precipitate was filtered off, washed with water and recrystallised
twice from ethanol (with charcoal), to give the nitrile 9a (3.1 g,
47%), mp 119–120 ЊC (Found: C, 43.35; H, 2.6; N, 25.3.
C8H6N4O4 requires C, 43.25; H, 2.7; N, 25.2%); νmax/cmϪ1 3320
(N–H), 1520 and 1330 (NO2); δH 4.25 (2H, d, CH2), 7.15 (1H,
t, 4-H), 8.10 (1H, t, NH) and 8.36 (2H, d, 3- and 5-H);
N-(o-Nitroaryl)glycines 12
N-(2,6-Dinitrophenyl)glycine 12a. The literature procedure18
was modified as follows. A solution of glycine (4.15 g, 55 mmol)
and sodium hydrogen carbonate (9.25 g, 110 mmol) in water
(30 cm3) was added to a solution of 1-chloro-2,6-dinitrobenzene
(10 g, 49 mmol) in methanol (100 cm3) and the mixture was
heated under reflux for 1.5 h and the solvent evaporated. Water
(500 cm3) was added to the residue and the insoluble (copper-
coloured) solid was filtered off and treated with dilute hydro-
chloric acid until the colour had changed to bright yellow. The
product was then filtered off and recrystallised from methanol,
giving the glycine 12a (6.78 g, 57%), mp 173–175 ЊC (lit.,17
173 ЊC); δH (CDCl3 ϩ [2H6]DMSO) 3.71 (2H, d, CH2), 6.86 (1H,
t, 4-H), 8.21 (2H, d, 3- and 5-H) and 9.06 (1H, br s, NH);
JCH
7.0, J3,4 = J4,5 8.0.
2,NH
N-Cyanomethyl-2-methyl-6-nitroaniline 9c. A mixture of 2-
methyl-6-nitroaniline (2.0 g, 13 mmol), paraformaldehyde (1.17
g, 39 mmol), potassium cyanide (2.54 g, 39 mmol), zinc chloride
(6.58 g, 48 mmol) and acetic acid (60 cm3) containing concen-
trated sulfuric acid (4 drops) was stirred and heated at 50–55 ЊC
for 7 h, then added to ice–water (300 cm3). The precipitate was
filtered off and recrystallised (twice) from ethanol, to give N,N-
bis(cyanomethyl)-2-methyl-6-nitroaniline (0.51 g, 17%), mp
113–114 ЊC (Found: C, 57.7; H, 4.4; N, 24.3. C11H10N4O2
JCH
4.4, J3,4 = J4,5 8.2.
2,NH
N-(2-Methyl-6-nitrophenyl)glycine 12c. N-Cyanomethyl-2-
methyl-6-nitroaniline 9c (2.0 g, 10.5 mmol) and concentrated
hydrochloric acid (25 cm3) were heated together under reflux for
1.5 h, and the resulting solution then added to ice–water (150
cm3). The precipitate was filtered off and recrystallised from
ethanol–water, giving the glycine 12c (1.66 g, 76%), mp 137–
139 ЊC (Found: C, 51.8; H, 4.7; N, 13.3. C9H10N2O4 requires C,
requires C, 57.4; H, 4.4; N, 24.3%); νmax/cmϪ1 2245w (C᎐N),
᎐
᎐
1525 and 1340 (NO2); δH 2.43 (3H, s, CH3), 4.35 (4H, s,
2 × CH2) and 7.35–7.85 (3H, m, Ar-H). The filtrate from the
original recrystallisation was concentrated under reduced pres-
sure to give a yellow solid (0.82 g) which was shown (TLC) to be
a mixture of the starting methylnitroaniline and both mono-
and bis-cyanomethyl compounds.
51.4; H, 4.8; N, 13.3%); νmax/cmϪ1 1720 (C᎐O), 1530 and 1325
᎐
Repetition of the experiment using 2-methyl-6-nitroaniline
(4.5 g, 30 mmol), paraformaldehyde (2.63 g, 90 mmol), potas-
sium cyanide (5.71 g, 90 mmol), zinc chloride (9.88 g, 73
mmol) and acetic acid (140 cm3) containing concentrated sul-
furic acid (4 drops) gave a solid product which was chrom-
atographed on silica gel (200 g) in petroleum. Elution with
ether–petroleum (1:9) gave unreacted amine (1.29 g; 29%
recovery) and elution with ether–petroleum (3:7) then gave
N-cyanomethyl-2-methyl-6-nitroaniline, 9c (1.60 g, 29%), mp
75 ЊC (Found: C, 56.7; H, 4.7; N, 22.1. C9H9N3O2 requires C,
(NO2); δH 2.36 (3H, s, CH3), 3.98 (2H, s, CH2), 6.86 (1H, t,
4-H), 7.43 (1H, br d, 3-H) and 7.80 (1H, dd, 5-H); J3,4 8, J4,5
8.5, J3,5 1.6.
N-[2-Nitro-4-(trifluoromethyl)phenyl]glycine 12d. Potassium
carbonate (3.46 g, 25 mmol) and glycine (1.88 g, 25 mmol) were
added to a solution of 4-chloro-3-nitrobenzotrifluoride [1-
chloro-2-nitro-4-(trifluoromethyl)benzene] (4.51 g, 20 mmol) in
ethanol (60 cm3) and the mixture heated under reflux for 24 h.
The resulting solution was acidified (HCl), and the yellow pre-
cipitate filtered off, dried and recrystallised from toluene, giving
the glycine 12d (3.06 g, 58%), mp 161–162 ЊC (Found: C, 40.8;
H, 2.5; N, 10.45. C9H7F3N2O4 requires C, 40.9; H, 2.7; N,
10.6%); δH [(CD3)2CO] 4.30 (2H, d, CH2), 7.27 (1H, d, 6-H),
7.80 (1H, dd, 5-H), 8.37–8.50 (1H, m, 3-H), 8.75 (1H, br s, NH)
56.5; H, 4.7; N, 22.0%); νmax/cmϪ1 3325 (N᎐H), 2240w
᎐
(C᎐N), 1535 and 1330 (NO ); δ 2.39 (3H, s, CH3), 4.25
᎐
2
H
2H, d, CH2), 6.40 (1H, t, NH), 7.08 (1H, t, 4-H), 7.55 (1H, br d,
3-H) and 7.85 (1H, dd, 5-H); JCH
7.5, J3,4 = J4,5 8, J3,5 1.6.
2,NH
Later fractions contained mixtures of 9c and the bis-
cyanomethyl compound.
and 9.70 (1H, br s, CO2H); JCH
5, J3,5 2, J5,6 10; m/z 264
2,NH
(Mϩ ), 245 and 219 (100%).
N-Cyanomethyl-2,4-difluoro-6-nitroaniline
9h.
2Ј,4Ј-
N-[2,4-Dinitro-6-(trifluoromethyl)phenyl]glycine 12g. Glycine
(2.63 g, 35 mmol) and sodium hydrogen carbonate (5.04 g,
60 mmol) were added to a solution of 2-chloro-3,5-dinitro-
Difluoroacetanilide, mp 119–120 ЊC (from ethanol; lit.,16
120.9 ЊC) was obtained (yield 87%) from 2,4-difluoroaniline
and a threefold excess of acetic anhydride at room tem-
perature. Nitration of this amide according to a published
method 17 gave 2Ј,4Ј-difluoro-6Ј-nitroacetanilide (yield 83%),
mp 132–134 ЊC (from ethanol; lit,17 142–143 ЊC); δH [(CD3)2CO]
2.20 (3H, s, CH3) and 7.52–7.92 (2H, m, Ar-H); m/z
216 (2%), 201, 175, 174, etc. Hydrolysis of the acetyl group
using concentrated sulfuric acid 16 gave 2,4-difluoro-6-
nitroaniline (yield 78%), mp 81–82 ЊC (from ethanol; lit.,16
85.5–86.5 ЊC); δH 5.90 (2H, br, NH2), 7.00–7.10 (1H, symm. m,
5-H) and 7.50 (1H, dt, 3-H); J3,5 = J3,6-F 3, J3,4-F 9, J5,4-F = J5,6-F
10.
benzotrifluoride
[2-chloro-1,5-dinitro-3-(trifluoromethyl)-
benzene] (8.12 g, 30 mmol) in methanol (150 cm3). The mixture
was heated under reflux for 5 h, then cooled and filtered, and the
filtrate concentrated under reduced pressure. The orange resi-
due was stirred with a mixture of dichloromethane (30 cm3) and
hydrochloric acid (5 ; 20 cm3), then filtered off, washed with
water and recrystallised from methanol–water, giving the gly-
cine 12g in almost quantitative yield (9.15 g); mp 161–162 ЊC
(Found: C, 34.8; H, 1.75; N, 13.35. C9H6F3N3O6 requires C,
35.0; H, 2.0; N, 13.4%); δH [(CD3)2CO] 4.25 (2H, s, CH2), 8.80
(1H, m, 5-H) and 9.27 (1H, d, 3-H); J3,5 3.
2,4-Difluoro-6-nitroaniline (2.61 g, 15 mmol), paraformalde-
hyde (1.35 g, 45 mmol), zinc chloride (15.54 g, 114 mmol) and
potassium cyanide (2.93 g, 45 mmol) were combined and acetic
acid (40 cm3) containing concentrated sulfuric acid (2 drops)
was added. The mixture was stirred and heated at 50 ЊC for
6 h and then kept at room temperature overnight. The mixture
was added to ice–water and the product was filtered off and
recrystallised from methanol, giving the nitrile 9h (2.88 g, 90%),
mp 121–122 ЊC (Found: C, 44.9; H, 2.2; N, 19.6. C8H5F2N3O2
requires C, 45.1; H, 2.4; N, 19.7%); δH [(CD3)2CO] 4.65 (2H, dd,
CH2), 7.68 (1H, 16 lines, 3-H), 7.75 (1H, br s, NH) and 7.93
(1H, 8 lines, 5-H); δF Ϫ119.6 (16 lines, 2-F) and Ϫ122.0 (8 lines,
N-(2,4-Difluoro-6-nitrophenyl)glycine 12h. The nitrile 9h (4.10
g, 19 mmol) was heated with acetic acid (90 cm3) and aqueous
sulfuric acid (50% v/v; 220 cm3) at 100 ЊC for 2.5 h and the
mixture then added to crushed ice. The precipitate was filtered
off and recrystallised from ethanol to give the glycine 12h (3.10
g, 70%), mp 156–158 ЊC (Found: C, 41.2; H, 2.3; N, 11.9.
C8H6F2N2O4 requires C, 41.4; H, 2.6; N, 12.1%) νmax/cmϪ1 3390
(N–H) and 1710br (C᎐O); δ [(CD ) CO] 4.45 (2H, d, CH ), 7.55
᎐
H
3
2
2
(1H, symm. m, 3-H) and 7.87 (1H, symm. m, 5-H); JCH
5, J3,5 3.2, J5,F -4 9.2, J5,F -2 2.0, J3,F -4 8.0, J3,F -2 14.0.
2,NH
N-(o-Nitroaryl)glycine esters 13
4-F); J3,N H 0.4, JCH
9.0, J5,2-F 2.0, J5,4-F 8.0, J3,2-F 13.4.†
7.2, JCH
4, J3,5 3.2, JF,F 2.0, J3,4-F
N-(2,6-Dinitrophenyl)glycine ethyl ester 13a. A solution of N-
(2,6-dinitrophenyl)glycine 12a (2.29 g, 9.5 mmol) in ethanol (60
cm3) containing concentrated sulfuric acid (1.3 g) was heated
under reflux for 4 h, then concentrated under reduced pressure,
cooled in ice and the precipitate filtered off and washed with
2,NH
2,2-F
† The coupling constants were obtained by computer simulation.
J. Chem. Soc., Perkin Trans. 1, 1997
1379