[ CAS No. 539-48-0 ]

Name: 539-48-0|1,4-Phenylenedimethanamine|98%
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Quality Control of [ 539-48-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 539-48-0 ]

Product Details of [ 539-48-0 ]

CAS No. :	539-48-0	MDL No. :	MFCD00009821
Formula :	C₈H₁₂N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ISKQADXMHQSTHK-UHFFFAOYSA-N
M.W :	136.19	Pubchem ID :	68315
Synonyms :

Calculated chemistry of [ 539-48-0 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	41.79
TPSA :	52.04 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-7.17 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.28
Log Po/w (XLOGP3) :	-0.05
Log Po/w (WLOGP) :	0.3
Log Po/w (MLOGP) :	0.94
Log Po/w (SILICOS-IT) :	1.05
Consensus Log Po/w :	0.7

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.96
Solubility :	14.8 mg/ml ; 0.108 mol/l
Class :	Very soluble
Log S (Ali) :	-0.59
Solubility :	34.8 mg/ml ; 0.256 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.46
Solubility :	0.474 mg/ml ; 0.00348 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Safety of [ 539-48-0 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3259
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 539-48-0 ]

* 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.

Upstream synthesis route of [ 539-48-0 ]
Downstream synthetic route of [ 539-48-0 ]

[ 539-48-0 ] Synthesis Path-Upstream 1~13

1
[ 623-26-7 ]
[ 10406-25-4 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
92.1%	With hydrogen In ammonia; 1,3,5-trimethyl-benzene at 50℃;	EXAMPLE 5 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5percent by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 molpercent, the yield of 4-cyanobenzylamine was 88.8 molpercent and the yield of p-xylynenediamine was 5.8 molpercent. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of the catalyst A. The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 molpercent, the yield of 4-cyanobenzylamine was 0.2 molpercent and the yield of p-xylynenediamine was 92.1 molpercent.
87.7%	With hydrogen In ammonia; 1,3,5-trimethyl-benzene at 50℃;	EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5percent by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 molpercent, the yield of 4-cyanobenzylamine was 88.8 molpercent and the yield of p-xylynenediamine was 5.8 molpercent. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of Ni-diatomaceous earth pellets (manufactured by Nikki Chemical Co., Ltd.; Ni supported amount = 46percent by weight). The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 molpercent, the yield of 4-cyanobenzylamine was 0.5 molpercent and the yield of p-xylynenediamine was 87.7 molpercent.

Reference： [1] Patent: EP1449825, 2004, A1, . Location in patent: Page 5
[2] Patent: EP1449825, 2004, A1, . Location in patent: Page 5

2
[ 623-26-7 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
98.7%	With hydrogen In 1,2,4-Trimethylbenzene; ammonia at 80℃; for 24 h;	The procedure of Example 1 was repeated except for using terephthalonitrile in place of isophthalonitrile and changing the amount of Catalyst A to 0.6 g, the pretreatment gas to a mixed gas (methanol:nitrogen=4:96 by volume), and the pretreatment conditions to atmospheric pressure, 250° C., a flow rate of 0.18 NL/h, and 3 h. After 24 h of the hydrogenation, the conversion of terephthalonitrile was 100 mol percent, the yield of p-xylylenediamine was 98.7 mol percent, and the yield of high-boiling condensation products was 1.3 mol percent.
92.4%	With hydrogen In 1,2,4-Trimethylbenzene; ammonia at 80℃; for 24 h;	The procedure of Example 12 was repeated except for omitting the pretreatment. After 24 h of the hydrogenation, the conversion of terephthalonitrile was 100 mol percent, the yield of p-xylylenediamine was 92.4 mol percent, and the yield of high-boiling condensation products was 7.6 mol percent.
92%	With hydrogen In ethanol at 95℃; for 1 h;	(1) 100g of terephthalonitrile and 3g of Raney-Ni and 400mL of ethanol were added into a 1L hydrogenation kettle, H2 was continuously charged, The reaction pressure during the system is always maintained at 7MPa. The reaction temperature 95 for 1h, cooling. When the temperature in the reaction vessel was lowered to room temperature, the solution was vented to give p-xylylenediamine (purity of 99percent or more) by filtration and recrystallization in a yield of 92percent

35.6%

With hydrogen In ammonia; 1,3,5-trimethyl-benzene at 50℃;

COMPARATIVE EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of the catalyst A, and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.4 molpercent and the yield of p-xylynenediamine was 35.6 molpercent.

Reference： [1] ChemCatChem, 2014, vol. 6, # 2, p. 538 - 546
[2] Russian Journal of Applied Chemistry, 2003, vol. 76, # 8, p. 1304 - 1309
[3] Patent: US2008/39658, 2008, A1, . Location in patent: Page/Page column 5
[4] Patent: US2008/39658, 2008, A1, . Location in patent: Page/Page column 5
[5] Patent: CN105016939, 2017, B, . Location in patent: Paragraph 0144; 0145
[6] ChemSusChem, 2017, vol. 10, # 5, p. 842 - 846
[7] Angewandte Chemie - International Edition, 2016, vol. 55, # 47, p. 14653 - 14657[8] Angew. Chem., 2016, vol. 128, # 47, p. 14873 - 14877,5
[9] Patent: EP1449825, 2004, A1, . Location in patent: Page 6
[10] Vestnik Akad.Kazachsk.S.S.R., 1959, vol. 15, # 6, p. 92[11] Chem.Abstr., 1960, p. 10944
[12] Doklady Akademii Nauk SSSR, 1957, vol. 112, p. 880[13] Doklady Chemistry, 112-117<1957>141,
[14] Doklady Akademii Nauk SSSR, 1957, vol. 112, p. 880[15] Doklady Chemistry, 112-117<1957>141,
[16] Vestnik Akad.Kazachsk.S.S.R., 1959, vol. 15, # 6, p. 92[17] Chem.Abstr., 1960, p. 10944
[18] Journal of the American Chemical Society, 2016, vol. 138, # 28, p. 8781 - 8788
[19] Patent: CN105001032, 2018, B, . Location in patent: Paragraph 0146; 0147
[20] Patent: CN105016940, 2018, B, . Location in patent: Paragraph 0143; 0144

3
[ 623-26-7 ]
[ 10406-25-4 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
88.8%	With hydrogen In ammonia; 1,3,5-trimethyl-benzene at 50℃;	EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5percent by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 molpercent, the yield of 4-cyanobenzylamine was 88.8 molpercent and the yield of p-xylynenediamine was 5.8 molpercent. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of Ni-diatomaceous earth pellets (manufactured by Nikki Chemical Co., Ltd.; Ni supported amount = 46percent by weight). The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 molpercent, the yield of 4-cyanobenzylamine was 0.5 molpercent and the yield of p-xylynenediamine was 87.7 molpercent. EXAMPLE 5 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5percent by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 molpercent, the yield of 4-cyanobenzylamine was 88.8 molpercent and the yield of p-xylynenediamine was 5.8 molpercent. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of the catalyst A. The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50°C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 molpercent, the yield of 4-cyanobenzylamine was 0.2 molpercent and the yield of p-xylynenediamine was 92.1 molpercent.

Reference： [1] Patent: EP1449825, 2004, A1, . Location in patent: Page 5
[2] Patent: US6392083, 2002, B1, . Location in patent: Page column 5-6
[3] Patent: EP1454895, 2004, A1, . Location in patent: Page 7; 8

4
[ 589-29-7 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane In tert-Amyl alcohol at 150℃; for 20 h; Inert atmosphere; Cooling	Example 6Direct Single-Stage Amination of Alcohols andHydroxy Acids by Means of Ammonia Over aHomogeneous Ruthenium Catalyst and Xantphos ata high V7J Vgas (according to the invention)Under an argon atmosphere, m g of starting material, mRU g of [carbonylchlorohydridotris(triphenylphosphane)ruthenium(II)] and mp g of 9,9-dimethyl-4,5-bis (diphenylphosphino)xanthene as catalyst and V07 ml of 2-methyl-2-butanol as solvent were introduced into a 50 mlsteel tube. The vessel was closed, pressurized three times with 20 bar of argon and depressurized each time. The vessel was then cooled by means of dry ice and m g of ammonia were condensed in. The reactor is heated to T° C. and maintained at this temperature for 20 hours. Afier cooling to room temperature, the reactor was depressurized and opened, the solvent was removed on a rotary evaporator and the residue was dissolved in methanol and then analysed by gas chromatography. Reaction parameters and conversions and selectivities to the desired reaction product are shown in Tab. 5. The results show that many different hydroxy-thnctionalized substrates can be aminated by the method described.

Reference： [1] Patent: US2013/331580, 2013, A1, . Location in patent: Paragraph 0063
[2] Angewandte Chemie - International Edition, 2011, vol. 50, # 33, p. 7599 - 7603
[3] Chemistry - A European Journal, 2013, vol. 19, # 52, p. 17702 - 17706

5
[ 626-17-5 ]
[ 623-26-7 ]
[ 1477-55-0 ]
[ 539-48-0 ]

Reference： [1] Patent: EP1760070, 2007, A1, . Location in patent: Page/Page column 8

6
[ 1220120-58-0 ]
[ 539-48-0 ]

Reference： [1] European Journal of Organic Chemistry, 2010, # 6, p. 1021 - 1025

7
[ 100-97-0 ]
[ 623-25-6 ]
[ 539-48-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 5361
[2] Zhurnal Obshchei Khimii, 1956, vol. 26, p. 548;engl.Ausg.S.585

8
[ 3010-82-0 ]
[ 539-48-0 ]

Reference： [1] Patent: CN105001032, 2018, B,

9
[ 100-21-0 ]
[ 539-48-0 ]

Reference： [1] Patent: CN105001032, 2018, B,

10
[ 7325-46-4 ]
[ 539-48-0 ]

Reference： [1] Zhurnal Obshchei Khimii, 1956, vol. 26, p. 1130,1132; engl. Ausg. S. 1283, 1285

11
[ 24424-99-5 ]
[ 539-48-0 ]
[ 108468-00-4 ]

Yield	Reaction Conditions	Operation in experiment
47%	at 0 - 20℃; for 2.5 h;	A solution of di-ferf-butyl dicarbonate (19.0g, 87 mmol) in dichloromethane (50 ml) was added dropwise to a cooled (0°C) suspension of para-xyiylenediamine (44.0 g, 323 mmol) in dichloromethane (200ml) over a period of 30 minutes. The resulting suspension was then allowed to warm to room temperature over a period of 2 hours. The reaction mixture was washed with 1N aqueous sodium hydroxide (300 ml) and the organic phase separated, dried (sodium sulfate) and reduced in vacua to give a colourless solid. Purification by flash column chromatography eluting with dichloromethane:methanol:880 ammonia (97:3:0 changing to 94:6:1 by volume) gave the title compound as a colourless solid (9.61 g, 47percent).
42%	With triethylamine In dichloromethane for 4.75 h;	A solution of t-Boc2O (1.6 g, 7.34 mmol) in DCM (30 mL) was added dropwise over 45 minutes to a stirring solution of 1,4-bis(aminomethyl)xylene (2.0 g, 14.7 mmol) and TEA (5 mL, 36.7 mmol) in 50 mL of DCM. After stirring for 4 h, the reaction was diluted with water and extracted thrice with 75 mL each of DCM. The combined extracts were washed with water, 5percent citric acid, brine, dried (Na2SO4) and concentrated, to give a white solid 0.73 g (27) (42percent). 1H NMR (500 MHz, CD3OD) δ7.26 (mn, 5H), 4.83 (br s, 1H), 4.29 (m, 2H), 3.85 (s, 2H), 1.46 (s, 9H); MS (AP+) m/z 237.4 (M+H+).
0.5 g	With triethylamine In dichloromethane at 0 - 20℃; for 2 h;	To a 50 mL flask was added 1,4-phenylenedimethanamine (1 g, 7.34 mmol), TEA (1.11 g, 1.54 mL, 11 mmol) and DCM (10 mL). Then a solution of Boc-anhydride (801 mg, 852 μL, 3.67 mmol) in DCM (10 mL) was added drop-wise at 0° C. The mixture was warmed to r.t. and stirred for 2 hours. The mixture was then diluted with 20 mL DCM and 30 mL water. The suspension was separated and the water layer was extracted with 20 mL DCM. The organic layers were combined and washed with sat. NH₄Cl, dried over Na₂SO₄and concentrated to give a 0.5 g tert-butyl 4-(aminomethyl)benzylcarbamate (compound 60A) as a white solid. MS: calc'd 237 (M+H)⁺, measured 237 (M+H)⁺.

Reference： [1] Journal of Materials Chemistry, 2008, vol. 18, # 41, p. 4917 - 4927
[2] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 19, p. 4189 - 4206
[3] Journal of Organic Chemistry, 1996, vol. 61, # 25, p. 8811 - 8818
[4] Journal of the American Chemical Society, 2008, vol. 130, # 18, p. 6025 - 6039
[5] Patent: WO2004/108675, 2004, A1, . Location in patent: Page 115
[6] Patent: US2004/14763, 2004, A1, . Location in patent: Page 23
[7] Journal of Organic Chemistry, 2001, vol. 66, # 9, p. 3027 - 3034
[8] Journal of Medicinal Chemistry, 1989, vol. 32, # 2, p. 391 - 396
[9] Patent: US2006/155120, 2006, A1, . Location in patent: Page/Page column 25
[10] Patent: US5656660, 1997, A,
[11] Patent: US5830920, 1998, A,
[12] Patent: US2003/191158, 2003, A1, . Location in patent: Page/Page column 15
[13] Patent: US4624943, 1986, A,
[14] Patent: US6656448, 2003, B1, . Location in patent: Page column 65
[15] Patent: US2016/257653, 2016, A1, . Location in patent: Paragraph 0441; 0442

12
[ 24424-99-5 ]
[ 539-48-0 ]
[ 20580-52-3 ]
[ 108468-00-4 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium hydroxide In 1,4-dioxane; water at 20℃; Cooling with ice	1,4-Bis(aminomethyl)benzene (30 g, 220.3 mmol) was dissolved/suspended in 1 M aq NaOH (220 mL, 220.3 mmol). 1,4-Dioxane was added (250 mL) and the solution was cooled in an ice-water bath. Di-tert-butyl dicarbonate (48.1 g, 220.3 mmol) was added dropwise in 1,4-dioxane (150 mL) over a period of 2 h. The ice-water bath was removed and the mixture was allowed to stand at rt overnight. The volume was reduced to about 250 mL under reduced pressure. The white solid was separated by filtration, washed twice with ice-cold water (2 .x. 100 mL) and dried in vacuo. White solid (47.6 g of a mixture of 3 and di-Boc-protected 1,4-bis(aminomethyl)benzene (55:45), 22 g (42percent related to 3); ¹H NMR (300 MHz, MeOH-d₄): δ (ppm) 1.44 (s, 24H, tert-butyl, 3 and 'di-Boc'), 3.84 (s, 2H, CH₂-NH₂), 4.19 (s, 3.3H, CH₂-NH, 'di-Boc'), 4.20 (s, 2H, CH₂-NH, 3), 7.2 (s, 3.3H, CH^Ar, 'di-Boc'), 7.29 (m, 4H, CH^Ar, 3); MS (CI, NH₃): m/z 254 [M+NH₄]⁺, 354 ['di-Boc'+NH₄]⁺; C₁₃H₂₀N₂O₂ (236.2).

