[ CAS No. 109-78-4 ]

Name: 109-78-4|3-Hydroxypropionitrile|97%
Brand: Ambeed
SKU: A141843
Rating: 98 (22 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 109-78-4 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 109-78-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 109-78-4 ]

SDS Specification

Alternatived Products of [ 109-78-4 ]

Product Details of [ 109-78-4 ]

CAS No. :	109-78-4	MDL No. :	MFCD00002826
Formula :	C₃H₅NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WSGYTJNNHPZFKR-UHFFFAOYSA-N
M.W :	71.08	Pubchem ID :	8011
Synonyms :

Calculated chemistry of [ 109-78-4 ]

Physicochemical Properties

Num. heavy atoms :	5
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.67
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	17.45
TPSA :	44.02 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.4 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.8
Log Po/w (XLOGP3) :	-0.94
Log Po/w (WLOGP) :	-0.11
Log Po/w (MLOGP) :	-0.78
Log Po/w (SILICOS-IT) :	-0.25
Consensus Log Po/w :	-0.25

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.38
Solubility :	170.0 mg/ml ; 2.39 mol/l
Class :	Highly soluble
Log S (Ali) :	0.5
Solubility :	225.0 mg/ml ; 3.16 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.06
Solubility :	62.0 mg/ml ; 0.873 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.08

Safety of [ 109-78-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P501-P260-P264-P280-P302+P352-P312-P337+P313-P305+P351+P338-P362+P364-P332+P313	UN#:	N/A
Hazard Statements:	H302+H312-H315-H319-H373	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 109-78-4 ]

* 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 [ 109-78-4 ]
Downstream synthetic route of [ 109-78-4 ]

[ 109-78-4 ] Synthesis Path-Upstream 1~16

1
[ 111-44-4 ]
[ 109-78-4 ]
[ 4441-30-9 ]

Reference： [1] Patent: GB901187, 1958, ,

2
[ 55-86-7 ]
[ 109-78-4 ]
[ 5317-33-9 ]

Reference： [1] Patent: GB901187, 1958, ,

3
[ 109-78-4 ]
[ 51036-79-4 ]

Reference： [1] Journal of the American Chemical Society, 1953, vol. 75, p. 3398

4
[ 120-72-9 ]
[ 109-78-4 ]
[ 6639-06-1 ]

Reference： [1] Zhurnal Obshchei Khimii, 1955, vol. 25, p. 1959,1962; engl. Ausg. S. 1905, 1907

5
[ 109-89-7 ]
[ 109-78-4 ]
[ 622-93-5 ]

Reference： [1] Patent: US9469595, 2016, B1, . Location in patent: Page/Page column 7; 8
[2] Patent: WO2016/209629, 2016, A1, . Location in patent: Paragraph 0054

6
[ 660-68-4 ]
[ 109-89-7 ]
[ 109-78-4 ]
[ 622-93-5 ]

Reference： [1] Patent: WO2016/209629, 2016, A1, . Location in patent: Paragraph 0052; 0053

7
[ 109-78-4 ]
[ 616-38-6 ]
[ 110-67-8 ]

Reference： [1] Zhurnal Obshchei Khimii, 1947, vol. 17, p. 272[2] Chem. Zentralbl., 1948, vol. 119, p. 521

8
[ 107-31-3 ]
[ 109-78-4 ]
[ 110-67-8 ]
[ 2141-62-0 ]

Reference： [1] Zhurnal Obshchei Khimii, 1947, vol. 17, p. 272[2] Chem. Zentralbl., 1948, vol. 119, p. 521

9
[ 186581-53-3 ]
[ 109-78-4 ]
[ 110-67-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1930, vol. 484, p. 17
[2] Justus Liebigs Annalen der Chemie, 1930, vol. 484, p. 17

10
[ 64-17-5 ]
[ 109-78-4 ]
[ 623-72-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydrogenchloride; thionyl chloride In water at 0 - 20℃; for 6 h; Reflux	Ethanol (1L) was placed in a three-necked flask, stirred and cooled to 0 ° C.Concentrated hydrochloric acid (80 mL) was added dropwise slowly.Then slowly add thionyl chloride (132 mL).The system slowly rise to room temperature.3-Hydroxypropionitrile (250 g) was slowly added dropwise, and the system was refluxed for 6 hours.A large amount of white powder appeared.The system was cooled to 0 ° C and the pH was adjusted to about 7 with solid sodium carbonate.Filtration, concentration of the filtrate, distillation to obtain 208 g of ethyl 3-hydroxypropionate, yield 50percent

Reference： [1] Patent: CN108314665, 2018, A, . Location in patent: Paragraph 0065-0069

11
[ 921-26-6 ]
[ 40615-39-2 ]
[ 109-78-4 ]
[ 98796-51-1 ]

Reference： [1] Tetrahedron Letters, 1986, vol. 27, # 2, p. 199 - 202

12
[ 56183-63-2 ]
[ 40615-39-2 ]
[ 109-78-4 ]
[ 98796-51-1 ]

Reference： [1] Tetrahedron Letters, 1986, vol. 27, # 20, p. 2271 - 2274

13
[ 108-18-9 ]
[ 109-78-4 ]
[ 102691-36-1 ]

Reference： [1] Monatshefte fur Chemie, 2010, vol. 141, # 7, p. 809 - 815
[2] Chemical Communications, 2015, vol. 51, # 55, p. 11088 - 11091
[3] Journal of Organic Chemistry, 1996, vol. 61, # 24, p. 8642 - 8647
[4] Patent: US5863905, 1999, A,
[5] Patent: WO2004/58779, 2004, A1, . Location in patent: Page 4
[6] Patent: WO2004/58779, 2004, A1, . Location in patent: Page 4-5
[7] Patent: US2016/333034, 2016, A1, . Location in patent: Paragraph 0035-0038

14
[ 56183-63-2 ]
[ 109-78-4 ]
[ 102691-36-1 ]

Reference： [1] Chemistry Letters, 1986, p. 1401 - 1404
[2] Patent: WO2004/55030, 2004, A1, . Location in patent: Page 4

15
[ 108-18-9 ]
[ 109-78-4 ]
[ 7719-12-2 ]
[ 102691-36-1 ]

Reference： [1] Tetrahedron, 1990, vol. 46, # 2, p. 487 - 502

16
[ 133728-84-4 ]
[ 109-78-4 ]
[ 98796-53-3 ]

Reference： [1] Patent: US6335439, 2002, B1, . Location in patent: Example 14

[ 109-78-4 ] Synthesis Path-Downstream 1~69

1
[ 186581-53-3 ]
[ 109-78-4 ]
[ 110-67-8 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1930,vol. 484,p. 17
[2]Justus Liebigs Annalen der Chemie,1930,vol. 484,p. 17

2
[ 120-72-9 ]
[ 109-78-4 ]
[ 6639-06-1 ]

Reference： [1]Zhurnal Obshchei Khimii,1955,vol. 25,p. 1959,1962; engl. Ausg. S. 1905, 1907

3
[ 292638-85-8 ]
[ 109-78-4 ]
[ 106-71-8 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; hydroquinone unter Entfernen des entstehenden Methanols;
	With sulfuric acid
	With toluene-4-sulfonic acid

Reference： [1]Marvel et al. [Industrial and Engineering Chemistry, 1955, vol. 47, p. 344,347]
[2]Ratchford; Rehberg; Fisher [Journal of the American Chemical Society, 1944, vol. 66, p. 1865]
[3]Ratchford; Rehberg; Fisher [Journal of the American Chemical Society, 1944, vol. 66, p. 1865]

4
[ 95-92-1 ]
[ 109-78-4 ]
[ 109-94-4 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

5
[ 95-92-1 ]
[ 109-78-4 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
    Chemisches Zentralblatt,1948,vol. 119,p. 521
[2]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
    Chemisches Zentralblatt,1948,vol. 119,p. 521
[3]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
    Chemisches Zentralblatt,1948,vol. 119,p. 521

6
[ 67-63-0 ]
[ 109-78-4 ]
[ 689-12-3 ]

Reference： [1]Zhurnal Obshchei Khimii,1940,vol. 10,p. 867
Chemisches Zentralblatt,1940,vol. 111,p. 3173

7
[ 74-96-4 ]
[ 109-78-4 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

8
[ 64-67-5 ]
[ 109-78-4 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

9
[ 107-31-3 ]
[ 109-78-4 ]
[ 110-67-8 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

