Isatin imines in the reaction with iminophosphine: X-ray structure of phospholane derivatives

Article abstract of DOI:10.1080/00397911.2013.800210

3-Imino-1-methyl-indolin-2-one (2a) reacts with phosphorus hexamethyltriamide 1(1:1 mol) in dry toluene at room temperature to give the dimeric spirophospholane 4a. On the other hand, the reaction of 3-(4-arylimino)-1-methylindoline-2-ones 2b-2c with tris

Full text of DOI:10.1080/00397911.2013.800210

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Isatin Imines in the Reaction with Iminophosphine. X-
Ray Structure of Phospholane Derivatives
Mona Hizkial Nasr Arsanious a & Soher Said Maigali a
a Department of Organometallic and Organometalloid Chemistry , National Research
Centre , Dokki , Giza , Egypt
Accepted author version posted online: 27 Aug 2013.
To cite this article: Synthetic Communications (2013): Isatin Imines in the Reaction with Iminophosphine. X-Ray Structure of
Phospholane Derivatives, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, DOI: 10.1080/00397911.2013.800210
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Isatin imines in the reaction with iminophosphine. X-ray structure of phospholane
derivatives
Mona Hizkial Nasr Arsanious1,*, Soher Said Maigali1
1Department of Organometallic and Organometalloid Chemistry, National Research
Centre, Dokki, Giza, Egypt
Corresponding author: E-mail: mona.arsanious@gmail.com
Abstract
3-Imino-1-methyl-indolin-2-one (2a) reacts with phosphorus hexamethyltriamide1 (1:1
mol) in dry toluene at room temperature to give the dimericspirophospholane4a. On the
other hand, the reaction of 3-(4-arylimino)-1-methylindoline-2-ones 2b-2c with
trisdimethylaminophosphine1 in boiling toluene gave phosphoramides4b, 4c.
Furthermore, 1-benzyl-3-(4-arylimino)indolin-2-one 3a-3c react with aminophosphine1
in excess as solvent at 1100C for 6-8h to give phosphonami5a-5c. Possible reaction
mechanism are considered and the structural assignments are based on spectroscopic date
and X-ray analysis.
KEYWORDS: 1-Isatin-3-imine derivatives, phosphorus hexamethyltriamide,
dimericspirophospholane, dimethylphosphoramides.
INTRODUCTION
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Isatin [2,3-dioxindole] and their derivatives have gained unique importance due to the
broad spectrum of pharmacological activities which are reflected by their use as
antimicrobial, antiviral, anticonvulsant, antioxidant and anticancer agents. [1-4] Isatin
scaffolds are widely used as starting materials for the synthesis of a broad range of
heterocyclic compounds such as indoles and quinolines. They also display a very
interesting class in organophosphorus synthesis, such as organophosphorus derivatives
containing isatin-3-hydrazones which were effective as chemo-therapeutants against
fungle pathogens of sugarcane.[5-8] Moreover, tris(dimethylamino) phosphine attracted
particular interest as a reagent for phosphorus organic synthesis. [9-10] These
observations prompted us to study the reaction of iminophospine1 with isatine imine
derivatives 2 and 3 to produce new phosphorane adducts as part of our continuing interest
in organophosphorus chemistry ( Scheme 1). [11-12]
RESULTS AND DISCUSSION
3-Imino-1-methyl-indolin-2-one (2a) reacts with phosphorus hexamethyltriamide1 (1:1)
mol in dry toluene (30 ml) with stirring at room temperature to give the
dimericspirophospholane4a in a colorless crystalline form with good yield (60%). The
presence of both P=O and P-N(CH3)2groups in structure of 4a was confirmed by
characteristic IR bands at 1230 and 1320, 860 cm-1, respecti-vely. [13] The presence of a
large band at 3200 cm-1 and a medium one at 1627 cm-1 indicates the existence of a NH-P
as well as carbonyl- amide groups. Structure 4a was suggested by its 1H NMR spectrum,
which shows two CH3 protons as a doublet centered at (3.12 ppm) with a large coupling
constant (3JHP = 10.7 Hz) characteristic of PN(CH3)2 group. [14]
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Also, a broad band was present at δ 2.35 in 1H NMR spectrum disappeared with D2O,
characteristic of 2 NH of spirophospholane4a. Conclusive assignment for 4a came from
its 13C NMR spectrum, which showed two peaks at δ 85.2, and 84.6 (2JCP =73.9 Hz)
corresponding to C-3 and C-3\ of the spirophospholane structure.[14] Also,13C NMR
spectrum indicated signal at 26.1 due to substituted methyl groups at position one.
