Reactivity of allenylphosphonates and allenylphosphine oxides toward 9-chloroacridines and acridone- A facile route to new N-substituted acridones

Article abstract of DOI:10.1007/s12039-013-0498-3

Base-mediated addition of acridones to allenylphosphonates/allenylphosphine oxides (OCH2CMe2CH2O)P(O)CH=C=CR1R2 {R1 = R2 = Me (1), R1 = R2 = [-CH2- ]5 (2)}, Ph2P(O)C(H)= C=CR1R2 {R1 = R2 = Me (3), R1 = R2 = [-CH2- ]5 (4)} and (EtO)2P(O)C(H)=C=CMe2 (5) in DMF results in the regiospecific formation of phosphono-acridones and acridonylphosphine oxides. The acridone addition products were also obtained in the reaction of allenes 1 and 2 with 9-chloroacridine under [Pd]-catalysed conditions, along with (unexpected) a-acridinyl substituted allenes. In contrast, 9-benzyl-6-chloro-purine reacted with 1 affording a β-substituted purinone phosphonate. Allenes 1-2 did not react with acridones in the absence of base (CsF), but in the presence of Pd(OAc)2/DMF (or DMA)/pivalic acid rearranged to give 1,3-butadienes probably via [Pd]-allyl complexes. The phosphono-acridones were amenable to Horner-Wadsworth-Emmons (HWE) reaction and led to N-substituted acridones. Key products have been characterized by single-crystal X-ray crystallography. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-013-0498-3

c
J. Chem. Sci. Vol. 125, No. 6, November 2013, pp. 1405–1417. ꢀ Indian Academy of Sciences.
Reactivity of allenylphosphonates and allenylphosphine oxides
toward 9-chloroacridines and acridone– A facile route
to new N-substituted acridones
A LEELA SIVA KUMARI, VENU SRINIVAS and K C KUMARA SWAMY∗
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
e-mail: kckssc@uohyd.ac.in; kckssc@yahoo.com
MS received 4 June 2013; revised 16 August 2013; accepted 21 August 2013
Abstract. Base-mediated addition of acridones to allenylphosphonates/allenylphosphine oxides
1
2
1
2
1
2
−
(OCH21CMe2CH2O)P(O)CH=C=CR R {R = R = Me (1), R = R = [−CH2 ]5 (2)}, Ph2P(O)C(H)=
2
1
2
1
2
−
C=CR R {R = R = Me (3), R = R = [−CH2 ]5 (4)} and (EtO)2P(O)C(H)=C=CMe2 (5) in DMF results
in the regiospecific formation of phosphono-acridones and acridonylphosphine oxides. The acridone addition
products were also obtained in the reaction of allenes 1 and 2 with 9-chloroacridine under [Pd]-catalysed con-
ditions, along with (unexpected) α-acridinyl substituted allenes. In contrast, 9-benzyl-6-chloro-purine reacted
with 1 affording a β-substituted purinone phosphonate. Allenes 1–2 did not react with acridones in the absence
of base (CsF), but in the presence of Pd(OAc)2/DMF (or DMA)/pivalic acid rearranged to give 1,3-butadienes
probably via [Pd]-allyl complexes. The phosphono-acridones were amenable to Horner–Wadsworth–Emmons
(HWE) reaction and led to N-substituted acridones. Key products have been characterized by single-crystal
X-ray crystallography.
Keywords. Allenylphosphonate/allenylphosphine oxide; acridone; 9-chloroacridine;
9-benzyl-6-chloro-purine; Horner–Wadsworth–Emmons reaction.
1. Introduction
attack occurred at the β-position of the allenes (cf.
scheme 1, compound 9).6a One of our initial objec-
tives was to utilize the analogous reactions of allenes
with 9-chloroacridine7 to obtain phosphonoacridines,
since substituted acridines [e.g., Amsacrine, a drug
used in acute lymphoblastic leukemia] are phar-
maceutically important.8 However, in our reactions
using allenylphosphonates, we also obtained acridone
(formed by hydrolysis of 9-chloroacridine) addition
products. Acridone derivatives are important synthetic
targets in medicinal chemistry and pharmaceutical
industry and exhibit a variety of biological activi-
ties.9a Recently, Kelly et al. have reported an encour-
aging results with the use of an acridone derivative
against drug-resistant malarial parasites both in vitro
and in mice models.9b,c Studies have also shown
that N-substituted acridone derivatives display high
antiviral activity against the hemorrhagic fever caus-
ing arenavirus JUNV,9d bovine viral diarrhea virus
(BVDV);9e moreover, these derivatives are antago-
nists to P2X4 receptors and have the ability for
the treatment of neuropathic pain and neurodegene-
rative diseases.9f Acridonium-based fluorescent probes
were shown to have the ability of detecting the
anions (like F−, Cl−, AcO−, etc.).9g Apart from these,
Allenes (or 1,2-dienes) are valuable synthons both
industrially and biologically because of the availabili-
ty of two cumulative double bonds.1,2 Allenylphos-
phonates and allenylphosphine oxides (phosphorylated
allenes, e.g., 1–5) that constitute a subclass of allenes
are also used as versatile building blocks in organic
chemistry.3 Our research group has reported that
the nucleophilic addition of amines/nucleobases to
allenylphosphonates by using 1 and related allenes
resulted in the formation of β-aminophosphonates (e.g.,
6–8); here stereochemistry of the products depends on
the type of amine used.4 Recently, rhodium/gold cata-
lysed intermolecular hydroamination of allenes lead-
ing to branched allylic amines has been reported
independently by Kimber et al.,5a Breit et al.5b and
Widenhoefer et al.5c We have previously reported the
synthesis of phosphono-benzofurans,6a,c pyrazoles,3c
–chromenes,6b –oxindoles,6d and indolo-lactones6e by
[Pd]-catalysed reactions from inexpensive phospho-
rylated allenes. In most of the [Pd]-catalysed reac-
tions using iodoarenes, we observed that the initial
∗For correspondence
1405

1406
A Leela Siva Kumari et al.
O
O
O
O
Ph
O
EtO
EtO
P
H
R1
R2
R1
R2
P
P
Ph
Me
Me
H
H
R1 = R2 = Me (1)
R1,R2 = [-CH2-]5 (2)
R1 = R2 = Me (3)
R1,R2 = [-CH2-]5 (4)
5
O
H
H
O
O
H
O
H
O
O
O
O
P
H
H
NH2
P
P
H
H
O
N
H
N
H
N
N
H
H
O
N
6
7
8
NH2
O
C
O
O
O
ArI/Pd(OAc)2
Ph3P/K2CO3/DMF
P
Me
Me
Ar
P
O
Z
C
C
O
H
H
C
C
H
C
C
H
1
9
Me
Scheme 1. Palladium catalysed Heck-type arylation showing the attack at the β-position of allenylphosphonate 1.
10-substituted acridones are used as antipsoriatic Elemental analyses were carried out on a CHN ana-
agents.9h Therefore, there is continuing interest in the lyzer. Mass spectra were recorded using LC-MS and
development of an efficient and versatile methods to HRMS (ESI-TOF) equipment.
access N-substituted acridone derivatives. Thus, in the
Allenylphosphonates 1–3 and allenylphosphine
first part, we report simple base-mediated addition of oxides 4–5 were prepared by literature methods.12
N–H bond of acridone to phosphorylated allenes 1–5 Acridones 10–12 and 9-chloro-acridine were prepared
to give the corresponding phosphonoyl acridone and by following a reported method.13
acridonyl phosphine oxide derivatives in good to high
yields. Since these products are obtained alongside the
2.1 Representative procedure for the synthesis
of acridonyl allylphosphonates/allylphosphine
oxides 13–23
acridinyl allene when [Pd]-catalysed reaction of allenes
with 9-chloroacridines, this part will be discussed
next. This reaction is then compared with that using
9-benzyl-6-chloropurine. In the presence of the [Pd]
catalyst, instead of acridone addition, allene to buta-
diene rearrangement occurs. This is discussed later.
Finally, we have shown that phosphonoyl acridones
can be conveniently utilized to prepare N-substituted
acridones via Horner–Wadsworth–Emmons reaction.10
A mixture of allene (one among 1–5) (1.0 mmol),
acridone (one among 10–12) (1.0 mmol), and CsF
(0.303 g, 2.0 mmol) in DMF (5 mL) was heated at
100◦C for 4–6 h. When the starting material was con-
sumed fully (31P NMR or TLC), the solvent was
removed, reaction mixture quenched with water (5 mL)
and extracted with ethyl acetate (2 × 30 mL). The com-
bined organic layer was washed with water (2×20 mL),
brine solution (20 mL), dried (Na2SO4) and then the
solvent removed to obtain the crude material which
was purified by column chromatography using silica
gel with ethyl acetate/hexane (3:2) mixture as eluent to
afford the corresponding product among 13–23.
2. Experimental
Solvents were dried according to known methods as
appropriate.11 1H, 13C, and 31P NMR spectra (1H,
400 MHz; 13C, 100 MHz; 31P, 162 MHz) were recorded
using a 400 MHz spectrometer in CDCl3 with shifts re-
ferenced to SiMe4 (δ = 0) or 85% H3PO4 (δ = 0).
IR spectra were recorded on an FTIR spectrophotome-
ter. Melting points were determined by using a local
hot-stage melting point apparatus and are uncorrected.
2.1a Compound 13: Yield 0.35 g (86%, Pale yellow
solid) M.p.: 170–172◦C; IR (KBr, cm−1) 3069, 2957,
1
1634, 1601, 1485, 1458, 1264, 1063, 1017. H NMR