Reference： [1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 9, p. 2859 - 2878

13
[ 539-48-0 ]
[ 6627-89-0 ]
[ 108468-00-4 ]

Reference： [1] Patent: US2013/281515, 2013, A1, . Location in patent: Paragraph 0178; 0179

[ 539-48-0 ] Synthesis Path-Downstream 1~68

1
[ 623-26-7 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
98.7%	With hydrogen;Ni(NO3)2, Cu(NO3)2, Cr(NO3)3, Na2CO3; calcined at 380 deg C for 18 h; pretreatment is given in full text; In 1,2,4-Trimethylbenzene; ammonia; at 80℃; for 24h;Product distribution / selectivity;	The procedure of Example 1 was repeated except for using terephthalonitrile in place of isophthalonitrile and changing the amount of Catalyst A to 0.6 g, the pretreatment gas to a mixed gas (methanol:nitrogen=4:96 by volume), and the pretreatment conditions to atmospheric pressure, 250 C., a flow rate of 0.18 NL/h, and 3 h. After 24 h of the hydrogenation, the conversion of terephthalonitrile was 100 mol %, the yield of p-xylylenediamine was 98.7 mol %, and the yield of high-boiling condensation products was 1.3 mol %.
92.4%	With hydrogen;Ni(NO3)2, Cu(NO3)2, Cr(NO3)3, Na2CO3; calcined at 380 deg C for 18 h; In 1,2,4-Trimethylbenzene; ammonia; at 80℃; for 24h;Product distribution / selectivity;	The procedure of Example 12 was repeated except for omitting the pretreatment. After 24 h of the hydrogenation, the conversion of terephthalonitrile was 100 mol %, the yield of p-xylylenediamine was 92.4 mol %, and the yield of high-boiling condensation products was 7.6 mol %.
92%	With hydrogen; In ethanol; at 95℃; under 52505.3 Torr; for 1h;	(1) 100g of terephthalonitrile and 3g of Raney-Ni and 400mL of ethanol were added into a 1L hydrogenation kettle, H2 was continuously charged, The reaction pressure during the system is always maintained at 7MPa. The reaction temperature 95 for 1h, cooling. When the temperature in the reaction vessel was lowered to room temperature, the solution was vented to give p-xylylenediamine (purity of 99% or more) by filtration and recrystallization in a yield of 92%

80%	With sodium tetrahydroborate; copper ferrite; In water; for 0.25h;Reflux; Green chemistry;	General procedure: As a representative example, in a round-bottom flask (15 mL) equipped with a magnetic stirrer, benzonitrile (1 mmol, 0.103 g) was dissolved in H2O (2 mL). Afterward, CuFe2O4 (0.2 mmol, 0.048 g) was added and the mixture was stirred. Then, NaBH4 (2 mmol, 0.076 g) was also added, and the resulting mixture continued to stir at reflux for 5 min. Upon completion of the reaction (monitored by TLC), the mixture was cooled to room temperature, and the catalyst was separated by an external magnet. The reaction mixture was extracted with ethyl acetate (EtOAc) (2 x 4 mL). The organic layers were combined together and dried over anhydrous sodium sulfate (Na2SO4). The solvent was evaporated under reduced pressure. The pure colorless liquid benzylamine was obtained in 95% yield.
35.6%	With hydrogen;catalyst A; In ammonia; 1,3,5-trimethyl-benzene; at 50℃; under 36753.7 Torr;	COMPARATIVE EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of the catalyst A, and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.4 mol% and the yield of p-xylynenediamine was 35.6 mol%.
	With hydrogen; In ethanol; at 95℃; under 52505.3 Torr; for 1h;	(1) Add 100g of terephthalonitrile and 3g of Raney-Ni to a 1L hydrogenation tank,400 mL of ethanol was continuously charged with H2 so that the pressure of the system was always maintained at 7 MPa during the reaction. After the reaction was performed at a reaction temperature of 95C for 1 hour, the temperature was lowered. Until the reactorWhen the temperature was lowered to room temperature, the gas was released, and p-xylylenediamine (having a purity of 99% or more) was obtained by filtration and recrystallization. The yield was 92% by weight.
	With hydrogen; In ethanol; at 95℃; under 52505.3 Torr; for 1h;	(1) 100 g of terephthalonitrile and 3 g of Raney-Ni, 400 mL of ethanol are charged in a 1L hydrogenation reactor, and H2 is continuously charged, so that the pressure of the system is always maintained at 7 MPa during the reaction. After the reaction was performed at a reaction temperature of 95C for 1 hour, the temperature was lowered. When the temperature in the reaction vessel was lowered to room temperature, the mixture was degassed, and p-xylylenediamine (with a purity of 99% or more) was obtained by filtration and recrystallization. The yield was 92% by weight.

Reference： [1]ChemCatChem,2014,vol. 6,p. 538 - 546
[2]Russian Journal of Applied Chemistry,2003,vol. 76,p. 1304 - 1309
[3]Patent: US2008/39658,2008,A1 .Location in patent: Page/Page column 5
[4]Patent: US2008/39658,2008,A1 .Location in patent: Page/Page column 5
[5]Patent: CN105016939,2017,B .Location in patent: Paragraph 0144; 0145
[6]ChemSusChem,2017,vol. 10,p. 842 - 846
[7]Research on Chemical Intermediates,2019
[8]Angewandte Chemie - International Edition,2016,vol. 55,p. 14653 - 14657
 Angew. Chem.,2016,vol. 128,p. 14873 - 14877,5
[9]Patent: EP1449825,2004,A1 .Location in patent: Page 6
[10],1959,vol. 15,p. 92
 Chem.Abstr.,1960,p. 10944
[11]Doklady Akademii Nauk SSSR,1957,vol. 112,p. 880
 Doklady Chemistry, 112-117<1957>141,
[12]Doklady Akademii Nauk SSSR,1957,vol. 112,p. 880
 Doklady Chemistry, 112-117<1957>141,
[13],1959,vol. 15,p. 92
 Chem.Abstr.,1960,p. 10944
[14]Journal of the American Chemical Society,2016,vol. 138,p. 8781 - 8788
[15]Patent: CN105001032,2018,B .Location in patent: Paragraph 0146; 0147
[16]Patent: CN105016940,2018,B .Location in patent: Paragraph 0143; 0144
[17]Chemical Science,2018,vol. 9,p. 8553 - 8560
[18]Green Chemistry,2019,vol. 21,p. 830 - 838

2
[ 24424-99-5 ]
[ 539-48-0 ]
[ 108468-00-4 ]

Yield	Reaction Conditions	Operation in experiment
47%	In dichloromethane; at 0 - 20℃; for 2.5h;	A solution of di-ferf-butyl dicarbonate (19.0g, 87 mmol) in dichloromethane (50 ml) was added dropwise to a cooled (0C) suspension of para-xyiylenediamine (44.0 g, 323 mmol) in dichloromethane (200ml) over a period of 30 minutes. The resulting suspension was then allowed to warm to room temperature over a period of 2 hours. The reaction mixture was washed with 1N aqueous sodium hydroxide (300 ml) and the organic phase separated, dried (sodium sulfate) and reduced in vacua to give a colourless solid. Purification by flash column chromatography eluting with dichloromethane:methanol:880 ammonia (97:3:0 changing to 94:6:1 by volume) gave the title compound as a colourless solid (9.61 g, 47%).
42%	With triethylamine; In dichloromethane; for 4.75h;	A solution of t-Boc2O (1.6 g, 7.34 mmol) in DCM (30 mL) was added dropwise over 45 minutes to a stirring solution of 1,4-bis(aminomethyl)xylene (2.0 g, 14.7 mmol) and TEA (5 mL, 36.7 mmol) in 50 mL of DCM. After stirring for 4 h, the reaction was diluted with water and extracted thrice with 75 mL each of DCM. The combined extracts were washed with water, 5% citric acid, brine, dried (Na2SO4) and concentrated, to give a white solid 0.73 g (27) (42%). 1H NMR (500 MHz, CD3OD) delta7.26 (mn, 5H), 4.83 (br s, 1H), 4.29 (m, 2H), 3.85 (s, 2H), 1.46 (s, 9H); MS (AP+) m/z 237.4 (M+H+).
	In 1,4-dioxane; at 22 - 25℃; for 5h;	C. Synthesis of Mono-boc-p-xylylenediamine p-xylylenediamine (Aldrich 27,963-3) (50.0 g, 367 mmol) was transferred to a 3-neck round bottom flask equipped with a mechanical stirrer and addition funnel. The p-xylylenediamine was dissolved in dioxane (900 mL) at 22-25 C. Di-t-butyldicarbonate (Aldrich 20,524-9) (40.0 g, 367 mmol) was dissolved in dioxane (500 mL), and added to the addition funnel, and the solution was added dropwise to the stirring solution slowly over 5 hours at 22-25 C. Any precipitate was filtered and then washed with dioxane (200 mL). The filtrate was concentrated until a volume of 300 mL was achieved (under reduced pressure). The concentrated solution was poured into water (700 mL) over 5 minutes to precipitate the di-boc side product. The precipitate was filtered and washed with water (300 mL). The precipitate was discarded. The filtrate was extracted with ethyl acetate (3500 mL). The extracts were combined and the organic layer washed with water (1500 mL), saturated aqueous NaCl (1*500 mL) and dried over sodium sulfate. The organics were concentrated under vacuum to a constant weight (at room temperature) to obtain 1 as a pale beige solid. (22.30 g, 99% purity by area).

	In 1,4-dioxane;	EXAMPLE 1 Bis(p-xylylenediamineglycine)-1,4-benzenedimethanol dicarbamate Reagents and solvents were used as received from the commercial suppliers, except for dioxane which was passed through a column of basic alumina using flash chromatography techniques before use. A solution containing 10 milliliters (mL) di-tert-butyl dicarbonate (0.044 moles (mol), 1.0 equivalents (equiv)) in dioxane (100 mL) was added dropwise to a solution of 47 grams (g) p-xylylenediamine (0.35 mol, 8.0 equiv) in dioxane (300 mL) over a period of 7 h. The resulting white suspension was stirred at 23 C. for 14 h and concentrated. The residue was partitioned between ethyl acetate (three portions), water (four portions), and saturated aqueous sodium chloride. The organic layer was dried over magnesium sulfate and concentrated, providing crude N-Boc-p-xylylenediamine (9.69 g) as a pale yellow solid.
	In dichloromethane;	A. 15 g of 4-aminomethyl-benzylamine were dissolved in 600 ml of methylene chloride and treated within 2.5 hours with a solution of 8.0 g of di-tert.-butyl dicarbonate in 80 ml of methylene chloride. Thereupon, the separated precipitate was filtered off and discarded and the mother liquor was evaporated. The thus-obtained residue was chromatographed on silica gel with hexane/ethyl acetate/methanol; there thus being obtained tert.-butyl (4-aminomethyl-benzyl)-carbamate, MS: m/z 179 ([M-tert.-butyl]+).
	In dichloromethane; at 0 - 20℃; for 18h;	A solution of di-tert-butyl-dicarboxylate (4.62 g, 21.2 mmol) dissolved in dichloromethane (50 ml) was added to a solution of 4-aminomethyl-benzylamine (14.4 g, 106 mmol) in dichloromethane (50 ml) at 0 C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 18 hours. The reaction mixture was then washed sequentially with water (100 ml) and a 10% aqueous solution of citric acid (200 ml) and the organic phase disgarded. The pH of the aqueous phase was then adjusted to pH higher than 8 by addition of 0.88 ammonia and extracted with dichloromethane (3-fold 200 ml). The combined organic extracts were then dried over anhydrous magnesium sulphate and the solvent removed in vacuo giving (4-aminomethyl-benzyl)-carbamic acid tert-butyl ester (4.29 g) as a white solid. 1H NMR (400 MHz, CDCl3): delta=7.22-7.26 (4H, d), 4.80-4.90 (1H, brs), 4.23-4.30 (2H, m), 3.82 (2H, s), 1.43 (2H, s), 1.38 (2H, s) ppm. LRMS (electrospray): m/z [M-H]+237.
	With sodium carbonate; In hydrogenchloride; dichloromethane;	EXAMPLE 3 1,4-Bis(aminomethyl)benzene (10 g, 73.4 mmol) was dissolved in methylene chloride (150 ml) and was treated at room temperature with di-tert-butyl dicarbonate (5.62 ml, 24.5 mmol) and the resulting solution was stirred at room temperature for 46 hr. The reaction was then diluted with chloroform, washed with water, dried (MgSO4) and evaporated. The residue was dissolved in a minimum of 1N hydrochloric acid, washed with chloroform, made basic with solid sodium carbonate (pH=9) and extracted with ethyl acetate. The ethyl acetate extracts were combined, dried (MgSO4) and evaporated to give pure mono-Boc-1,4-bis(aminomethyl)benzene whose structure was confirmed by 1 H NMR and CI-MS [(M+H+ =237].
	In DMF (N,N-dimethyl-formamide); for 1.16667h;	A. Preparation of (4-aminomethyl-benzyl)carbamic acid tert-butyl ester. To a stirred solution of 5.3 grams of p-xylenediamine 10 in 20 ml of dimethylformamide was added a solution of 2.12 grams of di-tert-butyl-dicarbonate in 50 ml of dimethylformamide by syringe pump over 1 hour. After stirring an additional 10 minutes the volatiles were removed under reduced pressure and the resulting material was chromatographed on silica gel eluting with 5% MeOH/CHCl3 affording 2 grams of the desired compound. LRMS found 237.2 (M+H)+1.
0.5 g	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	To a 50 mL flask was added 1,4-phenylenedimethanamine (1 g, 7.34 mmol), TEA (1.11 g, 1.54 mL, 11 mmol) and DCM (10 mL). Then a solution of Boc-anhydride (801 mg, 852 muL, 3.67 mmol) in DCM (10 mL) was added drop-wise at 0 C. The mixture was warmed to r.t. and stirred for 2 hours. The mixture was then diluted with 20 mL DCM and 30 mL water. The suspension was separated and the water layer was extracted with 20 mL DCM. The organic layers were combined and washed with sat. NH4Cl, dried over Na2SO4 and concentrated to give a 0.5 g tert-butyl 4-(aminomethyl)benzylcarbamate (compound 60A) as a white solid. MS: calc'd 237 (M+H)+, measured 237 (M+H)+.