10
[ 93-89-0 ]
[ 109-78-4 ]
[ 2141-62-0 ]

11
[ 55-86-7 ]
[ 109-78-4 ]
[ 5317-33-9 ]

Reference： [1]Patent: GB901187,1958,

12
[ 109-78-4 ]
[ 616-38-6 ]
[ 110-67-8 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

13
[ 60-29-7 ]
[ 141-52-6 ]
[ 109-78-4 ]
[ 109-94-4 ]
[ 2141-62-0 ]

Reference： [1]Zhurnal Obshchei Khimii,1947,vol. 17,p. 272
Chemisches Zentralblatt,1948,vol. 119,p. 521

14
[ 109-78-4 ]
[ 109-94-4 ]
[ 2141-62-0 ]

15
[ 109-78-4 ]
[ 590-92-1 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2009,vol. 52,p. 341 - 349
[2]Organic Syntheses 3 <New York 1923>,S.25,
[3]Patent: DE410185,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 15,p. 137

16
[ 109-78-4 ]
[ 156-87-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With ammonium hydroxide; hydrogen; silver nitrate In methanol at 45 - 75℃; High pressure; Inert atmosphere; Autoclave;	1-10 A method for preparing 3-aminopropanol comprises the following steps: The nickel catalyst and silver nitrate are sucked into the high pressure reduction kettle through a vacuum pump, and then methanol and 3-hydroxypropionitrile are inhaled.Close the vacuum valve, open the vent valve, and replace the air in the kettle with nitrogen, at least three times.0.2MPa each time and slowly exhausted to vent, after the replacement is completed, close the vent valve and the vent valve, open the ammonia valve,Start stirring, open the jacket cooling water, and pass liquid ammonia;After the ammonia is completed, the stirring is stopped and the ammonia valve is closed, the hydrogen valve is opened, and the hydrogen gas is replaced three times to remove the residual nitrogen gas.Each time 0.2MPa and slowly exhaust venting, after the end of the replacement, close the valve and then start stirring and open the steam valve to raise the temperature to 45 °C to start the hydrogen.Keep the pressure inside the kettle 3MPa, the reduction kettle jacket and the inner coil pass the cooling water,The reaction temperature in the autoclave was controlled at 75 °C. When the hydrogen pressure no longer drops, it indicates that the reaction has reached the end point, stop stirring, and let stand for half an hour.Cool with jacket water to a temperature of 40 ° C in the kettle, relieve pressure, and then replace it three times with nitrogen.After that, it was pressed into the high-level settling tank with nitrogen gas to stand still for 6 hours.A small amount of catalyst and impurities are collected in the lower layer, and the upper layer is distilled. The nickel catalyst at the bottom of the reduction vessel still settles to the bottom, and the methanol is replenished for use.Put the upper layer of the settling tank into the distillation pot, open the vent valve, and heat up.When the liquid temperature starts at 95 ° C, the liquid is collected to collect methanol;After the methanol is collected, the temperature of the cooling kettle is 60 ° C for vacuum distillation, and the vacuum is kept below -0.09 MPa.When the top temperature reaches 90 ° C, the former fraction (very small amount of methanol) is collected, and when the top temperature reaches 95 ° C, the main fraction is collected.When the main fraction is collected, the temperature of the liquid is controlled to 110 ° C until the end of the collection, and the chromatographic test is performed.The content is more than 99% as a qualified product, and the yield is 98%. The molar ratio of 3-hydroxypropionitrile to aqueous ammonia was 1:1.15; the Raney nickel catalyst was used in an amount of 0.006% by mass of 3-hydroxypropionitrile.
88%	With hydrogen; nickel In isopropyl alcohol at 60℃; 20-24 h;
80%	With ammonium hydroxide; hydrogen at 80℃; for 6h; Sealed tube;	1.2 (2) Add the pure 3-hydroxypropionitrile to the high-pressure reaction kettle,Add wet Raney nickel catalyst (addition amount is 6wt% of 3-hydroxypropionitrile mass),Close the kettle lid, replace the air in the kettle with nitrogen three times, and then replace it with hydrogen once.Then press in 80g of liquid ammonia as a solvent and pressurize it with hydrogen to 8MPa,After holding the reaction at 80 for 6h, it was cooled to room temperature and ammonia gas was absorbed by the tail gas absorption device.The kettle liquid was filtered with suction, and the filter cake was washed with dichloromethane,The filtrate was concentrated under reduced pressure and prepared by rectification to obtain pure 3-aminopropanol with a yield of 80%.

	With nickel; formamide at 130℃; Hydrogenation_.unter Druck, anschliessendes Erhitzen mit wss.Natronlauge;
	With ammonia; nickel at 75 - 90℃; Hydrogenation_.unter Druck;
	With ammonia; nickel at 75 - 90℃; Hydrogenation_.unter Druck;
	With nickel; formic acid ethyl ester at 130℃; Hydrogenation_.unter Druck, anschliessendes Erhitzen mit wss.Natronlauge;
95 g (86.5%, corr.)	With ammonia In methanol	4.a (a) (a) Methanol/Ammonia, 75 bar (7.5 MPa) Hydrogen 100 g (1.39 mol, 99% according to GC) of 3-hydroxypropionitrile in 100 ml of methanol were placed in a 500 ml steel stirring autoclave equipped with a gasification stirrer. The solution was saturated with 60 g of gaseous ammonia. Subsequently, 10 g of Raney nickel were added and, after flushing with nitrogen, the autoclave was closed. The autoclave was pressurized to 22 bar (2.2 MPa) with hydrogen and the mixture was heated to 100° C. within one hour. The mixture was hydrogenated further at 100° C. while increasing the hydrogen pressure to 75 bar (7.5 MPa). After cooling the contents of the autoclave were filtered over 25 g of Speedex-Dicalite and rinsed with methanol. The major part of the methanol was removed by distillation at about 25 mbar (2.5 kPa)/40° C. This gave 108 g of a blue colored residue, which still contained some methanol. Distillation over a 10 cm packed column at 2-3 mbar (0.2-0.3 kPa) gave 95 g (86.5%, corr.) of 3-aminopropanol as a colorless distillate, b.pt. 59-63° C./2-3 mbar (0.2-0.3 kPa); content according to GC: 95.3%; 1H-NMR (CDCl3, 400 MHz): 1.68 (quint., J=6 Hz, 2H), 2.97, 2.3 (b, 3H), 2.97 (t, J=7 Hz, 2H), 3.81 (t, J=6 Hz, 2H); IR (film, cm1): 3350 (b, OH, NH2), 1050 (J). The residue weighed 6.5 g.
	With hydrogen In isopropyl alcohol	4.d (d) (d) Isopropanol, 50 Bar (5.0 MPa) Hydrogen 100 g (1.39 mol, 99% according to GC) of 3-hydroxypropionitrile were placed in 100 g of isopropanol in a 500 ml steel stirring autoclave equipped with a gasification stirrer. 10 g of Raney nickel were added thereto while gassing with nitrogen and the autoclave was closed. The mixture was hydrogenated for 7 hours at 100° C. and 50 bar/5.0 MPa hydrogen pressure. Working up of the reaction, as in the foregoing variants (a)-(c), gave 112 g of a green-blue, oily residue, which was distilled, as usual, at 2-3 mbar/0.2-0.3 kPa. In this manner there were obtained 71.7 g (57.6%, corr.) of 3-aminopropanol as a colorless oil, b.pt. 61.3-64.7° C./2-3 mbar (0.2-0.3 kPa). Content according to GC: 84.1%. 1H-NMR (CDCl3, 400 MHz): identical with the spectrum given previously under (b). The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention and all such modifications are intended to be included within the scope of the following claims.
	With ammonia; hydrogen	4.c (c) (c) Ammonia, 50 bar (5.0 MPa) Hydrogen 200 g (2.78 mol, 99% according to GC) of 3-hydroxypropionitrile were placed in a 500 ml steel stirring autoclave equipped with a gasification stirrer, 20 g of Raney nickel were added and, after closing the autoclave, 60 g of ammonia were compressed in from a steel cylinder. After the additional compression of 22 bar (2.2 mbar) of hydrogen, the mixture was heated to 100° C., the hydrogen pressure was increased to 50 bar (5.0 MPa) and the mixture was hydrogenated at this temperature for 4 hours. After cooling the ammonia was evaporated off and the residue was filtered with methanol over 25 g of Speedex-Dicalite, rinsed with methanol and the major part of the methanol was removed under reduced pressure. This gave 211 g of a green-blue, oily residue, which was distilled over a 10 cm packed column at 2-3 mbar/0.2-0.3 kPa. In this manner there were obtained 182.2 g (83%, corr.) of 3-aminopropanol as a colorless oil, b.pt. 60-62.3° C./2-3 mbar (0.2-0.3 kPa). The oil crystallized at about 0° C. Content according to GC: 95.1%. 1H-NMR (CDCl3, 400 MHz): identical with the spectrum given previously under (b).
89.7 g (81%, corr.)	With ammonia In methanol	4.b (b) (b) Methanol/Ammonia, 50 bar (50 MPa) Hydrogen 100 g (1.39 mol; 99% according to GC) of 3-hydroxypropionitrile were placed in 100 ml of methanol. The solution was saturated at 15-20° C. with 25 g of gaseous ammonia and thereafter transferred into a 500 ml steel stirring autoclave equipped with a gasification stirrer. Then 10 g of Raney nickel were added and, after flushing with nitrogen, the autoclave was closed. The autoclave was pressurized to 22 bar (2.2 MPa) with hydrogen and the mixture was heated to 100° C. within one hour. The hydrogen pressure was increased to 50 bar (5.0 MPa) and the 3-hydroxypropionitrile was hydrogenated for a further 5 hours at 100° C. After cooling the mixture was filtered over 25 g of Speedex-Dicalite, rinsed with methanol and the major part of the methanol was removed under reduced pressure. This gave 104 g of a blue-green residue. Distillation over a 10 cm packed column at 2-3 mbar/0.2-0.3 kPa gave 89.7 g (81%, corr.) of 3-aminopropanol as a colorless oil, b.pt. 60.2-64° C./2-3 mbar (0.2-0.3 kPa). The oil crystallized at about 0° C. Content according to GC: 93.6%; 1H-NMR (CDCl3, 400 MHz): 1.68 (quint., J=6 Hz, 2H), 2.27 (b, OH, NH2, 3H), 2.97 (t, J=7 Hz, 2H), 3.81 (t, J=6 Hz, 2H).
	With ammonia; hydrogen at 100℃;	1 Ethylene cyanohydrin (450 kg/h) was converted together with ammonia (850 kg/h) in the presence of hydrogen at a pressure of 180 bar and a temperature of 100° C. in a tubular reactor. The catalyst used was a catalyst according to Example A of EP-A-0742045. The catalyst hourly space velocity was 0.3 kg of ECHD/kg of catalyst/hour.The reaction output was introduced into a distillation column which was operated at column top pressure of 17 bar (ammonia removal). The distillation column had 12 theoretical plates. The feed point was in the region of the 10th plate. The bottom temperature was 185° C.The output from the ammonia removal was analyzed by gas chromatography and comprised: 93 area % of 3-aminopropanol;2.5 area % of ammonia;3.0 area % of dihydroxypropylamine0.3 area % of diaminopropyl ether0.2 area % of ethanediol
	With ammonia; nickel at 75 - 90℃; Hydrogenation_.unter Druck;
	With ammonia; nickel at 75 - 90℃; Hydrogenation_.unter Druck;
	With ammonia; hydrogen at 100℃;	10 The catalyst prepared by the above method was evaluated in a fixed bed reactor. Before the reaction, it was activated in a hydrogen atmosphere, the temperature was 500°C, the pressure was normal pressure, the volumetric space velocity of hydrogen gas was 1500h-1, and the activation time was 5h. After the activation treatment, the temperature was lowered to the reaction temperature. The reaction temperature is 100, the reaction pressure is 8.0MPa, the liquid volumetric space velocity of 3-hydroxypropionitrile is 0.5h-1, the volumetric space velocity of hydrogen gas is 1000h-1, and the molar ratio of ammonia to 3-hydroxypropionitrile is 5.0:1.0 . For sampling and analysis, Agilent 7890 gas chromatograph was used for analysis. The chromatographic column was a DB-35 capillary column and the detector was a hydrogen flame detector. N,N-dimethylformamide (DMFA) was used as an internal standard for quantitative analysis. The results of the reaction are summarized in Table 1.

