524-40-3

Basic information

• Product Name: RICININE
• Synonyms: RICININE;1,2-dihydro-4-methoxy-1-methyl-2-oxo-3-pyridinecarbonitril;1,2-dihydro-4-methoxy-1-methyl-2-oxo-nicotinonitril;1,2-dihydro-4-methoxy-1-methyl-2-oxonicotinonitrile;recinine;ricinin;NICOTINONITRILE,1,2-DIHYDRO-4-METHYL-2-OXO-;1,2-Dihydro-4-methoxy-1-methyl-2-oxo-3-pyridinecarbonitrile
• CAS NO: 524-40-3
• Molecular Formula: C₈H₈N₂O₂
• Molecular Weight: 164.16
• EINECS: 208-359-7
• Product Categories: Agro-Products;Heterocycles;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Aromatics
• Mol File: 524-40-3.mol
• Article Data: 6

Chemical Properties

• Melting Point: 201.5°
• Boiling Point: 291.62°C (rough estimate)
• Flash Point: 2℃
• Appearance: /
• Density: 1.2739 (rough estimate)
• Vapor Pressure: 1.07E-05mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: ?20°C
• PKA: -4.93±0.62(Predicted)
• Water Solubility: 2.7g/L(10 oC)
• CAS DataBase Reference: RICININE(CAS DataBase Reference)
• NIST Chemistry Reference: RICININE(524-40-3)
• EPA Substance Registry System: RICININE(524-40-3)

Safety Data

• Hazard Codes: T,Xn,F
• Statements: 25-36-20/21/22-11
• Safety Statements: 45-36/37-16
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• RTECS: QT3100000
• Hazardous Substances Data: 524-40-3(Hazardous Substances Data)

Usage

Description

First isolated by Tuson from the seeds of Ricinus communis (castor-oil seed), the alkaloid was subsequently examined by Soave, Schultze and Evans. The base crystallizes from H20 in colourless prisms or leaflets and sublimes at 170-lS0°C/ 20 mm. It is soluble in hot H20 or CHCI3, only sparingly so in EtOH and insoluble in petroleum ether, is neutral in reaction, optically inactive and forms no normal salts although the mercurichloride, m.p. 204°C has been prepared. The alkaloid reduces KMn04 and may be hydrolyzed by alkalies to MeOH and ricininic acid which forms brilliant, slender needles, m.p. 296-8°C (dec.). The structure of ricinine has been confirmed by synthesis from 4-chloroquinoline. Other syntheses have also been achieved. The base is not particularly toxic and the poisonous character of castor-oil seeds has been shown to be due to a more complex substance, ricin, the toxicity of which may be destroyed by heating.

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 524-40-3 differently. You can refer to the following data:
1. An alkaloid extract from the seeds of the castor-oil plant (Ricinus communalis). It is a central nervous system stimulant that could potentially be a cognition-enhancing agent used for the treatment of human amnesias. It also has bactericidal effects on t
2. Ricinine is an alkaloid extract from the seeds of the castor-oil plant (Ricinus communalis). Ricinine is a central nervous system stimulant that could potentially be a cognition-enhancing agent used for the treatment of human amnesias. Ricinine also has bactericidal effects on three pests and heptaprotective activity.

Hazard

Toxic by ingestion.

Safety Profile

A poison by ingestion and subcutaneous route. When heated to decomposition it emits toxic vapors of NOx.

References

Tuson.,J. Chern. Soc., 17,195 (1864) Soave., Chern. Soc. Abstr., i, 386 (1896) Schultze., ibid, i, 42 (1898) Evans., J. Arner. Chern. Soc., 22, 39 (1900) Maqueen, Philippe., Cornpt. rend., 138, 506 (1904) Maqueen, Philippe., ibid, 139, 840 (1904) Winterstein, Keller, Weinhagen., Arch. Pharrn., 255,513 (1917) Bottcher., Ber., 51,673 (1918) Spath, Tschelnitz., Monatsh., 42,251 (1921) Spath, Koller., Ber., 56, 880, 2454 (1923) Spath, Koller., ibid, 58,2124 (1925) Schroeter et ai., ibid, 65, 432 (1932) Reitmann., Chern. Abstr., 29,4359 (1935)

InChI:InChI=1/C8H8N2O2/c1-10-4-3-7(12-2)6(5-9)8(10)11/h3-4H,1-2H3

Synthetic route

4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile (21642-98-8) + methyl iodide (74-88-4) → ricinin (524-40-3)

Conditions	Yield
Stage #1: 4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile With potassium tert-butylate; tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 0℃; Stage #2: methyl iodide In tetrahydrofuran at 20℃;	90%
With potassium carbonate In acetonitrile for 10h; Reflux;	78%

2,4-Dimethoxy-pyridin-3-carbonitril (95689-37-5) → ricinin (524-40-3)

Conditions	Yield
With methyl iodide at 130℃; for 6h;	70%
With methyl iodide at 155℃;

