* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
General procedure: 2-aminobenzonitrile (1mmol), and KCC-1/IL NPs (0.0007g) were added. The autoclave was closed, purged twice with CO2 gas, pressurized with 0.8MPa of CO2 and then heated at 70°C for 60min. Then the reactor was cooled to ambient temperature, and the resulting mixture was transferred to a 50mL round bottom flask. Upon completion, the progress of the reaction was monitored by TLC when the reaction was completed, EtOH was added to the reaction mixture and the KCC-1/IL NPs were separated by distillation under vacuum. Then the solvent was removed from solution under reduced pressure and the resulting product purified by recrystallization using n-hexane/ethyl acetate.
91%
With fibrous nanosilica functionalized with sodium tripolyphosphate and 3-aminopropyltriethoxysilane In neat (no solvent) at 70℃; for 0.833333 h; Autoclave; Green chemistry
General procedure: 2-aminobenzonitrile (1 mmol) and KCC-1/STPP NPs (0.7 mg) were mixed together. The autoclave was closed, purged twice with CO2 gas, pressurized to 1.5 MPa of CO2, and heated at 70°C for 50 min. Then, the reactor was cooled to ambient temperature and the resulting mixture was transferred to a 50 mL round-bottom flask. During completion, the reaction progress was monitored by TLC. Following its completion, EtOH was added to the reaction mixture and the catalyst was separated by filtration. Afterwards, the solvent was removed from the solution under reduced pressure and the resulting product was purified by recrystallization using n-hexane/ethyl acetate. The products are known and their sample characterization data is presented in the Supplemental Materials.
81%
With {Eu[N(SiMe3)2](μ-O:κ2-C6H5C(O)NC6H3(iPr)2)(THF)}2; 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 100℃; for 24 h;
Under anhydrous, anaerobic, argon protection, 0.0999 g (7.5 × 10 -5 mol){L2Eu [N (SiMe3) 2] · THF} 2, followed by 11.2 μL (7.5 × 10 -5 mol) of DBU,Under the protection of carbon dioxide bag, add 2mL dimethyl sulfoxide,After adding 0.3107 g (1.5 x 10-3 mol) of 2-amino-5-nitrobenzonitrile,The reaction was stirred in a constant temperature bath at 100 ° C. After 24 hours,The reaction was quenched by adding 5 mL of 2 mol / L hydrochloric acid and suction filtration. The solid was washed with 3 × 5 mL of hydrochloric acid, then with toluene and ether, the residual solvent was removed and the solid was dried to give the product in a yield of 81percent
Reference：
[1] Catalysis Communications, 2015, vol. 72, p. 91 - 96
[2] Catalysis Science and Technology, 2016, vol. 6, # 5, p. 1435 - 1441
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 2018, vol. 193, # 8, p. 535 - 544
[4] Tetrahedron, 2002, vol. 58, # 16, p. 3155 - 3158
[5] RSC Advances, 2015, vol. 5, # 31, p. 24670 - 24674
[6] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 4, p. 1764 - 1771
[7] European Journal of Organic Chemistry, 2016, vol. 2016, # 14, p. 2555 - 2559
[8] Patent: CN105153048, 2017, B, . Location in patent: Paragraph 0120; 0121
[9] Green Chemistry, 2014, vol. 16, # 6, p. 3142 - 3148
[10] ChemCatChem, 2016, vol. 8, # 1, p. 244 - 250
[11] Heteroatom Chemistry, 2012, vol. 23, # 3, p. 276 - 280
[12] Catalysis Science and Technology, 2014, vol. 4, # 6, p. 1608 - 1614
[13] ChemSusChem, 2017, vol. 10, # 6, p. 1145 - 1151
[14] Tetrahedron Letters, 2004, vol. 45, # 38, p. 7073 - 7075
[15] Patent: WO2008/70823, 2008, A2, . Location in patent: Page/Page column 4-5; 10-11; 6/14
[16] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 153 - 157
[17] Patent: EP1970373, 2008, A1, . Location in patent: Page/Page column 44
[18] Inorganic Chemistry, 2012, vol. 51, # 23, p. 13001 - 13008
[19] RSC Advances, 2016, vol. 6, # 112, p. 111079 - 111089
8
[ 17420-30-3 ]
[ 68-12-2 ]
[ 6943-17-5 ]
[ 32618-85-2 ]
Reference：
[1] Organic Process Research and Development, 2016, vol. 20, # 12, p. 2067 - 2073
[2] Organic Letters, 2009, vol. 11, # 6, p. 1193 - 1196
With p-nitrobenzenesulfonic acid; palladium diacetate In tetrahydrofuran; water at 80℃; for 48 h; Inert atmosphere; Schlenk technique
General procedure: Under a N2 atmosphere, a Schlenk tube was charged with 2-aminobenzonitrile 1 (0.3 mmol),sodium arylsulfinate 2 (0.6 mmol), Pd(OAc)2 (10 mol percent), bpy (20 mol percent), p-NBSA (10 equiv), THF (2 mL), and H2O (1 mL) at room temperature. The reaction mixture was stirred vigorously at 80 °C for 48 h. The mixture was poured into ethyl acetate, which was washed with saturated NaHCO3 (2 × 10 mL) and then brine (1 × 10 mL). After the aqueous layer was extracted with ethyl acetate, the combined organic layers were dried over anhydrous MgSO4 and evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane/ethyl acetate) to afford the desired products 3.