N-substituted acridones from allenylphosphonates
1407
(400 MHz, CDCl3) δ 0.73 and 0.91 (2 s, 6H, 2 CH3), δ 20.3, 20.7, 21.3, 22.7, 25.3, 27.6 (d, J(P-C) =
1.52 (d, 3H, J(P-H) = 5.8 Hz, = CCH3(A)), 2.24 135.8 Hz, PCH2), 32.4 (d, J(P-C) = 5.7 Hz, C(Me)2),
(d, 3H, J(P-H) = 4.5 Hz, = CCH3(B)), 3.00 (d, 2H, 75.3 (d, J(P-C) = 5.9 Hz), 75.5 (d, J(P-C) = 6.1 Hz),
J(P-H) = 21.1 Hz, PCH2), 3.34 (dd→t, 2H, J(P-H) = 115.3, 116.7, 119.2, 119.5 (d, J(P-C) = 10.9 Hz),
J(H-H) ∼ 11.2 Hz, OCH2), 3.78 (dd→t, 2H, J(P-H) = 122.2 (d, J(P-C) = 9.2 Hz), 123.3, 127.7, 129.8, 134.1,
J(H-H) ∼ 11.6 Hz, OCH2), 7.32 (t, 2H, J(H-H) = 136.5, 139.4, 140.3, 142.7 (d, J(P-C) = 10.2 Hz), 177.0
7.4 Hz, Ar-H), 7.48 (d, 2H, J(H-H) = 8.8 Hz, Ar-H), (C=O); 31P NMR (162 MHz, CDCl3) δ 19.6; HRMS
7.68–7.72 (m, 2H, Ar-H), 8.56–8.58 (m, 2H, Ar-H). (ESI) Calcd. for C23H26BrNO4P [M++H] 490.0784 and
13C NMR (100 MHz, CDCl3) δ 20.3, 20.8, 21.3, 21.4, 492.0784. Found: 490.0783 and 492.0766.
27.6 (d, J(P-C) = 135.1 Hz, PCH2), 32.4 (d, J(P-C) =
6.0 Hz, C(Me)2), 75.4, 75.5, 116.9, 119.6, 121.9, 122.2,
127.6, 133.8, 140.6, 178.2 (C=O). 31P NMR (162 MHz,
CDCl3) δ 19.5. LC/MS m/z 412 [M+1]+; Anal.Calcd.
for C23H26NO4P: C, 67.14; H, 6.37; N, 3.40. Found: C,
66.95; H, 6.45; N, 3.56.
2.1d Compound 16: Yield 0.38 g (85%, pale yellow
solid). M.p.: 178–180◦C; IR (neat, cm−1) 2964, 2926,
2888, 2241, 1671, 1600, 1375, 1266, 1063, 1014, 734.
1H NMR (400 MHz, CDCl3) δ 0.73 and 0.89 (2 s, 6H,
2 CH3), 1.41 (d, 2H, cyclohexyl-H), 1.59 (br s, 2H,
cyclohexyl-H), 1.86 (br s, 4H, cyclohexyl-H), 2.66
(br s, 2H, cyclohexyl-H), 3.01 (d, 2H, J = 21.2 Hz,
PCH2), 3.32–3.37 (m, 2H, OCH2), 3.75–3.81 (m, 2H,
OCH2), 7.28–7.32 (m, 2H, Ar-H), 7.52–7.55 (d, J =
8.8 Hz, 2H, Ar-H), 7.66–7.70 (m, 2H, Ar-H), 8.56
(d, J = 8.0 Hz, 2H, Ar-H). 13C NMR (100 MHz,
CDCl3) δ 21.3 (d, J(P-C) = 6.3 Hz), 26.0, 26.8,
27.18, 27.23 (d, J(P-C) = 134.9 Hz, PCH2), 29.9,
31.1, 32.3 (d, J(P-C) = 6.0 Hz, CMe2), 75.3 (d,
J(P-C) = 6.2 Hz), 116.1 (d, J(P-C) = 10.8 Hz), 117.0,
121.8, 122.1, 127.4, 133.6, 140.8, 148.8 (d, J(P-C) =
2.1b Compound 14: Yield 0.36 g (85%, green
solid). M.p.: 172–176◦C; IR (KBr, cm−1) 3071,
2973, 1632, 1601, 1495, 1480, 1271, 1059,
1007. 1H NMR (400 MHz, CDCl3) δ 0.74 and
0.94 (2 s, 6H, 2 CH3), 1.52 (d, 3H, J(P-H) =
5.6 Hz, = CCH3(A)), 2.24 (d, 3H, J(P-H) =
4.4 Hz, = CCH3(B)), 2.50 (s, 3H, Ar-CH3), 3.00 (d, 2H,
J(P-H) = 20.8 Hz, PCH2), 3.33–3.38 (m, 2H, OCH2),
3.35–3.80 (m, 2H, OCH2), 7.31 (t, 1H, J(H-H) =
7.6 Hz, Ar-H), 7.40 (d, 1H, J(H-H) = 8.8 Hz, Ar-H),
7.46 (d, 1H, J(H-H) = 8.4 Hz, Ar-H), 7.52–7.55 (m,
1H, Ar-H), 7.68–7.71 (m, 1H, Ar-H), 8.37 (br s, 1H,
Ar-H), 8.57–8.59 (m, 1H, Ar-H). 13C NMR (100 MHz,
CDCl3) δ 20.3 (d, J(P-C) = 3.0 Hz, C=CCH3), 20.7 (d,
J(P-C) = 3.0 Hz, C=CCH3), 20.8, 21.2, 21.4, 27.4 (d,
J(P-C) = 135.0 Hz, PCH2), 32.3 (d, J(P-C) = 6.0 Hz,
C(Me)2), 75.4, 75.5, 116.8 (d, J(P-C) = 12.4 Hz,
PCC=CMe2), 119.7, 119.8, 121.6, 122.0 (d, J(P-C) =
2.0 Hz), 126.7, 127.5, 131.5, 133.5, 135.2, 138.6, 140.4,
142.1, 142.2, 178.0 (C=O). 31P NMR (162 MHz,
CDCl3) δ 19.5. LC/MS m/z 426 [M]+. Anal. Calcd.
for C24H28NO4P: C, 67.75; H, 6.63; N, 3.29. Found: C,
67.85; H, 6.54; N, 3.41.
31
9.8 Hz), 178.1 (C=O). P NMR (162 MHz, CDCl3) δ
19.8. HRMS (ESI) calcd. for C26H31NO4P [M++H]:
452.1991. Found: 452.1992.
2.1e Compound 17: Yield 0.41 g (90%, brown
solid). M.p.: 168–170◦C; IR (KBr, cm−1) 3047,
2959, 2926, 1638, 1600, 1501, 1479, 1337,
1271, 1063, 1019, 816. 1H NMR (400 MHz,
CDCl3) δ 0.73 and 0.90 (2 s, 6H, 2 CH3),
1.40–1.41 (m, 2H, cyclohexyl-H), 1.58 (br s,
2H, cyclohexyl-H), 1.85 (br s, 4H, cyclohexyl-H),
2.47 (s, 3H, CH3), 2.63–2.67 (m, 2H, cyclohexyl-H),
3.01 (d, 2H, J(P-H) = 20.8 Hz, PCH2), 3.35 (t, J =
11.0 Hz, 2H, OCH2), 3.77 (m, 2H, J = 11.4 Hz, 2H,
OCH2), 7.28–7.30 (m, 1H, Ar-H), 7.44 (d, J = 8.4 Hz,
1H, Ar-H), 7.51 (d, J = 8.4 Hz, 2H, Ar-H), 7.65–
7.69 (m, 1H, Ar-H), 8.34 (s, 1H, Ar-H), 8.55 (dd,
2.1c Compound 15: Yield 0.39 g (80%, yellow
solid). M.p.: 160–162◦C; IR (KBr, cm−1) 2964, 2915,
1633, 1595, 1474, 1458, 1266, 1063, 1019, 811.
1H NMR (400 MHz, CDCl3) δ 0.78 and 0.88 (2 s,
6H, 2 CH3), 1.51 (d, 3H, J(P-H) = 5.8 Hz, =
CCH3(A)), 2.23 (d, 3H, J(P-H) = 4.3 Hz, =
CCH3(B)), 2.92–3.08 (m, 2H, PCH2), 3.30–3.47 (m,
2H, OCH2), 3.77–3.87 (m, 2H, OCH2), 7.34 (t,
1H, J(H-H) = 7.4 Hz, Ar-H), 7.43 (t, 2H, J(H-
H) = 8.6 Hz, Ar-H), 7.69–7.76 (m, 2H, Ar-H)
8.56 (d, 1H, J(H-H) = 8.0 Hz, Ar-H), 8.67 (d, 1H,
J(H-H) = 1.6 Hz, Ar-H). 13C NMR (100 MHz, CDCl3)
13
J = 1.4 and 8.8 Hz, 1H, Ar-H). C NMR (100 MHz,
CDCl3) δ 20.8, 21.3 (d, J(P-C) = 10.1 Hz), 26.0, 26.8,
27.15 (d, J(P-C) = 134.8 Hz, PCH2), 27.2, 29.9, 31.0,
32.3 (d, J(P-C) = 6.0 Hz, CMe2), 75.4 (d, J(P-C) =
6.0 Hz), 116.2 (d, J(P-C) = 10.8 Hz), 116.9 (d, 3 J(P-C) =
12.0 Hz), 121.5, 122.0, 126.7, 127.4, 131.5, 133.4,
135.1, 138.9, 140.7, 148.7 (d, J(P-C) = 9.9 Hz), 178.0
(C=O).31P NMR (162 MHz, CDCl3) δ 19.8. HRMS
(ESI) calcd. for C27H32NO4PNa [M++Na] 488.1966.
Found: 488.1961.

