t, 3J = 7.1 Hz, 6 H, 2 OCH2CH3), 1.34 [s, 9
To stirred suspension of LiAlH4 tablets (10 g, 263 mmol) in Et2O
(300 mL) was added dropwise 10b (28.8 g, 106.1 mmol) at 0Ð5¡C.
Stirring was continued at r.t. for 1 d. Then the mixture was hydro-
lyzed at 0Ð5¡C by dropwise addition of degassed H2O until the H2
evolution ceased. Anhyd Na2SO4 was added, the mixture filtered
and the solid thoroughly washed with Et2O. The Et2O phase was ex-
tracted with cold degassed 10% aq H2SO4 (100 mL) to remove 8b.
Then the Et2O layer was washed with H2O until neutral and dried
(Na2SO4). Hexane (10 mL) was added and most of the Et2O was
evaporated in vacuum to give 6.7 g (43%) of 3b, which may be re-
crystallized from hexane; colorless crystals; mp 115Ð116¡C (Lit.4
mp 116Ð117¡C).
H, C(CH3)3], 4.12 (m, 4 H, 2 OCH2CH3), 7.11 (dd ÒtÓ, 3J = 7.6 Hz,
4
3
4
4JPH = 3.1 Hz, J = 1.0 Hz, 1 H, H-5), 7.52 (ÒtÓd, J = 7.4, J =
3
3
4
1.2 Hz, 1 H, H-4), 7.60 (ddd, J = 7.7 Hz, JPH = 14.5 Hz, J =
1.6 Hz, 1 H, H-6), 8.63 (ÒtÓ br, 3J = 7.4 Hz, 4JPH = 7.4, 1 H, H-3),
10.55 (br, 1 H, NH).
13C NMR: d = 16.2 (d, 3J = 6.6 Hz, CH3), 27.5 [s, C(CH3)3], 40.2 (s,
2
1
CMe3), 62.6 (d, J = 5.2 Hz, CH2), 114.0 (d, J = 180.2 Hz, C-1),
121.1 (d, 3J = 11.5 Hz, C-3), 122.8 (d, 3J = 13.8 Hz, C-5), 132.5 (d,
2J = 6.0 Hz, C-6), 133.9 (d, 4J = 2.3 Hz, C-4), 143.0 (d, 2J = 7.2 Hz,
C-2), 177.8 (s, CO).
31P NMR: d = 19.9 .
Synthesis 1999, No. 2, 264–269 ISSN 0039-7881 © Thieme Stuttgart · New York

268
R. K. Bansal et al.
PAPER
1H NMR: d = 2.66 (d, 3JPH = 12.0 Hz, 3 H, CH3), 7.12 (ÒtÓdd, 3J =
ca. 7, 7.6 Hz, 4JPH= 2.1 Hz, 4J = 1 Hz, 1 H, H-5), 7.28 (ÒttÓ, 3J = ca.
31P NMR: d = 30.8 (dm, 1JPH = ca. 500 Hz).
13C NMR: d = 26.5 (d, 3J = 5.9 Hz, C(CH3)3], 33.4 (s, CMe3), 68.0
(d, 1J = 72.4 Hz, C-2), 112.6 (d, 3J = 7.8 Hz, C-7), 113.3 (d, 1J = 99.3
Hz, C-3a), 119.3 (d, 3J = 10.9 Hz, C-5), 130.4 (d, 2J = 7.0 Hz, C-4),
135.0 (d, 4J = 1.8 Hz, C-6), 154.9 (d, 2J = 21.9 Hz, C-7a).
7, 8.2 Hz, 5JPH= 1 Hz, 4J = 1 Hz, 1 H, H-6), 7.50 (dÒqÓ, 3J = 8.2 Hz,
3
4JPH= 1.8 Hz, 4J = 1 Hz, 1 H, H-7), 7.96 (ddd, J = 7.6 Hz, 3JPH
=
3.6, 4J = 1 Hz, 1 H, H-4), 9.06 (br, 1 H, NH).
13C NMR: d = 17.5 (d, 2J = 22.6 Hz, CH3), 113.0 (s, C-7), 120.2 (d,
8c
4
2
3J = 11.4 Hz, C-5), 124.1 (d, J = 2.2 Hz, C-6), 128.2 (d, J =
20.0 Hz, C-4), 141.0 (d, 1J = 42.3 Hz, C-3a), 142.3 (d, 2J = 5.7 Hz,
C-7a), 173.7 (d, 1J = 51.0 Hz, C-2).
1H NMR: d = 1.04 [s, 9 H, C(CH3)3], 2.05 (br s, 1 H, NH), 2.96 (s,
2 H, NCH2), 3.56 (d, 1JPH = 199.4 Hz, 2 H, PH2), 6.55Ð6.65 (m, 2 H,
H-6, H-4), 7.25 (m, 1 H, H-5), 7.45 (m, 1 H, H-3).
31P NMR (CDCl3): d = 73.0 (d = 69.8 in MeOH4).
31P NMR (C6D6): d = 75.5.
31P NMR: d = Ð154.9.
31P NMR (THF-d8): d = 71.1.
2-Phenyl-1H-1,3-benzazaphosphole (3d)
To a stirred suspension of LiAlH4 tablets (8 g, 210 mmol) in Et2O
(250 mL) was added 10d (24.6 g, 73.9 mmol) in small portions at
0Ð5¡C. Stirring was continued at r.t. for 1 d. Then the yellow mix-
ture was hydrolyzed cautiously at 0Ð5¡C by degassed H2O until the
H2 evolution was slow. Anhyd Na2SO4 was added, the mixture was
filtered and thoroughly washed with Et2O. The Et2O phase, contain-
ing 3d and a contamination of 8d (31P NMR: d = Ð157) and two sec-
ondary phosphanes (31P NMR: d = Ð46.9, Ð57.2), was treated with
cold degassed 10% aq H2SO4 (100 mL), washed with a little cold
water and dried (Na2SO4). Hexane (10 mL) was added and most of
the Et2O was evaporated in vacuum to give 11.6 g (74%) of a yellow
solid slightly contaminated with 8d. Spectroscopic pure 3d was ob-
tained by repeated crystallization from a small amount of toluene;
mp 162Ð165¡C (Lit.4 mp 127Ð129¡C).
MS (EI, 70 eV): m/z (%) = 149.4 (100, M+), 148.3 (92), 117.2 (16),
107.2 (22), 77 (20), 57 (26), 39 (30).
The acid extract of 8b was rendered alkaline with excess 10% aq
NaOH solution, 8b was extracted with Et2O (2 × 50 mL) and the
ethereal solution dried (Na2SO4). Evaporation of the solvent afford-
ed 3.0 g (19%) of crude 8b; bp 45Ð50¡C/0.01 Torr.
31P NMR: d = Ð153.3.
2-tert-Butyl-1H-1,3-benzazaphosphole (3c) and 2-Phosphanyl-
N-neopentylaniline (8c)
A solution of 10c (21.3 g, 68 mmol) in Et2O (20 mL) was added
dropwise at 0Ð5¡C to a suspension of LiAlH4 tablets (6 g,
158 mmol) stirred in Et2O (250 mL). Stirring was continued over-
night at r.t. Then the mixture was refluxed for 6 h, cooled to 0Ð5¡C
and hydrolyzed with degassed H2O until the H2 evolution ceased.
Anhyd Na2SO4 was added, the mixture filtered and the solid residue
thoroughly washed with Et2O. Removal of Et2O gave 10.2 g of a
syrupy mixture of 3c and 8c (ca. 3:1) contaminated with a small
amount of phosphanes with 31P NMR: d = Ð84.3, Ð75.6, 31.3. Pure
3c (6.0 g, 46%); mp 113Ð115¡C, was obtained by repeated recrys-
tallization from hexane.
3
4
4
1H NMR: d = 7.04 (ÒtÓm, J = ca. 7, 7.8 Hz, JPH = 2.1 Hz, J =
0.9 Hz, 1 H, H-5), 7.25 (ÒttÓ, 3J ca. 7.5 Hz, 5JPH= 1 Hz, 4J = 1 Hz, 1
H, H-6), 7.25Ð7.42 (m, 3 H, C6H5), 7.61 (dÒqÓ, 3J = 8.3 Hz, 4JPH
=
1.6 Hz, 4J = 0.8 Hz, 1 H, H-7), 7.95 (ddd, 3J = 7.8 Hz, 3JPH = 3.6, 4J
= 1 Hz, 1 H, H-4), 11.70 (br, 1 H, NH).
13C NMR: d = 113.6 (s, C-7), 120.5 (d, 3J = 11.8 Hz, C-5), 125.2 (d,
4J = ca. 2 Hz, C-6), 125.3 (d, 3J = 12.4 Hz, 2C-o), 128.8 (d, 2J = 21.0
Hz, C-4), 128.85 (d, 5J = 2.9 Hz, C-p), 129.1 (s, 2C-m), 134.9 (d, 2J
= 15.8 Hz, C-i), 141.4 (d, 1J = 41.1 Hz, C-3a), 142.9 (d, 2J = 6.7 Hz,
C-7a), 174.4 (d, 1J = 50.6 Hz, C-2).
31P NMR (CDCl3): d = 75.7 (72.1).
31P NMR (THF-d8): d = 75.1.
1H NMR: d = 1.49 [d, 4JPH = 1.2 Hz, 9 H, C(CH3)3], 7.10 (ÒtÓdd, 3J
ca. 7, 7.6 Hz, 4JPH= 2.1 Hz, 4J = 1 Hz, 1 H, H-5), 7.27 (ÒttÓ, 3J = ca.
7, 8.2 Hz, 5JPH= 1 Hz, 4J = 1 Hz, 1 H, H-6), 7.55 (dÒqÓ, 3J = 8.2 Hz,
3
4JPH= 1.8 Hz, 4J = 1 Hz, 1 H, H-7), 7.98 (ddd, J = 7.6 Hz, 3JPH
=
3.6, 4J = 1 Hz, 1 H, H-4), 9.68 (br, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 211.2 (100, M+), 183.2 (19), 107.2 (32),
91 (44).
13C NMR: d = 31.4 [d, 3J = 9.3 Hz, C(CH3)3], 35.8 (d, 2J =13.0 Hz,
CMe3), 113.2 (s, C-7), 120.1 (d, 3J = 10.8 Hz, C-5), 124.3 (d, 4J =
2.2 Hz, C-6), 128.6 (d, 2J = 21.1 Hz, C-4), 140.2 (d, 1J = 41.1 Hz,
C-3a), 142.4 (br, C-7a), 190.2 (d, 1J = 57.4 Hz, C-2).
31P NMR: d = 65.1.
MS (EI, 70 eV): m/z (%) = 191.4 (59, M+), 176.3 (100, M+ Ð Me),
Acknowledgement
We acknowledge support of this work by the Deutsche For-
schungsgemeinschaft and the Fond der Chemischen Industrie.
D.C.S. and N.G. thank the DFG and F.S. the state government of
Mecklenburg Vorpommern for fellowships.
148.3 (20), 144 (22), 136 (21), 135 (22), 107.2 (20).
C11H14NP
(191.2)
calcd
C
69.10
68.65
H
7.38
7.24
N
7.33
7.15
found
References
An attempt to separate 8c from 3c by extraction of the ethereal so-
lution with excess 10% aq H2SO4, washing of the Et2O layer with
H2O and drying with Na2SO4, gave a mixture of 3c and 11c (ratio
ca 1:1) which crystallized from hexane in the same ratio. To isolate
8c, the aqueous phase was rendered alkaline with a 10% NaOH so-
lution, the aqueous phase was extracted with Et2O, the Et2O phase
dried and distilled; bp 50Ð60¡C/0.01 Torr.
(1) Nixon, J. F. Chem. Rev. 1988, 88, 1327.
(2) Mathey, F.; Mercier, F. C. R. Acad. Sci., Ser. IIb 1997, 324,
701.
(3) Heinicke, J. Tetrahedron Lett. 1986, 27, 5699.
(4) Issleib, K.; Vollmer, R.; Oehme, H.; Meyer, H. Tetrahedron
Lett. 1978, 441.
Issleib, K.; Vollmer, R. Z. Anorg. Allg. Chem. 1981, 481, 22.
(5) Heinicke, J.; Tzschach, A. Tetrahedron Lett. 1982, 23, 3643.
(6) Bansal, R. K.; Karaghiosoff, K.; Gupta, N.; Schmidpeter, A.;
Spindler, C. Chem. Ber. 1991, 124, 475.
11c
1H NMR: d = 1.10 [d, 4JPH = 0.9 Hz, 9 H, C(CH3)3], 3.55 (dd, 2JPH
=
19.8 Hz, 3JHH= 3.9 Hz, 1 H, H-2), ca. 5.1 (v br s, 1 H, NH), 6.76 (dd,
3J = 8.3 Hz, 4JPH= 4.4 Hz, 1 H, H-7), 6.84 (ÒtÓd, 3J ca. 7.3, 8 Hz, 4JPH
= ca. 3.4 Hz, 1 H, H-5), 7.37 (ÒttÓ, 3J = ca. 7.3, 8.3 Hz, 5JPH = ca. 4J
= 1Ð1.4 Hz, 1 H, H-6), 7.68 (dd, br 3J ca. 8 Hz, 3JPH = ca. 8Ð9 Hz, 1
H, H-4), 8.26 (dd, 1JPH = 491.4 Hz, 3JHH= 3.9 Hz, 1 H, PH).
(7) Gupta, N.; Jain, C. B.; Heinicke, J.; Bansal, R. K.; Jones, P. G.
Eur. J. Inorg. Chem. 1998, 1079.
(8) Heinicke, J. Trends Organometal. Chem. 1994, 1, 307.
Synthesis 1999, No. 2, 264–269 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
1H-1,3-Benzazaphospholes
269
(9) Issleib, K.; Vollmer, R. Z. Chem. 1978, 18, 451.
(10) Tavs, P. Chem. Ber. 1970, 103, 2428.
(11) Balthazor, T. M.; Miles, J. A.; Stults, B. R. J. Org. Chem.
(15) Bentrude, W. G.; Setzer, W. N. In: Phosphorus-31 NMR Spec-
troscopy in Stereochemical Analysis, Methods in Stereo-
chemical Analysis; Verkade, J. G.; Quin, L.D., Eds.; VCH-
Verlagsgesellschaft: Weinheim, 1987; Vol. 8, p. 365.
(16) Heinicke, J.; Tzschach, A. J.Prakt. Chem. 1983, 325, 511.
(17) Kšrner, W. Gazz. Chim. Ital. 1874, 4, 330.
(18) Chattaway, F. D.; Wadmore, J. M. J. Chem. Soc. 1902, 81,
986.
1978, 43, 4538.
(12) Balthazor, T. M.; Grabiak, R. C. J. Org. Chem. 1980, 45,
5425.
(13) Rakhimov, A. I. Synthesis of Organophosphorus Compounds:
Homolytic Reactions (Russian), Nauka: Moscow, 1985.
(14) Berdnik, I.V.; Sentemov, V.V.; Shagvaleev, F. S.; Zykova, T.
V.; KrasilÕnikova, E. A. Zh. Obshch. Khim. 1988, 58, 302;
Chem. Abstr. 1989, 110, 135 343.
Synthesis 1999, No. 2, 264–269 ISSN 0039-7881 © Thieme Stuttgart · New York