Reference： [1]Current Patent Assignee: KUNSHAN XIANGHE FINE CHEMICAL PLANT - CN109456207, 2019, A Location in patent: Paragraph 0020-0089
[2]Regla, Ignacio; Reyes, Adelfo; Koerber, Claudia; Demare, Patricia; Estrada, Osvaldo; Juaristi, Eusebio [Synthetic Communications, 1997, vol. 27, # 5, p. 817 - 823]
[3]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN111056963, 2020, A Location in patent: Paragraph 0064; 0066
[4]Sekiya [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1950, vol. 70, p. 520,522,523][Chem.Abstr., 1951, p. 5640]
[5]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE573983, 1930, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 18, p. 818][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 18, p. 818] Tsuda; Sakamoto [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1943, vol. 68, p. 545][Chem.Abstr., 1950, p. 7232] King; Beer; Waley [Journal of the Chemical Society, 1946, p. 92]
[6]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE573983, 1930, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 18, p. 818][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 18, p. 818] Tsuda; Sakamoto [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1943, vol. 68, p. 545][Chem.Abstr., 1950, p. 7232] King; Beer; Waley [Journal of the Chemical Society, 1946, p. 92]
[7]Sekiya [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1950, vol. 70, p. 520,522,523][Chem.Abstr., 1951, p. 5640]
[8]Current Patent Assignee: KONINKLIJKE DSM N.V. - US2002/40163, 2002, A1
[9]Current Patent Assignee: KONINKLIJKE DSM N.V. - US2002/40163, 2002, A1
[10]Current Patent Assignee: KONINKLIJKE DSM N.V. - US2002/40163, 2002, A1
[11]Current Patent Assignee: KONINKLIJKE DSM N.V. - US2002/40163, 2002, A1
[12]Current Patent Assignee: BASF SE - US2012/149903, 2012, A1 Location in patent: Page/Page column 9
[13]Current Patent Assignee: ROCHE HOLDING AG - CH244837, 1945, A
[14]Current Patent Assignee: ROCHE HOLDING AG - CH244837, 1945, A
[15]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Dalian Institute of Chemical Physics (in: CAS) - CN111196763, 2020, A Location in patent: Paragraph 0110; 0111; 0116-0118; 0126

17
[ 109-78-4 ]
[ 503-66-2 ]

Yield	Reaction Conditions	Operation in experiment
92.1%		3-hydroxypropionitrile 8 (10 mmol) was added to saturated aqueous sodium hydroxide (20 ml), and the mixture was stirred under reflux for 8 h. After acidized by concentrated hydrochloric acid, the resulting mixture was extracted with ethyl acetate (50 ml × 3). The combined organic extracts were dried over anhydrous MgSO4 and filtered. The filtrate was concentrated under vacuum to afford 3-hydroxypropionic acid 9. Yield 92.1%, colourless oil. To a solution of 9 (5 mmol) and DIPEA (7.5 mmol) in CH2Cl2 (5 ml) was dropwise added a solution of TMSCl (6 mmol) in CH2Cl2 (5 ml) at 0 C. Then the mixture was stirred at rt for 1 h. After diluted in ethyl acetate (50 ml), the organic phase was washed with saturated brine (50 ml × 3), dried over anhydrous MgSO4 and filtered. The filtrate was concentrated under vacuum to afford crude product 3-trimehylsilylpropionic acid 10. Yield 95.0%, light yellow oil. To a solution of 10 (4 mmol) and shikonin (2 mmol) in CH2Cl2 (10 ml) were added DCC (5 mmol) and DMAP (0.3 mmol). The mixture was stirred at rt for 1 h. After filtration, the solvent of the filtrate was removed to give the residue which was purified by flash column chromatography to give 11. Yield 87.5%, red oil. To a solution of 11 (2 mmol) in EtOH (5 ml) was added acetic acid (0.5 ml). The mixture was stirred for 15 min at rt. After dissolved in ethyl acetate (50 ml), the resulting mixture was washed with saturated NaHCO3 (50 ml) and brine (50 ml). The organic phase was dried over anhydrous MgSO4 and filtered. The filtrate was concentrated under vacuum to afford the crude material which was purified by flash column chromatography to give 7a. Yield 74.5%.
89%	With hydrogenchloride; water; for 4h;	Add 275 g (2.04 mol) of 20% aqueous hydrocyanic acid solution and 0.5 g (catalyst) of triethylamine to a closed and pressure-resistant cyanide reaction kettle.Keep temperature at 15-20 , add 88.9g (2.0mol) of ethylene oxide (99%), and react for 2h;Sampling GC analysis showed that the ethylene oxide content was less than 1%. The reaction was stopped. 268.0 g (2.2 mol) of 30% hydrochloric acid was added to the reaction solution. After the addition, the temperature was raised to a boiling reaction for 4 hours.Sampling HPLC analysis of 3-hydroxypropionitrile content (calculated by area normalization method) less than 1%, cooling, neutralization with ammonia to pH = 4.0-4.5, and continuous chromatography separation (stationary phase: ammonium ion exchange resin; mobile phase : 0.008 mol / L HCl solution; flow rate: 16 mL / min; column temperature: 25 C.) to obtain an ammonium chloride solution and a 3-hydroxypropionic acid solution.The 3-hydroxypropionic acid solution was concentrated by distillation under reduced pressure and crystallized to obtain 163.4 g of a solid product with a content of 98.1% (determined by HPLC external standard method).The yield was calculated using the calculation method listed below and was 89.0% (calculated as ethylene oxide). After the ammonium chloride solution is concentrated, cooled and crystallized, and separated by a solid-liquid separator, ammonium chloride solids and mother liquor are obtained. The mother liquor contains a small amount of product, which can be recycled to the continuous chromatography process to recover some products and improve product yield.
68%	With water; calcium chloride; In aq. buffer; at 30℃; for 5h;pH 8.0;Catalytic behavior;	To evaluate the reusability of the immobilized cells, two kinds of reaction media, Tris-HCl buffer and distilled water, were used for batch reaction. The reaction was performed with free or immobilized cells (containing 20 g/L of wet cells) suspending in 10 mL of reaction medium contained 3.0 mol/L of substrate and 20 mmol/L of CaCl2 at 30C for 5 h. After each reaction, the beads were washed by distilled water and transferred to fresh reaction mixture. Repeated batch reaction was carried out under the same conditions as the first cycle.

