10-alkyl-2,7-dinitro-9(10H)-acridinones by tandem SNAr reactions

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10-Alkyl-2,7-dinitro-9(10H)-acridinones
by Tandem SNAr Reactions
Richard A. Bunce a & Matthew T. Grant a
a Department of Chemistry , Oklahoma State University , Stillwater,
Oklahoma, U.S.A
Published online: 09 Jun 2011.
To cite this article: Richard A. Bunce & Matthew T. Grant (2011) 10-Alkyl-2,7-dinitro-9(10H)-
acridinones by Tandem SNAr Reactions, Organic Preparations and Procedures International: The New
Journal for Organic Synthesis, 43:3, 265-275
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Organic Preparations and Procedures International, 43:265–275, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.581995
10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem
SNAr Reactions
Richard A. Bunce and Matthew T. Grant
Department of Chemistry, Oklahoma State University, Stillwater,
Oklahoma, U.S.A.
Our recent work has described several approaches to the synthesis of heterocyclic sys-
tems using tandem reaction processes terminated by a nucleophilic aromatic substitution
(SNAr) reaction.1–8 With this background, we were interested in the feasibility of preparing
substituted 9(10H)-acridinones in a single laboratory operation via two sequential SNAr
reactions. Based on our previous work, these structures would be expected from 2,2ꢀ-
difluorobenzophenone derivatives bearing strategically positioned electron-withdrawing
groups to activate the aromatic rings toward addition by nucleophilic amines. While 2,2ꢀ-
difluorobenzophenone could potentially undergo such a reaction, it was expected that further
activation would be necessary. The easiest activating group to introduce to this system is
the nitro function. This could be added by electrophilic aromatic substitution and would be
expected to add para to the fluoro substituents.9
Numerous studies have demonstrated that nitroacridinones possess significant bi-
ological activity. To date, these compounds have attracted attention as antibiotic,10
antiparasitic,11–13 antifungal12 and antiviral agents.12,14 Furthermore, several derivatives
have displayed potent anticancer properties10,15–18 and may have use in the treatment of
neurodegenerative diseases such as multiple sclerosis.19 Thus, nitroacridinones are worthy
targets for organic synthesis.
The syntheses of several potential cyclization substrates are illustrated in Scheme 1.
The synthesis begins with 2-bromofluorobenzene (1). Lithium-bromine exchange on 1 was
carried out in THF by addition of n-butyllithium at −78◦C, followed by warming to −30◦C.
The resulting solution of 2-fluorophenyllithium (2) was cooled to −78◦C and reacted with
0.5 equivalents of ethyl formate to give 2,2ꢀ-difluorobenzhydrol (3) in 89% yield. Oxidation
of 3 with chromic acid20 in aqueous acetone then afforded 2,2ꢀ-difluorobenzophenone (4)
in 90% yield.21 Double nitration of 4 was accomplished by treatment with 2.2 equiva-
lents of sodium nitrate in concentrated sulfuric acid at 0–5◦C to afford 2,2ꢀ-difluoro-5,5ꢀ-
dinitrobenzophenone (5) in 66% yield.22
Received December 3, 2010; in final form January 21, 2011.
Matthew T. Grant was an undergraduate Wentz Project Scholar in 2010–2011.
Address correspondence to Richard A. Bunce, Department of Chemistry, Oklahoma State
University, Stillwater, OK 74078-3071, USA. E-mail: rab@okstate.edu
265

266
Bunce and Grant
Scheme 1
Synthesis of Substrates 4, 5 and 8
To further explore the requirements of the proposed cyclization reaction, an unsymmet-
rical benzophenone derivative incorporating one single- and one double-activated aromatic
ring was also prepared by modification of the above synthesis. Treatment of 2 with 2-fluoro-
5-nitrobenzaldehyde (6)22 at −78◦C yielded benzhydrol 7 in 79% yield.23 Chromic acid
oxidation as above then furnished 2,2ꢀ-difluoro-5-nitrobenzophenone in 92% yield. Thus,
benzophenone derivatives with two single-activated and two double-activated rings (i. e. 4
and 5, respectively) as well as a substrate with one single-activated and one double-activated
ring (i.e. 8) were available for the current study.