Reference： [1]Journal of Materials Chemistry,2008,vol. 18,p. 4917 - 4927
[2]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4189 - 4206
[3]Journal of Organic Chemistry,1996,vol. 61,p. 8811 - 8818
[4]Journal of the American Chemical Society,2008,vol. 130,p. 6025 - 6039
[5]Patent: WO2004/108675,2004,A1 .Location in patent: Page 115
[6]Patent: US2004/14763,2004,A1 .Location in patent: Page 23
[7]Journal of Organic Chemistry,2001,vol. 66,p. 3027 - 3034
[8]Journal of Medicinal Chemistry,1989,vol. 32,p. 391 - 396
[9]Patent: US2006/155120,2006,A1 .Location in patent: Page/Page column 25
[10]Patent: US5656660,1997,A
[11]Patent: US5830920,1998,A
[12]Patent: US2003/191158,2003,A1 .Location in patent: Page/Page column 15
[13]Patent: US4624943,1986,A
[14]Patent: US6656448,2003,B1 .Location in patent: Page column 65
[15]Patent: US2016/257653,2016,A1 .Location in patent: Paragraph 0441; 0442

3
[ 23911-25-3 ]
[ 539-48-0 ]
(1:1-edtaxah)H₂ [ No CAS ]
(2:2-edtaxah)H₄ [ No CAS ]
(4:4-edtaxah)H₈ [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),1998,p. 2275 - 2279

4
[ 1477-55-0 ]
[ 108-77-0 ]
[ 539-48-0 ]
[ 1071-37-0 ]
[ 109-89-7 ]
[ 109-73-9 ]
N-{3-[(4-{4-[(4-butylamino-6-diethylamino-[1,3,5]triazin-2-ylamino)-methyl]-benzylamino}-6-diethylamino-[1,3,5]triazin-2-ylamino)-methyl]-benzyl}-guanidine; compound with perchloric acid [ No CAS ]

Reference： [1]Chemistry Letters,2000,p. 1018 - 1019

5
[ 4816-81-3 ]
[ 539-48-0 ]
1,4-di(N^α-tosyl-L-alanylamidomethyl)benzene [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 1379 - 1386

6
[ 539-48-0 ]
[ 14152-97-7 ]
1,4-bis[3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thioureidomethyl]benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In dichloromethane at 20℃; for 0.5h;

Reference： [1]Benito; Gomez-Garcia; Jimenez Blanco; Mellet; Garcia Fernandez [Journal of Organic Chemistry, 2001, vol. 66, # 4, p. 1366 - 1372]

7
[ 1955-46-0 ]
[ 539-48-0 ]
[ 69812-29-9 ]
5-(2-acetylamino-4-methyl-thiazole-5-sulfonylamino)-N-(4-aminomethyl-benzyl)-isophthalamide [ No CAS ]

Reference： [1]Medicinal Chemistry Research,1998,vol. 8,p. 187 - 205

8
[ 539-48-0 ]
[ 1079-66-9 ]
[ 509083-13-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With triethylamine; In dichloromethane; at 0 - 20℃; for 18.5h;	A solution of p-xylylenediamine (1.16 g, 8.50 mmol) in dichloromethane (100 mL) was treated with triethylamine (20 mL) by stirring at 0 C. To this solution chlorodiphenylphosphane (3.66 mL, 19.07 mmol) was added and stirred for 30 min. Then chlorodiphenylphosphane (3.66 mL, 19.07 mmol) was added again and the mixture was stirred for 18 h at room temperature. The solvent was evaporated to dryness under reduced pressure, and the remaining residue was treated with water (50 mL) by stirring. The resulting white precipitate was filtered off and washed with water (50 mL), twice with ethanol (40 mL), and twice with hexane (50 mL), and dried in vacuo. The product was recrystallized from dichloromethane/acetonitrile (1:2) affording colorless crystal plates, m.p. 195 C.

Reference： [1]Journal of Organometallic Chemistry,2002,vol. 664,p. 294 - 297
[2]Journal of Organometallic Chemistry,2012,vol. 715,p. 64 - 68

9
[ 539-48-0 ]
[ 62348-13-4 ]
3-methyl-1H-pyrrole-2,4-dicarboxylic acid 4-pentafluorophenyl ester 4-(1,2,2-trimethyl-propyl) ester [ No CAS ]
5-(4-[(isoxazole-5-carbonyl)-amino]-methyl}-benzylcarbamoyl)-4-methyl-1H-pyrrole-3-carboxylic acid 1,2,2-trimethyl-propyl ester [ No CAS ]

Reference： [1]Il Farmaco,2004,vol. 59,p. 119 - 123

10
[ 539-48-0 ]
(C₅H₁₁CHC₆H(CHO)OCH₂O)4 [ No CAS ]
C₁₄₄H₁₆₀N₈O₁₆ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 14120 - 14127

11
[ 20112-79-2 ]
[ 539-48-0 ]
C₁₁H₁₆N₄ [ No CAS ]

Reference： [1]Synthetic Communications,2007,vol. 37,p. 3173 - 3179

12
[ 623-26-7 ]
[ 10406-25-4 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
88.8%; 5.8%	With hydrogen;Pd-alumina; In ammonia; 1,3,5-trimethyl-benzene; at 50℃; under 36753.7 Torr;	EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5% by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 mol%, the yield of 4-cyanobenzylamine was 88.8 mol% and the yield of p-xylynenediamine was 5.8 mol%. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of Ni-diatomaceous earth pellets (manufactured by Nikki Chemical Co., Ltd.; Ni supported amount = 46% by weight). The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 mol%, the yield of 4-cyanobenzylamine was 0.5 mol% and the yield of p-xylynenediamine was 87.7 mol%. EXAMPLE 5 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5% by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 mol%, the yield of 4-cyanobenzylamine was 88.8 mol% and the yield of p-xylynenediamine was 5.8 mol%. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of the catalyst A. The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 mol%, the yield of 4-cyanobenzylamine was 0.2 mol% and the yield of p-xylynenediamine was 92.1 mol%.
	With hydrogen;sponge nickel (R-2400, product of W.R. Grace & Co.); In methanol; at 150℃; under 750.075 - 3750.38 Torr; for 1h;	Crude p-cyanobenzylamine was synthesized in accordance with the process described in Japanese Unexamined Patent Publication (kokai) No. 9-40630 as follows. Into a 100 ml autoclave, methanol (30 ml) and sponge nickel (R-2400, product of W.R. Grace & Co.) (1.0 g) were placed, and the internal pressure of the autoclave was elevated to 1.0 MPa by introducing hydrogen. The mixture contained in the autoclave was stirred while heating at 150 C. for one hour. Terephthalonitrile (5.0 g) and sodium hydroxide (0.1 g) were introduced into the reactor, and the internal pressure was elevated to 0.5 MPa at ambient temperature while introducing hydrogen. Under monitoring of the hydrogen absorbing rate, when the hydrogen pressure was dropped to 0.1 MPa, the pressure was elevated again to 0.5 MPa. This pressure control operation was repeated. Reaction was terminated when the hydrogen absorption ratio reached 115% of the theoretical value. From the thus-obtained reaction mixture, methanol was removed through distillation. The resultant mixture was subjected to a further distillation at a high temperature under a reduced pressure, thereby removing crude p-cyanobenzylamine. Through high-performance liquid chromatographic analysis of the distillate, the p-cyanobenzylamine content and the p-xylylenediamine content were found to be 93 mass % and 7 mass %, respectively.
	With ammonia; hydrogen;nickel; In methanol; m-xylylene; at 80 - 120℃; under 60006 Torr; for 4.5 - 6h;Conversion of starting material;	EXAMPLE 3; Hydrogenation; Into a 1-L autoclave equipped with an electromagnetic stirrer, 4 g of Raney nickel catalyst ("NDHT" manufactured by Kawaken Fine Chemicals Co., Ltd.) was charged. Then, 60 g of terephthalonitrile, 60 g of MX and 120 g of methanol were charged into the autoclave and the inner atmosphere thereof was replaced with nitrogen. After introducing 120 g of NH3, the autoclave was heated to 80C. Then, hydrogen gas was introduced into the autoclave to perform the hydrogenation under 8 MPaG at 80C. After initiating the hydrogenation, the reaction liquids were sampled at regular time intervals and analyzed by gas chromatography. After three hours from the initiation, the nitrile conversion reached 97.9 mol%. At this time, the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 79.0 mol%, and the yield of 4-cyanobenzylamine was 4.3 mol%. After three hours from the initiation, the reaction temperature was raised to 120C to continue the hydrogenation for 1.5 h (overall reaction time = 4.5 h). The results of gas chromatographic analysis showed that the nitrile conversion was 99.99 mol%, the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 83.9 mol%, and the yield of 4-cyanobenzylamine was 0.015 mol%. Purification of Xylylenediamine After releasing the pressure, MX and methanol were removed from the recovered reaction liquid in a rotary evaporator. By distilling the resultant solution under 0.5 kPa, p-xylylenediamine was obtained as the major distillate. The purity was 99.9% by weight or more and the content of 4-cyanobenzylamine was 0.016% by weight. COMPARATIVE EXAMPLE 3; Hydrogenation; The procedure of Example 3 was repeated except for performing the hydrogenation for 6 h at a constant reaction temperature of 80C. After 6 h of the initiation of hydrogenation, the reaction liquid was analyzed by gas chromatography. The residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 82.2 mol%, and the yield of 4-cyanobenzylamine was 0.4 mol%. Although the hydrogenation was continued longer than in Example 3, a larger amount of the intermediate 4-cyanobenzylamine remained.Purification of Xylylenediamine After releasing the pressure, MX and methanol were removed from the recovered reaction liquid in a rotary evaporator. By distilling the resultant solution under 0.5 kPa, p-xylylenediamine was obtained as the major distillate. The obtained p-xylylenediamine contained 0.4% by weight of 4-cyanobenzylamine. COMPARATIVE EXAMPLE 4; The procedure of Example 3 was repeated except for performing the hydrogenation for 4.5 h at a constant reaction temperature of 120C. The results of gas chromatographic analysis showed that the residue of terephthalonitrile was 0.0 mol%, the yield of p-xylylenediamine was 74.2 mol%, and the yield of 4-cyanobenzylamine was 0.01 mol%.

Reference： [1]Patent: EP1449825,2004,A1 .Location in patent: Page 5
[2]Patent: US6392083,2002,B1 .Location in patent: Page column 5-6
[3]Patent: EP1454895,2004,A1 .Location in patent: Page 7; 8

13
[ 623-26-7 ]
[ 10406-25-4 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
92.1%	With hydrogen;catalyst A; In ammonia; 1,3,5-trimethyl-benzene; at 50℃; under 36753.7 Torr;	EXAMPLE 5 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5% by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 mol%, the yield of 4-cyanobenzylamine was 88.8 mol% and the yield of p-xylynenediamine was 5.8 mol%. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of the catalyst A. The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 mol%, the yield of 4-cyanobenzylamine was 0.2 mol% and the yield of p-xylynenediamine was 92.1 mol%.
87.7%	With hydrogen;Ni-diatomaceous earth; In ammonia; 1,3,5-trimethyl-benzene; at 50℃; under 36753.7 Torr;	EXAMPLE 2 Hydrogenation of Terephthalonitrile Into a 100-ml autoclave, were charged 3.2 g of terephthalonitrile, 10.4 g of mesitylene, 10.0 g of liquid ammonia and 2.0 g of Pd-alumina pellets (manufactured by N.E. Chemcat Corporation; Pd content = 5% by weight), and the inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 94.8 mol%, the yield of 4-cyanobenzylamine was 88.8 mol% and the yield of p-xylynenediamine was 5.8 mol%. The reaction solution separated from the catalyst was charged into a 100-ml autoclave together with 10.0 g of liquid ammonia and 2.0 g of Ni-diatomaceous earth pellets (manufactured by Nikki Chemical Co., Ltd.; Ni supported amount = 46% by weight). The inner pressure was raised to 4.9 MPa by hydrogen gas. Then, the autoclave was shaken at 50C until the change of pressure was no longer appreciated. The analysis on the reaction product solution showed that the conversion of terephthalonitrile was 100 mol%, the yield of 4-cyanobenzylamine was 0.5 mol% and the yield of p-xylynenediamine was 87.7 mol%.

Reference： [1]Patent: EP1449825,2004,A1 .Location in patent: Page 5
[2]Patent: EP1449825,2004,A1 .Location in patent: Page 5

14
[ 539-48-0 ]
[ 322474-21-5 ]
[ 172348-54-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	In tetrahydrofuran; at 20℃; for 5.5h;	To a solution of p-xylylenediamine (6.44 g, 47.4 mmol) in THF (30 mL) is added a solution of 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea (6.63 g, 22.9 mmol) in THF (40 mL) within 0.5 hour. The solution is stirred at room temperature for 5 hours. The solvent is removed under reduced pressure, and the product is purified by column chromatography on silica gel using a mixture of methylene chloride/methanol as the eluant, to afford 8.0 g (92% yield) of 1-(N,N'-diBoc)-guanidinomethyl-4-aminomethyl benzene (Compound (f)). 1H NMR (CDCl3) delta 11.54 (br s, 1H), 8.56 (br s, 1H), 7.29 (s, 4H), 4.60 (d, 2H), 3.86 (s, 2H), 1.64 (br s, 2H), 1.52 (s, 9H), 1.48 (s, 9H).

Reference： [1]Patent: EP1105120,2005,B1 .Location in patent: Page/Page column 23-24

15
[ 539-48-0 ]
[ 501-53-1 ]
[ 164648-85-5 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 20 Benzyl (4-(aminomethyl)benzyl]carbamate A solution of benzylchloroformate (10.48ml, 74mmol) in dichloromethane (250ml) was added to an ice-cooled solution of 4-aminomethyl benzylamine (10g, 74mmol) and triethylamine (9.77ml, 74mmol), in dichloromethane (480ml) over 90 minutes. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate (450ml) and 1 M sodium hydroxide solution (300ml). The resulting mixture was filtered, the layers separated and the organic phase dried over magnesium sulphate and evaporated under reduced pressure. The residue was dissolved in hot ethyl acetate, the solution cooled in an ice-bath, the resulting solid filtered off, and the filtrate evaporated under reduced pressure to afford the title compound as a white solid, 7.44g. 1H NMR (DMSO-d6, 400MHz) delta: 3.63(s, 2H), 4.18(s, 2H), 5.01 (s, 2H), 7.12-7.39(m, 9H), 7.77(s, 1 H). LRMS: m/z ES+ 271 [M+Na+]
	With triethylamine; In dichloromethane; at 0 - 20℃; for 16h;	A solution of 1,4-bis(aminomethyl)benzene (10.0g, 74mmol) and triethylamine (9.8 ml, 74 mmol) in dichloromethane (480 ml) was cooled to 0C and treated with a solution of benzylchloroformate (10.5ml, 74mmol) in dichloromethane (250 ml). The resulting mixture was allowed to warm gradually to room temperature of a period of 16h. The solvent was removed in vacua and the residue partitioned between ethyl acetate (450 ml) and 1M aqueous sodium hydroxide (300 ml). The resulting biphasic mixture was filtered and the organic phase separated, dried (magnesium sulfate) and reduced in vacua to give a waxy solid. Trituration with hot ethyl acetate followed by concentration of the liquors gave the title compound as a waxy solid (7.4g).