With water; In aq. phosphate buffer; at 37℃;pH 7.0;Green chemistry; Enzymatic reaction;

General procedure: A typical reaction mixture (5 mL in 25 mL shake flask) contained thenitrile substrate and appropriate amount of E. coli cell mass expressingthe selected nitrilase suspended in 100mM phosphate buffer pH 7. Inthe case of mandelonitrile, conversion experiments were performed inaqueous buffer containing 10 % methanol to aid substrate solubility.The catalytic reaction was performed at 37 C with agitation at 150 rpmin an incubator shaker. Aliquots (100 mul) were withdrawn at regularpredetermined time intervals and quenched with 10 mul of 1M HCl. Thereaction mixture was centrifuged and filtered using a 0.45 mum syringefilter, and the product formed was monitored through HPLC analysis.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3934 - 3941
[2]Patent: CN110498740,2019,A .Location in patent: Paragraph 0037; 0045-0047; 0050-0052; 0053-0055
[3]Synthetic Communications,1991,vol. 21,p. 359 - 369
[4]Journal of Molecular Catalysis B: Enzymatic,2016,vol. 129,p. 37 - 42
[5]Journal of the Chemical Society. Perkin transactions II,1994,p. 2597 - 2602
[6]Tetrahedron Letters,1991,vol. 32,p. 341 - 344
[7]Tetrahedron Letters,1991,vol. 32,p. 341 - 344
[8]Journal of the Chemical Society. Perkin transactions I,1992,p. 137 - 140
[9]Patent: US2369491,1942,
[10]Organic Syntheses 7 <New York 1927>,S.55,
[11]Process Biochemistry,2020,vol. 94,p. 289 - 296

18
[ 109-78-4 ]
[ 494-52-0 ]
[ 71854-42-7 ]

Reference： [1]Zhurnal Obshchei Khimii,1955,vol. 25,p. 786; engl. Ausg. S. 753

19
[ 923-42-2 ]
[ 109-78-4 ]
[ 93024-22-7 ]

Reference： [1]Journal of Organic Chemistry,1961,vol. 26,p. 3757 - 3761

20
[ 288-88-0 ]
[ 81246-80-2 ]
[ 109-78-4 ]
[ 772-79-2 ]
[ 81265-94-3 ]

Reference： [1]Journal of Organic Chemistry,1982,vol. 47,p. 3623 - 3628

21
[ 288-88-0 ]
[ 81246-80-2 ]
[ 109-78-4 ]
[ 772-79-2 ]
[ 82444-82-4 ]

Reference： [1]Journal of Organic Chemistry,1982,vol. 47,p. 3623 - 3628

22
[ 288-94-8 ]
[ 81246-80-2 ]
[ 109-78-4 ]
[ 772-79-2 ]
[ 81279-40-5 ]

Reference： [1]Canadian Journal of Chemistry,1982,vol. 60,p. 111 - 120

23
[ 22059-21-8 ]
[ 74-85-1 ]
[ 109-78-4 ]

Reference： [1]Journal of Organic Chemistry,1989,vol. 54,p. 1815 - 1820
[2]Journal of Organic Chemistry,1989,vol. 54,p. 1815 - 1820

24
[ 72784-43-1 ]
[ 74-85-1 ]
[ 109-78-4 ]

Reference： [1]Journal of Organic Chemistry,1989,vol. 54,p. 1815 - 1820

25
[ 67-56-1 ]
[ 109-78-4 ]
[ 6149-41-3 ]

Yield	Reaction Conditions	Operation in experiment
47%		MeOH(50mL) was placedinathreeneckroundedflaskattachedacondenserandanadditionfunnelandwascooledat0C.ConcentratedHCl12M(4mL,38.8mmol,0.26eq,222mmolH2O,1.2eq)wasadded.Thionylchloride(6.6mL,91.5mmol,0.5eq)wasaddeddropwiseover10min,andthereactionmixturewaswarmeduptoroomtemperature.3-Hydroxypropionitrile(12.5mL,183mmol,1.0equiv)wasaddeddropwiseover20min,thenthemixturewasreluxedin 5h producing white precipitate. Then the reaction mixture was cooled in an ice bath,neutralized with Na2CO3. Solids were removed by filtration, the biphasic filtrate wasconcentratedunderreducedpressure,andthecrudematerialwaspurifiedbydistillation(0.25mmHg,41-44C,collectingfractionsinanicebath)toyieldmethyl-3-hydroxy-propionoate(8.9g,86mmol,47%).1HNMR(300MHz,CDCl3)delta3.84(t,J=6.1Hz,2H);3.63(s,3H);2.76(brs,1H,OH);2.55(td,J=5.8,1.6Hz,2H).

Reference： [1]Synthesis,1990,p. 459 - 460
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 2678 - 2702
[3]Tetrahedron Letters,2016,vol. 57,p. 5286 - 5289
[4]Journal of the American Chemical Society,2010,vol. 132,p. 6651 - 6653
[5]Tetrahedron Letters,1990,vol. 31,p. 5989 - 5992

26
[ 96-13-9 ]
Bis-[1,2,4]triazol-1-yl-phosphinic acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester [ No CAS ]
[ 109-78-4 ]
[ 76746-53-7 ]

Reference： [1]Tetrahedron Letters,1980,vol. 21,p. 2935 - 2936

27
[ 75-89-8 ]
[ 19935-76-3 ]
[ 109-78-4 ]
[ 52780-14-0 ]
3-[1-(3-Bromo-phenyl)-ethoxy]-propionitrile [ No CAS ]
1-(3-bromophenyl)ethyl trifluoroethyl ether [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 1373 - 1383

28
[ 75-89-8 ]
[ 456-16-6 ]
[ 109-78-4 ]
[ 403-41-8 ]
3-[1-(4-Fluoro-phenyl)-ethoxy]-propionitrile [ No CAS ]
1-(4-fluorophenyl)ethyl trifluoroethyl ether [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 1373 - 1383

29
[ 2566-19-0 ]
[ 109-78-4 ]
[ 125815-99-8 ]

Reference： [1]Tetrahedron Letters,1989,vol. 30,p. 3569 - 3572

30
[ 13726-67-5 ]
[ 109-78-4 ]
[ 130052-01-6 ]

Reference： [1]Tetrahedron Letters,1989,vol. 30,p. 3569 - 3572

31
[ 13726-67-5 ]
[ 109-78-4 ]
[ 156589-21-8 ]

Reference： [1]Synthesis,1993,p. 1261 - 1266

32
[ 4313-73-9 ]
[ 109-78-4 ]
[ 125816-02-6 ]