1408
A Leela Siva Kumari et al.
2.1f Compound 18: Yield 0.48 g (90%, pale yellow 7.29–7.40 (m, 8H, Ar-H), 7.53 (t, J = 7.1 Hz, 1H,
solid). M.p.: 176–178◦C; IR (KBr, cm−1) 3073, 2937, Ar-H), 8.15 (br s, 1H, Ar-H), 8.34 (d, J = 7.9 Hz,
2849, 1633, 1600, 1474, 1458, 1255, 1058, 1003, 816. 1H, Ar-H). 13C NMR (100 MHz, CDCl3) δ 20.4,
1H NMR (400 MHz, CDCl3) δ 0.79 and 0.91 (2 s, 6H, 20.7 (d, J(P-C) = 15.0 Hz, C=CCH3), 29.7, 33.9 (d,
2 CH3), 1.39–1.43 (m, 2H, cyclohexyl-H), 1.58–1.60 J(P-C) = 67.5 Hz, PCH2), 117.0 (d, J(P-C) = 5 Hz,
(m, 2H, cyclohexyl-H), 1.83–1.88 (m, 4H, cyclohexyl- PCC=CMe2), 120.8 (d, J(P-C) = 10.6 Hz), 121.2,
H), 2.64–2.65 (m, 2H, cyclohexyl-H), 2.92 (dd, J = 121.8, 126.7, 127.4, 128.2 (d, J(P-C) = 11.5 Hz),
21.2 and 6.3 Hz, 1H, PCHA HB), 3.09 (dd, J = 20.9 130.0, 131.1, 131.6, 132.5 (d, J(P-C) = 98.0 Hz, PC),
and 6.3 Hz, 1H, PCHA HB), 3.32–3.47 (m, 2H, OCH2), 132.7, 133.4, 135.0, 138.3, 140.1, 142.0 (d, J(P-C) =
3.79–3.90 (m, 2H, OCH2), 7.30–7.34 (m, 1H, Ar-H) 8.2 Hz), 177.6 (C=O). 31P NMR (162 MHz, CDCl3)
7.49 (t, J = 8.6 Hz, 2H, Ar-H), 7.68–7.75 (m, 2H, Ar- δ 26.6. HRMS (ESI) calcd. for C31H29NO2P [M++H]
H), 8.52–8.54 (m, 1H, Ar-H), 8.65 (d, J = 2.4 Hz, 1H, 478.1937. Found: 478.1934.
Ar-H). 13C NMR (100 MHz, CDCl3) δ 21.3, 25.9, 26.7,
27.1, 27.3 (d, J(P-C) = 135.4 Hz, PCH2), 29.9, 31.0,
2.1i Compound 21: Yield 0.45 g (87%, Yellow
solid). M.p.: 140–142◦C; IR (KBr, cm−1) 3057, 2926,
32.4 (d, J(P-C) = 5.8 Hz, C(Me)2), 75.2 (d, J(P-C) =
6.1 Hz), 75.4 (d, J(P-C) = 6.3 Hz), 115.2, 116.0 (d,
2854, 1643, 1594, 1495, 1435, 1336, 1292, 1177,
1
J(P-C) = 10.9 Hz), 116.9, 119.4, 122.1, 122.2, 123.2,
761. H NMR (400 MHz, CDCl3) δ 1.39–1.46 (m,
127.5, 129.6, 134.0, 136.3, 139.7, 140.6, 149.2 (d,
J(P-C) = 10.0 Hz), 176.8 (C=O). 31P NMR (162 MHz,
CDCl3) δ 19.8. HRMS (ESI) calcd. for C26H30BrNO4P
[M++H] 530.1097 and 532.1097. Found: 530.1098 and
532.1085. This compound was crystallized from ethyl
acetate/hexane (1:1) mixture at 25◦C. X-ray structure
was determined for this compound.
2H, cyclohexyl-H), 1.52–1.60 (m, 2H, cyclohexyl-H),
1.83–1.87 (m, 4H, cyclohexyl-H), 2.42 (s, 3H, Ar-
CH3), 2.77 (br s, 2H, cyclohexyl-H), 3.56 (d, 2H,
J(P-H) = 12.8 Hz, PCH2), 7.09–7.16 (m, 5H, Ar-H),
7.19–7.36 (m, 7H, Ar-H), 7.43–7.54 (m, 3H, Ar-H),
8.16 (s, 1H, Ar-H), 8.34 (d, J = 8.0 Hz, 1H, Ar-H).
13C NMR (100 MHz, CDCl3) δ 14.1, 20.7, 22.7, 26.1,
27.0, 27.6, 29.7, 30.1, 31.2, 32.0, 33.3 (d, J(P-C) =
2.1g Compound 19: Yield 0.39 g (85%, colorless 67.6 Hz, PCH2), 36.7, 117.1, 121.2, 121.8, 126.6,
solid). M.p.: 192–194◦C; IR (KBr, cm−1) 3057, 2957, 127.3, 128.3 (d, J(P-C) = 11.5 Hz, PCC=CMe2),
1
2905, 1634, 1601, 1483, 1433, 1265, 1167, 1117. H 130.0, 131.1, 132.3 (d, J(P-C) = 98.5 Hz, PC), 132.6,
NMR (400 MHz, CDCl3) δ 1.52 (d, 3H, J(P-H) = 133.3, 135.0, 138.7, 140.5, 149.0, 177.7 (C=O). 31P
4.4 Hz, =CCH3(A)), 2.24 (d, 3H, J(P-H) = 4.8 Hz, NMR (162 MHz, CDCl3) δ 26.8. HRMS (ESI) calcd.
=CCH3(B)), 3.60 (d, 2H, J(P-H) = 12.8 Hz, PCH2), for C34H33NO2P [M++H] 518.2249. Found: 518.2247.
7.10–7.14 (m, 4H, Ar-H), 7.18–7.22 (m, 2H, Ar-H),
7.25–7.35 (m, 6H, Ar-H), 7.43 (d, J(H-H) = 8.4 Hz,
2.1j Compound 22: Yield 0.52 g (90%, pale yel-
low solid). M.p.: 194–196◦C; IR (KBr, cm−1) 3057,
2970, 2926, 2854, 1638, 1479, 1332, 1271, 1167,
1123, 750. H NMR (400 MHz, CDCl3) δ 1.35–1.46
2H, Ar-H), 7.56–7.60 (m, 2H, Ar-H), 8.36–8.39 (m,
2H, Ar-H). 13C NMR (100 MHz, CDCl3) δ 20.5, 20.9,
34.0 (d, J(P-C) = 67.7 Hz, PCH2), 117.1, 120.9 (d,
J(P-C) = 9.1 Hz, PCC=CMe2), 121.5, 122.1, 127.5,
128.3, 128.4, 131.7, 132.5 (d, J(P-C) = 99.5 Hz,
PC), 133.6, 140.3, 142.1 (d, J(P-C) = 8.7 Hz), 177.8
(C=O). 31P NMR (162 MHz, CDCl3) δ 26.4. LC/MS
m/z 464 [M+1]+.Anal.Calcd. for C30H26NO2P: C,
77.74; H, 5.65; N, 3.02. Found: C, 77.63; H, 5.58;
N, 3.12; This compound was crystallized from ethyl
acetate/hexane (2:1) mixture at 25◦C. X-ray structure
was determined for this compound.
1
(m, 2H, cyclohexyl-H), 1.60–1.62 (m, 2H, cyclohexyl-
H), 1.83–1.93 (m, 4H, cyclohexyl-H), 2.76 (br s,
2H, cyclohexyl-H), 3.44 (dd, J = 20.1 and 3.8 Hz,
1H, PCHA HB), 3.63 (dd, J = 22.1 and 3.8 Hz, 1H,
PCHA HB), 7.06–7.10 (m, 2H, Ar-H), 7.16–7.20 (m,
2H, Ar-H), 7.23–7.32 (m, 5H, Ar-H), 7.36–7.46
(m, 4H, Ar-H), 7.52–7.55 (m, 1H, Ar-H), 7.60–7.63
(m, 1H, Ar-H), 8.37–8.40 (m, 2H, Ar-H). 13C NMR
(100 MHz, CDCl3) δ 26.0, 26.9, 27.6, 30.1, 31.3,
33.3 (d, J(P-C) = 67.4 Hz, PCH2), 114.9, 117.0,
120.0, 122.1 (d, J(P-C) = 15.6 Hz, PCC=CMe2),
123.0, 127.6, 128.2, 128.3, 128.4, 128.5, 129.5, 130.0,
131.7, 131.8 (d, J(P-C) = 96.8 Hz, PC), 132.5, 133.4,
133.9, 136.0, 139.5, 140.4, 149.4, 176.5 (C=O). 31P
NMR (162 MHz, CDCl3) δ 25.9. HRMS (ESI) calcd.
for C33H30BrNO2P [M++H] 582.1198 and 584.1198.
Found: 582.1193 and 584.1176.
2.1h Compound 20: Yield 0.42 g (88%, brown
solid). M.p.: 110–112◦C; IR (KBr, cm−1) 3058, 2921,
2855, 1638, 1600, 1496, 1441, 1342, 1293, 1189, 1117,
1
729. H NMR (400 MHz, CDCl3) δ 1.48 (d, 3H, J(P-
H) = 4.3 Hz, =CCH3(A)), 2.31 (d, 3H, J(P-H) =
3.0 Hz, =CCH3(B)), 2.42 (s, 3H, Ar-CH3), 3.54 (d, 2H,
J(P-H) = 12.7 Hz, PCH2), 7.06–7.24 (m, 6H, Ar-H),