Reference： [1]Patent: EP1577292,2005,A1 .Location in patent: Page/Page column 41
[2]Patent: WO2004/108675,2004,A1 .Location in patent: Page 101; 102
[3]Chemical Communications,2014,vol. 50,p. 12623 - 12625

16
[ 5900-58-3 ]
[ 124-09-4 ]
[ 5162-44-7 ]
[ 446-48-0 ]
[ 7209-38-3 ]
[ 74-96-4 ]
[ 4784-77-4 ]
[ 22288-78-4 ]
[ 542-69-8 ]
bromomethyl resin [ No CAS ]
9-fluorenyl-methoxycarbonyl-cyclohexyl alanine [ No CAS ]
[ 462-94-2 ]
[ 1458-98-6 ]
[ 78-77-3 ]
[ 1809-10-5 ]
[ 110-53-2 ]
[ 592-55-2 ]
[ 7328-91-8 ]
[ 871-76-1 ]
[ 105-83-9 ]
[ 144-48-9 ]
[ 929-59-9 ]
[ 107-59-5 ]
[ 5324-30-1 ]
[ 5428-54-6 ]
[ 27129-86-8 ]
[ 2417-72-3 ]
[ 2581-34-2 ]
[ 554-84-7 ]
[ 3385-21-5 ]
[ 126-38-5 ]
[ 636-93-1 ]
[ 88-30-2 ]
[ 620-13-3 ]
[ 823-78-9 ]
[ 5035-82-5 ]
[ 29022-11-5 ]
[ 539-48-0 ]
[ 35661-39-3 ]
[ 26759-46-6 ]
[ 20439-47-8 ]
[ 2615-25-0 ]
[ 6393-01-7 ]
[ 5372-81-6 ]
[ 35661-40-6 ]
[ 100-39-0 ]
[ 611-17-6 ]
[ 23915-07-3 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 2592-95-2 ]
[ 18880-00-7 ]
[ 88681-68-9 ]
[ 100063-22-7 ]
[ 75-03-6 ]
[ 106-94-5 ]
[ 104-81-4 ]
[ 589-10-6 ]
[ 107-15-3 ]
[ 109-76-2 ]
[ 110-60-1 ]
[ 7051-34-5 ]
[ 106-95-6 ]
[ 622-95-7 ]
[ 589-15-1 ]
[ 134-20-3 ]
[ 2550-36-9 ]
[ 89-92-9 ]
[ 456-41-7 ]
[ 766-80-3 ]
[ 459-46-1 ]
[ 874-98-6 ]
[ 402-49-3 ]
[ 870-63-3 ]
[ 85118-01-0 ]
[ 22115-41-9 ]
[ 3958-57-4 ]
[ 100-11-8 ]
[ 107-82-4 ]
[ 6482-24-2 ]
[ 3132-64-7 ]
[ 112883-41-7 ]
[ 3433-80-5 ]
[ 52727-57-8 ]
C₁₈H₁₅N₂O₃PolS [ No CAS ]
C₂₀H₂₀N₃OPolS [ No CAS ]
C₂₃H₁₉N₂O₂PolS [ No CAS ]
C₁₈H₂₃ClN₃OPolS [ No CAS ]
C₂₂H₂₆N₃OPolS [ No CAS ]
C₂₂H₂₃N₂O₅PolS [ No CAS ]
C₂₀H₂₆ClN₂O₃PolS [ No CAS ]
C₂₃H₂₂ClN₂O₃PolS [ No CAS ]
C₂₀H₂₁FN₃O₃PolS [ No CAS ]
C₂₂H₂₉N₂O₃PolS [ No CAS ]
C₂₁H₂₈N₃O₃PolS [ No CAS ]
C₁₉H₂₆N₃O₄PolS₂ [ No CAS ]
C₂₂H₃₀N₃OPolS [ No CAS ]
C₂₁H₂₈N₃O₄PolS [ No CAS ]
C₂₆H₂₆N₃OPolS [ No CAS ]
C₂₃H₁₅ClF₃N₂O₂PolS [ No CAS ]
C₂₄H₂₂N₃O₃PolS [ No CAS ]
C₂₃H₁₆ClF₂N₂O₂PolS [ No CAS ]
C₂₂H₂₂Br₂N₃OPolS [ No CAS ]
C₂₄H₂₆FN₂O₅PolS [ No CAS ]
C₂₅H₂₂FN₂O₄PolS [ No CAS ]
C₂₆H₂₂N₃O₄PolS [ No CAS ]
C₂₅H₂₅ClN₃O₃PolS [ No CAS ]
C₂₅H₁₈ClF₂N₂O₃PolS [ No CAS ]
C₂₉H₂₆N₃O₃PolS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS);	EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...

Reference： [1]Patent: US2004/102629,2004,A1 .Location in patent: Page 16-18

17
[ 539-48-0 ]
[ 322474-21-5 ]
[ 172348-54-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	In tetrahydrofuran; at 20℃; for 5h;	Preparation of 1-(N,N'-diBoc)-guanidinomethyl-4-aminomethylbenzene: To a solution of p-xylylenediamine (6.44 g, 47.4 mmol) in THF (30 mL) is added a solution of 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea (6.63 g, 22.9 mmol) in THF (40 mL) within 0.5 hour. The solution is stirred at room temperature for 5 hours. The solvent is removed under reduced pressure, and the product is purified by column chromatography on silica gel using a mixture of methylene chloride/methanol as the eluant, to afford 8.0 g (92% yield) of 1-(N,N'-diBoc)-guanidinomethyl-4-aminomethyl benzene (Compound (f)). 1H NMR (CDCl3) delta 11.54 (br s, 1H), 8.56 (br s, 1H), 7.29 (s, 4H), 4.60 (d, 2H), 3.86 (s, 2H), 1.64 (br s, 2H), 1.52 (s, 9H), 1.48 (s, 9H).

Reference： [1]Patent: US2004/10033,2004,A1 .Location in patent: Page/Page column 21

18
[ 539-48-0 ]
[ 1694-92-4 ]
[ 547720-26-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine; at 0 - 20℃; for 18h;	1,4-bis-(2-nitrobenzenesulfonamide)-xylylene; - To 13.62 g (100 mmole) of 1,4- xylylenediamine in 120 mL of dry pyridine in an ice bath under a stream of argon is added 48.76 g (220 mmole) of 2-nitrobenzenesulfonylchloride portionwise as a solid. The reaction is allowed to warm to room temperature and stir for 18 hr. A large portion of the pyridine is removed by rotoevaporation and the oily residue is dissolved in 250 mL of CH2Cl2 and washed with satd CUS04 then H20 and brine. Drying and evaporation gives a crude product as a yellowish solid. Purification by silica gel column chromatography using CHCl3/CH3OH 98: 2 gives 39.5 g (78%) of product as a white solid.

Reference： [1]Patent: WO2005/105729,2005,A1 .Location in patent: Page/Page column 22

19
[ 539-48-0 ]
[ 623-26-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 1-methyl-1H-imidazole; oxygen; copper(ll) bromide; In dimethyl sulfoxide; at 100℃; for 24h;	General procedure: To a 100 mL eggplant type Schlenk flask were added CuBr2 (67.0 mg, 0.3 mmol), corresponding amine (3 mmol) and a solution of NMI (73.8 mg, 0.9 mmol) in DMSO (6 mL). The flask was evacuated and purged with oxygen for three times before the flask was attached to a balloon filled with oxygen. Then the flask was heated at 100 C for 24 h. After the flask was cooled down and the reaction mixture turned into green color, water (15 mL) and dichloromethane (15 mL) was added into the mixture. The water layer was extracted with dichloromethane (5 mL x 3) and the organic layers were combined. After removing the solvent, residue was purified by column chromatography (PE/EA = 100:1) to give the product.

Reference： [1]Synthesis,2009,p. 945 - 950
[2]Synthesis,2010,p. 2631 - 2635
[3]Tetrahedron,2018,vol. 74,p. 4266 - 4271
[4]Advanced Synthesis and Catalysis,2014,vol. 356,p. 189 - 198
[5]Journal of the American Chemical Society,2018,vol. 140,p. 8662 - 8666
[6]ChemSusChem,2015,vol. 8,p. 92 - 96
[7]Organic and Biomolecular Chemistry,2016,vol. 14,p. 3356 - 3359

20
[ 539-48-0 ]
[ 459-57-4 ]
[ 478701-50-7 ]

Yield	Reaction Conditions	Operation in experiment
66%		To a solution of 4-fluorobenzaldehyde (2.482 g, 20.00 mmol) in a mixed solvent (20 mL of methylene chloride nd 10 mL of i-propanol) at rt, was added 1 ,4- <n="134"/>phenylenedimethanamine (1.362 g, 10 mmol, Aldrich). The reaction mixture was stirred at rt for 5 h. To this mixture, sodium borohydride (0.567 g, 15.0 mmol, 1.5 eq) was added, and it was stirred at rt overnight. The reaction mixture was quenched by adding 10 mL of MeOH and 10 mL of aq. NaHCC>3. The reaction mixture was extracted with EtOAc (3x50 mL). The combined organic extracts were dried, concentrated and purified by ISCO system, eluteing with CH?CVEtOAc to give the title compound (2.45 g, 66%) as a viscous material, MS (ESI): 353.1 (M + H)+.

Reference： [1]Patent: WO2009/152082,2009,A1 .Location in patent: Page/Page column 51; 132-133

21
[ 539-48-0 ]
[ 110-13-4 ]
[ 1182257-77-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With diethylenetriaminepentaacetic acid on magnetic Fe3O4 nanoparticles; In ethanol; water; at 20℃; for 0.25h;	General procedure: To a solution of amine (1 mmol) and hexan-2,5-dione (1 mmol) in EtOH-H2O (2 ml, 1:1) at room temperature was added catalyst (40 mg ~4 mol%). The mixture was stirred at this temperature for the required period of time (Table 3). The reaction was monitored using TLC (silica gel, 3:1 n-hexane-acetone). After completion of the reaction, 10 ml of ethanol was added, and the catalyst was removed using an external magnet. Concentration gave the crude product as a solid. The crude product was purified by recrystallization from ethanol to afford pure product. For the compounds that were oils (3h, 3m, 3o), identification was made by matching 1H-NMR and 13C-NMR values withthose in the literature.37,40
92%	With trichloroisocyanuric acid; In acetonitrile; at 20℃; for 0.166667h;	General procedure: To a solution of amine 1 (1 mmol) and 2,5-hexanedione 2 (1 mmol) in CH3CN (3 ml), TCCA (0.02 mmol) was added at rt. The mixture was allowed to stir at this temperature for the period time specified in Table 1. The reaction was monitored by thin layer chromatography (TLC)(3:1 n-hexane/acetone). After completion of the reaction, the solvent was evaporated. Then,CH2Cl2 (10 ml) was added, and the catalyst was removed by filtration. Evaporation of the solventunder reduced pressure gave the products. Further purification was achieved by TLC usingn-hexane/acetone (70:30) as the solvent system to afford the pyrroles.
78%	In water; at 100℃; for 0.25h;Green chemistry;	General procedure: A round bottom flask equipped with a magnetic stirrer was charged with primary aliphatic, aromatic amines (10 mmol), hexa-2,5-dione (10 mmol) and distilled water (5 mL). This suspension was refluxed at 100 C for 15 minutes. The reaction was monitored by TLC (4:1 n-hexane/ethylacetate). After the reaction mixture was cooled to room temperature, the product was washed with water and recrystallized from methanol. The resulting product was identified using FT-IR and NMR spectroscopy.

Reference： [1]Organic Preparations and Procedures International,2018,vol. 50,p. 465 - 481
[2]Tetrahedron Letters,2010,vol. 51,p. 2109 - 2114
[3]South African Journal of Chemistry,2009,vol. 62,p. 33 - 38
[4]Journal of Sulfur Chemistry,2013,vol. 34,p. 347 - 357
[5]Journal of Heterocyclic Chemistry,2013,vol. 50,p. E241-E246
[6]Synthetic Communications,2014,vol. 44,p. 1323 - 1332

22
[ 539-48-0 ]
[ 16225-26-6 ]
N-(4-aminomethylphenylmethyl)-3,5-di-t-butylbenzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3078 - 3087

23
[ 75-15-0 ]
[ 56187-04-3 ]
[ 539-48-0 ]
[ 1242063-54-2 ]

Reference： [1]ARKIVOC,2010,vol. 2010,p. 49 - 54

24
[ 67-56-1 ]
(dimethylglyoxime)2(H₂O)CoMe [ No CAS ]
[ 539-48-0 ]
[ 4151-80-8 ]
[ 7732-18-5 ]
[(cobalt(III)(methyl)(dimethylglyoxime(-H))(dimethylglyoxime(-2H)))2(CH3OBC6H4)2(α,,alpha.'-diamino-p-xylene)]*3.5H2O [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2010,vol. 363,p. 2113 - 2124

25
[ 1593-08-4 ]
[ 539-48-0 ]
[ 1269610-79-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	In ethanol; at 75℃; for 3h;	Quinoxaline-2-carbaldehyde 626 (1.58 g, 10 mmol) was dissolved in EtOH (150 mL) and 1, 4-xylylenediamine (0.63 g, 4.6 mmol) was then added and mixture was stirred at 75 C for 3 h. The mixture was then cooled to room temp and the precipitate was filtered and washed with EtOH (×3) to give the intermediate diimine as an off-white solid (1.82 g, 95%); mp = 185-186 C. The diimine (1.81 g, 4.3 mmol) was dissolved in MeOH (50 mL) and then cooled over an ice bath. Sodium cyanoborohydride (273 mg, 4.3 mmol) and acetic acid (4 mL) were added to the cooled solution and the suspended solid dissolved gradually whilst the mixture was stirred at room temp for 3 h. The volatile components were evaporated under diminished pressure. Ethyl acetate was then added to residue and this was then washed with aq NaHCO3. The aq layer was further extracted with EtOAc (3 × 10 mL). The combined organic layer was dried (MgSO4), filtered and the solvent was removed. Chromatography of the residue (EtOAc-MeOH, 2:1) gave 7 as a dark red solid (1.31 g, 72%); mp = 116-117 C; 1H NMR (CDCl3, 500 MHz): delta = 8.88 (s, 2H), 8.05-8.09 (m, 4H), 7.70-7.76 (m, 4H), 7.35 (s, 4H), 4.16 (s, 4H), 3.92 (s, 4H), 2.23 (s, 2H, NH); 13C NMR (125 MHz, CDCl3) delta 154.9 (C), 145.3, 141.9, 141.8 (each CH), 138.7 (C), 130.0, 129.3, 129.2, 129.0, 128.4 (each CH), 53.4, 52.8 (each CH2). HRMS (ESI): Found 443.1960 [M+Na]+, C26H24N6Na requires 443.1968.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 826 - 835

26
[ 24424-99-5 ]
[ 539-48-0 ]
[ 20580-52-3 ]
[ 108468-00-4 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium hydroxide; In 1,4-dioxane; water; at 20℃;Cooling with ice;	1,4-Bis(aminomethyl)benzene (30 g, 220.3 mmol) was dissolved/suspended in 1 M aq NaOH (220 mL, 220.3 mmol). 1,4-Dioxane was added (250 mL) and the solution was cooled in an ice-water bath. Di-tert-butyl dicarbonate (48.1 g, 220.3 mmol) was added dropwise in 1,4-dioxane (150 mL) over a period of 2 h. The ice-water bath was removed and the mixture was allowed to stand at rt overnight. The volume was reduced to about 250 mL under reduced pressure. The white solid was separated by filtration, washed twice with ice-cold water (2 × 100 mL) and dried in vacuo. White solid (47.6 g of a mixture of 3 and di-Boc-protected 1,4-bis(aminomethyl)benzene (?55:45), 22 g (42% related to 3); 1H NMR (300 MHz, MeOH-d4): delta (ppm) 1.44 (s, 24H, tert-butyl, 3 and ?di-Boc?), 3.84 (s, 2H, CH2-NH2), 4.19 (s, 3.3H, CH2-NH, ?di-Boc?), 4.20 (s, 2H, CH2-NH, 3), 7.2 (s, 3.3H, CHAr, ?di-Boc?), 7.29 (m, 4H, CHAr, 3); MS (CI, NH3): m/z 254 [M+NH4]+, 354 [?di-Boc?+NH4]+; C13H20N2O2 (236.2).