1,2-dihydro-4-methoxy-1-methyl-2-oxopyridine-3-carboxylic acid (16803-45-5) → ricinin (524-40-3)

Conditions	Yield
With ethylpolyphosphate; ammonia In chloroform 1a) 2 h, b) 80 deg C, 4 h;	56%

4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile (21642-98-8) + dimethyl sulfate (77-78-1) → ricinin (524-40-3)

Conditions	Yield
With sodium hydroxide at 0℃;	53%

2-Chloro-5-cyano-4-methoxy-N-methylpyrid-6-one (93769-12-1) → ricinin (524-40-3)

Conditions	Yield
With sulfuric acid; zinc

4-methoxypyridine-3-carbonitrile (74133-20-3) → ricinin (524-40-3)

Conditions	Yield
With dimethyl sulfate; benzene Behandeln des Reaktionsprodukts mit K3 in H2O;

2,4-Dimethoxy-pyridin-3-carbonitril (95689-37-5) + methyl iodide (74-88-4) → ricinin (524-40-3)

Conditions	Yield
at 120 - 130℃;
at 120 - 130℃; im Vakuum;
at 120 - 130℃; im Rohr;

chloroform (67-66-3) + 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyridine-3-carbonitrile; silver salt + methyl iodide (74-88-4) → ricinin (524-40-3)

methyl iodide (74-88-4) + silver salt of/the/ ricininic acid → ricinin (524-40-3)

Conditions	Yield
With chloroform

sodium-compound of/the/ ricininic acid → ricinin (524-40-3)

Conditions	Yield
With methyl bromide at 100℃;
With dimethyl sulfate; xylene

4-chloro-3-cyano-1-methylpyridin-2(1H)-one (62617-49-6) + sodium methylate (124-41-4) → ricinin (524-40-3) + ricininic acid

diazomethane (186581-53-3, 908094-01-9) + 4-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (520-78-5) → ricinin (524-40-3)

Conditions	Yield
In methanol; diethyl ether for 48h;	120 mg

1,1-Dicyan-4-(N,N-dimethylamino)-2-methoxybutadien-1,3 (95689-38-6) → ricinin (524-40-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / methanol / 15 h / Heating 2: 70 percent / CH3I / 6 h / 130 °C View Scheme

4-methoxy-1-methyl-2-pyridone (41759-19-7) → ricinin (524-40-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) BuLi / 1) THF, hexane, -78 deg C, 30 min, 2a) -78 deg C, 15 min 2: 56 percent / ethylpolyphosphate, NH3(g) / CHCl3 / 1a) 2 h, b) 80 deg C, 4 h View Scheme

4-hydroxy-2-pyridone (626-03-9) → ricinin (524-40-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 50 percent / 40percent aq. NaOH, triethylbenzylammonium bromide / benzene / 96 h / 70 °C 2: 1) BuLi / 1) THF, hexane, -78 deg C, 30 min, 2a) -78 deg C, 15 min 3: 56 percent / ethylpolyphosphate, NH3(g) / CHCl3 / 1a) 2 h, b) 80 deg C, 4 h View Scheme

ricinin (524-40-3) → 4-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (520-78-5)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 90℃; for 6h; Green chemistry; chemoselective reaction;	92%
With water; sodium hydroxide In tetrahydrofuran at 110℃; for 2h;	87.5%
With sodium hydroxide In water for 0.333333h;
With sodium hydroxide for 0.5h; Heating;	0.31 g

ricinin (524-40-3) → 5-bromo-4-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Conditions	Yield
With N-Bromosuccinimide; trifluoroacetic acid In acetonitrile for 8h; Reflux;	81%
With bromine In dichloromethane at 60℃; for 48h;	47.3%
With bromine In dichloromethane at 60℃; for 48h;

ricinin (524-40-3) → 4-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonamide

Conditions	Yield
With sulfuric acid at 80 - 90℃; for 6h;	72%
With polyphosphoric acid at 110℃; for 2h;	43.6%

ricinin (524-40-3) → pyridine (110-86-1)

Conditions	Yield
bei der Zinkstaub-Destillation;

ricinin (524-40-3) → 2-Chloro-5-cyano-4-methoxy-N-methylpyrid-6-one (93769-12-1)

Conditions	Yield
With chlorine; acetic acid

ricinin (524-40-3) → 1-methyl-1H-pyridine-2,4-dione (856956-19-9)

Conditions	Yield
With hydrogenchloride at 140℃;

ricinin (524-40-3) → 4-methoxy-1-methyl-2-pyridone (41759-19-7)

Conditions	Yield
With sulfuric acid

ricinin (524-40-3) → 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyridine-3-carbonitrile

Conditions	Yield
With aqueous alkali
With potassium hydroxide
With potassium carbonate

ricinin (524-40-3) → 6-bromo-4-methoxy-1-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile

Conditions	Yield
With water; bromine
With chloroform; bromine

ricinin (524-40-3) → 4-methoxy-1-methyl-2-oxo-piperidine-3-carbonitrile; hydrochloride

Conditions	Yield
With hydrogenchloride; platinum

ricinin (524-40-3) + zinc dust → α.γ-dipyridyl

Conditions	Yield
beim Erhitzen auf Dunkelrotglut;

hydrogenchloride (7647-01-0) + ricinin (524-40-3) → 1-methyl-1H-pyridine-2,4-dione (856956-19-9)

Conditions	Yield
at 140℃; im Rohr;

ricinin (524-40-3) + sulfuric acid (7664-93-9) → 1-methyl-4-methoxy-pyridone-(2)

ricinin (524-40-3) + water (7732-18-5) + barium permanganate → hydrogen cyanide (74-90-8) + succinic acid (110-15-6) + ammonia (7664-41-7) + oxalic acid (144-62-7)

ricinin (524-40-3) + chloroform (67-66-3) + bromine (7726-95-6) → bromoricinine

ricinin (524-40-3) + water (7732-18-5) + bromine (7726-95-6) → bromoricinine

ricinin (524-40-3) + chlorine (7782-50-5) + acetic acid (64-19-7) → chlororicinine

ricinin (524-40-3) + alkali → methanol (67-56-1) + ricininic acid

Upstream product

• 93769-12-1 2-Chloro-5-cyano-4-methoxy-N-methylpyrid-6-one 
• 74133-20-3 4-methoxypyridine-3-carbonitrile 
• 95689-37-5 2,4-Dimethoxy-pyridin-3-carbonitril 
• 74-88-4 methyl iodide 
• 67-66-3 chloroform 
• 16803-45-5 1,2-dihydro-4-methoxy-1-methyl-2-oxopyridine-3-carboxylic acid 
• 21642-98-8 4-methoxy-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 77-78-1 dimethyl sulfate 
• 62617-49-6 4-chloro-3-cyano-1-methylpyridin-2(1H)-one 
• 124-41-4 sodium methylate 
• 186581-53-3 diazomethane 
• 520-78-5 4-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 95689-38-6 1,1-Dicyan-4-(N,N-dimethylamino)-2-methoxybutadien-1,3 
• 41759-19-7 4-methoxy-1-methyl-2-pyridone 

Downstream Products

• 110-86-1 pyridine 
• 93769-12-1 2-Chloro-5-cyano-4-methoxy-N-methylpyrid-6-one 
• 41759-19-7 4-methoxy-1-methyl-2-pyridone 
• 520-78-5 4-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 74-90-8 hydrogen cyanide 
• 110-15-6 succinic acid 
• 7664-41-7 ammonia 
• 144-62-7 oxalic acid 

Relevant articles and documents

Syntheses with Nitriles, LXXII. Ricinine - A Simple Synthesis

Cyclization of 1,1-dicyano-4-(N,N-dimethylamino)-2-methoxy-1,3-butadiene leads to 4-methoxy-2(1H)-pyridone-3-carbonitrile and 2,4-dimethoxy-pyridine-3-carbonitrile.Methylation of both products yields ricinine. - Keywords: 4-Methoxy-1-methyl-2(1H)-pyridone-3-carbonitrile; Alkaloid synthesis

A practical procedure for the selective N-alkylation of 4-alkoxy-2-pyridones and its use in a sulfone-mediated synthesis of N-methyl-4-methoxy-2-pyridone

It has been found that selective N-alkylation of 4-alkoxy-2-pyridones can be achieved under anhydrous, mild conditions with tetrabutylammonium iodide and potassium tert-butoxide being employed as the catalyst and the base, respectively. The procedure was applied to the preparation of 4-methoxy-1-methyl-2-pyridone, a valuable building block for heterocycle synthesis.

Lithiation of 4-Methoxy-2-pyridones. Synthetic Entry to Tenellin and Funiculosin, and Related Natural 3,5-Disubstituted 4-Oxy-2-pyridones

Lithiation of 4-methoxy-2-pyridone with butyllithium at -78 deg C occurs at the C-3 position exclusively.Subsequent reactions with MeOD, MeI, CO2, benzaldehyde or (E)-but-2-enal then lead to the corresponding C-3-substituted derivatives. in a one-pot procedure, treatment of 1,2-dihydro-4-methoxy-1-methyl-2-oxopyridine-3-carboxylic acid with ammonia in the presence of a polyphosphate buffer at 80 deg C produced natural ricinine in 58percent overall yield.A convenient three-step synthesis of 5-aryl- and 5-alkyl-substituted 4-methoxy-2-pyridones is described.Lithiation of these substrates, followed by reaction with electrophiles, provided a convenient route to 3,5-disubstituted 4-oxy-2-pyridones, and a synthetic entry to natural products, e. g. tenellin and funiculosin, containing this structural feature.