N-substituted acridones from allenylphosphonates
1409
2.1k Compound 23: Yield 0.35 g (88%, gummy 88.8 (d, J(P-C) = 199.1 Hz, P-C=C=C), 99.3 (d, J(P-
liquid); IR (neat, cm−1) 3069, 2975, 2915, 1638, C) = 16.0 Hz, P-C=C=C), 125.2, 125.3, 126.0, 126.5,
1
1605, 1479, 1458, 1353, 1260, 1030, 767. H NMR 129.8, 130.1, 138.5, 148.9, 211.4. 31P NMR (162 MHz,
(400 MHz, CDCl3) δ 0.90 (t, J = 7.0 Hz, 6H, 2 CH3), CDCl3) δ 8.7. LC/MS m/z 285 [M+1]+; Anal.Calcd.
1.50 (d, 3H, J(P-H) = 5.6 Hz, = CCH3(A)), 2.17 (d, for C23H24NO3P: C, 70.22; H, 6.15; N, 3.56. Found: C,
3H, J(P-H) = 4.4 Hz, = CCH3(B)), 2.96 (d, 2H, J(P- 70.12; H, 6.10; N, 3.61. This compound was crystal-
H) = 22.0 Hz, PCH2), 3.67–3.79 (m, 4H, 2 OCH2), lized from ethyl acetate/hexane (1:1) mixture at 25◦C.
7.27–7.31 (m, 2H, Ar-H), 7.42 (d, 2H, J = 8.4 Hz, Ar- X-ray structure was determined for this compound.
H), 7.65–7.69 (m, 2H, Ar-H), 8.54 (d, 2H, J = 1.2 Hz,
Ar-H). 13C NMR (100 MHz, CDCl3) δ 15.9 (d, J(P-
2.2b Compound 25: Yield 0.09 g (20%, pale brown
C) = 5.8 Hz, OCH2CH3), 20.4 (d, J(P-C) = 21.4 Hz,
solid; combined yield of 16+25 by 31P NMR was
C=CCH3), 29.1 (d, J(P-C) = 141.0 Hz, PCH2), 61.7
(d, J(P-C) = 6.2 Hz, OCH2CH3), 120.7 (d, J(P-C) =
12.2 Hz, PCC=CMe2), 121.7, 122.1, 127.5, 133.5,
140.7, 141.0 (d, J(P-C) = 10.5 Hz), 178.1 (C=O). 31P
NMR (162 MHz, CDCl3) δ 24.2. HRMS (ESI) calcd.
for C22H27NO4P [M++H] 400.1678. Found: 400.1680.
>95%). M.p.: 210–212◦C; IR (KBr, cm−1) 2975, 2926,
2849, 1967, 1539, 1457, 1325, 1260, 1057, 1002, 986,
1
838, 777. H NMR (400 MHz, CDCl3) δ 0.52 and
0.90 (2 s, 6H, 2 CH3), 1.42–1.47 (m, 4H, cyclohexyl-
H), 1.71–1.73 (m, 2H, cyclohexyl-H), 2.24–2.29 (m,
2H, cyclohexyl-H), 2.43–2.48 (m, 2H, cyclohexyl-H),
3.60–3.66 (m, 2H, OCH2), 4.06–4.11 (m, 2H, OCH2),
7.58 (t, J = 7.6 Hz, 2H, Ar-H), 7.79 (t, J = 7.6 Hz,
2H, Ar-H), 8.24 (d, 2H, J = 8.8 Hz, Ar-H), 8.36
(d, J = 8.8 Hz, 2H, Ar-H). 13C NMR (100 MHz,
CDCl3) δ 20.9, 21.3, 25.6, 26.5, 29.7, 32.3 (d, J(P-
C) = 6.0 Hz, CMe2), 75.9 (d, J(P-C) = 6.0 Hz, P-
O-C), 88.2 (d, J(P-C) = 197.0 Hz, P-C), 105.6 (d,
J(P-C) = 15.0 Hz, P-C=C=C), 125.3, 126.0, 126.6,
129.6, 130.1, 138.8, 148.8, 208.1.31P NMR (162 MHz,
CDCl3) δ 8.9. HRMS (ESI) calcd. for C26H29NO3P
[M+H]+: 434.1886. Found: 434.1882. This compound
was crystallized from ethyl acetate/hexane (1:1) mix-
ture at 25◦C. X-ray structure was determined for this
compound.
2.2 Synthesis of α-acridinyl allenylphosphonate
derivatives 24 and 25
A mixture of allene (1 or 2) (0.216 g, 1.0 mmol), 9-
chloroacridine (0.213 g, 1.0 mmol), Pd(OAc)2 (5 mol%)
and CsF (0.303 g, 2.0 mmol) in DMF (5 mL) was heated
at 100◦C for 4–6 h. When the starting material was
consumed fully (31P NMR or TLC), the solvent was
removed, reaction mixture quenched with water (5 mL)
and extracted with ethyl acetate (2 × 30 mL). The com-
bined organic layer was washed with water (2×20 mL),
brine solution (20 mL), dried (Na2SO4) and then the sol-
vent was removed to obtain the crude material which
was purified by column chromatography using silica
gel with ethyl acetate/hexane (3:2) mixture as eluent
to afford the corresponding product 24 or 25. Reaction
using PPh3/K2CO3 in place of CsF did not give these
products. Note: Along with these, we obtained the cor-
responding acridone derivatives also. Rest of the allenes
(3–5), when treated with 9-chloroacridine gave only
acridone derivatives.
2.3 Synthesis of phosphono-purine derivative 27
In a 25 mL round-bottomed flask, a mixture of allene
(0.098 g, 0.4 mmol), 9-benzyl 6-chloro-purine (0.100 g,
0.4 mmol), Pd(OAc)2 (0.092 g, 0.04 mmol) and K2CO3
(0.113 g, 0.81 mmol), PPh3 (0.032 g, 0.12 mmol) in
DMF (2 mL) solvent was heated at 100◦C for 12 h.
When the starting material was consumed fully (31P
2.2a Compound 24: Yield 0.08 g [20%, white solid; NMR or TLC), the solvent was removed, reaction mix-
combined yield of 13+24 was > 90%]. Melting ture quenched with water (5 mL) and extracted with
point (M.p.): 184–186◦C; IR (KBr, cm−1) 2946, 2907, ethyl acetate (2 × 20 mL). The combined organic layer
1958, 1634, 1601, 1485, 1458, 1265, 1061, 1011. was washed with water (2 × 10 mL), brine solution
1H NMR (400 MHz, CDCl3) δ 0.47 and 0.88 (2 s, (10 mL), dried (Na2SO4) and then the solvent was
6H, 2 CH3), 1.91–1.93 (m, 6H, =C(CH3)2), 3.57– removed to obtain the crude material which was puri-
3.61 (m, 2H, OCH2), 4.12–4.18 (m, 2H, OCH2), fied by column chromatography using silica gel with
7.61 (d, 2H, J(H-H) ∼ 7.8 Hz, Ar-H), 7.82 (d, 2H, ethyl acetate/methanol (9:1) mixture as eluent to afford
J(H-H) ∼ 7.8 Hz, Ar-H), 8.27 (∼t, 2H, J(H-H) the product 27. Yield 0.127 g (67%, white solid). M.p.:
∼7.8 Hz, Ar-H), 8.38 (∼t, 2H, J(H-H) ∼7.8 Hz, Ar- 228–230◦C; IR (neat, cm−1) 3112, 3063, 3030, 2948,
H). 13C NMR (100 MHz, CDCl3) δ 19.0, 19.1, 20.8, 2849, 1677, 1573, 1540, 1507, 1441, 1358, 1266, 1057,
21.3, 32.2 (d, J(P-C) = 6.0 Hz, CMe2), 75.7, 75.8, 1008, 816. 1H NMR (400 MHz, CDCl3)) δ 1.00 (s, 6H,