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 2859 - 2878

27
[ 60239-18-1 ]
[ 539-48-0 ]
[ 1314043-15-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine; diisopropyl-carbodiimide; In water; acetonitrile;	DOTA (1.0 g, 1.93 mmol), 1,4-bis(aminomethyl)benzene (263 mg, 1.93 mmol) and diisopropyl-carbodiimide (DIC, 244 mg, 1.93 mmol) were dissolved in a mixture of water/MeCN/pyridine (1:1:0.2, 50 mL) and reacted overnight. The solvents were removed and the crude product was purified by column chromatography on silica gel using H2O/MeCN 1:1 + 0.1% TFA as the mobile phase. The product was isolated as lightly yellow solid after lyophilization (760 mg, 1.46 mmol, 75% yield). Rf = 0.45 (H2O/MeCN 1:1 + 0.1% TFA)1H NMR (500 MHz, water-d2, 25 C, TMS): delta = 7.45 (d, 2H, 3J(H,H) = 8.3 Hz); 7.38 (d, 2H, 3J(H,H) = 8.3 Hz); 4.35 (br s, 2H); 4.14 (br s, 2H); 3.86-2.89 (br m, 24H). 13C NMR (125 MHz, water-d2, 25 C, TMS): delta = 163.30; 162.94; 139.16; 131.72; 129.27; 128.10; 55.54; 55.45; 55.39; 50.85; 50.48; 50.42; 48.65; 48.55; 48.54; 48.50; 48.46; 48.30; 42.89. ESI-MS (m/z) for [M+H]+ (calculated): 523.27 (523.28), (m/z) for [M+K]+ (calculated): 561.23 (561.24).

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 3864 - 3874

28
[ 539-48-0 ]
[ 137076-54-1 ]
[ 1314043-18-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: 1,4,7-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane-10-acetic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.0333333h; Stage #2: p-xylylidenediamine In N,N-dimethyl-formamide for 0.5h;	2.2.6. Tris-tBu-(phenylene-1,4-dimethylamino-)DOTA (P-amino-DOTA) (8) A solution of HBTU (314.5 mg, 830 μmol) in DMF (1.5 mL) was added to tris-tBu-DOTA (500 mg, 874 μmol) followed by DIPEA (149 μL, 874 μmol) and reacted for 2 min. Subsequently, the mixture was added to a solution of 1,4-bis(aminomethyl)benzene (297 mg, 2.18 mmol) in DMF (250 μL) and reacted for 30 min. After acidification with 1 M HCl (200 μL), the product was purified by semi-preparative HPLC with 0-50% MeCN + 0.1% TFA in 8 min as the gradient (Rt = 4.3 min). The product was obtained as slightly green, highly hygroscopic solid after lyophilization (390 mg, 565 μmol, 68% yield).1H NMR (500 MHz, acetone-d6, 25 °C, TMS): δ = 7.47 (d, 2H, 3J(H,H) = 8.1 Hz); 7.39 (d, 2H, 3J(H,H) = 7.9 Hz); 5.01 (br s, 2H); 4.61-3.13 (br m, 24H); 4.49 (br s, 2H); 1.53 (s, 9H); 1.46 (s, 18H). 13C NMR (125 MHz, acetone-d6, 25 °C, TMS): δ = 160.60; 160.25; 140.10; 130.29; 129.53; 128.85; 55.70; 55.68; 55.22; 55.19; 55.16; 52.27; 52.24; 50.80; 50.66; 50.09; 49.97; 28.34; 28.32. ESI-MS (m/z) for [M+H]+ (calculated): 691.48 (691.47).

Reference： [1]Location in patent: experimental part Waengler, Carmen; Schaefer, Martin; Schirrmacher, Ralf; Bartenstein, Peter; Waengler, Bjoern [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 12, p. 3864 - 3874]

29
[ 589-29-7 ]
[ 539-48-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tert-Amyl alcohol; at 150℃; for 20h;Inert atmosphere; Cooling;	Example 6Direct Single-Stage Amination of Alcohols andHydroxy Acids by Means of Ammonia Over aHomogeneous Ruthenium Catalyst and Xantphos ata high V7J Vgas (according to the invention)Under an argon atmosphere, m g of starting material, mRU g of [carbonylchlorohydridotris(triphenylphosphane)ruthenium(II)] and mp g of 9,9-dimethyl-4,5-bis (diphenylphosphino)xanthene as catalyst and V07 ml of 2-methyl-2-butanol as solvent were introduced into a 50 mlsteel tube. The vessel was closed, pressurized three times with 20 bar of argon and depressurized each time. The vessel was then cooled by means of dry ice and m g of ammonia were condensed in. The reactor is heated to T C. and maintained at this temperature for 20 hours. Afier cooling to room temperature, the reactor was depressurized and opened, the solvent was removed on a rotary evaporator and the residue was dissolved in methanol and then analysed by gas chromatography. Reaction parameters and conversions and selectivities to the desired reaction product are shown in Tab. 5. The results show that many different hydroxy-thnctionalized substrates can be aminated by the method described.

Reference： [1]Patent: US2013/331580,2013,A1 .Location in patent: Paragraph 0063
[2]Angewandte Chemie - International Edition,2011,vol. 50,p. 7599 - 7603
[3]Chemistry - A European Journal,2013,vol. 19,p. 17702 - 17706

30
[ 1355023-63-0 ]
[ 539-48-0 ]
N,N'-(1,4-phenylenebismethylene)bis{(2'S)-2'-tert-butoxycarbonylamino-4'-[5''-deoxy-5''-(methylamino)-2'',3''-O-(1'''-methylethylidene)adenosyl]butanamide} [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;	PyBOP (200 mg, 0.383 mmol) and DIPEA (67 muL, 0.38 mmol) were added to a stirred solution of p-xylylenediamine (7a) (18 mg, 0.13 mmol) and the acid 62 (200 mg, 0.383 mmol) in DMF (4 mL) and the reaction mixture was stirred at room temperature for 18 h. The crude product was purified by ion exchange chromatography (SCX), eluting with saturated ammonia in methanol solution, followed by flash chromatography (gradient elution: 3:97-6:94 saturated ammonia in methanol solution-CH2Cl2) to yield a mixture of the diamide and an unwanted side product. A second flash chromatography (gradient elution: 6:94-12:88 methanol-CH2Cl2) gave the diamide 8a (100 mg, 68%; 4:1 mixture of diastereoisomers) as a colourless foam; Rf 0.17 (7:93 saturated ammonia in methanol solution-CH2Cl2); numax/cm-1 (film) 3328, 3197, 2979, 2464, 1651, 1601 and 1417; [a]+20.4 (c 1.00 in CH2Cl2); deltaH (500 MHz; methanol-d4) 8.29 (2H, s, Ade 8-Hmaj), 8.27 (2H, s, Ade 8-Hmin), 8.24 (2H, s, Ade 2-H), 7.247.19 (4H, m, 2H, 3H, 5-H and 6-H), 6.18 (2H, d, J 2.6, 1''-H), 5.51-5.49 (2H, m, 2''Hmin), 5.495.45 (2H, m, 2''-Hmaj), 5.03-5.01 (2H, m, 3''-Hmin), 4.99 (2H, dd, J 6.4 and 3.4, 3''Hmaj), 4.43-4.31 (6H, m, 4''H, 1-CH2 and 4-CH2), 4.13-4.08 (2H, m, 2'H), 2.68 (2H, dd, J 13.3 and 5.6, 5''-HA), 2.63 (2H, dd, J 13.3 and 7.7, 5''HB), 2.502.41 (4H, m, 4'-H), 2.21 (6H, s, NMe), 1.94-1.85 (2H, m, 3'-HA), 1.76-1.68 (2H, m, 3'-HB), 1.60 (6H, s, CMe2), 1.44 (18H, s, t-Bu) and 1.39 (6H, s, CMe2); deltaC (75 MHz; methanol-d4) 175.0 (amide C=O), 158.0 (carbamate C=O), 157.7, 154.4 (Ade C-2), 150.6, 142.2 (Ade C-8), 139.2 (C-1 and C4), 129.0 (C-2, C-3, C-5 and C-6), 120.9, 116.0 (CMe2), 91.9 (C1''min), 91.7 (C1''maj), 86.3 (C4''), 85.3 (C-2''), 84.9 (C3''), 81.0 (CMe3), 61.1 (C-5''min), 60.9 (C5''maj), 55.9 (C-4'), 55.2 (C-2'), 44.0 (1-CH2 and 4CH2), 43.2 (NMemaj), 43.0 (NMemin), 30.7 (C-3'), 29.1 (CMe3), 27.8 (CMe2) and 25.9 (CMe2); m/z (ES+) 1143.6 (100%, MH+), 572.3 (80%, MH22+); (Found: MH+ 1143.6092; C54H78N16O12 requires MH+ 1143.6058). Analysis of the product by 500 MHz 1H NMR spectroscopy revealed that partial epimerisation occurred at the 2'-position under these conditions.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 278 - 284

31
[ 539-48-0 ]
[ 29754-58-3 ]
C₂₈H₂₄N₂O₈ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1213 - 1218

32
[ 539-48-0 ]
[ 29754-58-3 ]
[ 321708-31-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1213 - 1218

33
[ 539-48-0 ]
[ 1355462-28-0 ]
C₁₁₂H₁₃₄N₈O₄₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 48h;Inert atmosphere;	To 16 (250 mg, 0.227 mmol) in dry DMF (5 mL) was added PyBop (130 mg, 0.250 mmol) and DIPEA (35 mg, 0.273 mmol). The suspension was stirred under argon until a clear solution was obtained. To this was added p-xylylenediamine (15 mg, 0.111 mmol). The reaction mixture was stirred for 48 h under argon and the volatile materials were removed under reduced pressure. Column chromatography of the residue (ethyl acetate-cyclohexane, 3:7 to 8:2 gradient elution) gave a protected diamide intermediate as a white solid (200 mg, 77 %). This protected diamide (50 mg, 0.0218 mmol) was dissolved in MeOH (anhydrous, 5 mL) and a catalytic amount of NaOMe (0.1 mL of a 1 mMol solution in MeOH) was added and the resulting solution was stirred for 1 h at 0 C temperature. The reaction was quenched by the addition of Amberlite IR 120, resin which was then filtered off and the solvent was removed. The resulting residue was purified using RP silica to give 4 (26 mg, 70%); 1H-NMR (500 MHz, DMSOD6) = 8.45 (t, J = 5.16 Hz; 2 H), 8.04 (s, 2 H; C=CHN), 7.37-7.28 (m, 20 H; 4C6H5), 7.19-7.18 (broad s, 4 H; C6H4), 5.78-5.70 (m, 2 H; CH=CH2,), 5.63 (d, J = 9.26 Hz, 2 H), 5.56 (d, J = 5.82 Hz, 2 H), 515-5.10 (m, 4 H; CH=CH2), 5.00 (d, J = 10.2 Hz, 2 H), 4.90 (s, 2 H), 4.83 (s, 2 H) overlapping with 4.80 (d, J = 4.88 Hz, 2 H), 4.73 (dd, J = 10.40 Hz and 1.94 Hz, 4 H), 4.66 (d, J = 4.70 Hz, 4 H), 4.63 (s, 2 H), 4.57 (d, J = 11.36 Hz, 4 H), 4.53 (d, J = 4.41 Hz, 2 H), 4.38 (dd, J = 15.27 Hz and J = 6.29 Hz, 2 H), 4.27 (d. J = 7.11 Hz, 2 H), 4.20 (dd, J = 14.83 Hz and 5.11 Hz, 2 H), 4.04 (ddd, J = 9.56 Hz, 4.7 Hz and 4.46 Hz, 2 H; H-1), 4.00 (d, J = 6.95 Hz, 2 H), 3.85-3.78 (m, 8 H), 3.67-3.49 (m, 12 H), 3.37-3.29 (m, 12 H), 2.47-2.41 (m, 2 H; CH2CH=CH2), 2.36-2.30 (m, 2 H; CH2CH=CH2); 13C NMR (125 MHz, DMSOD6) delta = 145.98 (CH=C), 138.31, 138.29, 138.26, 138.22, 138.11, 128.15, 128.14, 128.11, 128.08, 128.04, 128.01, 127.98, 127.92, 127.85, 127.76, 127.69, 127.66, 127.64, 127.62, 127.39, 127.35, 125.16, 124.03, 122.83, 122.82, 119.42, 103.69, 86.82, 79.74, 79.59, 77.64, 75.52, 75.05, 73.02, 71.83, 71.76, 70.95, 70.36, 67.87, 60.26, 34.39, 30.24, 0.03. HRMS (ESI), found [M+H+] 1705.7017; C84H105N8O30 requires 1705.6937.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 313 - 318

34
[ 539-48-0 ]
[ 142770-42-1 ]
[ 1351934-59-2 ]

Reference： [1]Biochemical Pharmacology,2012,vol. 83,p. 57 - 68

35
[ 539-48-0 ]
[ 620169-99-5 ]
[ 1379771-94-4 ]

Yield	Reaction Conditions	Operation in experiment
45%		General procedure: The precursor quinoline tetramer acid (100 mg, 0.1 mmol, 2.05 equiv), HBTU (114 mg, 0.3 mmol, 3 equiv), and HOBt (27 mg, 0.2 mmol, 2 equiv) were dissolved in anhydrous DMF under nitrogen. DIEA (173 muL, 1 mmol, 10 equiv) was added and the reaction mixture was stirred at room temperature for 30 min. The diamine (1 equiv) was added and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was poured into water, extracted three times with toluene, dried over Na2SO4, filtered, and concentrated. The crude was purified by silica-gel chromatography eluting with toluene/ethyl acetate 90/10 v/v, yielding the expected compound as a yellow solid.