Reference：
[1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 41, p. 8204 - 8211
12
[ 619-24-9 ]
[ 17420-30-3 ]
[ 87331-46-2 ]
[ 6393-40-4 ]
Reference：
[1] Journal of Organic Chemistry, 1998, vol. 63, # 15, p. 4878 - 4888
[2] Journal of Organic Chemistry, 1996, vol. 61, # 9, p. 2934 - 2935
13
[ 49675-77-6 ]
[ 17420-30-3 ]
Yield
Reaction Conditions
Operation in experiment
72%
With sodium carbonate In N,N-dimethyl-formamide at 140℃; for 1 h;
A mixture of compound 12 (4.18g, 0.02mol) and Na2CO3 (1.0g) in DMF (40ml) was heated to 140°C for 1h. The mixture was poured into 100ml of ice water. The solution was extracted with CH2Cl2 (50ml×3). The organic phase was washed three times with water and then dried over anhydrous sodium sulfate and evaporated under reduce pressure, giving crude product as brown liquid. The curde product was purified by column chromatography over silica gel (using petroleum / EtOAc=2:1) to afford 20 as a yellow solid 2.34g with a yield of 72percent. mp 208~210°C.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 11, p. 2589 - 2593
14
[ 16588-02-6 ]
[ 17420-30-3 ]
Reference：
[1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1985, vol. 25, # 4, p. 137 - 138
[2] Recueil des Travaux Chimiques des Pays-Bas, 1924, vol. 43, p. 718
[3] Recueil des Travaux Chimiques des Pays-Bas, 1946, vol. 65, p. 468,474
[4] Patent: CN105418458, 2016, A, . Location in patent: Paragraph 0024
15
[ 619-24-9 ]
[ 17420-30-3 ]
Reference：
[1] Journal of Organic Chemistry, 1998, vol. 63, # 15, p. 4878 - 4888
[2] Journal of Organic Chemistry, 1986, vol. 51, # 25, p. 5039 - 5040
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 11, p. 2589 - 2593
27
[ 91-56-5 ]
[ 17420-30-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 11, p. 2589 - 2593
28
[ 873-32-5 ]
[ 17420-30-3 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1924, vol. 43, p. 718
29
[ 544-92-3 ]
[ 121-87-9 ]
[ 17420-30-3 ]
Reference：
[1] Journal of the Indian Chemical Society, 1996, vol. 73, # 11, p. 629 - 630
30
[ 873-32-5 ]
[ 17420-30-3 ]
[ 87331-46-2 ]
Reference：
[1] Russian Journal of Organic Chemistry, 1996, vol. 32, # 11, p. 1682 - 1689
31
[ 16588-02-6 ]
[ 7664-41-7 ]
[ 17420-30-3 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1924, vol. 43, p. 718
32
[ 17420-30-3 ]
[ 16313-65-8 ]
Yield
Reaction Conditions
Operation in experiment
24.63 g
at 130℃; for 0.666667 h;
Step 1 A mixture of 2-amino-5-nitrobenzonitrile (25.39 g) and sulfuric acid (70 ml) was stirred at 130° C. for 40 min. The reaction mixture was gradually added to ice water, and the precipitate was collected by filtration and washed with water, ethanol and diethyl ether to give 2-amino-5-nitrobenzamide (24.63 g).
Reference：
[1] Archiv der Pharmazie, 1994, vol. 327, # 9, p. 571 - 579
[2] Patent: EP1953148, 2008, A1, . Location in patent: Page/Page column 130
[3] Patent: US2015/329556, 2015, A1, . Location in patent: Paragraph 1771
[4] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 568 - 576
33
[ 17420-30-3 ]
[ 19230-50-3 ]
Reference：
[1] Magnetic Resonance in Chemistry, 1989, vol. 27, # 11, p. 1007 - 1011
34
[ 17420-30-3 ]
[ 14346-13-5 ]
Yield
Reaction Conditions
Operation in experiment
98%
With 3 % platinum on carbon; ammonia; hydrogen In ethanol at 50℃; Autoclave
Step 1: Add 3 kg of 2-cyano-4-nitroaniline, 15 L of ethanol, 80 g of 3percent Pt / C catalyst and 300 mL of ammonia (chemically pure) to a 20 L autoclave, replace with nitrogen, replace with hydrogen, warm to 50 ° C, The pressure is kept at 1.6MPa, the reaction is not to absorb hydrogen, and then the reaction material after the reaction is filtered to obtain filtrate; Step 2, the filtrate described in step 1 is precipitated and crystallized at a temperature of -10 ° C for 18 hours to obtain a solid-liquid mixture; Step 3, solid-liquid separation of the solid-liquid mixture in the second step is carried out under the protection of nitrogen to obtain the solid and the filtrate, and then the solid is dried in a vacuum drying box, and then the solid is dried at 130 ° C ~ 136 ° C under vacuum distillation, to be white 2, 5-diaminobenzonitrile; Step 4: The filtrate described in step 3 is concentrated in vacuum at 45 ° C to 1/5 of the volume of the filtrate.The reduced filtrate was repeated in steps 2 and 3 and combined with 2, 5-diaminobenzonitrile in step 3 to afford 2.4 kg of product 2. 5-diaminobenzonitrile. The mass purity of 2,5-diaminobenzonitrile prepared in this example was not less than 99.5percent and the yield was 98.0percent.
89%
With hydrazine hydrate In ethanol at 80℃; for 1 h; Inert atmosphere
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
82%
With palladium diacetate; hydrazine hydrate; potassium hydroxide In water at 50℃; for 8 h; Inert atmosphere; Green chemistry
General procedure: To an oven-dried reaction flask with Teflon coated stir bar purgedwith argon, Pd(OAc)2 0.01 mmol, IL4 0.08 mmol, KOH (or K2CO3)0.30 mmol, nitroarene 1 1.0 mmol and degassed HPLC grade water1.5 mL were added, and the mixture was stirred for 5 min under argonat room temperature. Then, 0.5 mL of hydrazine hydrate aqueous solution(~5.0 mmol) was syringed into the flask at the same temperature.After stirring for additional 5 min, the reaction was heat to 50 °C,and stirring for 8 h under argon. After completion, the reaction mixturewas extracted by methyl tertiary butyl ether (MTBE) (3 × 2 mL), andthe organic layer was collected and filtered through a bed of silica gellayered over Celite. The volatiles were removed in vacuo to afford theproduct 2. In some cases, further column chromatography on silica gelwas required to afford the pure desired products.