Substrate 5 (both rings double-activated) offered the best chance for success and, thus,
was the first case studied. A solution of 1.0 mmol of 5 in DMF was heated to 60◦C and
1.1 mmole of benzylamine was added. The reaction immediately turned from tan to dark
yellow and the reaction was heated at 60◦C for 48 h. Aqueous workup afforded a sparingly
soluble yellow solid, which was triturated with boiling 1:1 chloroform:ethanol to afford
10-benzyl-2,7-dinitro-9(10H)-acridinone (9a) in 82% yield. A total of 7 other amines were
reacted with 5 and the results are summarized in Table 1. Since the nitrogen must add twice
to form the central ring, primary amines were necessary and unhindered cases afforded the
best yields.24
Our results for the attempted cyclization with substrate 8 (one ring double-activated)
with three different amines are given in Table 2. In this case, addition occurred only to
the double-activated ring to give a near-quantitative yield of the hydrogen-bond-stabilized
products 10. The desired cyclization products were totally absent from the reaction mixture.
Attempts to cyclize adducts 10 under more forcing conditions (100◦C in DMF for 48 h)
were unsuccessful. Cyclizations using substrate 4 (both rings single-activated) also proved
unsatisfactory. Reaction of 4 with benzylamine at 100◦C for 48 h resulted in only 8% of
the acridinone product.25

10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem SNAr Reactions
267
Table 1
Summary of Cyclization Results for 5
R
Product
Yield (%)
a
b
c
d
e
f
PhCH2−
9a
9b
9c
9d
9e
9f
82
79
78
81
62
77
76
73
4-CH3OPhCH2−
4-ClPhCH2−
4-CF3PhCH2−
PhCH2CH2−
n-C6H13−
g
h
i-C4H9−
9g
9h
i-PrOCH2CH2CH2−
In summary, we have successfully developed a tandem SNAr reaction for the synthesis
of 10-alkyl-2,7-dinitro-9(10H)-acridinones. The reaction is successful when both aromatic
rings are double-activated, but fails in substrates having fewer electron-withdrawing groups.
The current reaction demonstrates the feasibility of this strategy for preparing selected
acridinones. While the products of the current reaction have potential use as precursors to
pharmaceutical agents, additional methodology would be necessary to expand the reaction
to structures with more diverse functionality.
Table 2
Summary of Reaction Results for 8
R
Product
Yield (%)
a
f
g
PhCH2−
n-C6H13−
i-C4H9−
10a
10f
10g
95
96
92

268
Bunce and Grant
Experimental Section
Unless otherwise indicated, all reactions were run under dry nitrogen in oven-dried glass-
ware. Commercial anhydrous N,N-dimethylformamide (DMF) was stored under nitrogen
and transferred by syringe into reactions where it was used. Tetrahydrofuran (THF) was
dried over potassium hydroxide pellets and distilled from lithium aluminum hydride under
nitrogen. Other reagents and solvents were used as received. Reactions were monitored by
thin layer chromatography (TLC) on silica gel GF plates (Analtech No. 21521). Preparative
separations were performed using flash column chromatography26 on silica gel (Grade 62,
60–200 mesh) mixed with UV-active phosphor (Sorbent Technologies No. UV-5); band
elution was monitored using a hand-held UV lamp. Melting points were uncorrected. IR
1
spectra were run as thin films on sodium chloride disks. H and 13C NMR spectra were
measured at 300 MHz and 75 MHz, respectively, and were referenced to internal tetra-
methylsilane; coupling constants (J) are reported in Hz. Low-resolution mass spectra
(EI/DP) were run at 30 eV.
2,2ꢀ-Difluorobenzhydrol (3)
The general procedure of Herold and co-workers21 was modified. A 250-mL, three-necked,
round-bottomed flask, equipped with a rubber septum, a magnetic stirrer and an argon
atmosphere, was charged with a solution of 4.40 g (25.0 mmol) of 1-bromo-2-fluorobenzene
(1) in 50 mL of dry THF and the flask was cooled to −78◦C. Once cooled, 10.0 mL
(25.0 mmol) of 2.5 M n-butyllithium in hexanes was added dropwise to the mixture over a
period of 30 min. The reaction turned light brown during the addition. The reaction mixture
was stirred for 10 min at −78◦C, warmed to −30◦C over 1 h, recooled to −78◦C and 0.92 g
(1.0 mL, 12.5 mmol) of freshly distilled ethyl formate in 5 mL of THF was added dropwise.