Reference： [1]Tetrahedron,2012,vol. 68,p. 4464 - 4469

36
[ 1268356-58-6 ]
[ 539-48-0 ]
2BF₄^(1-)*C₂₂H₂₂Fe₂N₂O₄⁽³⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In dichloromethane; at 24℃;Inert atmosphere;	General procedure: A Schlenk tube equipped with a magnetic bar was charged with a solution of compound 1 (0.521 g, 1.54 mmol) in CH2Cl2 (20 ml) and a solution of PDA (0.209 g, 1.54 mmol) in CH2Cl2 (10 ml) added. The mixture was stirred for 5 h and allowed to stand under nitrogen at room temperature overnight after which a yellow precipitate settled at the bottom of the Schlenk tube. The mother liquor was syringed off, the residue washed with 4 portions of CH2Cl2 (4 × 10 ml) and dried under reduced pressure to give 15 as a yellow solid. Yield: 0.317 g, 62%. Anal. Calc. for C22H22B2F8Fe2N2O4: C, 39.81; H, 3.34; N, 4.22. Found: C, 39.68; H, 3.26; N, 4.18%. 1H NMR (400 MHz, acetone-d6): delta 5.58 (s, 10H, Cp), 3.89 (s, 2H, NH2), 3.68 (br, 4H, CH2), 7.34 (s, 4H, =CH). 13C NMR (400 MHz, acetone-d6): delta 87.56 (Cp), 56.54 (CH2), 129.63 (=CH), 139.95 (C-CH2), 212.28 (CO). IR (solid state) vmax(cm-1): 2054, 1999 (CO); 3319, 3284 (NH2). Decomposes at temperature >160 C.

Reference： [1]Journal of Organometallic Chemistry,2012,vol. 717,p. 52 - 60

37
[ 539-48-0 ]
BF₄^(1-)*C₁₁H₁₃FeO₃ [ No CAS ]
2BF₄^(1-)*C₃₂H₄₂Fe₂N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In dichloromethane; at 24℃;Inert atmosphere;	General procedure: A Schlenk tube equipped with a magnetic bar was charged with a solution of compound 1 (0.521 g, 1.54 mmol) in CH2Cl2 (20 ml) and a solution of PDA (0.209 g, 1.54 mmol) in CH2Cl2 (10 ml) added. The mixture was stirred for 5 h and allowed to stand under nitrogen at room temperature overnight after which a yellow precipitate settled at the bottom of the Schlenk tube. The mother liquor was syringed off, the residue washed with 4 portions of CH2Cl2 (4 × 10 ml) and dried under reduced pressure to give 15 as a yellow solid. Yield: 0.317 g, 62%. Anal. Calc. for C22H22B2F8Fe2N2O4: C, 39.81; H, 3.34; N, 4.22. Found: C, 39.68; H, 3.26; N, 4.18%. 1H NMR (400 MHz, acetone-d6): delta 5.58 (s, 10H, Cp), 3.89 (s, 2H, NH2), 3.68 (br, 4H, CH2), 7.34 (s, 4H, =CH). 13C NMR (400 MHz, acetone-d6): delta 87.56 (Cp), 56.54 (CH2), 129.63 (=CH), 139.95 (C-CH2), 212.28 (CO). IR (solid state) vmax(cm-1): 2054, 1999 (CO); 3319, 3284 (NH2). Decomposes at temperature >160 C.

Reference： [1]Journal of Organometallic Chemistry,2012,vol. 717,p. 52 - 60

38
[ 539-48-0 ]
[ 53-86-1 ]
[ 1408281-48-0 ]

Yield	Reaction Conditions	Operation in experiment
63.9%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	General procedure: Method 2: to the solution of Indomethacin (100 mg, 0.28 mmol), the corresponding amine (0.28 mmol), and PyBOP (145.7 mg, 0.28 mmol) in anhydrous dimethylformamide was added triethylamine (56.5 mg, 0.56 mmol) and the mixture was stirred at room temperature for 2 h. Then saturated sodium chloride solution was added. The reaction mixture was extracted using ethyl acetate (3 x 50 ml). The combined organic layers werewashed successively with water, 5% aqueous sodium bicarbonate, and then concentrated under vacuum. The obtained crude product was purified by recrystallization or silica gel column chromatography.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 56,p. 17 - 29,13

39
[ 54221-96-4 ]
[ 539-48-0 ]
[ 1433897-11-0 ]

Reference： [1]Organometallics,2013,vol. 32,p. 2952 - 2962

40
[ 539-48-0 ]
[ 6627-89-0 ]
[ 108468-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 80℃;Reflux;	Preparation of 1-(-N-Boc-aminomethyl)-4-(aminomethyl)benzene [0178] [0179] Tert-butylphenyl carbonate (2.7 mL, 14.7 mmol) was added dropwise to a solution of p-xylylenediamine (2 g, 14.7 mmol) in ethanol (20 mL) at 80 C. The reaction mixture was refluxed overnight. The solution was then cooled to room temperature and any solids were removed, which leaves a yellow solution. The solution was then concentrated to 10 mL and diluted with water (60 mL). The solution pH was adjusted to 3 with 2M HCl followed by an extraction with dichloromethane (3×75 mL). The water solution pH was then adjusted to pH 12 followed by extraction with dichloromethane (3×75 mL). The organic solutions were combined and washed with sodium bicarbonate (2×75 mL), dried with sodium sulfate, and concentrated down to a white solid. Characterization matches previously published literature (M. A. Ghanem, et al., ?Covalent modification of glassy carbon surface with organic redox probes through diamine linkers using electrochemical and solid-phase synthesis methodologies?, Journal of Materials Chemistry, (2008), 18(41), pg 4917-4927).

Reference： [1]Patent: US2013/281515,2013,A1 .Location in patent: Paragraph 0178; 0179

41
[ 539-48-0 ]
[ 589-29-7 ]

Yield	Reaction Conditions	Operation in experiment
22%	With water; sodium hydroxide; In methanol; at 240℃; for 2h;Inert atmosphere; Autoclave;	Examples 26 to 29 [0035] In a stainless steel pressure resistant vessel having an inner capacity of 40 mL equipped with a thermometer and a manometer, the amine shown in Table 3 below was charged along with methanol, water and sodium hydroxide at a molar ratio of amine/methanol/water/sodium hydroxide of 1/55/35/0.7, and the vessel was sealed under a nitrogen atmosphere. The mixture was heated and held at 240C for 2 hours. After cooling, the reaction solution was taken out, and after neutralizing sodium hydroxide, was analyzed. The results are shown in Table 3. [0036] Table 3 Aromatic amine Conversion ratio of raw material (%) Alcohol formed Yield (%) Example 26 benzylamine 100 benzyl alcohol 96 Example 27 o-methoxybenzylamine 97 o-methoxybenzyl alcohol 48 Example 28 m-methoxybenzylamine 100 m-methoxybenzyl alcohol 65 Example 29 m-chlorobenzylamine 100 m-chlorobenzyl alcohol 91 Example 30 4-(dimethylamino)benzylamine dihydrochloride 92 4-dimethylaminobenzyl alcohol 12 Example 31 p-xylylenediamine 100 p-xylylene glycol

Reference： [1]Patent: EP2657214,2013,A1 .Location in patent: Paragraph 0036; 0037

42
[ 90-14-2 ]
[ 539-48-0 ]
N,N'-di-[1]naphthyl-p-xylylenediamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With palladium diacetate; sodium tosylate; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 130 - 135℃; for 24h;	Synthesis of Intermediate 110127] First, 18.7 g (73.4 mmol) of i-iodonaphthalene,9.88 g (102.8 mmol) of sodium tert-butoxide (both manufactured by: Wako Pure Chemical Industries, Ltd.), 5.0 g (36.7 mmol) of p-xylenediamine (manufactured by: Tokyo Chemical Industry Co., Ltd.), 0.27 g (0.57 mmol) of 2-dicyclohexy- lphosphino-2?,4?,6?-triisopropylbiphenyl (manufactured by:Aldrich) and 0.054 g (0.28 mmol) of palladium acetate (manufactured by: Wako Pure Chemical Industries, Ltd.) were dispersed in 36 mL of xylene and reacted at 130 to 135 C. for 24 hours. Afier the reaction, the resultant was cooled to room temperature. Crystals thus precipitated were filtered and then washed with methanol. Next, the crystals were washed with water and dried to obtain 9.79 g (yield 69%) of intermediate 1 represented by the following chemical formula (1).10128] From the following analysis result, the obtained compound was confirmed to be a desired compound.10129] MS (ESI) (m/z): 389(+)10130] Values of elemental analysis: CHN actual measurement values (86.72%, 6.54%, 6.97%); theoretical values (86. 56%, 6.23%, 7.21%)
69%	With palladium diacetate; sodium t-butanolate; XPhos; In 5,5-dimethyl-1,3-cyclohexadiene; at 130 - 135℃; for 24h;	Synthesis of Intermediate 1First, 18.7 g (73.4 mmol) of 1-iodonaphthalene (manufactured by Wako Pure Chemical Industries, Ltd.), 9.88 g (102.8 mmol) of sodium tert-butoxide, 5.0 g (36.7 mmol) of p-xylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.), 0.27 g (0.57 mmol) of 2-dicyclohexylphosphino-2?,4?,6?-triisopropylbiphenyl (manufactured by Aldrich) and 0.054 g (0.28 mmol) of palladium acetate (manufactured by Wako Pure Chemical Industries, Ltd.) were dispersed in 36 mL of xylene and reacted at 130 to 1350C for 24 hours. After the reaction, the resultant was cooled to room temperature to precipitate crystals. The crystals were washed with methanol and then water, followed by drying, thereby obtaining 9.79 g (yield 69%) of the intermediate 1 represented by the following chemical formula (1).From the following analysis result, the obtained compound was confirmed to be a desired compound.MS(ESI) (m/z): 389(+)Values of elemental analysis: CHN actual measurement values (86.72%, 6.54%, 6.97%); theoretical values (86.56%, 6.23%, 7.21%)
69%	With palladium diacetate; sodium t-butanolate; XPhos; In 5,5-dimethyl-1,3-cyclohexadiene; at 130 - 135℃; for 24h;	First, 18.7 g (73.4 mmol) of 1-iodonaphthalene, 9.88 g (102.8 mmol) of sodium tert-butoxide (both manufactured by Wako Pure Chemical Industries, Ltd.), 5.0 g (36.7 mmol) of p-xylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.), 0.27 g (0.57 mmol) of 2-dicyclohexylphosphino-2?,4?,6?-triisopropylbiphenyl (manufactured by Aldrich) and 0.054 g (0.28 mmol) of palladium acetate (manufactured by Wako Pure Chemical Industries, Ltd.) were dispersed in 36 mL of xylene and reacted at 130 to 135 C. for 24 hours. After the reaction, the resultant was cooled to room temperature. Crystals thus precipitated were filtered and then washed with methanol. Next, the crystals were washed with water and dried to obtain 9.79 g (yield 69%) of intermediate 1 represented by the following chemical formula (1).

69%

With acetic acid; sodium t-butanolate; XPhos; In 5,5-dimethyl-1,3-cyclohexadiene; at 130 - 135℃; for 24h;

18.7 g (73.4 mmol) of 1-iodonaphthalene manufactured by Wako Pure Chemical Industries, Inc.,Sodium butoxide 9.88 g (102.8 mmol), manufactured by Tokyo Chemical Industry Co., Ltd. on p-phenylenediamine5.0 g (36.7 mmol), 2-dicyclohexylphosphino-2, 4 ', 6'-? 0.27 g (0.57 mmol) of triisopropylbiphenyl, acetic acid manufactured by Wako Pure Chemical Industries, Ltd.0.05 mug (0.28 mmol) was dispersed in xylenol 36 mL and reacted130-135 C for 24 hours. After completion of the reaction, the mixture was cooled at room temperature- and the precipitated crystals are filtered and washed with methanol. Then byWater and washed to obtain 9.79 g (69% yield) of the following chemistryIntermediates 1 represented by the formula (1).

Reference： [1]Patent: US2014/39201,2014,A1 .Location in patent: Paragraph 0127; 0128; 0129; 0130
[2]Patent: US2015/353472,2015,A1 .Location in patent: Page/Page column 0102; 0103; 0104; 105
[3]Patent: CN103834237,2016,B .Location in patent: Paragraph 0403-0405
[4]Patent: TWI550030,2016,B .Location in patent: Page/Page column 27

43
[ 109-86-4 ]
[ 539-48-0 ]
[ 1612251-42-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); potassium hydroxide; In toluene; at 110℃; for 12h;Inert atmosphere;	General procedure: An oven dried 10 mL round bottom flask equipped with a stir bar was brought into the glove box with a reflux condenser. The flask was charged with [RuHCl(CO)(HN(CH2CH2PPh2)2)] (4) (6.0 mg, 0.01 mmol, 1mol%), KOH (8.2 mg, 0.15 mmol, 15mol%), toluene (1.0mL), an amine (1 mmol, 1.0 equiv), and an alcohol (1mmol, 1.0equiv) in that order. After all reagents have been added to the flask, the reflux condenser was attached and secured with a Keck clamp. The top of the condenser was sealed with a septum and the whole apparatus was then removed from the glove box. Once outside the glove box, the apparatus was equipped to nitrogen flow by inserting an inlet needle supplying a positive pressure of nitrogen into the septum, and an outlet needle connected to an oil bubbler. The reaction mixture was heated at reflux in a silicone oil bath overnight (12h), then allowed to cool to rt, and the conversion determined by GC-MS (CI). The resulting residue was subjected to flash chromatography with the indicated solvent system to obtain the purified amide in the reported isolated yield.

Reference： [1]Tetrahedron,2014,vol. 70,p. 4213 - 4218

44
[ 539-48-0 ]
[ 541-41-3 ]
[ 4182-40-5 ]

Yield	Reaction Conditions	Operation in experiment
59%	With triethylamine; In tetrahydrofuran; at 20℃; for 24h;Cooling with ice;	General procedure: To a THF (100 mL) solution of 5 g (36.7 mmol) of the xylylenediamine and 10.2 mL (7.4 g, 73.4 mmol) of TEA were added dropwise 7.0 mL (7.9 g, 73.4 mmol) of ethyl chloroformate with vigorous stirring in an ice bath. The reaction mixture was additionally stirred for 24 h at room temperature. The suspension was filtered and the THF solution was evaporated to dryness. The obtained solid was solubilized in ethyl acetate and filtered to separate the insoluble solids. The ethyl acetate solution was evaporated to obtain the solid product.