160.3 mg
With palladium 10% on activated carbon; hydrogen In methanol at 20℃;
A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) and palladium/ charcoal (10 mg, 10 wt percent) in methanol (3 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/2) to give 160.3 mg of the titled compound as a pale yellow solid. [0551] 1H-NMR (400 MHz, CDCl3) δ 6.79 (d, 1H), 6.72 (s, 1H), 6.61 (d, 1H), 4.01 (brs, NH), 3.45 (brs, NH)
the step (3) in the liquid ammonia the niter chlorine mixes the fluid for aminolysis reaction, after the reaction to the terminal point 80 C lower distillation recovery solvent; aminolysis reaction temperature is 110 C, aminolysis reaction pressure is 2.6 MPa; the end point of the reaction is determined in the liquid chromatograph;
With ammonium hydroxide; copper(l) iodide; at 200℃; for 6.5h;Autoclave; Green chemistry;
General procedure: In a typical experiment, p-CNB (1 g, 6.35 mmol), CuI (0.635 mmol),commercial 25% aqueous NH3 solution (10 mL, NH3/p-CNB molar ratio21/1) were loaded into a 50 mL stainless steel reactor and sealed. Thematerial of the autoclave used is AISI 316 L, for which the compositionis Cr 16-18%, Ni 10-14%, Mo 2-3%, MnQ2%, Si Q1%, CQ0.03%,SQ0.03%, PQ0.045%, and the other part is Fe. After being heated to200 C, the reaction was conducted while stirring with a magneticstirrer (1200 rpm). The pressure of the vapor phase (NH3 and H2O) wasabout 3 MPa at the reaction temperature. After stirring for 1 h, the reactorwas cooled to room temperature and the reaction mixture wasseparated by centrifugation. The solid substrate and product were dissolvedin ethanol and analyzed by a gas chromatograph (Shimadzu GC-2010) equipped with a capillary column (Rtx-5 capillary column: 30m×0.25mm ×0.25 Tm, carrier: N2) and a flame ionization detector(FID) and gas chromatograph-mass spectrometer (GC-MS, Agilent 5890,HP-5). o-Xylene was used as an internal standard for quantitativeanalysis. The liquid phase was also analyzed by gas chromatograph andno p-CNB or p-NAN were detected. The carbon balance was near 99%and trace amount of other unidentified byproducts were observed.
With ammonia; In chlorobenzene; at 120℃; under 24002.4 Torr; for 2.5h;Autoclave;
f. adding <strong>[16588-02-6]2-chloro-5-nitrobenzonitrile</strong> in step e to chlorobenzene for dissolution;g. transporting the <strong>[16588-02-6]2-chloro-5-nitrobenzonitrile</strong> solution to the autoclave;h. The liquid ammonia is sent to the high pressure reactor through a compression pump for 2.5 h, the reaction temperature in the autoclave is 120 C, and the pressure in the autoclave is 3.2 Mpa;i. The pressure of the high pressure reactor is collected to collect excess liquid ammonia and separate the chlorobenzene and the reaction product;j. The reaction product in step i is washed and dried to obtain 2-amino-5-nitrobenzonitrile.The yield of 2-amino-5-nitrobenzonitrile obtained by drying was 89%, and the HPLC purity was 99.2%.
Step 1 A mixture of 2-amino-5-nitrobenzonitrile (25.4 g) and sulfuric acid (70 mL) was stirred at 130C for 40 min. The reaction mixture was added slowly to ice water, and the precipitate was collected by filtration, washed with water, ethanol and diethyl ether to give 2-amino-5-nitrobenzamide (24.6 g).
24.63 g
With sulfuric acid; at 130℃; for 0.666667h;
Step 1 A mixture of 2-amino-5-nitrobenzonitrile (25.39 g) and sulfuric acid (70 ml) was stirred at 130 C. for 40 min. The reaction mixture was gradually added to ice water, and the precipitate was collected by filtration and washed with water, ethanol and diethyl ether to give 2-amino-5-nitrobenzamide (24.63 g).
Stage #1: 5-nitroanthranilonitrile With naphthalene-1,5-disulfonate In ethyl acetate at 50℃; for 0.166667h;
Stage #2: With tert.-butylnitrite In ethyl acetate at 25℃; for 0.333333h;
Stage #3: N-ethyl-N-(2-cyanoethyl)aniline With hydrogenchloride In water at 0 - 5℃; for 0.266667h;
2.4 Typical procedure for coupling
General procedure: N,N-Diethylaniline (10mmol) was dissolved in 80mL water with 1.2mL 37% hydrochloric acid and then the salmon pink diazonium salt of 2,4-dinitroaniline was quickly added within 2minat 0°C-5°C followed by adjusting the pH to 4-5 with 2M NaOH solution. The reaction endpoint was confirmed by color reaction using H-acid. The precipitated dye was filtered, washed with water and dried at 80°C to afford the crude product. The crude yield was 95.0% and the degree of purity was 97.0%.
With KCC-1/IL NPs; at 70℃; under 6000.6 Torr; for 1h;Autoclave;
General procedure: 2-aminobenzonitrile (1mmol), and KCC-1/IL NPs (0.0007g) were added. The autoclave was closed, purged twice with CO2 gas, pressurized with 0.8MPa of CO2 and then heated at 70C for 60min. Then the reactor was cooled to ambient temperature, and the resulting mixture was transferred to a 50mL round bottom flask. Upon completion, the progress of the reaction was monitored by TLC when the reaction was completed, EtOH was added to the reaction mixture and the KCC-1/IL NPs were separated by distillation under vacuum. Then the solvent was removed from solution under reduced pressure and the resulting product purified by recrystallization using n-hexane/ethyl acetate.