Furthermore, the mass spectrum of the compound 4a confirmed the expected molecular
weight (M+ 1 = 412) corresponding to molecular formula C20H22N5O3P. X-ray Crystal
structure analysis unambiguously confirms the structure 4a (Fig. 1, Table I, II). [15-19]
On the other hand, we have found that the reaction of 3-(4-chlorophenylimino)-1-methyl-
indoline-2-one (2b) with trisdimethylaminophosphine1 in boiling toluene gave colorless
crystalline compound formulated 4b as diindolinoneaminophosphorane structure, by
using column chromatography that allowing its purification and complete characteri-
zation. The assigned phosphoramide structure 4b isbased on the presence of a amino
group NH-R1 band at 3340 cm-1 in its IR spectrum , a D2O exchangeable 1H NMR
spectrum showed signal at a 5.15 ppm, and at 2.92, 3.01 ppm as two doublet due to P-
[N(CH3)2]2 (coupling 3JHP = 10.70 Hz) with phosphorus. The 13C NMR spectrum of 4b
showed peak at δ 85.0 corresponding to C- 3 (2JCP = 73.9 Hz) and C-3\, and at 171.3,
172.6 for 2C=O. Furthermore, the mass spectrum of the compound confirmed the
expected molecular weight (M+ = 676) corresponding to molecular formula C34H35
Cl2N6O3P.
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Similarly, dimethylaminophosphine1 reacts with one mol equivalent of 2c in boiling
toluene to give colorless crystalline compound 4c (Scheme 2). The structure of the
new compound 4careassigned on the basis of its full set of spectral data (cf.
Experimental).
We propose the reaction course for formation of 4a-c, initially neucleophilic attackof
phosphorus imine 1 on the C-3 of isatine imine 2a-c to generate the dipolar intermediate
(A). Molecular rearrangement of (A), followed by addition of another molecule of isatin-
imine 2a-c lead to the formation of the dipolar structure (B), may added molecule of
water (unavoidable moisture), with elimination of two molecules of secondary
methylamine to give the final cyclic form 4a, whereas open structure 4b-c are formed via
elimination of one molecule of secondry amine (Scheme 2). [20]
We have also investigated the reaction of iminophosphine1 with 1-benzyl-3-(4-
arylimino)indolin-2-one 3a-3c to establish whether they would behave in a similar
manner. Thus, we have found that the reaction of 1with 3a and\ or 3b, 3c in excess of
aminophosphine1 as solvent at temperature 1100C for 6-8h to give adducts 5a-c (Scheme
3). The structural assignments for 5a-c were deduced from their elemental analyses, IR,
1H,13C, and mass spectral data (cf. Experimental).
Products 5a-c werepresumablyformed viainitially neucleophilic attackof trisdimethyl-
aminophosphine1 at C-3 of isatine imine 3a-c to generate dipolar intermediate (A) 1:1
mol addition. Molecular rearrangement of (A), followed by added molecule of water
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(unavoidable moisture), with elimination of one molecule of secondary methylamine
lead to the formation of the final form 5a-c (Scheme 3).
Isoindigo[1,1\H-bis(indolyl-3-indeno)-2,2\-dione] and its 1- and 1,1\-substituted deriva-
tives in the recent years attract attention of researchers not only as dyes, but also as the
substances with specific biological activity( antileukemic, antiinflammation and others). [
21,22]
We study the reaction of phosphorus hexamethyltriamide with N-methylisatin. The
reaction proceeds under mild conditions (toluene, 250C) for 1h and leads to the formation
of 6 as deep red crystals (Scheme 4). Structure of isoindigo6 was confirmed by mass
spectrum and X-ray analysis (Fig. 2, Table III, IV).
Fig 2 Molecular structure of 6with aromatic numbering scheme; anisotropic displacement
parameters are drawn at the 30% level and the hydrogen atoms are shown as spheres of
arbitrary radii.