1410
A Leela Siva Kumari et al.
2 CH3), 1.48–1.60 (m, 4H, cyclohexyl-H), 1.74–1.75 217.0993. This compound had been previously pre-
(m, 2H, cyclohexyl-H), 1.90–1.97 (m, 2H, cyclohexyl- pared in our laboratory; the IR/NMR data are consis-
H), 2.31–2.47 (m, 2H, cyclohexyl-H), 3.14 (dd, 1H, tent with the ones reported before.14
J = 16.4 and 3.2 Hz, PCHAHB), 3.37 (dd, J = 16.0
and 3.2 Hz, 1H, PCHA HB), 3.64 (t, J = 11.8 Hz, 1H,
OCHAHB), 3.83 (t, J = 11.8 Hz, 1H, OCHA HB), 4.00 (t,
2.4b Compound 29: Yield 0.136 g (67% white
J = 10.8 Hz, 1H, OCHAHB), 4.14 (t, J = 10.8 Hz, 1H,
solid). M.p.: 120–122◦C; IR (KBr, cm−1) 3036, 3013,
2926, 2893, 1627, 1589, 1474, 1260, 1052, 1014, 860.
1H NMR (400 MHz, CDCl3) δ 1.02 (s, 3H, CH3),
1.11 (s, 3H, CH3), 1.59–1.70 (m, 4H, cyclohexenyl-
H), 2.12–2.20 (m, 4H, cyclohexenyl-H), 3.78–3.84 (m,
2H, OCH2), 4.20 (dd→t, J = 10.2 Hz, 2H, OCH2),
5.55 (dd→t, J ∼ 18.0 Hz, 1H, = CH), 6.15 (br s,
1H, = CH), 7.10–7.20 (dd, J ∼ 18.0, 22.8 Hz, 1H, =
OCHA HB), 5.32 (s, 2H, CH2Ar), 7.30–7.38 (m, 5H, Ar-
13
H), 7.72 (s, 1H, Ar-H), 7.80 (s, 1H, Ar-H). C NMR
(100 MHz, CDCl3) δ 21.4 (d, J(P-C) = 11.0 Hz),
26.0, 26.2, 27.1, 27.5, 30.4 (d, J(P-C) = 94.0 Hz),
32.6 (d, J(P-C) = 5.8 Hz, CMe2), 47.6, 75.3 (d, J(P-
C) = 6.2 Hz), 75.6 (d, J(P-C) = 6.2 Hz), 118.9 (d,
J(P-C) = 12.5 Hz), 124.0, 128.0, 128.6, 129.1, 135.0,
140.0, 144.7 (d, J(P-C) = 11.1 Hz), 148.0, 149.3,
156.6. 31P NMR (162 MHz, CDCl3) δ 21.6. HRMS
(ESI) calcd. for C25H31N4O4PNa [M++Na]: 505.1981.
Found: 505.2004. X-ray structure was determined for
this compound after crystallization from methanol.
13
CH). C NMR (100 MHz, CDCl3) δ 21.4, 21.6, 22.0,
23.7, 26.3, 32.4 (d, J(PC) = 5.5 Hz), 75.2 (d, J(PC) =
5.8 Hz), 107.2 (d, J(PC) = 192.0 Hz), 135.2 (d, J(PC)
= 23.9 Hz), 139.2, 153.6 (d, J(PC) = 6.2 Hz). 31P
NMR (162 MHz, CDCl3) δ 17.1. HRMS (ESI) calcd.
for C13H22O3P [M++H]: 257.1306. Found: 257.1306.
2.4 Synthesis of phosphono-butadienes 28 and 29
by using allenylphosphonates 1 and 2
2.5 Horner–Wadsworth–Emmons reaction using
the acridonyl allylphosphonate 16: Synthesis
of alkenyl-acridone derivatives 30–37
To Pd(OAc)2 (0.14 mmol) and allenylphosphonate
(1 or 2) (1.4 mmol) in a 25 mL RBF, was added
dimethylformamide (DMF) [or dimethylacetamide
(DMA)]/ pivalic acid mixture (5 mL; 4:1) and then the
reaction mixture was gradually heated from room tem-
perature to 120◦C in air with the stirring continued for
1 h. The mixture was cooled to 25◦C, quenched with
water (5 mL) and extracted with EtOAc (3 × 20 mL).
The whole organic layer was washed with water (3 ×
20 mL), dried (Na2SO4), filtered, and filtrate concen-
trated. The residue was subjected to column chro-
matography (hexane/ EtOAc; 3:2) to afford the product
28 or 29.
The phosphonate 16 (0.100 g, 0.22 mmol) was dis-
solved in dry THF (2 mL) and added drop-wise (10 min)
to a suspension of NaH (0.44 mmol) in THF (3 mL) at
0◦C with stirring. The mixture was stirred further at
this temperature for 0.5 h. Then aldehyde (0.33 mmol)
in THF (2 mL) was added and the mixture stirred for
12 h at room temperature. Water (10 mL) was added
and the aqueous layer thoroughly extracted with ethyl
acetate (3 × 20 mL). The organic layer was collected,
dried (Na2SO4), filtered and the solvent removed from
the filtrate to give a residue that was purified by column
chromatography [silica gel, ethyl acetate-hexane (1:4)]
to give one of the compounds 30–37.
2.4a Compound 28: Yield 0.124 g (62% white
solid). M.p.: 90–92◦C; IR (KBr, cm−1) 3084, 3002,
2964, 2876, 1632, 1595, 1479, 1375, 1255, 1058, 1003, 2.5a Compound 30: Yield 0.082 g (94%, pale yellow
866. 1H NMR (400 MHz, CDCl3) δ 1.04 (s, 3H, CH3), solid). M.p.: 210–212◦C; IR (KBr, cm−1) 3057, 3030,
1.11 (s, 3H, CH3), 1.87 (s, 3H, CH3), 3.80–3.87 (m, 2986, 2943, 2849, 1632, 1600, 1490, 1457, 1364, 975,
2H, OCH2), 4.17–4.23 (m, 2H, OCH2), 5.34–5.36 (m, 756. 1H NMR (400 MHz, CDCl3) δ 1.37–1.40 (m, 2H,
2H, = CH2), 5.66–5.75 (dd→t, J ∼ 18.0 Hz, 1H, = cyclohexyl-H), 1.62 (br s, 2H, cyclohexyl-H), 1.81–
CH), 7.23–7.27 (m, 1H, = CH). 13C NMR (100 MHz, 1.88 (m, 4H, cyclohexyl-H), 2.81 (t, J(H-H) = 6.0 Hz,
CDCl3) δ 17.7, 21.4, 21.6, 32.5 (d, J(PC) = 5.7 Hz), 2H, cyclohexyl-H), 5.86 (d, J(H-H) = 16 Hz, 1H,
75.4 (d, J(PC) = 5.8 Hz), 112.0 (d, J(PC) = 190.1 Hz), CHA = CHB), 7.16–7.24 (m, 5H, Ar-H), 7.30 (t, J(H-
124.7, 140.7 (d, J(PC) = 23.9 Hz), 152.9 (d, J(PC) = H) = 7.6 Hz, 2H, Ar-H), 7.34–7.36 (m, 2H, Ar-H),
5.9 Hz). 31P NMR (162 MHz, CDCl3) δ 15.4. HRMS 7.44 (d, J(H-H) = 15.6 Hz, 1H, CHA=CHB), 7.59–
(ESI) calcd. for C10H18O3P [M++H]: 217.0993. Found: 7.63 (m, 2H, Ar-H), 8.61 (d, J = 8.0 Hz, 2H, Ar-H).