The reaction was stirred for 15 min at −78◦C, then slowly warmed to −30◦C and quenched
with 10 mL of saturated aqueous ammonium chloride. The mixture was transferred to
a separatory funnel containing 100 mL of saturated aqueous ammonium chloride and
extracted with ether (3 × 100 mL). The combined ether extracts were washed once with
water and saturated aqueous sodium chloride, then dried (MgSO4) and concentrated under
vacuum to give crude 3 as a yellow oil. A small amount of 5-nonanol present in this product
was removed by warming to 60◦C at 1 mmHg. This yielded 2.43 g (89%) of 3, which was
used without further purification. IR: 3350, 1225 cm−1; 1H NMR (CDCl3): δ 7.43 (t, J =
7.7 Hz, 2 H), 7.26 (m, 2 H), 7.13 (t, J = 7.7 Hz, 2 H), 7.02 (t, J = 8.8 Hz, 2 H), 6.40 (d,
J = 3.3 Hz, 1 H), 2.53 (br s, 1 H); 13C NMR (CDCl3): δ 160.0 (d, J = 246.8 Hz), 129.4 (2 d,
J ≈ 8.3 and 3.0 Hz), 128.0 (d, J = 2.7 Hz), 124.2, 115.4 (d, J = 21.8 Hz), 64.5; ms: m/z
220 (M+).
Anal. Calcd for C13H10F2O: C, 70.90; H, 4.55. Found: C, 71.04; H, 4.61.
2,2ꢀ-Difluorobenzophenone (4)
The general procedure of Danishefsky and co-workers23 was used. A 100-mL, one-necked,
round-bottomed flask, equipped with a magnetic stirrer and an addition funnel, was charged
with a solution of 1.92 g (8.75 mmol) of 3 in 40 mL of acetone. The solution was stirred and
4.45 mL of freshly prepared Jones reagent (ca 2.95 M, 13.1 mmol, 1.5 equiv)20 was slowly

10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem SNAr Reactions
269
added dropwise over a period of 45 min. The reaction mixture was stirred for an additional
15 min and then quenched with 20 mL of ice water followed by 3.75 mL of saturated
aqueous sodium bisulfite. The resulting mixture was saturated with sodium chloride and
extracted with ether (4 × 50 mL). The combined extracts were washed three times with
water and once with saturated sodium bicarbonate and saturated aqueous sodium chloride,
then dried (MgSO4) and concentrated under vacuum. The resulting yellow oil was distilled
in vacuo to give 1.72 g (90%) of 4 as a colorless oil, bp 118–120◦C at 1.5 mmHg (lit.21
bp 119◦C at 1.5 mmHg). IR: 1667 cm−1; 1H NMR (CDCl3): δ 7.71 (td, J = 7.7, 1.6 Hz,
2 H), 7.54 (m, 2 H); 7.26 (t, J = 7.7 Hz, 2 H), 7.11 (dd, J = 10.4, 9.3 Hz, 2 H); 13C NMR
(CDCl3): δ 189.7, 161.0 (d, J = 254.8 Hz), 134.2 (d, J = 9.4 Hz), 130.8, 127.5 (d, J =
13.0 Hz), 124.3, 116.2 (d, J = 22.3 Hz); ms: m/z 218 (M+).
Anal. Calcd for C13H8F2O: C, 71.56; H, 3.67. Found: C, 71.53; H, 3.68.
2,2ꢀ-Difluoro-5,5ꢀ-dinitrobenzophenone (5)
The 2,2ꢀ-difluorobenzophenone prepared above was nitrated using the general procedure of
Gale and Wilshire,22 adjusted to give double nitration. A solution of 1.46 g (17.2 mmol) of
finely ground sodium nitrate in 20 mL of concentrated sulfuric acid was prepared at room
temperature in a 100-mL, three-necked, round-bottomed flask, equipped with an addition
funnel and a magnetic stirrer. This solution was cooled to 0◦C (ice-salt bath) and 1.70 g
(7.80 mmol) of 4 was slowly added over a period of 30 min. The reaction mixture was
stirred at 0◦C for 1 h, the solution was poured onto 100 g of crushed ice and the mixture
was extracted with 1:1 benzene:ether (3 × 50 mL). The combined organic layers were
washed once with water and saturated aqueous sodium chloride, then dried (MgSO4) and
concentrated under vacuum. The resulting light brown solid was recrystallized from ethanol
to give 1.58 g (66%) of 5 as pale yellow crystals, mp 136–137◦C. IR: 1677, 1534, 1352 cm−1
;
1H NMR (CDCl3): δ 8.70 (dd, J = 6.0, 2.7 Hz, 2 H), 8.51 (ddd, J = 9.3, 3.8, 2.7 Hz, 2 H),
7.37 (t, J = 9.3 Hz, 2 H); 13C NMR (CDCl3): δ 184.7, 164.0 (d, J = 265.1 Hz), 144.6,
130.0 (d, J = 11.5 Hz), 130.0, 127.0 (t, J = 2.1 Hz), 117.8 (d, J = 25.4 Hz); ms: m/z 308
(M+).