Worthy to mention that dialkylphosphites react with N-methylisatin to form dioxindole-
3-phosphonic esters whereas trialkyl phosphates effect the conversion of isatin into color-
less oxaphosphorane structure. [7b, 8b, 23]
From the results of the present investigation, it could be concluded that the reaction of
phosphorus hexamethyltriamide1 with one molecule of 3-imino-1-methyl-indlin-2-one
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(2a) at room tempera-ture gives the spirophospholane4a, whereas the reaction of 1 with
2b-c in boiling toluene affords the open structure diindolinephosphonate adducts 4b-c .
On the other hand, one molecule of 1-benzyl-3-(4-arylimino)indolin-2-ones (3a-c)
reactswith aminophosphine1 in excess at 110 0C to yield phosphonamide adducts 5a-c.
Spirophospholane4a and phosphoramides4b-c and 5a-c were formed via molecular
rearrangement with elimination of two and one molecule of secondry amine respectively.
1,1\-Methyl-bis(indolyl-3-indeno)-2,2\-dione6 was obtained from the reaction of
trisdimethylaminophosphine1 with N-methyl isatin. The X-ray analysis has confirmed
structures of both compounds 4a and 6. Therefore, these reactions lead to different
products, depending on the reaction conditions as well as the stability of the reaction
intermediates.
EXPERIMENTAL
Melting points were determined in open glass capillaries using an Electrothermal IA 9100
series digital melting point apparatus (Electrothermal, Essex, U.K.) and IR spectra were
measured in KBr pellets with a Perkin- Elmer infracord spectrophotometer model 157.
The 1H-NMR, 13C-NMR, and 31P-NMR spectra were recorded in CDCl3 as a solvent on a
Joel-500(125 MHz) spectrometer respectively, and the chemical shifts were recorded in δ
values relative to TMS as internal reference. The mass spectra were recorded at 70 eV
with a krotos MS equipment or Vario EI Instrument. The reported yields are of pure
isolated materials obtained.
Reaction Of Trisdimethylaminophosphine 1 With Isatin Imine 2a
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Trisdimethylaminophosphine1 (1mmol)was added to a solution of isatin imine 2a
(1mmol)in dry toluene (30 mL), and the resulting mixture was stirring at room
temperature for 4h (TLC) in the presence of atmospheric moisture.[24] After
evaporation of the volatile material under reduced pressure, the residue was subjected to
silica gel column chromatography to give the product 4a
Spirophospholane Adduct 4a
Eluent: petroleum ether- acetone (85/15, v/v). product 4a was obtained as colorless
crytals, yield 60 %, m.p.225-226 oC ; IR (KBr): 3200, 1627,1230, 1320, 860 cm-1 ; H1
NMR δ: 2.86 (s, 6H, 2NCH3-isatin), 3.12(d, 6H, 3JHP = 10.7Hz , P-N[CH3]2), 2.35 (br, 2H,
2NH), 6.59-6.56 (m, 2H, Ar), 7.04-7.01(m, 2 H, Ar), 7.29-7.27 (m, 2H, Ar), 7.78-7.58
(m, 2H, Ar); 13C NMR δ: 26.1(NCH3), 38.0 [(N (CH3)2], 84.8 (d, 2JCP = 73.9 Hz, C-3),
171.3,172.6 (2 CO),144.8, 131.9,128.4,127.2, 123.3, 122.8, 121.9; 31P NMR δ: 15.88 ;
MS(EI): m/z 412 (M+1) ; C20H22N5O3P( 411.39): calcd.C, 58.39; H, 5.39, N, 17.02; P,
7.53 % ; found: C, 57.69; H 5.16; N 16.92; P 7.40 %
X-Ray Crystallographic Study [15-19]: A single crystal of 4a was grown by crystallization
from cyclohexane. The crystal structure was solved and refined, using maXus (Nonius,
Delft and Mac Science, Japan). Mokα (λ= 0.71073 Å) and a graphite monochromator
were used for data collection.
A summary of the crystal analysis parameters is given
in the Table I,II. Details are contained in CCDC file No 84146 at Cambridge
Crystallographic Center.