91%
With fibrous nanosilica functionalized with sodium tripolyphosphate and 3-aminopropyltriethoxysilane; In neat (no solvent); at 70℃; under 11251.1 Torr; for 0.833333h;Autoclave; Green chemistry;
General procedure: 2-aminobenzonitrile (1 mmol) and KCC-1/STPP NPs (0.7 mg) were mixed together. The autoclave was closed, purged twice with CO2 gas, pressurized to 1.5 MPa of CO2, and heated at 70C for 50 min. Then, the reactor was cooled to ambient temperature and the resulting mixture was transferred to a 50 mL round-bottom flask. During completion, the reaction progress was monitored by TLC. Following its completion, EtOH was added to the reaction mixture and the catalyst was separated by filtration. Afterwards, the solvent was removed from the solution under reduced pressure and the resulting product was purified by recrystallization using n-hexane/ethyl acetate. The products are known and their sample characterization data is presented in the Supplemental Materials.
81%
With {Eu[N(SiMe3)2](mu-O:kappa2-C6H5C(O)NC6H3(iPr)2)(THF)}2; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 100℃; for 24h;
Under anhydrous, anaerobic, argon protection, 0.0999 g (7.5 × 10 -5 mol){L2Eu [N (SiMe3) 2] · THF} 2, followed by 11.2 muL (7.5 × 10 -5 mol) of DBU,Under the protection of carbon dioxide bag, add 2mL dimethyl sulfoxide,After adding 0.3107 g (1.5 x 10-3 mol) of 2-amino-5-nitrobenzonitrile,The reaction was stirred in a constant temperature bath at 100 C. After 24 hours,The reaction was quenched by adding 5 mL of 2 mol / L hydrochloric acid and suction filtration. The solid was washed with 3 × 5 mL of hydrochloric acid, then with toluene and ether, the residual solvent was removed and the solid was dried to give the product in a yield of 81%
1,8-diazabicyclo[5.4.0]undec-7-ene; In tetrahydrofuran; under 760.051 Torr;
SynthesisPeptidomimetics 37-44 were synthesized via solid phase peptide synthesis, using Suzuki couplings employing various boronic acids and aryl bromides. Intermediates display hydrophobic substituents from the aromatic spacer (Abz). The simple quinazoline scaffolds derived from commercially available starting materials. The synthesis of the quinazolines cores 45a-b was accomplished by the cyclization of 4-nitroanthranilic acid by the reaction with sodium isocyanate or cyclization employing a carbon dioxide atmosphere with catalytic DBU (1 ,8-diazabicyclo[5.4.0]undec-7-ene) from 4- and 5-nitro precursors respectively Figure 10. Alkylation was followed by reduction of the nitro group followed by coupling with A- nitrobenzoyl chloride via anilide formation to provide 48a-b. Reduction to the aniline, coupling with AcArg(Pmc)-OH, and deprotection of the guanidine protecting group afforded 50a-b.A convergent synthesis using methyl-4-amino-2-bromobenzoate or methyl-4-aminobenzoate and 4-nitroaniline created non-peptidic inhibitors 56aa-ci, as seen in Figure 13. Suzuki coupling of the bromoaniline with the corresponding boronic acid, employing PdCI2(dppf) as a catalyst, created compounds 51a followed by reductive amination utilizing N-Boc- aminoacetaldehyde produced compounds 52a-c. A series of deprotections followed by guanidinylation of the resulting amine afforded the N-terminal portions of the inhibitor 53a-c. The C-terminal hydrophobic portion of the molecule was synthesized via alkylation of A- nitroaniline with the corresponding bromide and subsequent reduction of the nitro group utilizing tin (II) chloride, producing compounds 55a-i. Coupling of compounds 53a-c and 55a- i followed by Boc deprotection under acidic conditions produced inhibitors 56aa-ci. Inhibitors64a-b were derived from a similar synthesis, but in place of the reductive amination step, 48c was reacted with Boc-Gly-OH to provide the amide intermediate compound 62 which was manipulated in a similar manner to provide inhibitors 64a-b, seen in Figure 16.The synthesis of inhibitors 57aa-fa was designed to employ a late stage Suzuki coupling to provide faster access to a number of derivatives at the R1 position, while keeping R2 as a <n="13"/>benzyl substituent, see Figure 15. Commercially available methyl-4-amino-3-bromobenzoate was saponified under basic conditions followed by amide bond formation with compound 55a to provide compound 59a. This intermediate was then reacted with different boronic acid derivatives PdCI2(dppf) as a catalyst to provide 60aa-fa. A series of functional group transformations provided inhibitors 57aa-fa. The indole scaffold was readily derived from commercially available 4-iodoaniline and Boc- GIy-OH, which were reacted to form iodo-amide compound 65, seen in Figure 17. Sonagashira cross-coupling of compound 65 and ethynyl-trimethyl-silane (TMS-acetylene) followed by removal of the silyl protecting group afforded terminal alkyne compound 66. A consecutive Sonagashira cross-coupling with 2-iodo-4-nitroaniline followed by cycloisomerization employing catalytic copper (II) acetate41 afforded indole scaffold compound 68. Reduction of the nitro to the amine followed by alkylation with the cooresponding bromide provided compound 70a-b. A series of functional group transformations, similar to the reactions depicted in Figures 10 and 13, provided inhibitors 71a-b. It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween. Now that the invention has been described,
(1) DBU(32.7 g) was added to a solution of 2-amino-5-nitrobenzonitrile(11.69 g) in DMF(135 mL) at room temperature and the mixture was stirred under carbon dioxide atmosphere at room temperature overnight. The reaction solution was cooled to 0C, and 1N hydrochloric acid(1350 mL) was added dropwise. The precipitated crystals were filtered, washed with diethyl ether and dried to give 6-nitro-1H-quinazolin-2,4-dione(14.13 g) as a yellow powder. APCI-MS(m/e):206[M-H]-.