Anal. Calcd for C13H6F2N2O5: C, 50.65; H, 1.95; N, 9.09. Found: C, 50.68; H, 1.97;
N, 9.05.
2,2ꢀ-Difluoro-5-nitrobenzhydrol (7)
In a 250-mL three-necked, round-bottomed flask, equipped with a rubber septum, a mag-
netic stirrer and an argon atmosphere, 4.40 g (25.0 mmol) of 1 was subjected to lithium-
bromine exchange as described for the preparation of 3. To the resulting solution of 2 at
−78◦C was slowly added a solution of 4.22 g (25.0 mmol) of 2-fluoro-5-nitrobenzaldehyde
(6)22 in dry THF. The reaction mixture was stirred for 30 min with warming to −50◦C
and then quenched with 10 mL of saturated aqueous ammonium chloride. The mixture
was transferred to a separatory funnel containing 100 mL of saturated aqueous ammonium
chloride and extracted with ether (3 × 100 mL). The combined ether extracts were washed
once with water and saturated aqueous sodium chloride, then dried (MgSO4) and concen-
trated under vacuum to give 5.23 g (79%) of 7 an orange oil, which was carried on without

270
Bunce and Grant
further purification. IR: 3422, 1530, 1352, 1227 cm−1; 1H NMR (CDCl3): δ 8.51 (dd, J =
6.0, 2.7 Hz, 1 H), 8.20 (ddd, J = 8.8, 4.4, 2.7 Hz, 1 H), 7.41 (td, J = 7.7, 1.6 Hz, 1 H), 7.32
(m, 1 H), 7.16 (apparent t, J ≈ 8.0 Hz, 2 H), 7.06 (t, J = 9.3 Hz, 1 H), 6.42 (d, J = 3.3
Hz, 1 H), 2.75 and 2.69 (2 s, 1 H); 13C NMR (CDCl3): δ 163.0 (d, J = 258.8 Hz), 159.8 (d,
J = 247.6 Hz), 144.4, 131.6 (d, J = 15.5 Hz), 130.2 (d, J = 8.3 Hz), 128.3 (d, J = 12.9
Hz), 127.9 (d, J = 3.4 Hz), 125.2 (d, J = 10.3 Hz), 124.6, (d, J = 3.7 Hz), 124.1 (d, J =
6.3 Hz), 116.5 (d, J = 24.0 Hz), 115.7 (d, J = 21.2 Hz), 63.8; ms (30 eV): m/z 265 (M+).
Anal. Calcd for C13H9F2NO3: C, 58.87; H, 3.40; N, 5.28. Found: C, 58.98; H, 3.49;
N, 5.19.
2,2ꢀ-Difluoro-5-nitrobenzophenone (8)
By using the procedure outlined for the preparation of 4, 5.20 g (19.6 mmol), benzhydrol
7 was oxidized using 1.5 equivalents of chromic acid to give a brown oil. Purification by
flash chromatography using increasing concentrations (10% to 40%) of ether in hexanes
gave 4.73 g (92%) of 8 as an orange oil, which crystallized on standing to a yellow-orange
1
solid, mp 68–70◦C. IR: 1670, 1533, 1354 cm−1; H NMR (CDCl3): δ 8.59 (dd, J = 6.0,
2.7 Hz, 1 H), 8.44 (ddd, J = 9.3, 4.4, 3.3 Hz, 1 H), 7.82 (td, J = 7.7, 2.2 Hz, 1 H), 7.63
(m, 1 H), 7.33 (2 t, J ≈ 7.7 Hz, 2 H), 7.15 (dd, J = 10.9, 9.3 Hz, 1 H); 13C NMR (CDCl3):
δ 187.0, 163.8 (d, J = 264.8 Hz), 161.3 (d, J = 255.8 Hz), 144.2, 135.5 (d, J = 8.9 Hz),
131.0, 128.9 (d, J = 10.6 Hz), 128.8 (obscured d), 126.6 (d, J = 4.6 Hz), 125.9 (d, J =
12.3 Hz), 124.8 (d, J = 3.4 Hz), 117.5 (d, J = 24.6 Hz), 116.4 (d, J = 22.0 Hz); ms: m/z
263 (M+).