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Reaction Of Trisdimethylaminophosphine 1 With Isatin Imine 2b-C
Trisdimethylaminophosphine1 (1mmol)was added to a solution of isatin imine 2b or 2c
(1mmol)in dry toluene (30 mL), and the resulting mixture was refluxed for 2-6 h (TLC)in
the presence of atmospheric moisture. [24] After evaporation of the volatile material under
reduced pressure, the residue was subjected to silica gel column chromatography to give
the products 4b-c, respectively.
N-(4-Chlorophenyl)-N,N,N\,N\-Tetramethyl-N-{3-[(4-Chlorophenyl)Amino]-1,1\-
Dimethyl-2,2\-Dioxo-1\,2,2\,3-Tetrahydro-1H,3\H-3,3\-Biindol-3\-Yl}Phosphoric
Triamide4b
Eluent: petroleum ether- acetone (85/15, v/v). product 4b was obtained as colorless
crystals, yield 65 %, m.p.235 oC ; IR (KBr): 3340,1627,1240,1325, 860 cm-1 ; H1 NMR δ:
3
2.60 (s, 6H, 2NCH3), 2.92, 3.01{2d, 12H, JHP =10.7 Hz, P[N(CH3)2 ]2 },5.15( br, 1H,
NH-exchangeable with D2O), 6.07- 6.03(4H, m, Ar),6.59 - 6.55(2H, m, Ar), 6.92 - 6.89
(2H, m, Ar), 6.98 - 6.97 (4H, m, Ar),7.23-7.21(4H, m, Ar); 13C NMR δ: 24.7(NCH3),
36.5[(N(CH3)2], 85.2 ( d, 2JCP =73.9 Hz, C-3), 72.8, 171.3, 172.6 (2CO), 143.8,
131.9,128.4,127.2,124.5, 121.9,119.3; MS(EI): m/z 676(M+) ; C34 H35 Cl2N6O3P (676.56
): calcd. C, 60.27; H, 5.21; Cl, 10.46; N, 12.40 ; P, 4.57 % ; found C 60.40, H, 4.95; Cl
10.15; N, 12.14 , P 4.35 %.
N-(4-Nitrophenyl)-N,N,N\,N\-Tetramethyl-N-{3-[(4-Nitrophenyl)Amino]-1,1\-
Dimethyl-2,2\-Dioxo-1\,2,2\,3-Tetrahydro-1H,3\H-3,3\-Biindol-3\-Yl}Phosphoric
Triamide4c
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Eluent: petroleum ether- acetone (85/15, v/v). product 4c was obtained as colorless
crystals, yield 67 %, m.p. 230 oC ; IR (KBr): 3425, 1620, 1245, 1318, 865 cm-1 ; H1
NMR δ: 2.30 (s, 6H, 2NCH3), 2.85, 3.04 {2d, 12H, 3 JHP = 10.7 Hz, P[N(CH3)2 ]2
},4.91(br,1H,NH exchangeable with D2O), 6.01-6.00(4H, m, Ar), 6.59-6.50 (2H, d, Ar),
6.95-6.94 (4H, m, Ar), 7.23-7.19 (6H, m, Ar); MS(EI): m/z 700 (M+2 ) ;
C34H35N8O7P(698.24 ) : calcd.C,58.45, H 5.05, N 16.04, P 4.43 % ; found C 58.35, H
5.45, N 15.54, P 4.23 %.
General Method
Isatin imine 3a-c (1mmol) were dissolved in excess oftrisdimethylaminophosphine1 (5
mL), and the resulting mixture was heated at 1100C for 6-8 h (TLC),in the presence of
air moisture. [24] After evaporation of the volatile material under reduced pressure, the
residue was subjected to silica gel column chromatography to give the products 5a-c,
respectively.