N-substituted acridones from allenylphosphonates
1411
13C NMR (100 MHz, CDCl3) δ 26.3, 27.0, 27.9, 30.45, 1H, CHA = CHB), 7.28–7.33 (m, 4H, Ar-H), 7.37 (d,
30.52, 116.6, 119.8, 121.6, 122.0, 126.6, 127.4, 127.7, J = 8.8 Hz, 2H, Ar-H), 7.59–7.64 (m, 3H, CHA =
128.0, 128.6, 130.0, 133.8, 136.5, 141.8, 146.5, 178.2 CHB + Ar-H), 8.01 (d, J = 8.0 Hz, 2H, Ar-H), 8.61–
(C=O). HRMS (ESI) calcd. for C28H26NO [M++H]: 8.63 (m, 2H, Ar-H). 13C NMR (100 MHz, CDCl3)
392.2014. Found: 392.2013.
δ 26.2, 27.1, 28.0, 30.75, 30.80, 116.2, 118.2, 121.6,
121.9, 122.1, 123.9, 124.2, 127.0, 127.4, 127.6, 133.9,
141.6, 143.1, 146.9, 150.6, 178.1 (C=O). HRMS (ESI)
calcd. for C28H25N2O3 [M++H]: 437.1865. Found:
437.1866.
2.5b Compound 31: Yield 0.074 g (84%, pale yel-
low solid). M.p.: 170–172◦C; IR (KBr, cm−1) 3063,
2959, 2921, 2855, 1627, 1600, 1479, 1457, 1359, 1293,
1
1162, 1041, 932, 751. H NMR (400 MHz, CDCl3)
δ 1.35–1.37 (m, 2H, cyclohexyl-H), 1.61 (br s, 2H, 2.5e Compound 34: Yield 0.096 g (93%, pale yellow
cyclohexyl-H), 1.80–1.87 (m, 4H, cyclohexyl-H), 2.27 solid). M.p.: 192–194◦C; IR (KBr, cm−1) 3052, 2964,
(s, 3H, CH3), 2.80 (t, J(H-H) = 6.2 Hz, 2H, cyclohexyl- 2921, 2849, 1638, 1594, 1480, 1364, 1293, 1162, 1074,
H), 5.85 (d, J(H-H) = 15.6 Hz, 1H, CHA = CHB), 7.04 937, 674. 1H NMR (400 MHz, CDCl3) δ 1.37 (br s, 2H,
(d, J(H-H) = 7.6 Hz, 2H, Ar-H), 7.14 (d, J = 8.0 Hz, cyclohexyl-H), 1.61 (br s, 2H, cyclohexyl-H), 1.80–
2H, Ar-H), 7.30 (t, J(H-H) = 7.8 Hz, 2H, Ar-H), 7.35– 1.88 (m, 4H, cyclohexyl-H), 2.80 (t, J(H-H) = 6.0 Hz,
7.41 (m, 3H, CHA = CHB + Ar-H), 8.01 (d, J = 2H, cyclohexyl-H), 5.80 (d, J(H-H) = 16 Hz, 1H,
8.0 Hz, 2H, Ar-H), 8.62 (d, J = 8.0 Hz, 2H, Ar-H). CHA = CHB), 7.10 (d, J = 8.0 Hz, 2H, Ar-H), 7.28–
13C NMR (100 MHz, CDCl3) δ 21.2, 26.3, 27.0, 27.9, 7.35 (m, 6H, Ar-H), 7.42 (d, J(H-H) = 15.6 Hz, 1H,
30.4, 30.5, 116.7, 118.4, 121.6, 121.9, 126.5, 127.4, CHA = CHB), 7.59–7.63 (m, 2H, Ar-H), 8.61 (d,
13
127.8, 129.3, 130.0, 133.8, 138.0. 141.8, 145.6, 178.2 J = 7.6 Hz, 2H, Ar-H). C NMR (100 MHz, CDCl3)
(C=O). HRMS (ESI) calcd. for C29H28NO [M++H]: δ 26.3, 27.0, 30.0, 30.5, 30.6, 116.5, 120.5, 121.7,
406.2171. Found: 406.2172.
122.0, 127.4, 127.5, 128.1, 128.7, 131.7, 133.8, 135.5,
141.7, 147.3, 178.1 (C=O). HRMS (ESI) calcd. for
C28H25BrNO [M++H]: 470.1119 and 472.1119. Found:
470.1116 and 472.1097
2.5c Compound 32: Yield 0.085 g (91%, pale yellow
solid). M.p.: 110–112◦C; IR (KBr, cm−1) 3063, 2937,
2855, 1737, 1638, 1600, 1507, 1485, 1457, 1364, 1178,
1
1030, 942, 751. H NMR (400 MHz, CDCl3) δ 1.35– 2.5f Compound 35: Yield 0.071 g (77%, pale yel-
1.37 (m, 2H, cyclohexyl-H), 1.60 (br s, 2H, cyclohexyl- low solid). M.p.: 120–122◦C; IR (KBr, cm−1) 3057,
H), 1.78–1.86 (m, 4H, cyclohexyl-H), 2.80 (t, J(H- 2921, 2849, 1638, 1600, 1479, 1457, 1364, 1293, 1266,
1
H) = 6.0 Hz, 2H, cyclohexyl-H), 3.75 (s, 3H, OCH3), 1172, 1085, 937, 762. H NMR (400 MHz, CDCl3) δ
5.82 (d, J(H-H) = 15.6 Hz, 1H, CHA=CHB), 6.76 (d, 1.37–1.43 (m, 2H, cyclohexyl-H), 1.61–1.68 (m, 2H,
J(H-H) = 15.6 Hz, 2H, CHA = CHB + Ar-H), 7.18 (d, cyclohexyl-H), 1.80–1.91 (m, 4H, cyclohexyl-H), 2.80
J(H-H) = 8.7 Hz, 2H, Ar-H), 7.30 (d, J = 7.9 Hz, 2H, (t, J(H-H) = 6.2 Hz, 2H, cyclohexyl-H), 5.81 (d, J(H-
Ar-H), 7.36 (d, J = 8.7 Hz, 2H, Ar-H), 7.58–7.62 (m, H) = 16 Hz, 1H, CHA = CHB), 7.15–7.20 (m, 4H,
3H, Ar-H), 8.61 (d, J = 8.0 Hz, 2H, Ar-H). 13C NMR Ar-H), 7.27–7.34 (m, 4H, Ar-H), 7.40 (d, J(H-H) =
(100 MHz, CDCl3) δ 26.3, 27.0, 27.9, 30.4, 30.5, 55.3, 15.7 Hz, 1H, CHA=CHB), 7.59–7.63 (m, 2H, Ar-H),
114.0, 116.7, 117.8, 121.6, 121.9, 127.3, 127.9, 129.3, 8.61 (d, J = 8.0 Hz, 2H, Ar-H). 13C NMR (100 MHz,
129.5, 133.7, 141.8, 145.0, 159.5, 178.2 (C=O). HRMS CDCl3) δ 26.3, 27.0, 27.9, 30.5, 30.6, 116.5, 120.4,
(ESI) calcd. for C29H28NO2 [M++H]: 422.212. Found: 121.7, 122.0, 127.5, 127.8, 128.6, 128.7, 133.5, 133.8,
422.2119.
135.0, 141.7, 147.2, 178.1 (C=O). HRMS (ESI) calcd.
for C28H25ClNO [M++H]: 426.1624. Found: 426.1626.
2.5d Compound 33: Yield 0.065 g (68%, yellow
solid). M.p.: 190–192◦C; IR (KBr, cm−1) 3054, 2926, 2.5g Compound 36: Yield 0.045 g (49 %, pale yel-
2849, 1638, 1605, 1512, 1479, 1342, 1293, 1161, 1118, low solid). M.p.: 257–259◦C; IR (KBr, cm−1) 3057,
942, 767. 1H NMR (400 MHz, CDCl3) δ 1.40–1.43 (m, 2975, 2926, 2849, 2219, 1638, 1600, 1479, 1457, 1359,
1
2H, cyclohexyl-H), 1.61–1.67 (m, 2H, cyclohexyl-H), 1288, 1178, 937, 745. H NMR (400 MHz, CDCl3) δ
1.85–1.94 (m, 4H, cyclohexyl-H), 2.85 (t, J(H-H) = 1.40–1.43 (m, 2H, cyclohexyl-H), 1.60–1.63 (m, 2H,
6.2 Hz, 2H, cyclohexyl-H), 5.91 (d, J(H-H) = 15.6 Hz, cyclohexyl-H), 1.84–1.93 (m, 4H, cyclohexyl-H), 2.83