With N-iodo-succinimide; sodium nitrite In N,N-dimethyl-formamide at 20℃; for 4h;
73.9%
Stage #1: 5-nitroanthranilonitrile With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Inert atmosphere;
Stage #2: With potassium iodide In water at 0 - 20℃; Inert atmosphere;
2.1.1. 2-Iodo-5-nitrobenzonitrile (3)
A solution of sodium nitrite (2.88 g, 41.7 mmol) in water (10 mL) was added dropwise to a solution of 2-amino-5-nitrobenzonitrile (5.10 g, 31.2 mmol) in conc. hydrogen chloride aqueous solution (40 mL) at 0 °C under N2 gas, and stirred for 30 min at 0 °C. A solution of potassium iodide (33.1 g, 199 mmol) in water (50 mL) was added dropwise to the solution. After stirring at 0 °C for 3 h and then overnight at room temperature, the product was extracted with dichloromethane. The organic layer was washed with 10% sodium hydroxide aq. solution, 5% sodium hydrogen carbonate aq. solution, and water. The organic layer was dried with sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel column chromatography (dichloromethane:hexane 2:1 v/v) to obtain the desired product 3 as a pale yellow solid (6.32 g, 73.9%)
65%
Stage #1: 5-nitroanthranilonitrile With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h;
Stage #2: With potassium iodide In water at 0 - 20℃; Further stages.;
Stage #1: 5-nitroanthranilonitrile With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h;
Stage #2: With sodium iodide In water at 0 - 20℃;
With tin(IV) chloride; In toluene; for 4.0h;Reflux;
First, 3.2 g of 2-cyano-4-nitroaniline, 30 mL of acetone and 100 mL of toluene were placed in a 250 ml round bottom flask, cooled to 0 C, and then 3.0 mL of SnCl4 was slowly added dropwise. Next, the reaction system was refluxed for 4 h, then cooled to room temperature and the solid was suction filtered to give the intermediate a. 2.0 g of intermediate a and 540 mg of ammonium chloride were mixed in a system of 50 mL (ethanol: water = 2:1) and 2.6 g of reduced iron powder was added at 60 C. Then the temperature was raised to 85 C for 2 hours, cooled to room temperature. The solvent was dried, and the mixture was filtered by suction. The filtrate was spin-dried. The obtained slag layer was recrystallized from a mixture of petroleum ether and ethyl acetate to obtain a starting material A1.
With tin(IV) chloride; In toluene; for 4.5h;Cooling with ice; Reflux;
4-Nitro-2-cyanoaniline (1.6 g, 10 mmol) and a certain amount of acetone were dissolved in anhydrous toluene, and tin tetrachloride (1.2 ml, 10 mmol) was slowly added dropwise to the above reaction solution in an ice water bath. The reaction solution was then refluxed for 4.5 h.After stopping the reaction, a large amount of solid precipitated during cooling to room temperature, and the solid was suction filtered.After washing with a small amount of diethyl ether, 2-methyl-6-nitro-4-aminoquinoline was obtained.Next, the reduced nitro group is reduced to an amino group by ammonium chloride catalysis.It is further reacted with 2,4-dichloro-5-fluoropyrimidine in ethanol under reflux conditions under the catalysis of N,N-diisopropylethylamine (DIEA). The solid precipitated in the suction filtration reaction gives 2a-3 .Finally, the intermediate 2a-3 and 3,4,5-trimethoxyaniline were synthesized according to 3a-1.final product,Total yield: 46percent; purity: 99percent.
With 3 % platinum on carbon; ammonia; hydrogen; In ethanol; at 50.0℃; under 12001.2 Torr;Autoclave;
Step 1: Add 3 kg of 2-cyano-4-nitroaniline, 15 L of ethanol, 80 g of 3% Pt / C catalyst and 300 mL of ammonia (chemically pure) to a 20 L autoclave, replace with nitrogen, replace with hydrogen, warm to 50 C, The pressure is kept at 1.6MPa, the reaction is not to absorb hydrogen, and then the reaction material after the reaction is filtered to obtain filtrate; Step 2, the filtrate described in step 1 is precipitated and crystallized at a temperature of -10 C for 18 hours to obtain a solid-liquid mixture; Step 3, solid-liquid separation of the solid-liquid mixture in the second step is carried out under the protection of nitrogen to obtain the solid and the filtrate, and then the solid is dried in a vacuum drying box, and then the solid is dried at 130 C ~ 136 C under vacuum distillation, to be white 2, 5-diaminobenzonitrile; Step 4: The filtrate described in step 3 is concentrated in vacuum at 45 C to 1/5 of the volume of the filtrate.The reduced filtrate was repeated in steps 2 and 3 and combined with 2, 5-diaminobenzonitrile in step 3 to afford 2.4 kg of product 2. 5-diaminobenzonitrile. The mass purity of 2,5-diaminobenzonitrile prepared in this example was not less than 99.5% and the yield was 98.0%.
89%
With hydrazine hydrate; In ethanol; at 80.0℃; for 1.0h;Inert atmosphere;
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
82%
With palladium diacetate; hydrazine hydrate; potassium hydroxide; In water; at 50.0℃; for 8.0h;Inert atmosphere; Green chemistry;
General procedure: To an oven-dried reaction flask with Teflon coated stir bar purgedwith argon, Pd(OAc)2 0.01 mmol, IL4 0.08 mmol, KOH (or K2CO3)0.30 mmol, nitroarene 1 1.0 mmol and degassed HPLC grade water1.5 mL were added, and the mixture was stirred for 5 min under argonat room temperature. Then, 0.5 mL of hydrazine hydrate aqueous solution(~5.0 mmol) was syringed into the flask at the same temperature.After stirring for additional 5 min, the reaction was heat to 50 C,and stirring for 8 h under argon. After completion, the reaction mixturewas extracted by methyl tertiary butyl ether (MTBE) (3 × 2 mL), andthe organic layer was collected and filtered through a bed of silica gellayered over Celite. The volatiles were removed in vacuo to afford theproduct 2. In some cases, further column chromatography on silica gelwas required to afford the pure desired products.