Anal. Calcd for C13H7F2NO3: C, 59.32; H, 2.66; N, 5.32. Found: C, 59.35; H, 2.70;
N, 5.24.
Representative Procedure for the Cyclization of Dinitroacridinones:
10-Benzyl-2,7-dinitro-9(10H)-acridinone (9a)
A 50-mL, one-necked, round-bottomed flask, equipped with a magnetic stirrer and a con-
denser, was charged with 77 mg (0.25 mmol) of 5 and 2.5 mL of anhydrous DMF. The
mixture was heated with stirring to 60◦C and 29.4 mg (0.030 mL, 0.28 mmol) of benzyl-
amine was added. The mixture was stirred at 60◦C for 48 h, then cooled and added to 50 mL
of saturated aqueous sodium chloride. The mixture was extracted with dichloromethane
(3 × 25 mL) and the combined organic layers dried (MgSO4) and concentrated under
vacuum. Further concentration at 1 mmHg removed the DMF. The resulting solid was
triturated with ether and collected to give 77 mg (82%) of 9a as a yellow solid, which was
spectroscopically pure. An analytical sample could be obtained by trituration of the solid
in boiling 1:1 chloroform:ethanol followed by filtration, mp 282–284◦C. IR: 1652, 1522,
1329 cm−1; 1H NMR (DMSO-d6): δ 8.97 (d, J = 2.7 Hz, 2 H), 8.54 (dd, J = 9.3, 2.7 Hz,
2 H), 7.90 (d, J = 9.9 Hz, 2 H), 7.35 (m, 3 H), 7.26 (d, J = 6.6 Hz, 2 H), 5.96 (s, 2 H);
13C NMR27 (DMSO-d6): δ 175.8, 145.7, 142.1, 134.7, 129.0, 128.8, 127.7, 125.8, 122.7,
121.3, 118.9, 50.5; ms: m/z 375.
Anal. Calcd for C20H13N3O5: C, 64.00; H, 3.47; N, 11.20. Found: C, 64.05; H, 3.51;
N, 11.12.

10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem SNAr Reactions
10-(4-Methoxybenzyl)-2,7-dinitro-9(10H)-acridinone (9b)
271
This compound was prepared from 77 mg (0.25 mmol) of 5 and 38 mg (0.036 mL,
0.28 mmol) of 4-methoxybenzylamine to give 80 mg (79%) of 9b as a yellow powder, mp
264–266◦C. IR: 2837, 1664, 1513, 1333 cm−1; 1H NMR (DMSO-d6): δ 9.00 (d, J = 2.7 Hz,
2 H), 8.54 (dd, J = 9.3, 2.7 Hz, 2 H), 7.91 (d, J = 9.3 Hz, 2 H), 7.18 (d, J = 8.8 Hz,
2 H), 6.92 (J = 8.8 Hz, 2 H), 5.88 (s, 2 H), 3.71 (s, 3 H); 13C NMR (DMSO-d6): δ 175.9,
158.8, 145.7, 142.1, 128.0, 127.1, 126.3, 122.7, 121.3, 118.9, 114.3, 55.1, 50.1; ms: m/z
405 (M+).
Anal. Calcd for C21H15N3O6: C, 62.22; H, 3.70; N, 10.37. Found: C, 62.29; H, 3.75;
N, 10.28.
10-(4-Chlorobenzyl)-2,7-dinitro-9(10H)-acridinone (9c)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 39 mg (0.034 mL,
0.28 mmol) of 4-chlorobenzylamine to give 80 mg (78%) of 9c as yellow crystals, mp
300–302◦C. IR: 1648, 1522, 1327 cm−1; 1H NMR (DMSO-d6): δ 8.96 (d, J = 2.7 Hz, 2 H),
8.53 (dd, J = 9.3, 2.7 Hz, 2 H), 7.88 (d, J = 9.9 Hz, 2 H), 7.44 (d, J = 8.2 Hz, 2 H), 7.29
(d, J = 8.2 Hz, 2 H), 5.95 (s, 2 H); 13C NMR (DMSO-d6): δ 175.8, 145.6, 142.1, 133.7,
132.3, 128.9, 128.8, 127.8, 122.6, 121.4, 118.8, 50.0; ms: m/z 409/411 (ca 3:1, M+).
Anal. Calcd for C20H12ClN3O5: C, 58.61; H, 2.93; N, 10.26. Found: C, 58.67; H, 2.94;
N, 10.19.
10-(4-Trifluoromethylbenzyl)-2,7-dinitro-9(10H)-acridinone (9d)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 48 mg (0.039 mL,
0.28 mmol) of 4-(trifluoromethyl)benzylamine to give 90 mg (81%) of 9d as yellow
crystals, mp 282–284◦C. IR: 1655, 1524, 1323 cm−1; 1H NMR (DMSO-d6): δ 9.01 (d, J =
2.7 Hz, 2 H), 8.54 (dd, J = 9.3, 2.7 Hz, 2 H), 7.90 (d, J = 9.3 Hz, 2 H), 7.75 (d, J = 8.2 Hz,
2 H), 7.50 (d, J = 8.2 Hz, 2 H), 6.08 (s, 2 H); 13C NMR (DMSO-d6): δ 175.9, 145.7, 142.2,
139.7, 128.9, 126.8, 125.9, 125.8 (q, J = 3.0 Hz), 124.6 (q, J = 260.3 Hz), 122.7, 121.5,
118.8, 50.3; ms: m/z 443 (M+).
Anal. Calcd for C21H12F3N3O5: C, 56.88; H, 2.71; N, 9.48. Found: C, 56.95; H, 2.74;
N, 9.43.
10-(2-Phenylethyl)-2,7-dinitro-9(10H)-acridinone (9e)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 33 mg (0.035 mL,
0.28 mmol) of 2-phenylethylamine to give 60 mg (62%) of 9e as a yellow powder, mp
1
316–318◦C. IR: 1649, 1534, 1327 cm−1; H NMR (DMSO-d6): δ 9.01 (d, J = 2.7 Hz,
2 H), 8.58 (dd, J = 9.3, 2.7 Hz, 2 H), 8.16 (d, J = 9.3 Hz, 2 H), 7.42 (d, J = 7.1 Hz,
2 H), 7.31 (t, J = 7.1 Hz, 2 H), 7.26 (t, J = 7.1 Hz, 1 H), 4.87 (t, J = 7.7 Hz, 2 H), 3.16 (t,
J = 7.7 Hz, 2 H); 13C NMR (DMSO-d6); δ 175.6, 145.0, 141.9, 137.0, 129.1, 128.6, 128.5,
126.8, 122.8, 121.1, 118.9, 47.7, 32.5; ms: m/z 298 (M+-C7H7).
Anal. Calcd for C21H15N3O5: C, 64.78; H, 3.86; N, 10.80. Found: C, 64.84; H, 3.88;
N, 10.69.

272
Bunce and Grant
10-Hexyl-2,7-dinitro-9(10H)-acridinone (9f)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 28 mg (0.036 mL,
0.28 mmol) of hexylamine to give 71 mg (77%) of 9f as a yellow powder, mp
216.5–218.5◦C. IR: 1655, 1528, 1330 cm−1; 1H NMR (DMSO-d6): δ 9.32 (d, J = 2.7 Hz,
2 H), 8.57 (dd, J = 9.3, 2.7 Hz, 2 H), 7.65 (d, J = 9.3 Hz, 2 H), 4.44 (t, J = 8.2 Hz, 2 H),
2.01 (quintet, J = 8.2, Hz, 2 H), 1.64 (quintet, J = 7.1 Hz, 2 H), 1.46 (m, 4 H), 0.97 (t,
J = 7.1 Hz, 3 H); 13C NMR (DMSO-d6): δ 175.3, 144.8, 141.7, 128.6, 122.6, 120.8, 118.7,
47.0, 31.1, 26.7, 25.5, 22.1, 13.9; ms: m/z 369 (M+).
Anal. Calcd for C19H19N3O5: C, 61.79; H, 5.15; N, 11.38. Found: C, 61.87; H, 5.19;
N, 11.31.
10-Isobutyl-2,7-dinitro-9(10H)-acridinone (9g)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 20 mg (0.027 mL,
0.28 mmol) of isobutylamine to give 65 mg (76%) of 9g as a yellow powder, mp 284–285◦C.
IR: 1652, 1530, 1330 cm−1; 1H NMR (DMSO-d6): δ 8.99 (d, J = 2.7 Hz, 2 H), 8.55 (dd,
J = 9.3, 2.7 Hz, 2 H), 8.24 (d, J = 9.3 Hz, 2 H), 4.56 (d, J = 7.7 Hz, 2 H), 2.27 (nonet,
J = 6.6 Hz, 1 H), 0.99 (d, J = 6.6 Hz, 6 H); 13C NMR (DMSO-d6): δ 175.8, 145.6, 141.8,
128.3, 122.8, 121.1, 119.6, 52.1, 27.3, 19.5; ms: m/z 341 (M+).
Anal. Calcd for C17H15N3O5: C, 59.82; H, 4.40; N, 12.32. Found: C, 59.90; H, 4.42;
N, 12.27.
10-(3-Isopropoxypropyl)-2,7-dinitro-9(10H)-acridinone (9h)
This compound was prepared from 77 mg (0.25 mmol) of 5 and 32 mg (0.038 mL,
0.28 mmol) of 3-isopropoxypropylamine to give 71 mg (74%) of 9h as a yellow powder,
mp 200–202◦C. IR: 1655, 1524, 1331 cm−1; 1H NMR (DMSO-d6): δ 8.87 (d, J = 2.7 Hz,
2 H), 8.49 (dd, J = 9.3, 2.7 Hz, 2 H), 8.06 (d, J = 9.9 Hz, 2 H), 4.56 (t, J = 7.1 Hz, 2 H),
3.56 (m, 3 H), 2.05 (m, 2 H), 1.14 (d, J = 6.0 Hz, 6 H); 13C NMR (DMSO-d6): δ 175.2,
145.0, 141.6, 128.4, 122.5, 120.8, 118.5, 71.0, 64.0, 44.5, 27.4, 21.9; ms: m/z 385 (M+).
Anal. Calcd for C19H19N3O6: C, 59.22; H, 4.94; N, 10.91. Found: C, 59.33; H, 4.97;
N, 10.79.
Representative Reaction with 2,2ꢀ-Difluoro-5-nitrobenzophenone (8):
2-(Benzylamino)-5-nitro-2ꢀ-fluorobenzophenone (10a)
This compound was prepared as described for 9a from 66 mg (0.25 mmol) of 8 and
29.4 mg (0.030 mL, 0.28 mmol) of benzylamine to give 83 mg (95%) of 10a as a yellow
powder, mp 166–168◦C. IR: 3288, 1634, 1535, 1330 cm−1; 1H NMR (CDCl3): δ 9.96 (br
s, 1 H), 8.38 (t, J = 2.7 Hz, 1 H), 8.19 (dd, J = 9.3, 2.7 Hz, 1 H), 7.55 (m, 1 H), 7.45 (td,
J = 7.7, 1.6 Hz, 1 H), 7.40–7.33 (complex, 5 H), 7.32 (t, J = 7.7 Hz, 1 H), 7.21 (t, J = 9.3
Hz, 1 H), 6.78 (d, J = 9.3 Hz, 1 H), 4.62 (d, J = 5.5 Hz, 2 H); 13C NMR (CDCl3): δ 195.1,
159.0 (d, J = 250.8 Hz), 154.9, 136.4, 136.0, 132.9 (d, J = 8.3 Hz), 132.3, 130.4, 129.8
(d, J = 2.9 Hz), 129.0, 127.9, 127.1, 127.1 (obscured d), 124.6 (d, J = 3.4 Hz), 116.4 (d,
J = 21.5 Hz), 116.2, 112.1, 47.2; ms: m/z 350 (M+).

10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem SNAr Reactions
273
Anal. Calcd for C20H15FN2O3: C, 68.57; H, 4.29; N, 8.00. Found: C, 68.61; H, 4.31;
N, 7.96.
2-(Hexylamino)-5-nitro-2ꢀ-fluorobenzophenone (10f)
This compound was prepared from 66 mg (0.25 mmol) of 8 and 28 mg (0.036 mL,
0.28 mmol) of hexylamine to give 83 mg (96%) of 10f as a yellow powder, mp 59–60◦C.
IR: 3289, 1631, 1534, 1327 cm−1; 1H NMR (CDCl3): δ 9.62 (br s, 1 H), 8.35 (t, J = 2.7
Hz, 1 H), 8.23 (dd, J = 9.3, 2.7 Hz, 1 H), 7.54 (m, 1 H), 7.43 (td, J = 7.1, 1.6 Hz, 1 H),
7.30 (t, J = 7.1 Hz, 1 H), 7.21 (t, J = 9.3 Hz, 1 H), 6.79 (d, J = 9.9 Hz, 1 H), 3.38 (q, J =
6.6 Hz, 2 H), 1.78 (quintet, J = 7.1 Hz, 2 H), 1.58–1.28 (complex, 6 H), 0.91 (distorted t,
J = 7.1 Hz, 3 H); 13C NMR (CDCl3): δ 195.0, 159.0 (d, J = 250.5 Hz), 155.1, 135.4, 132.8,
(d, J = 8.3 Hz), 132.6, 130.4, 129.7 (d, J = 2.9 Hz), 127.2 (d, J = 16.5 Hz), 124.6 (d,
J = 3.4 Hz), 116.4 (d, J = 21.5 Hz), 115.7 111.6, 43.2, 31.4, 28.7, 26.7, 22.5, 14.0; ms:
m/z 344 (M+).
Anal. Calcd for C19H21FN2O3: C, 66.28; H, 6.10; N, 8.14. Found: C, 66.23; H, 6.13;
N, 8.11.
2-(Isobutylamino)-5-nitro-2ꢀ-fluorobenzophenone (10g)
This compound was prepared from 66 mg (0.25 mmol) of 8 and 20 mg (0.027 mL,
0.28 mmol) of isobutylamine to give 73 mg (92%) of 10g as a yellow powder, mp 85–86◦C.
IR: 3287, 1629, 1583, 1327 cm−1; 1H NMR (CDCl3): δ 9.73 (br s, 1 H), 8.36 (t, J = 2.7
Hz, 1 H), 8.22 (dd. J = 9.3, 2.7 Hz, 1 H), 7.55 (m, 1 H), 7.44 (td, J = 7.7, 1.6 Hz, 1 H),
7.30 (t, J = 7.7 Hz, 1 H), 7.21 (t, J = 9.3 Hz, 1 H), 6.79 (d, J = 9.9 Hz, 1 H), 3.21 (dd, J =
6.6, 5.5 Hz, 2 H), 2.07 (nonet, J = 6.6 Hz, 2 H), 1.09 (d, J = 6.6 Hz, 6 H); 13C NMR
(CDCl3): δ 195.0, 159.0 (d, J = 250.5 Hz), 155.2, 135.3, 132.8 (d, J = 8.0 Hz), 132.6,
130.4, 129.8 (d, J = 2.9 Hz), 127.1 (d, J = 16.3 Hz), 124.6 (d, J = 3.4 Hz), 116.4 (d, J =
21.5 Hz), 115.6, 111.6, 50.8, 28.0, 20.4; ms: m/z 316 (M+).
Anal. Calcd for C17H17FN2O3: C, 64.56; H, 5.38; N, 8.86. Found: C, 64.72; H, 5.43;
N, 8.77.
Acknowledgments
M. T. G. thanks Oklahoma State University for a Wentz Project Scholarship. Funding for
the 300 MHz NMR spectrometer of the Oklahoma Statewide Shared NMR Facility was
provided by NSF (BIR-9512269), the Oklahoma State Regents for Higher Education, the
W. M. Keck Foundation, and Conoco, Inc. Finally, the authors wish to thank the OSU
College of Arts and Sciences for funds to upgrade our departmental FT-IR and GC-MS
instruments.
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were difficult to purify.

10-Alkyl-2,7-dinitro-9(10H)-acridinones by Tandem SNAr Reactions
275
25. The reaction run on the same scale with 2,2-ꢀdifluorobenzophenone gave 8% of 10-benzyl-
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