Reference： [1]Tetrahedron Letters,1989,vol. 30,p. 3569 - 3572

33
[ 106941-25-7 ]
[ 109-78-4 ]
9-(2-phosphonomethoxyethyl)adenine 2-cyanoethyl ester [ No CAS ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1994,vol. 59,p. 1853 - 1869

34
[ 81246-80-2 ]
[ 109-78-4 ]
[ 772-79-2 ]
[ 81265-94-3 ]

Reference： [1]Canadian Journal of Chemistry,1982,vol. 60,p. 111 - 120

35
[ 81279-39-2 ]
[ 109-78-4 ]
[ 772-79-2 ]
[ 81279-43-8 ]

Reference： [1]Canadian Journal of Chemistry,1982,vol. 60,p. 111 - 120

36
[ 770-12-7 ]
[ 109-78-4 ]
[ 7387-57-7 ]
[ 78098-69-8 ]

Reference： [1]Heterocycles,1981,vol. 15,p. 761 - 776

37
[ 109-78-4 ]
[ 7387-57-7 ]
[ 15074-54-1 ]
[ 78098-70-1 ]

Reference： [1]Heterocycles,1981,vol. 15,p. 761 - 776

38
[ 10035-10-6 ]
[ 109-78-4 ]
[ 590-92-1 ]

Reference： [1]Journal of the American Chemical Society,1917,vol. 39,p. 1437

39
[ 109-78-4 ]
nickel kieselguhr [ No CAS ]
[ 14002-33-6 ]
[ 14002-34-7 ]
[ 156-87-6 ]

Reference： [1]Patent: DE573983,1930,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 18,p. 818

40
[ 140-11-4 ]
[ 109-78-4 ]
[ 6328-48-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzene at 40 - 50℃;

Reference： [1]Tschelinzew; Benewolenskaja; Dubinin [Zhurnal Obshchei Khimii, 1947, vol. 17, p. 272][Chemisches Zentralblatt, 1948, vol. 119, p. 521]

41
[ 506-13-8 ]
[ 109-78-4 ]
[ 497070-10-7 ]

Yield	Reaction Conditions	Operation in experiment
67%	With dicyclohexyl-carbodiimide In pyridine at 0 - 20℃; for 24.5h;

Reference： [1]Ushioda, Masatoshi; Kadokura, Michinori; Moriguchi, Tomohisa; Kobori, Akio; Aoyagi, Morihiro; Seio, Kohji; Sekine, Mitsuo [Helvetica Chimica Acta, 2002, vol. 85, # 9, p. 2930 - 2945]

42
[ 3898-66-6 ]
[ 109-78-4 ]
[ 623172-50-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 3141 - 3152

43
[ 62-53-3 ]
[ 109-78-4 ]
[ 31121-11-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With hydrogen In methanol at 20℃; for 53h;
81%	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 53h;

Reference： [1]Sajiki, Hironao; Ikawa, Takashi; Hirota, Kosaku [Organic Letters, 2004, vol. 6, # 26, p. 4977 - 4980]
[2]Ikawa, Takashi; Fujita, Yuki; Mizusaki, Tomoteru; Betsuin, Sae; Takamatsu, Haruki; Maegawa, Tomohiro; Monguchi, Yasunari; Sajiki, Hironao [Organic and Biomolecular Chemistry, 2012, vol. 10, # 2, p. 293 - 304]

44
[ 2689-88-5 ]
[ 109-78-4 ]
3-(2-hydroxy-ethyl)-5,7-dihydro-[2]pyrindine-6,6-dicarboxylic acid diethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With 1,2-bis-(diphenylphosphino)ethane; cobalt(II) chloride; zinc In 1-methyl-pyrrolidin-2-one at 25℃; for 2h;

Reference： [1]Kase, Kouki; Goswami, Avijit; Ohtaki, Kazuhiko; Tanabe, Emi; Saino, Naoko; Okamoto, Sentaro [Organic Letters, 2007, vol. 9, # 5, p. 931 - 934]

45
benzyl 2-hex-1-yn-1-ylbenzoate [ No CAS ]
[ 109-78-4 ]
[ 2396-53-4 ]
[ 6328-48-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 75% 2: 7%	In chlorobenzene at 20℃; for 16h;

Reference： [1]Asao, Naoki; Aikawa, Haruo; Tago, Sakie; Umetsu, Kazuteru [Organic Letters, 2007, vol. 9, # 21, p. 4299 - 4302]

46
[ 69-78-3 ]
[ 109-78-4 ]
5,5'-dithiobis(2-nitrobenzoate)propionitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; ethanol; chloroform;	Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg,1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at room temperature. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 ml/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1 NMR ? 8.05 (d, 4H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
233 mg (36.8%)	In 1,4-dioxane; ethanol; chloroform;	Example 1 Synthesis of 5,5'-Dithiobis(2-nitrobenzoate)propionitrile <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> (500 mg, 1.26 mmol, Aldrich Chemical Company) was taken up in 4.0 mL dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol, Aldrich Chemical Company) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol, Aldrich Chemical Company) were added. The reaction mixture was stirred overnight at room temperature. The precipitate was removed by centrifugation, and the solvent concentrated under reduced pressure. The residue was washed with saturated sodium bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal (aspirator) yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 mL/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent (aspirator) afforded 233 mg (36.8%) of 5,5'-dithiobis(2-nitrobenzoate)propionitrile as a yellow oil. TLC (silica: 5% methanol in chloroform; Rf=0.51). H1 NMR 8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
233 mg (36.8%)	In 1,4-dioxane; ethanol; chloroform;	Example 11 Synthesis of 5,5'-Dithiobis(2-nitrobenzoate)propionitrile <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> (500 mg, 1.26 mmol, Aldrich Chemical Company) was taken up in 4.0 mL dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol, Aldrich Chemical Company) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol, Aldrich Chemical Company) were added. The reaction mixture was stirred overnight at room temperature. The precipitate was removed by centrifugation, and the solvent concentrated under reduced pressure. The residue was washed with saturated sodium bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal (aspirator) yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 mL/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent (aspirator) afforded 233 mg (36.8%) of 5,5'-dithiobis(2-nitrobenzoate)propionitrile as a yellow oil. TLC (silica: 5% methanol in chloroform; Rf=0.51). H1NMR ? 8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).

	In 1,4-dioxane; methanol; ethanol; chloroform;	Synthesis of Activated Disulfide Containing Co-monomers Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile: <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg, 1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at room temperature. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 ml/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1 NMR delta8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
	In 1,4-dioxane; methanol; ethanol; chloroform;	Synthesis of Activated Disulfide Containing Co-monomers Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile: <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg, 1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at room temperature. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 mn), flow rate=9.0 ml/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1 NMR delta8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
	In 1,4-dioxane; methanol; ethanol; chloroform;	Synthesis of Activated Disulfide Containing Co-monomers Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile: <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg,1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at room temperature. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 ml/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1NMR ? 8.05 (d, 4H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
	In 1,4-dioxane; ethanol; chloroform;	Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg,1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at RT. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 ml/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1 NMR ?8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
233 mg (36.8%)	In 1,4-dioxane; ethanol; chloroform;	Example 11 Synthesis of 5,5'-Dithiobis(2-nitrobenzoate)propionitrile <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> (500 mg, 1.26 mmol, Aldrich Chemical Company) was taken up in 4.0 mL dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol, Aldrich Chemical Company) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol, Aldrich Chemical Company) were added. The reaction mixture was stirred overnight at room temperature. The precipitate was removed by centrifugation, and the solvent concentrated under reduced pressure. The residue was washed with saturated sodium bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal (aspirator) yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 mL/min, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent (aspirator) afforded 233 mg (36.8%) of 5,5'-dithiobis(2-nitrobenzoate)propionitrile as a yellow oil. TLC (silica: 5% methanol in chloroform; Rf=0.51). H1NMR ? 8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).
	In 1,4-dioxane; ethanol; chloroform;	Synthesis of 5,5'-dithiobis(2-nitrobenzoate)propionitrile: <strong>[69-78-3]5,5'-dithiobis(2-nitrobenzoic acid)</strong> [Ellman's reagent] (500 mg,1.26 mmol) was dissolved in 4.0 ml dioxane. Dicylohexylcarbodiimide (540 mg, 2.6 mmol) and 3-hydroxypropionitrile (240 muL, 188 mg, 2.60 mmol) were added. The reaction mixture was stirred overnight at room temperature. The urea precipitate was removed by centrifugation. The dioxane was removed on rotary evaporator. The residue was washed with saturated bicarbonate, water, and brine; and dried over magnesium sulfate. Solvent removal yielded 696 mg yellow/orange foam. The residue was purified using normal phase HPLC (Alltech econosil, 250*22 nm), flow rate=9.0 mlmin, mobile phase=1% ethanol in chloroform, retention time=13 min. Removal of solvent afforded 233 mg (36.8%) product as a yellow oil. TLC (silica: 5% methanol in chloroform; rf=0.51). H1NMR ?8.05 (d, 4 H), 7.75 (m, 4H), 4.55 (t, 4H), 2.85 (t, 4H).