1412
A Leela Siva Kumari et al.
(t, J(H-H) = 6.1 Hz, 2H, cyclohexyl-H), 5.86 (d, J(H- 2.6b Compound 19: pale brown block, C30H26NO2P,
H) = 15.7 Hz, 1H, CHA = CHB), 7.29–7.33 (m, 6H, M = 463.49, Monoclinic, Space group P21/c,
Ar-H), 7.50 (d, J = 8.3 Hz, 2H, Ar-H), 7.55 (d, J(H- a = 11.072(2), b = 16.360(3), c = 15.858(4) Å,
H) = 15.7 Hz, 1H, CHA = CHB), 7.60–7.64 (m, 2H, β = 121.423(15), V = 2451.2(9) Å3, Z = 4, μ =
Ar-H), 8.60–8.63 (m, 2H, Ar-H). 13C NMR (100 MHz, 0.140 mm−1, data/ restraints/parameters: 4301/0/309,
CDCl3) δ 26.2, 27.0, 28.0, 30.68, 30.73, 110.8, 116.2, R indices (I > 2σ(I)): R1 = 0.0626, wR2 (all data) =
118.2, 121.8, 122.0, 123.4, 127.0, 127.4, 127.6, 128.0, 0.1858. CCDC No. 942496.
132.3, 133.9, 141.1, 141.6, 149.9, 178.1 (C=O). HRMS
(ESI) calcd. for C29H25N2O [M++H]: 417.1967 Found:
417.1968.
2.6c Compound 24: colourless block, C23H24NO3P,
= 393.40, Monoclinic, Space group P2/c,
M
a = 16.345(7), b = 6.288(3), c = 19.938(8) Å, β =
2.5h Compound 37: Yield 0.063 g (56 %, red solid).
M.p.: 190–192◦C; IR (KBr, cm−1) 3057, 2931, 2855,
1627, 1606, 1480, 1457, 1359, 1266, 1162, 1107, 1047,
96.169(7), V = 2037.3(15) Å3, Z = 4, μ
=
0.158 mm−1, data/ restraints/parameters: 3597/0/257,
R indices (I > 2σ(I)): R1 = 0.0489, wR2 (all data) =
0.1258. CCDC No. 942494.
1
959, 806, 751. H NMR (400 MHz, CDCl3) δ 1.37
(d, 2H, cyclohexyl-H), 1.61 (br s, 2H, cyclohexyl-H),
1.78–1.86 (m, 4H, cyclohexyl-H), 2.71 (t, 2H, J(H-
H) = 5.8 Hz, cyclohexyl-H), 3.85 (s, 5H, ferrocenyl-
H), 4.21–4.18 (m, 4H, ferrocenyl-H), 5.58 (d, J(H-
H) = 15.2 Hz, 1H, CHA = CHB), 6.92 (d, J(H-H) =
15.2 Hz, 1H, CHA = CHB), 7.31 (t, J(H-H) = 7.4 Hz,
2H, Ar-H), 7.40 (d, J = 8.4 Hz, 2H, Ar-H), 7.62–
7.66 (m, 2H, Ar-H), 8.63 (d, J = 8.0 Hz, 2H, Ar-H).
13C NMR (100 MHz, CDCl3) δ 26.4, 26.9, 27.8, 30.3,
30.4, 67.0, 68.3, 69.1, 69.4, 82.2, 116.5, 116.8, 121.7,
122.0, 127.4, 127.8, 129.4, 133.7, 141.8, 142.8, 178.3
(C=O). HRMS (ESI) calcd. for C32H30NOFe [M++H]:
500.1674. Found: 500.1675.
2.6d Compound 25: colourless needles, C26H28NO3P,
M = 433.46, Monoclinic, Space group P21/c, a =
6.3172(7), b = 14.0629(16), c = 27.295(3) Å, β =
108.966(12), V =2293.2(5) Å3, Z =4, μ=0.147 mm−1,
data/restraints/parameters: 3907/0/282, R indices (I >
2σ(I)): R1 = 0.0583, wR2 (all data) = 0.1090. CCDC
No. 942495.
2.6e Compound 27·1/2MeOH: colourless blocks,
C51H62N8O9P2, M = 993.03, triclinic, Space group P1,
a = 10.0712(12), b = 11.645(2), c = 11.8217(16) Å,
α = 85.489(12), β = 67.870(12), γ = 83.492(12),
V = 1275.0(3) Å3, Z = 1, μ = 0.149 mm−1, data/
restraints/parameters: 4473/327, R indices (I > 2σ(I)):
R1 = 0.0972, wR2 (all data) = 0.3057. The data qual-
ity was only moderate and hence the hydrogen atoms
on the solvent were not modelled; however, the basic
structure of the molecule was unambiguous. CCDC No.
946920.
2.6 X-ray structural analysis of 18–19, 24–25 and 27
Single crystal X-ray diffraction data for compounds
18 and 24 were collected on a Bruker AXS-SMART
diffractometer and that for 19, 25 and 27·1/2MeOH
were collected on an OXFORD diffractometer, using
Mo Kα (λ = 0.71073 Å) radiation. The structures were
determined and refined by standard methods.15 In the
structure of compound 18, the bromine at C11 and
hydrogen at C17 exchanged positions, leading to par-
tial occupancy at these positions while packing, but
the structure was refined well. Full details of the
X-ray structure solution and refinement as a CIF file are
available as Supplementary Information.
3. Results and discussion
The reaction of allenylphosphonates (OCH2CMe2CH2O)
P(O)CH=C=CR1R2 {R1 = R2 = Me (1), R1 = R2 =
−
[−CH2 ]5 (2)}, with various substituted acridones
2.6a Compound
18: pale
yellow
block, (10–12) at 100◦C in DMF solvent by using CsF as
C52H58Br2N2O8P2, M = 1060.76, triclinic, Space group base leads to the formation of acridonyl allylphos-
P1, a = 11.052(6), b = 11.233(6), c = 11.782(6) Å, phonates 13–18 (scheme 2). Although the reaction
α = 98.582(8), β = 106.272(7), γ = 112.690(7), worked well even by using one mol equivalent of CsF,
V = 1239.5(11) Å3, Z = 1, μ = 1.755 mm−1, more equivalents were used to ensure the completion
data/restraints/parameters: 4338/0/315, R indices of reaction in a shorter period. The products were
(I > 2σ(I)): R1 = 0.0661, wR2 (all data) = 0.1637. formed quantitatively (31P NMR) and the yields after
CCDC No. 942493.
isolation were >80%. By employing these conditions

N-substituted acridones from allenylphosphonates
1413
O
O
R1
P
H
H
N
O
R2
O
O
O
R
R1
R2
P
CsF (2 equiv)
H
N
+
H
DMF/100 oC
4-6 h
O
R1 = R2 = Me
R1R2 = [-CH2-]5
1
2
R
O
R = H (10), Me (11),
= Br (12)
R1 = R2 = Me, R = H
13
14
15
R1 = R2 = Me, R = Me
R1 = R2 = Me, R = Br
R1R2 = [-CH2-]5, R = H
R1R2 = [-CH2-]5, R = Me
R1R2 = [-CH2-]5, R = Br
16
17
18 (X-ray)
R1
N
Me
N
O
O
EtO
EtO
R2
Ph
Ph
Me
P
P
H
H
H
H
O
O
R
R1 = R2 = Me, R = H, 19 (X-ray)
23
R1 = R2 = Me, R = Me 20
R1R2 = [-CH2-]5, R = Me 21
R1R2 = [-CH2-]5, R = Br 22
Scheme 2. Synthesis of acridonyl allylphosphonates/allylphosphine oxides 13–23.
1
to allenylphosphine oxides Ph2P(O)C(H)=C=CR1R2
In all the above compounds, the H NMR spectra
1
2
1
2
−
{R = R = Me (3), R = R = [−CH2 ]5 (4)} and show a distinct peak in the region δ 3·0–4·0 [J(P–
the allenylphosphonate (EtO)2P(O)C(H)=C=CMe (5), H) ∼ 21·0 Hz] indicating the presence of PCH2 group.
we could also obtain acridonyl allylphosphine oxides Further confirmation of the structures is accomplished
(19–22) and acridonyl allylphosphonate 23. The reac- by the X-ray structure determination for compounds
tion did not occur in the absence of CsF (base); this 18–19 (figure 1). The C6–C7 (in 18) or C13–C14
observation is significant since normal amines or nucleo- (in 19) distances are in the single bond range, as
bases do not require the presence of CsF.4 Although required.
we have not investigated this point in detail, it appears
that the steric bulk and lower basicity of acridone spectrum of the reaction mixture shows the formation
requires fluoride activation. of a single product in each case. The other product (I) in
It may be noted that in the above reactions, 31P NMR
Figure 1. Molecular structures of 18 (left) and 19 (right). Selected bond dis-
tances are only given here. Compound 18 P1-C6 1.774(5), C6-C7 1.510(6),
N1-C7 1.452(5) Å; compound 19 P1-C13 1.813(3), C13-C14 1.515(4), N1-C14
1.451(4) Å. In the structure of compound 18, there is Br/H exchange of positions
at the carbon atoms C11 and C17.