Reference： [1]Journal of the Brazilian Chemical Society,2015,vol. 26

45
[ 539-48-0 ]
[ 35212-68-1 ]
C₁₂H₂₂N₃O₃P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With water; In 1,4-dioxane; at 120℃; for 12h;Sealed tube;	General procedure: To the aziridinephosphonate 5 (0.2 mmol, 36 mg), dissolved in 3 mL of H2O/dioxan (5:1), 200muL (5-15 molar excess) of an amine NH2R1 (for the structure of R1 see Scheme 1 and Table 1)was added. The reaction mixture was stirred in a sealed reactor, heated in an oil bath at 120Cfor 12 h. Volatile components were evaporated under reduced pressure. An excess of highlyvolatile amines was extracted by appropriate organic solvent. The obtained crude ammoniumsalts of ethyl 1,2-diaminoethylphosphonates (water phase) were purified by HPLC (WatersSpherisorb S10ODS2 column, flow 10 mL/min, gradient A:B 100:025:75 in 30 min), tR: 22.5min (11c), 19.5 min (11d), 25.2 min (11g), 20.9 min (11h), 24.5 min (11i), 27.8 min (11j), 24.5min (11k), 19.5 min (11l), 18.2 min (11m), 25.3 min (11n), 26.2 min (11p), 27.2 min (11q),22.5 min (11r), 22.5 min (11s), 23.6 min (11t) and 25.6 min (11u). For the yields see Table S1.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 117,p. 187 - 196

46
[ 539-48-0 ]
C₂₀H₂₆N₂O₄ [ No CAS ]
N,N'-[[N-[2-[(tert-butyloxyoxycarbonyl)amino]ethyl]-N-(naphthalen-9-ylmethyl)]glycyl]-p-xylylenediamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃;	General procedure: Compound 1 (0.74 g, 2.10 mmol), N-hydroxybenzotriazole (HOBT, 0.32 g,2.38 mmol) and diamine (0.95 mmol) were dissolved in 150 mL dichloromethane. Dicyclohexylcarbodiimide (DCC, 0.52 g, 2.50 mmol) was added when the mixture was cooled to 0 C in an ice-water bath. After stirring in the ice-water bath for 1 h, the mixture was stirred at room temperature overnight. The suspension was filtered and the solvent of the filtrate was removed under reduced pressure to obtain the crude product. Crude product was purified by column chromatography (ethylacetate: Methanol = 10:1, v/v) to yield the pure product as a white solid.

Reference： [1]Research on Chemical Intermediates,2016,vol. 42,p. 7329 - 7344

47
[ 539-48-0 ]
C₄₉H₆₁N₃O₆ [ No CAS ]
C₁₀₆H₁₃₀N₈O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		To a solution of compound3 (300 mg, 0.38 mmol) and NHS (87 mg, 0.76 mmol)in anhydrous THF (8 mL) was added DCC (274 mg g, 1.33 mmol). The resulting mixture was stirred atroom temperature and monitored with TLC (CH2Cl2/CH3OH,12/1, v/v). After 3.5 h, to the mixture was added a solution of p-bis(aminomethyl)benzene (23 mg, 0.17mmol) in anhydrous THF (1 mL). The resulting mixture was stirred at roomtemperature for 6 h, filtered and concentrated under reduced pressure. Theobtained residue was purified by chromatography on a silica gel column, elutedwith CH2Cl2/ CH3OH (8/1~6/1, v/v) to affordcompound 4 (173 mg, 53%) as a white solid having 1HNMR (400MHz, CD3OD) delta 7.39-7.38 (m, 20H), 7.16-7.12 (m, 16H), 6.76 (s, 2H),4.65-4.60 (m, 2H), 4.35-4.25 (m, 4H), 3.94 (s, 2H), 3.81 (s, 2H), 3.42-3.39 (m,2H), 3.05-3.00 (m, 2H), 2.88-2.82 (m, 2H), 2.36-0.99 (m, 54H), 0.93 (s, 6H),0.68 (s, 6H); 13C NMR (100 MHz, CD3OD) delta 175.1, 172.0, 142.1, 137.9, 137.2,136.3, 129.5, 128.0, 127.9, 127.2, 119.6, 75.5, 72.5, 71.4, 67.6, 53.3, 46.6,46.1, 42.4, 41.7, 41.5, 39.6, 39.0, 35.5, 35.1, 34.5, 32.6, 31.7, 30.3, 29.8,28.2, 27.3, 26.4, 22.9, 21.8, 16.5, 11.7; ESI-MS m/z: 1698.6 ([M+Na]+) and negative HR-ESI-MSfor C106H129O10N8 ([M-H]-) Calcd: 1673.98372; Found:1673.9812.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3665 - 3668

48
[ 2623-87-2 ]
[ 539-48-0 ]
C₁₂H₁₈N₂O₂*2H⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium carbonate; triethylamine; In N,N-dimethyl-formamide; at 70℃;	1,4-Xylene diamine (2.0 g, 15 mmol) was dissolved in 20 mL of dry DMF. Sodium carbonate was added (3.1 g, 29 mmol) to the solution. In a separate flask, 4-bromobutyric acid (2.5 g,15 mmol) was dissolved in 1 mL of dry DMF and deprotonated with 1.5 equivalences of triethylamine. 4-Bromobutyrate was added dropwise to the xylene diamine solution over 1 hour. The solution was then stirred at 70 C for 16 hours. Solid Na2CO3 was removed via filtration, and the solvent was removed under vacuum. The resulting solid was extracted CH2Cl2/water (3). The aqueous phase was kept, and water was removed under vacuum. The residue was recrystallized in 10% MeOH/90%CH2Cl2 (v/v). Solid 1,4-Xylene diamine was removed via filtration, leaving axle 3 as an orange oil in a 72% yield (2.35 g, 10.6 mmol). 1H-NMR: (D2O): delta 1.66 (2H, m), 2.17 (2H, t), 3.38 (2H, t), 4.21-4.28(4H, m), 7.27 (4H, S).13C-NMR: delta 27.76, 32.32, 38.75, 42.47, 60.76, 127.77, 129.11, 131.54, 133.35, 136.89,138.98, 176.14. Mass spectral analysis for C12H18N2O2-H+(cal. 223.14 found 223.14).

Reference： [1]Molecules,2016,vol. 21

49
[ 10406-24-3 ]
[ 539-48-0 ]
[ 127099-85-8 ]
m-aminomethylbenzoguanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium hydroxide; In butan-1-ol; at 120℃; for 5h;	10099] A 200 mE three-neck flask equipped with a thermometer sheath tube and a reflux condenser was charged with 2.0 g of<strong>[10406-24-3]3-cyanobenzylamine</strong>, 1.0 g of dicyandiamide, 0.1 g of potassium hydroxide, 12.0 g of m-xylenediamine and 25 g of 1 -butanol. The mixture was heated to reflux at 120 C. for 5 hours under agitation at normal pressure. Subsequently, crystals precipitated afier cooling were filtered off and washed with a small amount of methanol, and then vacuum-dried to obtain white crystals. It was confirmed that the white crystals were m-aminomethylbenzoguanamine based on the retention time in gas chromatography. The yield of m-aminomethylbenzoguanamine was 74%.

Reference： [1]Patent: US2016/176827,2016,A1 .Location in patent: Paragraph 0099

50
[ 539-48-0 ]
[ 2129-31-9 ]
C₄₆H₃₈N₂O₂P₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		General procedure: A mixture of 4-(diphenylphosphino)benzoic acid (0.500g, 1.63mmol), EDC.HCl (0.326g, 1.70mmol) and DMAP (0.0299g, 0.245mmol) in CH2Cl2 (20mL) was stirred for 20min. To this mixture was added a solution of 1,4-diaminobenzene (0.086g, 0.80mmol) in CH2Cl2 (20mL), the reaction mixture was stirred for 3h at ambient temperature, filtered to remove N?-(3-dimethylaminopropyl)-N-ethyl urea, washed with saturated aqueous NaHCO3 (3×5mL) and then saturated aqueous NaCl (5mL), and then dried over MgSO4. The mixture was filtered, the solvent was evaporated from the filtrate under vacuum, and the white product was purified by recrystallization from Et2O/MeOH at -20C.

Reference： [1]Polyhedron,2017,vol. 131,p. 46 - 51

51
[ 75-15-0 ]
[ 539-48-0 ]
[ 4891-38-7 ]
3-(4-((4-oxo-6-phenyl-2-thioxo-2H-1,3-thiazin-3(4H)-yl)methyl)benzyl)-2,3-dihydro-6-phenyl-2-thioxo-1,3-thiazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In water at 20℃; for 0.166667h; Sonication; Green chemistry;	Ultrasound irradiation method: General procedure: Ultrasound irradiation method: Amines 2a-d (2 mmol) or diamines 4a-c (1 mmol) was slowly added to a magnetically stirred solution ofcarbon disulfide (2 mmol) and monoacetylenic ester 1a-h (2 mmol) in water (4 mL) (in case of 2b, noneed to add water). After a pre-stirring of 1 min at rt, the vial was subjected to ultrasound irradiation for10 min. The completion of the reaction was monitored by TLC. The crude material formed was filteredand washed with chilled EtOH (3x5 mL) to afford pure title compounds.

Reference： [1]Arafa, Wael A. A.; Mohamed, Ashraf M.; Abdel-Magied, Ahmed F. [Heterocycles, 2017, vol. 94, # 8, p. 1439 - 1455]

52
[ 75-15-0 ]
[ 539-48-0 ]
[ 23326-27-4 ]
3-(4-((6-methyl-4-oxo-2-thioxo-2H-1,3-thiazin-3(4H)-yl)methyl)benzyl)-2,3-dihydro-6-methyl-2-thioxo-1,3-thiazin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In water at 20℃; for 0.166667h; Sonication; Green chemistry;	Ultrasound irradiation method: General procedure: Ultrasound irradiation method: Amines 2a-d (2 mmol) or diamines 4a-c (1 mmol) was slowly added to a magnetically stirred solution ofcarbon disulfide (2 mmol) and monoacetylenic ester 1a-h (2 mmol) in water (4 mL) (in case of 2b, noneed to add water). After a pre-stirring of 1 min at rt, the vial was subjected to ultrasound irradiation for10 min. The completion of the reaction was monitored by TLC. The crude material formed was filteredand washed with chilled EtOH (3x5 mL) to afford pure title compounds.

Reference： [1]Arafa, Wael A. A.; Mohamed, Ashraf M.; Abdel-Magied, Ahmed F. [Heterocycles, 2017, vol. 94, # 8, p. 1439 - 1455]

53
[ 539-48-0 ]
C₂₃H₂₆N₂O₆ [ No CAS ]
C₅₄H₆₀N₆O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.8%		General procedure: In a 100 mL flask, N-alpha-(tert-Butoxycarbonyl)-N-epsilon-1,8-naphthalimido-lysine (2) (1.50 g,3.50 mmol), trimethylamine (0.95 g, 9.60 mmol), 4-dimethylaminopyridine (DMAP, 0.39 g, 3.20 mmol),and different diamines (1.60 mmol) were dissolved in 50 mL methylene chloride. After stirring for5 min, 1-hydroxybenzotriazole (HOBt, 0.52 g, 3.85 mmol) was added into the mixture. The mixturewas stirred in an ice-water bath for 0.5 h. Then dicyclohexylcarbodiimide (DCC, 0.67 g, 3.50 mmol)was added into the mixture in batches. The mixture was warmed to room temperature and stirredovernight. Then, the mixture was washed with 5% citric acid solution (50 mL) and saturated sodium bicarbonate solution (50 mL). After drying with sodium sulfate, the solvent was evaporated in vacuoto obtain the crude product. After purification by silica gel column chromatography using petrolether/ethyl acetate (1:3, v/v), the pure oil product was obtained.

Reference： [1]Molecules,2018,vol. 23

54
[ 24463-19-2 ]
[ 539-48-0 ]
C₂₃H₂₂N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		1,4-di(aminomethyl) benzene (0.48 g, 3.53 mmol) and triethylamine (0.45 mL, 3.11 mmol) weremixed in 30 mL dry THF in a flask, stirring at room temperature for an hour. After that, 9-(chloromethyl)anthracene (0.40 g, 1.76 mmol) was added slowly to the solution, and the mixture was refluxedovernight. The mixture was filtered and evaporated to yield a yellow solid, which was purifiedby column chromatography with a 20:1 mixture of methylene dichloride/methanol. The product(Rf = 0.34) was collected as a pale yellow solid-ABAM (340 mg, 60%). Dissolving the pure productinto acetonitrile, bubbling hydrogen chloride gas in the solution, and then a white precipitate formed. The precipitate was collected and dried to give ABAM hydrochloride (390 mg, 94%). 1HNMR(600 MHzD2O) (ppm) = 4.12 (s, 2H, CH2), 4.38 (s, 2H, CH2), 5.14 (s, 2H, CH2), 7.42 (m, 2H, CH), 7.44 (d, 2H, CH),7.43 (t, 2H, CH), 7.52 (t, 2H, CH), 7.92 (d, 2H, CH), 8.05 (d, 2H, CH), 8.60 (s, 1H, CH). 13CNMR(150 MHzD2O) (ppm) = 134.18, 130.94, 130.84, 130.27, 130.03, 129.67, 129.46, 129.18, 127.35, 125.27, 121.78,119.78, 50.15, 42.59, 40.65. ESI-MS (positive ion): m/z 327.19 [ABAM + H+]+ (calcd. C23H23N2+ 327.18).
54%		a) Dissolve 3.5 mmol (480 mg) of compound 2 (p-xylylenediamine) in tetrahydrofuran (THF) at room temperature,A sufficient amount of triethylamine in THF was added and stirred for one hour;b) The solution obtained in step a is placed in an oil bath and heated to reflux. After the reflux begins,1.7 mmol (400 mg) of Compound 1 was slowly added dropwise using a constant pressure dropping funnel.(9-chloromethylhydrazine) in tetrahydrofuran (drop time 30 minutes);c) After the addition was complete, the reaction mixture was refluxed for a further 3 hours;d) After the mixture was cooled to room temperature, the solvent was removed by rotary evaporation and the residue was dissolved in dichloromethane. After the organic phase of dichloromethane is washed 3 times, it is dried over Na2SO4;e) Purification of the crude product by column chromatography, elution with a 10:1 mixture of dichloromethane and methanolThe liquid, TLC follow the collection of the elution of the Rf value of 0.35, the resulting eluate was removed by removing the solvent under reduced pressure to give 480mg of pure compound 3, a yield of 54%;

Reference： [1]Molecules,2018,vol. 23
[2]Patent: CN108101793,2018,A .Location in patent: Paragraph 0051-0056; 0058

55
[ 539-48-0 ]
[ 17606-70-1 ]
(Z)-3,3'-[1,4-phenylenebis(methylene)]bis[5-((Z)-benzylidene)-2-phenyl-3,5-dihydro-4H-imidazol-4-one] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium acetate; In ethanol; at 80℃; for 0.166667h;	General procedure: A mixture of (Z)-4-arylidene-2-phenyloxazol-5(4H)-ones (9a-c, 1 mmol) and diamines (10a-c, 0.5 mmol) in ethanol (10 mL) containing a catalytic quantity of NaOAc was sonicated for 10 min at 80C (monitored by TLC). The formed crude products were filtered, dried and recrystallized from dioxane containing a few drops of DMF.

Reference： [1]Arkivoc,2018,vol. 2018,p. 338 - 352

56
[ 15601-44-2 ]
[ 539-48-0 ]
(Z)-3,3'-[1,4-phenylenebis(methylene)]bis[5-((Z)-4-chlorobenzylidene)-2-phenyl-3,5-dihydro-4H-imidazol-4-one] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium acetate; In ethanol; at 80℃; for 0.166667h;	General procedure: A mixture of (Z)-4-arylidene-2-phenyloxazol-5(4H)-ones (9a-c, 1 mmol) and diamines (10a-c, 0.5 mmol) in ethanol (10 mL) containing a catalytic quantity of NaOAc was sonicated for 10 min at 80C (monitored by TLC). The formed crude products were filtered, dried and recrystallized from dioxane containing a few drops of DMF.