Reference： [1]Patent: US2003/166280,2003,A1
[2]Patent: US2001/36926,2001,A1
[3]Patent: US2001/44417,2001,A1
[4]Patent: US2002/137707,2002,A1
[5]Patent: US2002/137707,2002,A1
[6]Patent: US6627616,2003,B2
[7]Patent: US2004/72785,2004,A1
[8]Patent: US2005/20518,2005,A9
[9]Patent: US2004/106567,2004,A1

47
2-cyanoethyl 3-(furan-3-yl)-3-oxopropionate [ No CAS ]
[ 36878-91-8 ]
[ 555-16-8 ]
[ 21731-17-9 ]
[ 109-78-4 ]
[ 1238000-98-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; water; isopropyl alcohol;	Method B: A mixture of 894 mg of ethyl 3-(furan-3-yl)-3-oxopropionate (4.90 mmol) and 347 mg of 3-hydroxypropionitrile (4.88 mmol) was heated in an oil bath to 180-205 C. for 0.5 hrs. The reaction mixture was cooled and distilled under reduced pressure. Three fractions were obtained. 1 H NMR indicated that the third fraction (bp 100-140 C. (0.5 mm Hg)) was a 1:1 mixture of ethyl 3-(furan-3-yl)-3-oxopropionate and 2-cyanoethyl 3-(furan-3-yl)-3-oxopropionate. This mixture was used in the condensation step after spectral characterization. A solution of the 3-oxoesters (approximately 1.67 mmol), 192 mg of methyl 3-aminocrotonate (1.67 mmol), and 252 mg of 4-nitrobenzaldehyde (1.67 mmol) in 5 mL of isopropanol was heated at reflux temperature for 30 hrs, cooled, and the solvent was removed in vacuo. The residue was dissolved in 15 mL of dioxane and 15 mL of water (containing 35 mg of NaOH), stirred for 0.5 hr, and concentrated in vacuo. The residue was partitioned between ethyl acetate and water (20 mL each), separated, and the aqueous extract was washed with ethyl acetate (220 mL). The organic solutions were discarded. The aqueous extract was acidified with concentrated HCl (pH=3), and the resulting cloudy mixture was extracted with ethyl acetate (230 mL). The combined organic extracts were dried (Na2 SO4), and the solvent was removed in vacuo to give 2-(furan-3-yl)-1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(4-nitro)phenylpyridine-3-carboxylic acid as a yellow oil that partially solidified under reduced pressure.

Reference： [1]Patent: US5767131,1998,A

48
[ 88150-75-8 ]
[ 109-78-4 ]
[ 112641-31-3 ]

Yield	Reaction Conditions	Operation in experiment
	toluene-4-sulfonic acid; In water; ethyl acetate; toluene;	2-Cyanoethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy)-3-oxobutanoate Ethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl) ethoxy)-3-oxobutanoate (8g, 25mmoles) and 3-hydroxypropionitrile (12g, 170mmoles) were heated at 100 under N2 for 10 hours in toluene (100ml) containing a catalytic amount of 4-methylphenylsulphonic acid. Ethyl acetate and water were added; the organic layer was separated, washed with water, dried (MgSO4) and the solvent evaporated. Chromatography on silica eluding with ethyl acetate/petroleum ether (60-80) mixtures gave the title ester (8.9g). M/e 345 M+1+; NMR delta (CDCl3) 4.14 (s,2H), 3.53 (s,2H).

Reference： [1]Patent: EP225175,1988,A3

49
[ 3736-77-4 ]
[ 109-78-4 ]
[ 864837-10-5 ]

Yield	Reaction Conditions	Operation in experiment
51%	With boron trifluoride diethyl etherate In dimethyl amine at 120℃; for 15h;

Reference： [1]Saneyoshi, Hisao; Okamoto, Itaru; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo [Tetrahedron Letters, 2007, vol. 48, # 48, p. 8554 - 8557]

50
[ 109-78-4 ]
[ 134031-86-0 ]
C₃₇H₃₉N₄O₉P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	1H-tetrazole; In acetonitrile; at 20℃; for 0.333333h;	Example 12'-deoxythymidine monocyaniminomonophosphate370 mg (0.5 mmol) 3'-dimethoxytriyl-2'-deoxythymidine, 5'-[(2-cyanoethyl)- (N,N-diisopropyl)]-phosphoramidite (GlenResearch) is dissolved under argon in 2.5 ml anhydrous acetonitrile and firstly 2.2 ml of a 0.45 M solution of tetrazole in acetonitrile (Fluka) and then 150 mul (1.5 mmol) 3-hydroxypropionitrile are successively added. The reaction mixture is stirred for 20 minutes at room temperature and subsequently 1.56 ml of a 0.32 M solution of cyanogen azide in acetonitrile is added (cyanogen azide prepared according to: McMurry, J.E., et al., J. Organic Chemistry 38(16) (1973) 2821-7). After 30 minutes the solution is diluted <n="16"/>with ethyl acetate and shaken out with water. The organic phase is dried with sodium sulphate and the solvent is evaporated on a rotary evaporator. 8 ml 7 N methanolic ammonia solution is added to the residue and allowed to stand for 5 hours at room temperature in a sealed vessel. The solvent is removed, water is added to the residue and the water is also removed. The oily residue is dissolved in 40 ml of an 80 % acetic acid solution and stirred for 15 min at room temperature. The acetic acid is removed on a rotary evaporator. The residue is dissolved in 10 ml 37 % aqueous ammonia, afterwards the ammonia is removed and the product is purified over a DEAE Sephadex A25 anion exchanger (eluant gradient: from 0.1 M ammonium acetate solution pH = 7 in 120 minutes to 1 M ammonium acetate solution pH = 7). Mass (ESI) M/e 347.1 (calculated C11H15N4O7P 345.2), IH NMR (D2O, ppm) 7.76 (s, IH), 6.34 (t, IH), 4.42 (m, IH), 4.16 (m, IH), 4.04 (m, 2H), 2.36 (m, 2H), 1.94 (s, 3H), 31P NMR (D2O, ppm) 1.5.

Reference： [1]Patent: WO2008/128686,2008,A1 .Location in patent: Page/Page column 14-15

51
benzyl 2-hex-1-yn-1-ylbenzoate [ No CAS ]
[ 109-78-4 ]
[ 103-50-4 ]
[ 6328-48-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 75% 2: 7%	With (triphenylphosphine)gold(I) chloride; silver trifluoromethanesulfonate In chlorobenzene at 20℃; for 16h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Aikawa, Haruo; Tago, Sakie; Umetsu, Kazuteru; Haginiwa, Naomichi; Asao, Naoki [Tetrahedron, 2009, vol. 65, # 9, p. 1774 - 1784]

52
[ 302-79-4 ]
[ 109-78-4 ]
[ 1225383-34-5 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 5820 - 5826

53
[ 109-78-4 ]
[ 5336-08-3 ]
[ 1254077-05-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	In N,N-dimethyl-formamide at 20℃; for 1h;

Reference： [1]Location in patent: experimental part Falentin-Daudre, Céline; Beaupre, Daniel; Stasik-Boutbaiba, Imane [Carbohydrate Research, 2010, vol. 345, # 14, p. 1983 - 1987]