1414
A Leela Siva Kumari et al.
As regards characterization of substituted allenyl-
which the N–H hydrogen is connected to the γ -carbon
13
is not observed. Thus, the hydrogen moves regiospecifi- phosphonates 24–25, C NMR is quite useful. A dis-
cally to the carbon with the electron-withdrawing tinct doublet at ca ∼ δ 88 [1 J(P-C) = 197–199 Hz]
phosphoryl/phosphinoyl group.
is exhibited by the carbon α to the phosphorus. The
large value of 1 J(P-C) indicates that the phospho-
rus is attached to an sp2 carbon.6 The 31P NMR
chemical shifts are in the region expected for such
allenes and are close to those for 1–2. Final confirma-
tion of the structures for 24–25 was accomplished by
X-ray crystallography (figure 2). The C6-C7 and C7-C8
distances (double bond range) as well as the C6-C7-
C8 bond angle clearly prove the allenic structure in
both the cases. Steric factors during the formation of
the [Pd]-intermediate may be responsible for the for-
mation of the α-substituted products 24/25 in the case
of reaction using 9-chloroacridne. The allylphospho-
nate 27 is 9-benzyl-purinone addition product with a
purine nitrogen connected to β-carbon of the allene,
but after the substitution of –Cl by –OH and rearrange-
ment. For this compound, the P-CH2 protons showed an
AM pattern with coupling to phosphorus, thus exhibit-
ing two doublets of doublet. More convincingly, the
P–C carbon appeared in the aliphatic region [δ 30.4,
1 J(P-C) = 94.0 Hz] which readily shows that this is an
aliphatic carbon. The 31P NMR chemical shift [δ 21.6]
is also quite far from the precursor allenylphosphonate
[δ 10.0]; these data are consistent with the structure
of 27 as proposed in scheme 3. X-ray structure was
determined for 27·1/2MeOH after crystallization from
methanol (figure 3). The P-CH2 moiety (at C6) and the
carbonyl group (at C11) are clearly discernible by the
bond parameters associated with these atoms.
R1
H
R2
P
R3
R3
H
N
O
P
P
(R3,R3) = OCH2CMe2CH2O,
R3 = Ph, EtO
O
(I)
R
Not observed
As mentioned in the Introduction, we initially
intended to prepare acridinylphosphonates also by
using [Pd]-catalysis. Thus, when compounds 1–2 were
treated with 9-chloroacridine under the conditions
Pd(OAc)2/CsF/DMF, we obtained two products in
each case: Compound 13 (or 16) and the α-substituted
allene 24 (or 25). The products 13/16 must have arisen
from the in situ formed acridone via adventitious mois-
ture as encountered elsewhere.7 However, isolation of
the α-substituted products 24–25, albeit in ca 20% yield
was a surprise, because as mentioned in the Introduc-
tion (cf. scheme 1), the acridinyl residue should have
gone to the β-position. Hence, we checked the reac-
tion using 9-benzyl-6-chloropurine (26), since the C–Cl
bond in this compound is also fairly reactive. Although
use of CsF did not work (no product) even after 24 h,
Ph3P/K2CO3 as the base combination afforded the β-
substituted product 27.16 This purinone product must
have also formed in a manner similar to the acridone
products 13 or 16. The acridinyl and the acridone pro-
ducts [13/24 or 16/25] had essentially the same Rf value
(posing difficulties in isolation) and hence the 31P NMR
had to be used as the diagnostic tool during elution.
In the literature, it is reported that aniline under-
goes C–H activation and reacts with alkynes using
Pd(OAc)2/pivalic acid under aerobic conditions.17
Since the nitrogen of the acridone is connected to an
aromatic carbon, we wanted to see if acridone can be
Figure 2. Molecular structures of 24 (left) and 25 (right). Selected bond para-
meters: Compound 24 P-C6 1.794(2), C6-C7 1.306(3), C7-C8 1.294(3) Å, C6-C7-
C8 175.2(2)◦; Compound 25 P-C6 1.798(4), C6-C7 1.304(5), C7-C8 1.283(5) Å,
C6-C7-C8 173.6(5)◦.

N-substituted acridones from allenylphosphonates
1415
Cl
O
O
O
Pd(OAc)2 (5 mol%)
CsF (2 equiv)
R1
R2
P
(a)
+
DMF/100 oC/4-6 h
H
N
R1 = R2 = Me
R1R2 = [-CH2-]5
1
2
R1
O
O
R2
O
O
R1
R2
P
O
P
O
+
N
H
H
O
N
R1, R2 = Me
R1R2 = [-CH2-]5 25 (X-ray)
24 (X-ray)
R1, R2 = Me
13
R1R2 = [-CH2-]5 16
O
O
Cl
N
P
O
O
O
P
O
N
N
Pd(OAc)2, PPh3
N
(b)
+
N
K2CO3, DMF
100 oC, (H2O)
H
O
N
CH2Ph
N
N
PhCH2
27 (X-ray)
26
2
Scheme 3. [Pd]-catalysed reaction of allenylphosphonates 1–2 with 9-chloroacridine or 9-benzyl-6-chloropurine.
activated in a similar manner. However, no such acti- in the reaction and hence it is possible to obtain the
vation occurred and acridone also did not add to the 1,3-butadienes 28–29 in the absence of acridone.14
allene. Rather the rearranged product, the 1,3-butadiene
Compounds 13–23 possess a P(O)CH2- group and
28 was obtained probably via an allylic [Pd] intermedi- hence we surmised that these would be attractive pre-
ate of type II (scheme 4); subsequently the strong con- cursors for Horner–Wadsworth–Emmons (HWE) reac-
jugate base, pivalate anion, will abstract a proton from a tion.18 Initially, we used t-BuOK for the reaction using
terminal methyl group and the [Pd]-catalyst is released allyl acridone 16 but under these conditions, there
to form the product 28. Although there is a second pos- was no reaction with acridone. Use of NaH as the
3
sible structure for 28–29, the Jtrans(HH) value is more base afforded the HWE products 30–36 readily in
consistent with the proposed one. It is also worthwhile good yields (scheme 5). Even ferrocene carboxalde-
to note that in the absence of pivalic acid only traces of hyde reacted readily to afford the acridone derivative
the product were observed. In a similar manner, allene 2 37. Aromatic aldehydes containing electron-releasing
gave the 1,3-butadiene 29. Here acridone is not involved [Me, OMe] or electron-withdrawing groups [NO2, Br,
Figure 3. Molecular structure of 27·1/2MeOH. The solvent molecule
is not shown. Selected bond parameters: P1-C6 1.764(5), C6-C7
1.497(7), N2-C7 1.454(5) Å, C6-C7-N2 113.0(4)◦.

1416
A Leela Siva Kumari et al.
H
N
O
O
O
O
O
O
Me
Me
10
O
P
H
H
P
H
Conditions
Conditions
H
H
1
Me
28
Conditions: Pd(OAc)2/DMF (or DMA):pivalic acid (4:1)/ 120 oC, 1 h
Similarly
H
O
O
O
H
O
O
O
Me
Me
P
H
P
PdLn
II
H
A plausible intermediate
29
Scheme 4. [Pd]-catalysed rearrangement of allenylphosphonate 1–2 to phosphonobutadienes 28–29.
O
O
O
CHO
P
NaH, THF
+
E
R
O o
12 h
C
rt
N
N
R
O
O
16
R = H
= Me
= OMe
30
31
32
33
Similarly
= NO2
= Br
34
= Cl
= CN
35
36
N
Fe
O
37
Scheme 5. Horner–Wadsworth–Emmons reaction of 16 with aldehydes leading to the acridonyl-1,3-butadienes 30–37.
Cl and CN] worked well. The (E)-configuration at [Pd]-catalysed reaction of the allenylphosphonates
the newly formed double bond is corroborated by the led to the acridonyl allylphosphonates and the rather
corresponding 3 J(HH) values as well as the literature.18 unexpected α-substituted allenylphosphonates. In the
presence of a carboxylic (pivalic) acid and Pd(OAc)2,
allenylphosphonates with a terminal =CR2 [R = Me;
R2 = cyclohexyl] group undergo facile rearrangement
4. Summary
to 1,3-butadienyl substituted phosphonates.
Simple base-mediated (CsF) addition of acridone to
allenylphosphonates/allenylphosphine oxides leads to
acridonyl allylphosphonates wherein the nitrogen of
the acridone is bonded to the carbon β to phospho-
rus and the corresponding N–H hydrogen moves to the
α-carbon. These compounds are good substrates for
HWE reaction and are useful in generating a new class
of N-substituted acridones. In two examples studied,
Supplementary information
The electronic supporting information (CIF file con-
taining the details of crystal structures of com-
pounds reported in this work) can be seen in
www.ias.ac.in/chemsci.

N-substituted acridones from allenylphosphonates
1417
Acknowledgements
41 340; (b) Goodell J R, Ougolkov A V, Hiasa H,
Kaur H, Remmel R, Billadeau D D, Ferguson D M 2008
J. Med. Chem. 51 179
We thank the Department of Science and Technology
(DST), New Delhi for financial support and for setting
up of the National Single Crystal Diffractometer Facili-
ty at the University of Hyderabad. We also thank Uni-
versity with Potential for Excellence (UPE) programme
of the University Grants Commission (UGC), New
Delhi for equipment. KCK thanks DST for JC Bose
fellowship and ALSK thanks UGC for a fellowship.
9. (a) Kumar R and Kumari M 2011 J. Chem. Pharm. Res.
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2009 Nature 459 270; (c) Kelly J X, Smilkstein M J,
Cooper R A, Lane K D, Johnson R A, Janowsky A,
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