N-(4-Methoxphenyl)- N,N,N\,N\- Tetramethyl- N\-(1-Benzyl-2-Oxo-2,3-Dihydro-1H-
Indol-3-Yl)-Phosphoric Triamide5a
Eluent: petroleum ether- acetone (80/20, v/v). product 5a was obtained as colorless
crystals, yield 70%, m.p. 180-181 oC ; IR (KBr): 3042 CH2 Benzyl, 1718, 1242, 1320,
860 cm-1 ; H1 NMR δ: 2.40, 2.64 (2d, 12H, 3JHP = 7.50 Hz, 2[N(CH3)2], 3.71
(s,3H,OCH3),4.85 (s, 2H, CH2), 4.70, 4.59 (2d, 1H, 3JHP = 10.5, HC-N–P, asym. mol.25),
6.10- 6.09(m, 3H, Ar), 7.13-6.95(m, 5H, Ar),7.17-7.14 (m, 5H, Ar); 13C NMR δ: 27.0,
46.9, 54.3, 55.2,109.8, 124.3, 127.6, 128.7, 128.5, 135.8,144.8, 144.6,175.2 ; MS(EI):
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m/z 478 ; C26H31 N4 O3P(478.52 ): calcd.C,65.26, H, 6.53,N,11.71, P 6.47; found C,65.13,
H, 6.73,N,11.58, P 6.41%
N-(4-Chlorophenyl)- N,N,N\,N\- Tetramethyl- N\-(1-Benzyl-2-Oxo-2,3-Dihydro-1H-
Indol-3-Yl)-Phosphoric Triamide 5b
Eluent: petroleum ether- acetone (75/25, v/v). product 5b was obtained as pale yellow
crytals, yield 60 %, m.p.190 oC ; IR (KBr): 3049 CH2 Benzyl, 1720, 1246,1320, 870 cm-1
; H1 NMR δ: 2.38, 2.64 (2d, 12H, 2 [(NCH3)2],3JHP = 7.50 Hz) , 4.99 (s, 2H, CH2), 4.70,
4.52 (2d, 1H, 3JHP =10.7 Hz, HC-N –P, asym. mol), 6.40-6.37(m, 3H, Ar), 7.31-7.26 (m,
5H,Ar), 7.17- 7.23(m, 5H, Ar); 13C NMR δ: 25.5, 53.7, 68.4, 119.3, 120.2, 124.5, 127.0,
128.5, 129.0,136.2, 134.9, 141.9, 180.9 ; MS(EI): m/z 482 (M+) ; C25H28 ClN4 O2P
(482.94): calcd.C,62.17, H, 5.84, Cl, 7.34, N, 11.60; P, 6.41 % ; found C,62.52, H,5.70;
Cl, 7.22, N, 11.70,P, 6.30%.
N-(4-Nitrophenyl)- N,N,N\,N\- Tetramethyl- N\-(1-Benzyl-2-Oxo-2,3-Dihydro-1H-
Indol-3-Yl)-Phosphoric Triamide 5c
Eluent: petroleum ether- acetone (70/30, v/v). product 5c was obtained as pale yellow
crystals, yield 75 %, m.p. 173-174oC ; IR (KBr): 3049 CH2 Benzyl, 1246, 1718, 1230,870
cm-1 ; H1 NMR δ: 3.01, 3.17 (2d, 12H, 2[N(CH3)2],3JHP =10.7 Hz), 4.18, 4.59 (2d, 1H,3JHP
= 16.05 Hz, CH-N-P, asym. mol. [24]), 5.00 (s, 2H, CH2-benzyl), 6.53 (d, 1H, Ar), 6.92-6.86
(m, 5H, Ar),7.55 (d, 2H, Ar), 7.23-7.17 (m, 5H, Ar); 13C NMR δ: 24.7, 53.7, 69.6,
119.3,124.2, 127.5, 129.0, 134.9, 136.2, 141.9, 181.7; 31P NMR δ: 22.3; MS(EI): m/z 493
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(M+) ; C25H28 N5O4 P(493.49 ): calcd.C,60.85; H,5.72, N, 14.19, P, 6.28; found C, 60.65;
H,5.20; N, 13.91, P, 6.02 %.
Reaction Of Methyl-Isatin With Trisdimethylaminophosphine
Trisdimethylaminophosphine (1mmol) was added to a solution of methyl-isatin (1mmol)
in dry toluene with stirring for 1-2 h at room temperature. After evaporation of the
volatile material under reduced pressure, the residue was subjected to silica gel column
chromatography to give the Isoindigo6 as red crystals
1,1\-Methyl-Bis(Indolyl-3-Indeno)-2,2\-Dione6
Eluent: petroleum ether- acetone (95/5, v/v). product 6 was obtained as red crystals, yield
75 %, m.p.242.8-243 oC ;MS(EI): m/z (290); C28H27O6P(290.32 ): calcd.C,74.47; H,
4.86; N,9.65 %; found: C,74.87; H, 4.40; N,9.85 %.