54
[ 100-39-0 ]
[ 109-78-4 ]
[ 6328-48-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine at 150℃; for 1h; Inert atmosphere; Neat (no solvent);	General procedure: Alcohol (1 mmol), p-methoxybenzyl chloride (1.1 mmol) and diisopropylethylamine (2 mmol) were charged in reaction vessel equipped with magnetic stirring bar under nitrogen atmosphere. The mixture was refluxed in 150 °C bath for 2 h. The resulting mixture typically showed two phases. Ethyl acetate (5 mL) and 10% aqueous sodium bisulphate (5 mL) were added to the mixture and the organic phase extracted by three potions of EtOAc. Combined organic layer was dried over magnesium sulfate and the solvent evaporated in vacuo. Further purification was carried out by silica gel column chromatography.
70%	Stage #1: 3-Hydroxypropionitrile With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: benzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 2h;	67 3-Benzyloxypropionitrile (I-67) A 12.3 g (0.308 mol) portion of sodium hydride was suspended in tetrahydrofuran (200 ml), 20.0 ml (0.293 mol) of 3-hydronypropionitrile was added dropwise thereto while keeping the internal temperature below 0°C, and the mixture was stirred at the same temperature for 10 minutes. Subsequently, 36.6 ml (0.308 mol) of benzyl bromide was added thereto, and then N,N-dimethylformamide (40 ml) was added thereto by taking care of exothermic reaction. After 2 hours of stirring at 0°C, the reaction solution was concentrated, and the resulting residue was poured into saturated ammonium chloride aqueous solution. This was extracted with chloroform, and the organic layer was washed with brine and then dried over magnesium sulfate. The solvent was evaporated, and the thus obtained residue was applied to a silica gel column chromatography, and 33.0 g (70%) of the title compound was obtained as a pale yellow oily substance from a n-hexane-ethyl acetate (5:1 v/v) eluate. 1H-NMR (CDCl3)δ: 2.62 (2H, t, J= 6.4 Hz), 3.68 (2H, t, J= 6.4 Hz), 4.58 (2H, s), 7.25-7.37 (5H, m).
44%	With N-ethyl-N,N-diisopropylamine at 150℃; for 2h;	1 A mixture of 3-hydroxypropanenitrile (10.0 g, 141 mmol, 9.52 mL, 1.00 eq), (bromomethyl)benzene (24.1 g, 141 mmol, 16.7 mL, 1.00 eq) and N,N-diisopropylethylamine (21.8 g, 169 mmol, 29.4 mL, 1.20 eq) was heated to 150 °C and stirred at 150 °C for 2 h. The mixture was cooled to room temperature and diluted with sulfuric acid (1 M, 100 mL) and ethyl acetate (100 mL). The organic layer was washed with water (100 mL), dried over sodium sulfate, filtered and the filtrate was concentrated to afford a brown oil. The brown oil was distilled under vacuum (~5 torr) and collected the distillate between 140 to 150 °C to give 3- (benzyloxy)propanenitrile (10 0 g, 62.0 mmol, 44% yield) as colorless oil 1H NMR (400 MHz, CDC13) d = 7.43 - 7.28 (m, 5H), 4.58 (s, 2H), 3.68 (t, J = 6.4 Hz, 2H), 2.62 (t, J = 6.4 Hz, 2H).

24.7 g

Stage #1: 3-Hydroxypropionitrile With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.666667h; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃;

4-1.1 Synthesis of 3-(benzyloxy)propanenitrile (1) Synthesis of 3-(benzyloxy)propanenitrile To a suspension of sodium hydride (60% dispersion in mineral oil; 14.6 g) in tetrahydrofuran (281 mL), ethylene cyanohydrin (21.0 mL) was added dropwise at 0°C and the mixture was stirred at that temperature for 40 minutes. After adding benzyl bromide (44.4 mL) to the reaction mixture, the resulting mixture was stirred overnight as it was brought to room temperature. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate three times. The combined organic layers were washed with saturated brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate = 100:0-70:30) to give 3-(benzyloxy)propanenitrile as a colorless oil (24.7 g). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.63 (t, J=6.4 Hz, 2 H) 3.69 (t, J=6.4 Hz, 2 H) 4.59 (s, 2 H) 7.27 - 7.41 (m, 5 H).

Reference： [1]Location in patent: experimental part Gathirwa, Jeremiah W.; Maki, Toshihide [Tetrahedron, 2012, vol. 68, # 1, p. 370 - 375]
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1717238, 2006, A1 Location in patent: Page/Page column 60
[3]Current Patent Assignee: BLACK DIAMOND THERAPEUTICS INC - WO2020/68867, 2020, A1 Location in patent: Page/Page column 497
[4]Current Patent Assignee: TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - EP2881384, 2015, A1 Location in patent: Paragraph 0279; 0280

55
[ 109-78-4 ]
[ 150683-30-0 ]
C₂₉H₂₉ClN₃O₅P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		Example 27; A 3.0 g quantity (6.7 iranol) of <strong>[150683-30-0]tolvaptan</strong> (compound (2)) were added in small portions to a pyridine solution (15 ml) of 3.8 ml (20 mmol) of diphenyl phosphite, and the obtained mixture was stirred at room temperature for 0.5 hours. To this mixture was added 2.8 ml (40 mmol) of 3-hydroxypropionitrile, and stirring was performed at room temperature for 0.5 hours. To the obtained reaction mixture was added 1 N hydrochloric acid, and extraction was performed with ethyl acetate. The ethyl acetate layer was washed with water, dried over sodium sulfate, and then filtered, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate : methanol = 100 : 0 ? 10 : 1) . The purified product was concentrated under reduced pressure to give 2.8 g of white amorphous solid target compound. Yield: 75%1H-NMR (Toluene-d8, 100 0C) delta ppm : 1.4-2.0 (6H, m) , 2.33 (3H, s), 2.40 (3H, s), 3.1-3.8 (4H, m) , 5.40 (0.5H, d, J = 3.1Hz), 5.3-5.4 (IH, m), 6.5-6.7 (IH, m) , 6.7-6.9 (IH, m) , 6.9-7.2 (6H, m) , 7.2- 7.5 (2H, m), 7.76 (0.5H, d, J = 8.5 Hz)

Reference： [1]Patent: WO2007/74915,2007,A1 .Location in patent: Page/Page column 48

56
[ 68892-41-1 ]
[ 109-78-4 ]
[ 160107-22-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5'-O-dimethoxytrityl-N-isobutyryldeoxyguanosine With pyridine; diphenyl hydrogen phosphite for 2h; Inert atmosphere; Stage #2: 3-Hydroxypropionitrile for 2h;	A.1.1 Step 1-2N-Isobutyryl-3'-O-(2-Cyanoethyl)H-Phosphonate-5'O-Dimetoxytrityl deoxyguanosine (A4-I)2N-Isobutyryl-50-Dimetoxytrityl deoxyguanosine (0.5 g, 0.78 mmol) was dried by co-evaporation with dry toluene and suspended in dry pyridine (10 mL) under inert atmosphere. Diphenyl phosphite (250 μL, 1.3 mmol) was added and stirred for 2 h. 3-hydroxypropionitrile (150 μL, 2.16 mmol) was added. After stirring for 2 hr, the solvent was evaporated. The oily crude was used without further purification.

Reference： [1]Current Patent Assignee: HEBREW UNIVERSITY OF JERUSALEM; Yissum Research & Development (in: Hebrew University) - US2011/86813, 2011, A1 Location in patent: Page/Page column 27-28

57
[ 81256-89-5 ]
[ 109-78-4 ]
[ 1187644-14-9 ]

Yield	Reaction Conditions	Operation in experiment
		Step 4-2N-Isobutyryl-5'O-Dimetoxytrityl-3'O-tertbutyldimethylsilyl-2'-O-(2-cyanoethyl)H-Phosphonate Guanosine (A9-V)Compound (A9-IV) (0.78 mmol) was dried by co-evaporation with dry toluene and suspended in dry pyridine (10 mL) under inert atmosphere. Diphenyl phosphite (250 muL, 1.3 mmol) was added and stirred for 2 h. 3-hydroxypropionitrile (150 muL, 2.16 mmol) was added. After stirring for 2 hr, the solvent was evaporated. The oily crude was used without further purification.

Reference： [1]Patent: US2011/86813,2011,A1 .Location in patent: Page/Page column 32

58
[ 98-95-3 ]
[ 109-78-4 ]
[ 31121-11-6 ]
[ 62-53-3 ]

Yield	Reaction Conditions	Operation in experiment
	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 48h;

Reference： [1]Ikawa, Takashi; Fujita, Yuki; Mizusaki, Tomoteru; Betsuin, Sae; Takamatsu, Haruki; Maegawa, Tomohiro; Monguchi, Yasunari; Sajiki, Hironao [Organic and Biomolecular Chemistry, 2012, vol. 10, # 2, p. 293 - 304]

59
[ 109-78-4 ]
[ 4049-33-6 ]
[ 1304513-16-3 ]

Reference： [1]Molecular BioSystems,2011,vol. 7,p. 1312 - 1321

60
[ 1927-25-9 ]
[ 109-78-4 ]

Reference： [1]ChemSusChem,2015,vol. 8,p. 345 - 352
[2]Chemical Communications,2015,vol. 51,p. 6528 - 6531

61
[ 109-78-4 ]
[ 1009-93-4 ]
C₈H₁₄N₂O₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With aluminum dihydrogen phosphate	Scheme 16 depicts a synthesis scheme for 1ND1N. 1ND1N cannot be chemically dried with sodium (Na), calcium oxide (CaO), or calcium hydride (CaH2).

Reference： [1]Current Patent Assignee: ORBIA ADVANCE CORPORATION, S.A.B. DE C.V. - WO2016/54621, 2016, A1 Location in patent: Page/Page column 36; 37

62
[ 109-89-7 ]
[ 109-78-4 ]
[ 622-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	With formic acid; 5%-palladium/activated carbon; In water; at 20℃;	Example 9 3-Diethylaminopropanol Using Water Diethylamine (3.78 mL; 36.6 mmol; 2.5 equiv) and water (2.47 mL) were added to a 100-mL flask. Formic acid (96%; 1.21 mL; 30.7 mmol; 2.1 equiv) was added dropwise with a small exotherm. The cooling bath was removed and the mixture was allowed to warm to ambient temperature. 3-Hydroxypropionitrile (1.0 mL; 14.6 mmol) was added followed by 5% palladium on carbon (42.3% in water; 180 mg; 7.5 wt % based on hydroxypropionitrile). The mixture was stirred at RT and samples were removed and analyzed for conversion of 3-hydroxypropionitrile to 3-diethylaminopropanol by 1H NMR: 1 h, 39% conversion; 2 h, 52% conversion; 3 h, 60% conversion. 1H NMR (DMSO-d6): delta 3.42 (t, 2H, J=6.30 Hz); 2.46 (q, 4H, J=7.00 Hz); 2.45 (t, 2 h, J=6.80 Hz); 1.53 (m, 2H); 0.94 (t, 6H, J=7.10 Hz).
	With 5%-palladium/activated carbon; hydrogen; In water; at 20℃; under 3087.28 Torr; for 4h;	5% Palladium on carbon (49.5% in water; 218 mg; 5 wt% based on 3-hydroxypropionitrile) was added to a Parr pressure bottle. Water (3.21g) was added followed by diethylamine (2.68 g; 36.6 mmol; 1 .25 equiv) and 3- hydroxypropionitrile (2.08 g; 29.3 mmol). The mixture was placed under 45 psig hydrogen and shaken at ambient temperature. The reaction was stopped after 4h and sampled and analyzed by 1H NMR to indicate 72% conversion.

Reference： [1]Patent: US9469595,2016,B1 .Location in patent: Page/Page column 7; 8
[2]Patent: WO2016/209629,2016,A1 .Location in patent: Paragraph 0054

63
[ 1885-38-7 ]
[ 109-78-4 ]
[ 1616735-75-1 ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 1334 - 1337
Angew. Chem.,2017,vol. 129,p. 1354 - 1357,4

64
[ 660-68-4 ]
[ 109-89-7 ]
[ 109-78-4 ]
[ 622-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 5%-palladium/activated carbon; hydrogen; In water; at 20℃; under 3087.28 Torr; for 4h;	5% Palladium on carbon (49.5% in water; 218 mg; 5 wt% basedon 3-hydroxypropionitrile) was added to a Parr pressure bottle. Water (3.21g) was added followed by diethylamine (2.14 g; 29.3 mmol; 1.0 equiv). Diethylamine hydrochloride (0.802g; 7.32 mmol; 0.25 equiv) was added followed by 3-hydroxypropionitrile (2.08 g; 29.3 mmol). The mixture was placed under 45 psig hydrogen and shaken at ambient temperature. Thereaction was stopped after 4h and sampled and analyzed by 1H NMR to indicate 69% conversion. 1H NMR (DMSO-d6) O (ppm): 3.45 (t, 2H, J = 6.3 Hz); 2.50 (t, 2H, J= 7.4 Hz); 2.44 (q, 4H, J= 7.2 Hz); 1.54 (m(5), 2H, J= 6.3 Hz); 0.95 (t, 6H, J= 7.1 Hz).

Reference： [1]Patent: WO2016/209629,2016,A1 .Location in patent: Paragraph 0052; 0053

65
[ 64-17-5 ]
[ 109-78-4 ]
[ 623-72-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	With hydrogenchloride; thionyl chloride; In water; at 0 - 20℃; for 6h;Reflux;	Ethanol (1L) was placed in a three-necked flask, stirred and cooled to 0 C.Concentrated hydrochloric acid (80 mL) was added dropwise slowly.Then slowly add thionyl chloride (132 mL).The system slowly rise to room temperature.3-Hydroxypropionitrile (250 g) was slowly added dropwise, and the system was refluxed for 6 hours.A large amount of white powder appeared.The system was cooled to 0 C and the pH was adjusted to about 7 with solid sodium carbonate.Filtration, concentration of the filtrate, distillation to obtain 208 g of ethyl 3-hydroxypropionate, yield 50%

Reference： [1]Patent: CN108314665,2018,A .Location in patent: Paragraph 0065-0069

66
[ 1003-31-2 ]
[ 109-78-4 ]
C₈H₈N₄OS [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 1106 - 1109
Angew. Chem.,2019,vol. 131,p. 1118 - 1121,4

67
[ 109-78-4 ]
[ 131724-45-3 ]
C₁₈H₂₃N₅O₅ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 1106 - 1109
Angew. Chem.,2019,vol. 131,p. 1118 - 1121,4

68
[ 109-78-4 ]
[ 1515-95-3 ]
3-(1-(4-methoxyphenyl)ethoxy)propanenitrile [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 197 - 202
Angew. Chem.,2020,vol. 132,p. 203 - 208,6

69
[ 109389-30-2 ]
[ 109-78-4 ]
C₃₆H₃₇N₄O₉P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-tetrazole In acetonitrile at 20℃;

Reference： [1]Zheng, Song; Tran, Ai; Curry, Alyson M.; White, Dawanna S.; Cen, Yana [Organic and Biomolecular Chemistry, 2020, vol. 18, # 27, p. 5164 - 5173]

Same Skeleton Products

Related Products

Historical Records

Pharmaceutical Intermediates of
[ 109-78-4 ]

Clevidipine Butyrate Intermediates

[ 14205-39-1 ]

Methyl 3-aminobut-2-enoate

Related Functional Groups of
[ 109-78-4 ]

Aliphatic Chain Hydrocarbons

[ 110-67-8 ]

3-Methoxypropanenitrile

Similarity: 0.79

[ 123689-95-2 ]

(S)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 125103-95-9 ]

(R)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 2141-62-0 ]

3-Ethoxypropanenitrile

Similarity: 0.73

[ 19295-57-9 ]

3-Hydroxy-2,2-dimethylpropanenitrile

Similarity: 0.73

Alcohols

[ 123689-95-2 ]

(S)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 125103-95-9 ]

(R)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 19295-57-9 ]

3-Hydroxy-2,2-dimethylpropanenitrile

Similarity: 0.73

Nitriles

[ 110-67-8 ]

3-Methoxypropanenitrile

Similarity: 0.79

[ 123689-95-2 ]

(S)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 125103-95-9 ]

(R)-3-Hydroxybutanenitrile

Similarity: 0.73

[ 2141-62-0 ]

3-Ethoxypropanenitrile

Similarity: 0.73

[ 19295-57-9 ]

3-Hydroxy-2,2-dimethylpropanenitrile

Similarity: 0.73

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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. 109-78-4 ]

Quality Control of [ 109-78-4 ]

Related Doc. of [ 109-78-4 ]

Product Details of [ 109-78-4 ]

Calculated chemistry of [ 109-78-4 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 109-78-4 ]

Application In Synthesis of [ 109-78-4 ]

[ 109-78-4 ] Synthesis Path-Upstream 1~16

[ 109-78-4 ] Synthesis Path-Downstream 1~69

Pharmaceutical Intermediates of [ 109-78-4 ]

Clevidipine Butyrate Intermediates

Related Functional Groups of [ 109-78-4 ]

Aliphatic Chain Hydrocarbons

Alcohols

Nitriles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Pharmaceutical Intermediates of
[ 109-78-4 ]

Related Functional Groups of
[ 109-78-4 ]