Reference： [1]Arkivoc,2018,vol. 2018,p. 338 - 352

57
[ 57427-79-9 ]
[ 539-48-0 ]
(Z)-3,3'-[1,4-phenylenebis(methylene)]bis[5-((Z)-4-methylbenzylidene)-2-phenyl-3,5-dihydro-4H-imidazol-4-one] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium acetate; In ethanol; at 80℃; for 0.166667h;	General procedure: A mixture of (Z)-4-arylidene-2-phenyloxazol-5(4H)-ones (9a-c, 1 mmol) and diamines (10a-c, 0.5 mmol) in ethanol (10 mL) containing a catalytic quantity of NaOAc was sonicated for 10 min at 80C (monitored by TLC). The formed crude products were filtered, dried and recrystallized from dioxane containing a few drops of DMF.

Reference： [1]Arkivoc,2018,vol. 2018,p. 338 - 352

58
[ 539-48-0 ]
[ 1404219-84-6 ]
C₁₇H₂₂N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 20℃; for 24h;	General procedure: A mixture of pyrimidine N-oxide (0.5 mmol), correspondingdiamine (1.0 mmol) and DIPEA (129 mg, 1.0 mmol) inethanol (1 ml) was stirred at room temperature for 24 h. The solvent wasevaporated in vacuo, the product was purified by column chromatography.

Reference： [1]Mendeleev Communications,2018,vol. 28,p. 592 - 594

59
[ 60706-63-0 ]
[ 539-48-0 ]
N,N′-(1,4-phenylenebis(methylene))bis(2,3,5,6-tetramethylbenzenesulfonamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium carbonate; In dichloromethane; at 20℃;	General procedure: A solution of xylylenediamines 7a,b (2.5 mmol) in dichloromethane (50 mL) was added in dropwise manner to a stirred mixture of appropriate benzenesulfonyl chlorides 8a-m (5 mmol) and sodium carbonate (10 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 15-24 h (monitored by TLC), and distilled water (20 mL) was added. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×30 mL).The organic extracts were combined and washed with water (30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness under reduced pressure. The crude product was further purified by recrystallized or column chromatography on silica gel to obtain the pure product.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

60
[ 539-48-0 ]
[ 49584-26-1 ]
N,N′-(1,4-phenylenebis(methylene))bis(4-cyanobenzenesulfonamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium carbonate; In dichloromethane; at 20℃;	General procedure: A solution of xylylenediamines 7a,b (2.5 mmol) in dichloromethane (50 mL) was added in dropwise manner to a stirred mixture of appropriate benzenesulfonyl chlorides 8a-m (5 mmol) and sodium carbonate (10 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 15-24 h (monitored by TLC), and distilled water (20 mL) was added. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×30 mL).The organic extracts were combined and washed with water (30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness under reduced pressure. The crude product was further purified by recrystallized or column chromatography on silica gel to obtain the pure product.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

61
[ 50-00-0 ]
[ 106-41-2 ]
[ 539-48-0 ]
C₂₄H₂₂Br₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
Ca. 82%	In ethanol; toluene; for 51h;Reflux;	Compound 1 (2 eq., 10.38 g, i.e. 60 mmol) and then ethanol (51 ml) are poured into the round-bottomed flask. The presence of ethanol is important here, preventing the formation of an unstable intermediate of the triazine type. Compound 2 (1 eq., 4.13 g, i.e. 30 mmol), compound 3 (4 eq., 3.60 g, i.e. 120 mmol) and finally the toluene (102 ml) are subsequently introduced with stirring. The reaction medium is heated (approximately 75 C.) at reflux for 51 h and then the solvents and volatile residues are distilled off at 110 C. (under vacuum of 1 mbar) for evaporation. The final product is subsequently washed (100 ml methanol) and dried; a yellow-coloured powder is thus obtained. (0079) This powder is placed in methanol (100 ml per 15 g of powder) and the mixture is heated at reflux (65 C.) for 30 min. The solution is then left to cool to ambient temperature (approximately 20 C.) for crystallization of the monomer. The solid product obtained is isolated by filtration (Buchner filter). A white-coloured powder is thus obtained, after drying in an oven under vacuum at 50 C. overnight (reaction yield equal to approximately 82%). (0080) The 1H NMR spectrum (500 MHz) of the Monomer M-3 thus synthesized, dissolved in d8-THF, confirmed its chemical structure, with the following results: (0081) 3.87 (s, 4H), 3.92 (s, 4H), 4.86 (s, 4H), 6.66-6.68 (d, 2H), 7.09-7.10 (d, 2H), 7.19-7.22 (d, 2H), 7.31 (s, 4H).
82%	In ethanol; toluene; at 76℃; for 51h;Reflux;	For this synthesis, a 250-ml three-necked round-bottomed flask, equipped with a thermometer, a nitrogen inlet, a magnetic stirrer and a condenser, is provided. (0107) The synthesis is carried out according to the procedure diagrammatically represented in FIG. 22, as explained in detail below, starting from three compounds: a halogenated phenol (compound 1; 4-bromophenol; Aldrich product B75808), an aromatic diamine (compound 5; p-xylylenediamine; TCI Europe product D1018) and paraformaldehyde (compound 3; Aldrich product 158127), in the presence of two solvents (anhydrous toluene and anhydrous ethanol). (0108) Compound 1 (2 eq., 10.38 g, i.e. 60 mmol) and then ethanol (51 ml) are poured into the round-bottomed flask. The presence of ethanol is important in this instance, preventing the formation of an unstable triazine-type intermediate product. Compound 5 (1 eq., 4.13 g, i.e. 30 mmol), compound 3 (4 eq., 3.60 g, i.e. 120 mmol) and finally the toluene (102 ml) are subsequently introduced with stirring. The reaction medium is heated (approximately 75 C.) at reflux for 51 h and then the solvents and volatile residues are distilled off at 110 C. (under vacuum of 1 mbar) for evaporation. The final product is subsequently washed (100 ml methanol) and dried; a yellow-coloured powder is thus obtained. (0109) This powder is placed in methanol (100 ml per 15 g of powder) and the mixture is heated at reflux (65 C.) for 30 min. The solution is then left to cool to ambient temperature (approximately 20 C.) for crystallization of the monomer. The solid product obtained is isolated by filtration (Buechner filter). A white-coloured powder is thus obtained, after drying in an oven under vacuum at 50 C. overnight (reaction yield equal to approximately 82%). (0110) The 1H NMR spectrum (500 MHz) of the Monomer Mo-7 thus synthesized, dissolved in chloroform, confirmed its chemical structure, with the following results: 3.89 (s, 4H), 3.94 (s, 4H), 4.87 (s, 4H), 6.70 (s, 1H), 6.72 (s, 1H), 7.06 (s, 2H), 7.23 (s, 2H), 7.32 (s, 4H).

Reference： [1]Patent: US2020/87268,2020,A1 .Location in patent: Paragraph 0078-0081
[2]Patent: US2020/115394,2020,A1 .Location in patent: Page/Page column 0035; 0105-0110

62
[ 539-48-0 ]
[ 766-08-5 ]
C₂₂H₂₈N₂Si₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With iron(II)β-diketiminate complex In benzene-d6 at 80℃; for 24h;

Reference： [1]Coles, Nathan T.; Gasperini, Danila; King, Andrew K.; Mahon, Mary F.; Webster, Ruth L. [ACS Catalysis, 2020, vol. 10, # 11, p. 6102 - 6112]

63
[ 539-48-0 ]
[ 2900-27-8 ]
di-tert-butyl ((1S,1'S)-((1,4-phenylenebis(methylene))bis(azanediyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.6%	With diethyl cyanophosphonate; triethylamine In N,N-dimethyl-formamide at -15 - 20℃;	24.2 Step 2: di-tert-butyl ((1S,1'S)-((1,4-phenylenebis(methylene))bis(azanediyl))bis(2-oxo-1- phenylethane-2,1-diyl))dicarbamate To a solution of (S)-2-((tert-butoxycarbonyl)amino)-2-phenylacetic acid (700 mg, 2.78 mmol) in N,N-dimethylformamide (15 mL) at -15oC was added 1,4- phenylenedimethanamine (189 mg, 1.39 mmol) in N,N-dimethylformamide (5 mL). diethyl cyanophosphonate (680 mg, 4.17 mmol) and triethylamine (562 mg, 5.56 mmol) were then added successively. The mixture was stirred at room temperature overnight. The reaction was quenched with water (400 mL) to give a precipitate which was filtered and dried under high vacuum to give di-tert-butyl ((1S,1'S)-((1,4- phenylenebis(methylene))bis(azanediyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate (1.1 g, 1.83 mmol, 59.6% yield) as white solid. LCMS (2.5 min formic acid): Rt = 1.56 min, m/z: 502.7 [(M-Boc)+1]+

Reference： [1]Current Patent Assignee: UNIVERSITY OF NORTH CAROLINA SYSTEM; GLAXOSMITHKLINE PLC - WO2020/110056, 2020, A1 Location in patent: Page/Page column 194; 195

64
[ 539-48-0 ]
[ 100-21-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With tert.-butylhydroperoxide; sodium chloride; sodium hydroxide In water monomer at 90℃; for 8h; Green chemistry;	General procedure for the synthesis of 4-methoxy benzoicacid from 4-methoxy benzylamines General procedure: A 50 mL of round bottom flask was charged with a magneticbead,0.1 g (0.729 mmol) of 4- methoxy benzyl amine, 0.0084 g ofNaCl (20 mol%), 0.116 g of NaOH (4 equiv) and 0.336 g of aq. TBHP (5equiv) in 0.3 mL of deionised H2O and it was heated at 90 C for 8 h. Afterwards, the reaction mixture was neutralized by aq. HCl and extracted with EtOAc. The organic layer was dried over anhydrousNa2SO4 and after evaporation of the solvent, the crude mixture waspurified by the silica gel column chromatography with EtOAc:Hexane (06:94 v/v) as eluent. 4-methoxy benzoic acid was obtainedin 84% yield (93 mg).

Reference： [1]Jaiswal, Arvind Kumar; Kushawaha, Ajay Kishor; Pandey, Shubham; Sashidhara, Koneni V. [Tetrahedron, 2021]

65
[ 539-48-0 ]
[ 99-04-7 ]
N,N'-1,4-bisbenzyl-bis(3-methylbenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 3-methylbenzoic acid With 4-dimethylaminopyridine; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 1h; Stage #2: p-xylylidenediamine In dichloromethane	32 Example 32 preparation method of N,N'-1,4-bisbenzyl-bis(3-methylbenzamide) In a 100 mL monotuberculture flask, 3-methylbenzoic acid (1.63g, 12 mmol), DCC (3.09 g, 15 mmol), DMAP (18 mg, 0.15 mmol), dichloromethane (10 mL), stirred at 25 °C for 1 h, p-phenylenedimethylamine (0.68 g, 5 mmol) dissolved in dichloromethane (15 mL), placed in a constant pressure drops funnel, slowly drip addition, TLC monitoring reaction, after the raw material conversion is complete, stop the reaction, reduce pressure concentration, Silica gel column chromatography (dichloromethane: methanol = 100:1) was performed to obtain a white solid with a yield of 97%.

Reference： [1]Current Patent Assignee: HANGZHOU NORMAL UNIVERSITY - CN113845439, 2021, A Location in patent: Paragraph 0167-0170

66
[ 539-48-0 ]
[ 579-75-9 ]
N,N'-1,4-bisbenzyl-bis(2-methoxybenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: 2-Methoxybenzoic acid With 4-dimethylaminopyridine; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 1h; Stage #2: p-xylylidenediamine In dichloromethane	34 Example 34 preparation method of N,N'-1,4-bisbenzyl-bis(2-methoxybenzamide) In a 100 mL monoclonal flask, 2-methoxybenzoic acid (1.83 g, 12 mmol), DCC (3.09 g, 15 mmol), DMAP (18 mg, 0.15 mmol), dichloromethane (10 mL), stirred at 25 °C for 1 h, dissolved p-phenylenedimethylamine (0.68 g, 5 mmol) in dichloromethane (15 mL), placed in a constant pressure drip funnel, slow dropwise, TLC monitoring reaction, after the raw material conversion is complete, stop the reaction, reduce pressure concentration, Silica gel column chromatography (dichloromethane: methanol = 100:1) was performed to obtain a white solid with a yield of 91%.

Reference： [1]Current Patent Assignee: HANGZHOU NORMAL UNIVERSITY - CN113845439, 2021, A Location in patent: Paragraph 0175-0178

67
[ 539-48-0 ]
[ 586-38-9 ]
N,N'-1,4-bisbenzyl-bis(3-methoxybenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: 3-Methoxybenzoic acid With 4-dimethylaminopyridine; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 1h; Stage #2: p-xylylidenediamine In dichloromethane	35 Example 35 preparation method of N,N'-1,4-bisbenzyl-bis(3-methoxybenzamide) In a 100 mL monomous flask were added 3-methoxybenzoic acid (1.83 g, 12 mmol), DCC (3.09 g, 15 mmol), DMAP (18 mg, 0.15 mmol), dichloromethane (10 mL), stirred at 25 °C for 1 h, dissolvedp-phenylenedimethylamine (0.68 g, 5 mmol) in dichloromethane (15 mL), placed in a constant pressure drip funnel, slowly driped, TLC monitoring reaction, after the raw material conversion is complete, stop the reaction, reduce pressure concentration, Silica gel column chromatography (dichloromethane: methanol = 100:1) was performed to obtain a white solid with a yield of 94%.

Reference： [1]Current Patent Assignee: HANGZHOU NORMAL UNIVERSITY - CN113845439, 2021, A Location in patent: Paragraph 0179-0182

68
[ 455-38-9 ]
[ 539-48-0 ]
N,N'-1,4-bisbenzyl-bis(3-fluorobenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: meta-fluorobenzoic acid With 4-dimethylaminopyridine; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 1h; Stage #2: p-xylylidenediamine In dichloromethane	38 Example 38 preparation method of N,N'-1,4-bisbenzyl-bis(3-fluorobenzamide) In a 100 mL monomous flask, 3-fluorobenzoic acid (1.68 g, 12 mmol), DCC (3.09 g, 15 mmol), DMAP (18 mg, 0.15 mmol), dichloromethane (10 mL), stirred at 25 °C for 1 h, dissolved p-phenylenedimethylamine (0.68 g, 5 mmol) in dichloromethane (15 mL), placed in a constant pressure drops funnel, slowly drip addition, TLC monitoring reaction, after the raw material conversion is complete, stop the reaction, reduce pressure concentration, Silica gel column chromatography (dichloromethane: methanol = 100:1) was performed to obtain a white solid with a yield of 91%.

Reference： [1]Current Patent Assignee: HANGZHOU NORMAL UNIVERSITY - CN113845439, 2021, A Location in patent: Paragraph 0191-0194

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 539-48-0 ]

Quality Control of [ 539-48-0 ]

Related Doc. of [ 539-48-0 ]

Product Details of [ 539-48-0 ]

Calculated chemistry of [ 539-48-0 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 539-48-0 ]

Application In Synthesis of [ 539-48-0 ]

[ 539-48-0 ] Synthesis Path-Upstream 1~13

[ 539-48-0 ] Synthesis Path-Downstream 1~68

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry