10.1002/ejoc.202100948
European Journal of Organic Chemistry
FULL PAPER
The formylation was performed according to general procedure 3
starting from the quantities given above. The aldehyde compound
28 (yield: 985 mg, 82%) was isolated as a brown oil. 1H NMR (400
MHz, [D6]DMSO) δ = 9.70 (s, 1H, C[31]-H), 7.38 (dd, J = 4.3, 2.6
Hz, 2H, C[3, 5]-H), 7.26 (dd, J = 8.0, 1.5 Hz, 2H, C[10, 13]-H),
7.16 (td, J = 7.5, 1.7 Hz, 1H, C[12]-H), 7.03 (td, J = 7.3, 1.3 Hz,
1H, C[11]-H), 6.70 (d, J = 8.7 Hz, 1H, C[2]-H), 4.26 (t, J = 7.6 Hz,
2H, C[7]-H), 4.19 (s, 4H, C[15-16]-H), 4.10 (q, J = 7.1 Hz, 4H,
C[19-20]-H), 4.02 – 3.95 (m, 8H, C[17-18, 21-22]-H), 3.04 (t, J =
7.5 Hz, 2H, C[8]-H), 1.17 (t, J = 7.1 Hz, 6H, C[23-24]-H), 1.07 (t,
J = 7.1 Hz, 6H, C[25-26]-H). 13C {1H} NMR (101 MHz, [D6]DMSO)
δ = 190.8, 170.3, 170.2, 148.7, 144.5, 133.3, 130.6, 128.9, 127.1,
125.4, 124.6, 123.4, 116.0, 111.9, 68.3, 60.4, 60.2, 55.0, 53.8,
added dropwise. After stirring for 5 hours at 90 °C, the solution
was cooled to room temperature and poured on crushed ice. The
formed solids were filtered, and dried. The nitro compound 18
(yield: 9.0 g, 90%) was isolated as yellow crystals. Melting point:
153 °C. (Ref: 156 °C) The hydrogenation was carried out
according to general procedure 1, with some modification. Only 5
bar H2 was used, and 2 mol % PtO2 proved to be an effective
catalyst to terminate co-product formation. The amino compound
19 (brown crystal, yield: 3.0 g, 96%) was isolated starting from 4 g
of 18. Melting point: 96 °C. (Ref: 117 °C) The spectroscopic
properties of compounds 18 and 19 were in agreement with those
published previously.[17,28]
+
30.5, 29.1, 14.1, 14.0. HRMS (ESI+): m/z calcd for C31H41N2O10
([M+H]+): 601.27558, found: 601.27545.
The alkylation was carried out according to general procedure 2,
from 7 mmol of amine. The ethyl ester compound 20 (yield: 8.32
g, 87 %) was isolated as a brown oil. 1H NMR (400 MHz,
[D6]DMSO) δ = 7.37 (dd, J = 7.6, 1.6 Hz, 1H, C[12]-H), 7.30 – 7.16
(m, 2H, C[9, 11]-H), 7.06 (td, J = 7.3, 1.4 Hz, 1H, C[10]-H), 6.95
(dd, J = 7.5, 3.2 Hz, 1H, C[5]-H), 6.87 - 6.76 (m, 2H, C[3,4]-H),
6.70 (dd, J = 7.5, 3.2 Hz, 1H, C[2]-H), 5.06 (s, 2H, C[7]-H), 4.07
(s, 4H, C[14,15]-H), 4.04 (s, 4H, C[16,17]-H), 3.96 (q, J = 7.1 Hz,
4H, C[18,19]-H), 3.86 (q, J = 7.1 Hz, 4H, C[20,21]-H), 1.06-1.10
(t, J = 7.1 Hz, 12H, C[22-25]-H). 13C {1H} NMR (101 MHz,
[D6]DMSO) δ = 170.7, 170.5, 149.7, 149.4, 138.8, 131.0, 130.6,
128.5, 123.4, 122.0, 121.3, 120.8, 118.0, 113.2, 66.7, 60.1, 59.9,
The coupling to the fluorophore was carried out using the General
procedure 4 starting from 1 mmol starting material. The ethyl ester
protected fluorescent dye 35 (yield: 50 mg, 6%) was isolated as a
red powder. Melting point: decomposed at 118 °C. 1H NMR (400
MHz, CDCl3) δ = 7.56 (d, J=9.3 Hz, 2H, C[33, 42]-H), 7.49 – 7.09
(m, 4H, C[2, 3, 11, 12]-H), 7.05 – 6.95 (m, 3H, C[5, 10, 13]-H),
6.94 – 6.83 (m, 4H, C[34, 36, 39, 41]-H), 4.35 – 4.29 (m, 8H, C[15-
16, 19-20]-H), 4.14 (t, J=6.6 Hz, 2H, C[7]-H), 4.07 – 3.98 (m, 8H,
C[17-18, 21-22]-H), 3.67 (q, J=7.1 Hz, 8H, C[44-47]-H), 3.25 (t,
J=7.4 Hz, 2H, C[8]-H), 1.38 (td, J=7.2, 1.8 Hz, 18H, C[23-24, 48-
51]-H), 1.20 (t, J=7.1 Hz, 6H, C[25-26]-H). 13C {1H} NMR (101
MHz, CDCl3) δ = 190.8, 171.3, 170.7, 158.1, 155.4, 150.1, 149.0,
141.3, 133.7, 132.5, 130.8, 127.7, 125.3, 125.2, 124.5, 124.5,
123.2, 117.9, 114.6, 113.7, 113.3, 96.6, 61.2, 60.7, 55.1, 53.9,
46.1, 31.5, 14.4, 14.2, 12.7. HRMS (ESI+): m/z calcd for
C51H65N4O10+ ([M]+): 893.46952, found: 893.46984.
+
54.8, 53.3, 14.0, 13.9. HRMS (ESI+): m/z calcd for C29H38N2O9
([M+H]+): 559.26501, found: 559.26552.
The formylation was performed according to general procedure 3
using 3 mmol starting material. The aldehyde compound 29 (yield:
1
440 mg, 22 %) was isolated as a yellow oil. H NMR (400 MHz,
[D6]DMSO) δ = 9.74 (s, 1H, C[30]-H), 7.43 – 7.34 (m, 3H, C[3, 5,
9]-H), 7.27 (td, J = 7.7, 7.3, 1.7 Hz, 1H, C[11]-H), 7.21 (dd, J=8.2,
1.3 Hz, 1H, C[12]-H), 7.07 (td, J = 7.3, 1.3 Hz, 1H, C[10]-H), 6.72
(d, J = 8.2 Hz, 1H, C[2]-H), 5.11 (s, 2H, C[7]-H), 4.14 (s, 4H, C[14-
15]-H), 4.06 (s, 4H, C[16-17]-H), 3.95 (q, J = 7.1 Hz, 4H, C[18-
19]-H), 3.82 (q, J = 7.1 Hz, 4H, C[20-21]-H), 1.07 (td, J = 6.6, 6.1,
2.9 Hz, 14H, C[22-25]-H). 13C {1H} NMR (101 MHz, [D6]DMSO) δ
= 190.7, 170.6, 170.2, 149.8, 148.7, 144.8, 131.3, 130.2, 128.9,
125.5, 123.5, 122.2, 116.0, 111.6, 67.1, 60.2, 60.2, 56.1, 54.8,
The hydrolysis was carried out using General procedure 5 starting
from the quantities given above. The fluorescent dye 5b (yield: 15
mg, 41%) was isolated as a red powder. Melting point:
1
decomposed at 116 °C. H NMR (400 MHz, [D4]methanol) δ =
7.57 (d, J = 9.6 Hz, 2H, C[25, 34]-H), 7.28 – 7.23 (m, 2H, C[26,
33]-H), 7.13 – 6.96 (m, 7H, C[2-3, 5, 10-13]-H), 6.91 (d, J = 2.5
Hz, 2H, C[28, 31]-H), 4.38 (t, J = 7.5 Hz, 2H, C[7]-H), 4.23 (s, 4H,
C[15-16]-H), 3.85 (s, 4H, C[17-18]-H), 3.66 (q, J = 7.1 Hz, 8H,
C[36-39]-H), 3.19 (t, J = 7.6 Hz, 2H, C[8]-H), 1.29 (t, J = 7.1 Hz,
14H, C[40-43]-H). 13C {1H} NMR (101 MHz, [D4]methanol) δ =
175.4, 174.2, 159.7, 159.5, 157.0, 151.2, 150.6, 142.8, 135.1,
133.8, 132.4, 128.5, 126.1, 125.7, 124.9, 124.4, 118.5, 116.9,
115.3, 114.5, 97.4, 70.4, 56.1, 55.4, 46.9, 33.1, 13.0. HRMS
+
53.6, 14.0, 13.9. HRMS (ESI+): m/z calcd for C30H38N3O9
([M+H]+): 587.25993, found: 587.26038.
The coupling to the fluorophore was carried out using the general
procedure 4 starting from 0.38 mmol formyl compound. The ethyl
ester protected fluorescent dye 36 (yield: 49 mg, 15 %) was
isolated as purple powder. Melting point: decomposed at 121.1 °C.
1H NMR (400 MHz, CDCl3) δ 7.45 (td, J = 8.2, 7.7, 3.1 Hz, 3H,
C[3, 32, 41]-H), 7.30 – 7.24 (m, 2H, C[11, 12]-H), 7.18 – 7.13 (m,
1H, C[10]-H), 7.01 (d, J = 1.7 Hz, 1H, C[5]-H), 6.91 – 6.86 (m, 2H,
C[35-38]-H), 6.85 – 6.77 (m, 4H, C[2, 9, 33, 40]-H), 5.20 (s, 2H,
C[7]-H), 4.22 (s, 4H, C[14-15]-H), 4.05 – 3.96 (m, 8H, C[16-17,
18-19]-H), 3.93 (q, J = 7.1 Hz, 4H, C[20-21]-H), 3.63 (q, J = 7.1
Hz, 8H, C[43-46]-H), 1.34 (t, J = 7.0 Hz, 12H, C[47-50]-H), 1.23 (t,
J = 7.1 Hz, 6H, C[22-23]-H), 1.14 (t, J = 7.1 Hz, 6H, C[24-25]-H).
13C {1H} NMR (101 MHz, CDCl3) δ 171.3, 171.0, 158.2, 157.8,
155.3, 149.8, 149.5, 141.7, 132.6, 131.2, 131.0, 129.1, 124.7,
124.1, 123.7, 123.5, 117.4, 115.3, 113.7, 113.2, 96.6, 67.6, 61.1,
+
(ESI+): m/z calcd for C43H49N4O10 ([M]+): 781.34432, found:
781.34423.
Preparation of the fluorescent dye 6b.
The first step to achieve ethyl ester 20 was carried out following
the previously reported method.[18] 1.72 g (43 mmol, 1.2 equiv.)
NaH (60% in mineral oil) was suspended in 60 ml DMF, then 5 g
(36 mmol, 1.0 equiv.) 2-nitrophenol in 10 ml DMF was added
dropwise to this solution. The yellow solution of 2-nitrophenol
turned into red/orange. The mixture was stirred at room
temperature for 1 hour until the gas formation stopped, then 7.76
g (36 mmol, 1.0 equiv.) 2-nitrobenzyl bromide in 10 ml DMF was
14
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