palladium; In N-methyl-acetamide;
EXAMPLE XVI 2,5-Diamino-benzonitrile 10 g of 2-cyano-4-nitro-aniline are dissolved in 50 ml of dimethylformamide and, after addition of 0.5 g of palladium-on-charcoal (10%), are hydrogenated in a Parr apparatus at room temperature under a hydrogen pressure of 3 bar for 2 hours. After cooling, the mixture is filtered, the solvent is distilled off in a rotary evaporator and the residue is used further without further purification. Yield: 10.2 g (100% of theory) of a brown, chromatographically uniform oil, Rf value: 0.63 (Silica gel; methylene chloride/ethyl acetate/methanol=10:4:2)
With hydrogen;palladium 10% on activated carbon; In methanol; at 20.0℃;
A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) and palladium/charcoal (10 mg, 10 wt%) in methanol (3 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate = 1/2) to give 160.3 mg of the titled compound as a pale yellow solid.[742] 1H-NMR(400MHz, CDCl3) delta 6.79(d, 1H), 6.72(s, 1H), 6.61(d, 1H), 4.01(brs, NH), 3.45(brs, NH)
With hydrogen;palladium 10% on activated carbon; In methanol; at 20.0℃;
A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) and palladium/charcoal (10 mg, 10 wt%) in methanol (3 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate = 1/2) to give 160.3 mg of the titled compound as a pale yellow solid.[654] 1H-NMR(400MHz, CDCl3) delta 6.79(d, 1H), 6.72(s, 1H), 6.61(d, 1H), 4.01(brs, NH), 3.45(brs, NH)
160.3 mg
With palladium 10% on activated carbon; hydrogen; In methanol; at 20.0℃;
A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) and palladium/ charcoal (10 mg, 10 wt %) in methanol (3 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/2) to give 160.3 mg of the titled compound as a pale yellow solid. [0551] 1H-NMR (400 MHz, CDCl3) delta 6.79 (d, 1H), 6.72 (s, 1H), 6.61 (d, 1H), 4.01 (brs, NH), 3.45 (brs, NH)
a. 2,5-Diaminobenzonitrile To a solution of 80 grams (0.356 mole) of stannous chloride dihydrate in 200 ml. of concentrated hydrochloric acid is added in portions over the course of about 5 minutes, 16.314 grams (0.1 mole) of 5-nitroanthranilonitrile. Water cooling is used and the internal temperature rises to about 50. Stirring is continued for 4 hours and the mixture is allowed to stand overnight. The reaction mixture is cooled to 5 in an ice-bath and a cold 50% solution of sodium hydroxide added until the mixture is strongly basic. The mixture is extracted with methylene chloride. The methylene chloride extracts are washed with water and the solvent removed by distillation. There is obtained 11.51 grams (86.5%) of material melting at 85-87. Recrystallization from benzene-skellysolve B gives material melting at 86-7. The infrared spectrum is in agreement.
With SrCl2 modified silica sulfuric acid; In water; for 3h;Reflux; Green chemistry;
General procedure: o-Aminobenzonitriles 1 (6 mmol), cycloketones 2 (6.1 mmol), and catalyst S1-S9 (0.5 g) were added in water respectively and refluxed with stirring for about 3 h. After completion of the reaction (indicated by TLC), the catalyst was filtered and recovered, and the mixture was kept overnight. Then the obtained residue was filtered and recrystallized with ethanol to give the pure products 3
With p-nitrobenzenesulfonic acid; palladium diacetate In tetrahydrofuran; water at 80℃; for 48h; Inert atmosphere; Schlenk technique;
General Procedure for the Synthesis of o-Aminobenzophenones
General procedure: Under a N2 atmosphere, a Schlenk tube was charged with 2-aminobenzonitrile 1 (0.3 mmol),sodium arylsulfinate 2 (0.6 mmol), Pd(OAc)2 (10 mol %), bpy (20 mol %), p-NBSA (10 equiv), THF (2 mL), and H2O (1 mL) at room temperature. The reaction mixture was stirred vigorously at 80 °C for 48 h. The mixture was poured into ethyl acetate, which was washed with saturated NaHCO3 (2 × 10 mL) and then brine (1 × 10 mL). After the aqueous layer was extracted with ethyl acetate, the combined organic layers were dried over anhydrous MgSO4 and evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane/ethyl acetate) to afford the desired products 3.
To 2 g of 2-amino-5-nitrobenzonitrile 1, 25 mL of formic acid were added and the mixture was refluxed for 6 h while stirring. The reaction mixture was then poured on ice water resulting in the formation of a yellow precipitate which was separated by filtration to give compound 11.
With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 13h; Inert atmosphere;
1 (Synthesis of Compound 2)
A solution of compound 1 (5.00 g, 30.6 mmol), guanidine hydrochloride (3.50 g, 36.6 mmol) and potassium carbonate (10.1 g, 73.1 mmol) in dry DMF (70 mL) was heated and stirred at 120 ° C. under a nitrogen atmosphere for 13 hours. did. After cooling, volatiles were removed in vacuo. The remaining solid was washed with water and acetone to give compound 2 (5.74 g, 28.0 mmol, 92%) as an orange solid.
86%
Stage #1: guanidine hydrochloride With sodium hydroxide In ethanol at 20℃; for 0.333333h;
Stage #2: 5-nitroanthranilonitrile In propan-1-ol; ethanol for 6h; Reflux;
4.1.12 6-Nitroquinazoline-2,4-diamine (11)
Sodium hydroxide (3.4 g, 85 mmol) was added to a solution of guanidine hydrochloride (3.65 g, 38 mmol) in ethanol, and the reaction was stirred for 20 min at room temperature. The solution was then stirred under reflux for 6h with 5-nitroanthranilonitrile (5 g, 31 mmol) in 1-propanol (40 mL). Then, the mixture was cooled to 0°C. The solid was filtered off, washed with cold water, washed with cold ethanol and dried. An orange solid product was obtained (5.4 g, 86%, Mp: 360°C), TLC (2-butanol/acetic acid/water=80/20/5) Rf=0.4. IR (KBr): 3464 and 3440 (N-H), 1614 (C-H, aromatic), 1325 (NO2). 1H NMR (DMSO-d6): 6.77 (s, 2H, NH2), 7.22 (d, J=9, 1H, aromatic), 7.86 (s, 2H, NH2), 8.21 (dd, J1=3, J2=9, 1H, aromatic), 9.08 (d, J=3, 1H, aromatic); 13C NMR (DMSO-d6): 108.84, 121.92, 124.87, 126.63, 139.12, 157.28, 163.00, 163.025. Anal. Calcdfor C12H13N5O2: C, 46.83; H, 3.44; N, 34.13.