X-Ray Crystallographic Study15-19: A single crystal of 6 was grown by crystallization
from cyclohexane. The crystal structure was solved and refined, using maXus (Nonius,
Delft and Mac Science, Japan). Mokα (λ= 0.71073 Å) and a graphite monochromator
were used for data collection.
A summary of the crystal analysis parameters is given
in the Table III, IV. Details are contained in CCDC file No 883831 at Cambridge
Crystallographic Center.
ACKNOWLEDGMENT
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We thank Prof. Dr. Ibrahim S. A. Farag, Department of Solid State Physics, National
Research Centre, Giza, Egypt, and his coworker for doing X-ray diffraction analysis.
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Table 1. X-ray crystallographic analysis of compound 4a
Empirical formula
[C20H22N5O3P]. H2O
Formula weight
429
Wavelength / À
0.71073
Crystal system/space group
a /Å
8.7307 (4)
101.270(2)
α / °
b/Å
10.3102 (4)
99.532(2)
ß / °
c/ Å
12.0167(7)
100.226(3)
γ / °
V / Å3
1021.25(9)
Z
2
D calc (g/cm3)
µ ( mm-1 )
1.396
0.17
Color / Shape
Temp ( K)
Colorless/prismatic
298
Theta rang for collection
Independent reflections
2.910—27.485 °
5762
Data/restraints/parameters 352
Goodness of fit on F2
Final R indices [I>3σ (I)]
Rint 0.038
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R indices (all data)
0.204
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Table 2. Selected Bond Lengths (Å) and Angles (°)
Compound 4a
P1- N2
1.599(4)
1.418(6)
1.232(6)
1.394(7)
94.7(2)
P1- N5
1.600(4)
2.368(6)
1.211(6)
1.456(7)
105.8(2)
113.1 (2)
114.2(5)
P1-O6
1.458 (3)
1.458(7)
1.588(7)
1.351(7)
112.0(2)
42.64(12)
N2-C8
N2- C12
O3-C13
N11-C23
N5-P1-N7
N2-P1-N7
C27-N7-
C29
N7- C29
C8-C12
O4-C19
C10-C14
N2-P1-N5
N2-P1-O6
P1-N2-C8
N11-C13
O6-P1-N5
P1-N2-N5
110.9 (2)
116.4 (3)
P1-N7-C29 124.6(4)
C8-N2-C12 40.6(2)
P1-N2-C12 76.1(2)
P1-N-C27
121.2(4)
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Table 3. X-ray crystallographic analysis of compound 6
Empirical formula
Formula weight
Wavelength / À
Crystal system/space group
a /Å
C18H14N2O2
290
0.71073
7.0086 (2)
90.00
α / °
b/Å
12.3601 (5)
90.00
ß / °
c/ Å
15.7436(8)
90.00
γ / °
V / Å3
1363.82(10)
Z
4
D calc (g/cm3)
µ ( mm-1 )
1.414
0.09
Color / Shape
Temp ( K)
deep red/prismatic
298
Theta rang for collection
Independent reflections
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I>3σ (I)]
2.910—27.485 °
5762
352
0.036
Rint 0.036
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R indices (all data)
0.128
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Table 4. Selected Bond Lengths (Å) and Angles (°)
Compound 6
O1- C10
C8- C11
C17-N3-
C19
1.212 (4)
1.362(5)
124.1(3)
O2- C5
1.223(4)
1.398(5)
124.2(3)
N6-C10
N6- C20
C10-N6-
C20
1.362 (5)
1.459(4)
123.0(3)
N3- C17
O2-C5-N3
C9- N6-C20 125.3 (3)
C9-N6-C10 111.5 (3)
O1-C10-N6 123.4 (3)
C8-C11-
C16
132.9(3)
109.7(3)
C7-C12-
C17
118.1(3)
N3-C17-
C12
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Figure 1.
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Figure 2.
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Scheme 1.
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Scheme 2.
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Scheme 3.
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Scheme 4.
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