86%
Stage #1: guanidine hydrochloride With sodium hydroxide In ethanol at 20℃; for 0.333333h;
Stage #2: 5-nitroanthranilonitrile In propan-1-ol; ethanol for 6h; Reflux;
4.1.3. 6-Nitroquinazoline-2,4-diamine (3)
Sodium hydroxide (3.4 g, 85 mmol) was added to a solution ofguanidine hydrochloride (3.65 g, 38 mmol) in ethanol, and the reaction was stirred for 20 min at room temperature. The solutionwas then stirred under reflux for 6 h with 5-nitroanthranilonitrile(5 g, 31 mmol) in 1-propanol (40 mL). Then, the reaction mixturewas cooled to 0 C. The solid was filtered off, washed with coldwater,washed with cold ethanol and dried. An orange solid productwas obtained (5.4 g, 86%, Mp: 360 C), TLC (2-butanol/acetic acid/water 80/20/5) Rf 0.4. IR (KBr): 3464 and 3440 (NeH), 1614(CeH, aromatic), 1325 (NO2). 1H NMR (DMSO-d6): 6.77 (s, 2H, NH2),7.22 (d, J 9, 1H, aromatic), 7.86 (s, 2H, NH2), 8.21 (dd, J1 3, J2 9,1H, aromatic), 9.08 (d, J 3, 1H, aromatic); 13C NMR (DMSO-d6):108.84, 121.92, 124.87, 126.63, 139.12, 157.28, 163.00, 163.025. Anal.Calcd for C12H13N5O2: C, 46.83; H, 3.44; N, 34.13.
(3aSR,7aRS)-2,2,5-trimethyl-11-nitro-2,7,7a,8-tetrahydropyrrolo[3,2-l]acridin-6(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
Stage #1: 5-nitroanthranilonitrile With sulfuric acid In dichloromethane at 20 - 25℃; for 0.0833333h;
Stage #2: 2-methylmethoxybenzene; isobutyraldehyde In dichloromethane at 5 - 25℃; for 0.416667h; diastereospecific reaction;
Preparation of compounds 6a-g,i,j (General method).
General procedure: Dichloromethane (0.3 ml) was added to 2-amino-5-nitrobenzonitrile(3) (326 mg, 2 mmol), followed by theaddition of 94% H2SO4 (2 ml) and stirring for 5 min at 20-25°. The obtained solution was cooled (5-10°), stirred,and treated by dropwise addition of a mixture of theappropriate arene 1 (2 mmol) and isobutyric aldehyde (2)(0.23 ml, 2.5 mmol). The reaction mixture was stirred for25 min at 20-25°, poured into a mixture of crushed ice(15-20 g) with aqueous 25% ammonia solution (15 ml)with pH control (pH 7). The mixture was extracted withEtOAc (3×25 ml), the combined extracts were washed withH2O and dried over anhydrous Na2SO4. The solvent wasremoved by evaporation at reduced pressure. The residuewas crystallized and/or purified by column chromatography.
(3aSR,7aRS)-4,5-dimethoxy-2,2-dimethyl-11-nitro-2,7,7a,8-tetrahydropyrrolo[3,2-l]acridin-6(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%
Stage #1: 5-nitroanthranilonitrile With sulfuric acid In dichloromethane at 20 - 25℃; for 0.0833333h;
Stage #2: 1,2,3-trimethoxybenzene; isobutyraldehyde In dichloromethane at 5 - 25℃; for 0.416667h; diastereospecific reaction;
Preparation of compounds 6a-g,i,j (General method).
General procedure: Dichloromethane (0.3 ml) was added to 2-amino-5-nitrobenzonitrile(3) (326 mg, 2 mmol), followed by theaddition of 94% H2SO4 (2 ml) and stirring for 5 min at 20-25°. The obtained solution was cooled (5-10°), stirred,and treated by dropwise addition of a mixture of theappropriate arene 1 (2 mmol) and isobutyric aldehyde (2)(0.23 ml, 2.5 mmol). The reaction mixture was stirred for25 min at 20-25°, poured into a mixture of crushed ice(15-20 g) with aqueous 25% ammonia solution (15 ml)with pH control (pH 7). The mixture was extracted withEtOAc (3×25 ml), the combined extracts were washed withH2O and dried over anhydrous Na2SO4. The solvent wasremoved by evaporation at reduced pressure. The residuewas crystallized and/or purified by column chromatography.
(6aRS,14aSR)-13,13-dimethyl-10-nitro-6a,7,13,14-tetrahydrobenzo[a]pyrrolo[2,3-m]acridin-5(6H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
Stage #1: 5-nitroanthranilonitrile With sulfuric acid In dichloromethane at 20 - 25℃; for 0.0833333h;
Stage #2: isobutyraldehyde; 1-Methoxynaphthalene In dichloromethane at 5 - 25℃; for 0.416667h; diastereospecific reaction;
Preparation of compounds 6a-g,i,j (General method).
General procedure: Dichloromethane (0.3 ml) was added to 2-amino-5-nitrobenzonitrile(3) (326 mg, 2 mmol), followed by theaddition of 94% H2SO4 (2 ml) and stirring for 5 min at 20-25°. The obtained solution was cooled (5-10°), stirred,and treated by dropwise addition of a mixture of theappropriate arene 1 (2 mmol) and isobutyric aldehyde (2)(0.23 ml, 2.5 mmol). The reaction mixture was stirred for25 min at 20-25°, poured into a mixture of crushed ice(15-20 g) with aqueous 25% ammonia solution (15 ml)with pH control (pH 7). The mixture was extracted withEtOAc (3×25 ml), the combined extracts were washed withH2O and dried over anhydrous Na2SO4. The solvent wasremoved by evaporation at reduced pressure. The residuewas crystallized and/or purified by column chromatography.(6aR*,14aS*)-13,13-Dimethyl-10-nitro-6a,7,13,14-tetrahydrobenzo[a]pyrrolo[2,3-m]acridin-5(6H)-one (6a).The residue was separated by chromatography (eluentpetroleum ether - EtOAc, gradient from 5:1 to 3:1). Yield425 mg (59%), yellow crystals, mp 295°C (decomp.,acetone), Rf 0.34 (petroleum ether - acetone, 3:1). IR spectrum,ν, cm-1: 1317, 1615, 1636, 1681, 3060, 3116, 3147,3196, 3270, 3345. 1H NMR spectrum, δ, ppm (J, Hz): 1.47(3H, s, 13-3); 1.50 (3, s, 13-3); 2.11 (1H, d,J = 13.2, 14-2); 2.17 (1H, d, J = 13.2, 14-2); 2.88(1H, dd, J = 18.0, J = 2.8, 6-2); 3.10 (1H, dd, J = 18.0,J = 3.2, 6-2); 4.07 (1H, t, J = 3.2, 6a-CH); 5.03 (1H, br. s,NH); 6.46 (1, dd, J = 8.8, J = 0.4, H-8); 7.05 (1, dd,J = 7.6, J = 0.8, H-1); 7.33 (1H, td, J = 7.6, J = 1.2, H-3);7.46 (1H, td, J = 7.6, J = 1.6, H-2); 7.96 (1, dd, J = 9.2,J = 2.8, H-9); 8.03 (1, dd, J = 7.6, J =1.6, H-4); 8.84 (1H,d, J = 2.8, H-11). 13C NMR spectrum, δ, ppm: 29.4; 32.3;40.2; 48.6; 55.9; 58.8; 73.8; 114.3; 115.2; 124.1; 127.3;127.4; 127.8; 128.0; 130.9; 134.8; 139.5; 142.8; 150.4;164.6; 194.0. Mass spectrum, m/z (Irel, %): 361 [M]+ (81),346 [M-3]+ (100), 300 (10), 230 (11), 204 (16), 128(15). Found, %: C 69.96; H 5.22; N 11.66. C21H19N3O3.Calculated, %: C 69.79; H 5.30; N 11.63.
Multi-step reaction with 4 steps
1.1: N,N-dimethyl acetamide / 5 h / 75 °C
2.1: acetic acid / 2 h / 85 °C
3.1: Pd/C / tetrahydrofuran / 5 h / 20 °C
4.1: caesium carbonate / N,N-dimethyl-formamide / 1 h / 20 °C
4.2: 20 h / 125 °C / Sealed tube
Multi-step reaction with 5 steps
1: methanol; tert-butyl methyl ether / 40 °C
2: hydrogen; 10% Pd/C / tetrahydrofuran / 35 °C
3: tetrahydrofuran / -14 °C
4: acetic acid / Isopropyl acetate / 45 °C
5: p-toluenesulfonyl chloride; sodium hydroxide / tetrahydrofuran
Multi-step reaction with 5 steps
1.1: 90 min / 90 °C
2.1: 10% Pd/C; hydrogen / methanol / 5 h / 35 °C
3.1: tetrahydrofuran / 40 min / -5 °C / Sealed tube; Inert atmosphere
3.2: 90 min / 20 °C / Inert atmosphere
4.1: acetic acid / ethyl acetate / 40 °C
5.1: sodium hydroxide; p-toluenesulfonyl chloride / tetrahydrofuran / 1 d / 20 °C
Stage #1: 5-nitroanthranilonitrile With hydrogenchloride; sodium nitrite In water at 1℃; for 1h;
Stage #2: 3-[(2-hydroxyethyl)(phenyl)amino]propanenitrile In ethanol; water at 5 - 11℃; for 8.4h;
4
(1) The aqueous solution of an amino-containing aniline compound (the structural formula of the amino-containing aniline compound is: The mass fraction is 18%) is added to the hydrochloric acid solution (the mass fraction is 36.5%), the sodium nitrite aqueous solution (the mass fraction is 29%) is added with stirring, the diazotization reaction is carried out at 1°C, and the reaction time is 1h , The diazonium salt is obtained; wherein the molar ratio of the amino-containing aniline compound, sodium nitrite and hydrochloric acid is 1:1.02:4.1; (2) Add N-cyanoethyl-N-hydroxyethylaniline aqueous solution (15% by mass) to hydrochloric acid, and dilute with an appropriate amount of ethanol solution (95% by mass) to obtain N-cyanoethyl-N-hydroxy Ethyl aniline mixed solution, Then under stirring conditions, the diluted N-cyanoethyl-N-hydroxyethyl aniline mixed solution was cooled to 5°C and then added to the diazonium salt for coupling reaction (reacted at 1°C for 0.9h, and then heated to 11°C , Reaction 7.5h), After the reaction is complete, use 15% sodium hydroxide solution to adjust the pH to 6, and finally add distilled water to 2 times the total mass of the reaction system at the end of the reaction, wash and filter. After repeating 4 times, add ethanol at 5 times the weight of the last filter cake to increase the temperature to 68°C, and heat for 37 minutes. Filter while hot, and cool the filtrate to 2°C, separate out the crystals, filter with suction and dry at 62°C, to obtain special disperse dyes for anhydrous dyeing system; Among them, the molar ratio of N-cyanoethyl-N-hydroxyethyl aniline, hydrochloric acid and ethanol solution is 1:1.9:0.6; N-cyanoethyl-N-hydroxyethyl aniline and amino-containing aniline in the diazotization reaction The molar ratio of the compound is 1.02:1.
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