3- aminopropionitrile

Three hundred and thirty-three milliliters (5.0 moles) of acrylonitrile (Caution—toxic volatile substance) is added to 1625 ml. (25 moles) of concentrated aqueous ammonia solution in a round-bottom Pyrex flask. The flask is closed with a rubber stopper which is wired in. The mixture is shaken for a few seconds and then allowed to stand overnight behind a suitable barricade for protection against 

Two molar equivalents of sodamide are suspended in boiling xylene and one molar equivalent of quinoline is added. The mixture is heated to reflux until the rate of hydrogen evolution is low (approximately 1 hour). The cold reaction mixture is hydrolyzed by the cautious addition of excess water, and the xylene layer is separated and extracted with concentrated hydrochloric acid. The acid extracts are treated with excess sodium hydroxide and extracted with ether. The combined ethereal extracts and xylene layer are distilled, and the fraction boiling around 200°/30 mm. is recrystallized from toluene. The yield is 32% of white needles, m.p. 130°. 

A mixture of 34.8 g. (0.20 mole) of 8-nitroquinoline (p. 235), 0.25 g. of Adams platinic oxide catalyst [Org. Syntheses Coll. Vol. 1, 463 (1941)], 150 ml. of ethyl acetate, 25 ml. of absolute ethanol, and 25 ml. of ether is agitated in the presence of hydrogen [Org. Syntheses Coll. Vol. 1, 61 (1941)]. In 1.5 hours 3 molar equivalents of hydrogen are absorbed. The resulting solution of the amine is treated with 

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Aminopropionitrile (present in sweet peas) covalently inactivates lysyl oxidase, preventing intramolecular cross-linking of collagen and causing abnormalities in joints, bones, and blood vessels. 

The submitter has used the method to prepare the corresponding 1-pyrrolyl derivatives6 from the following amines in the indicated yields ethyl /3-aminobutyrate 88%, methyl -amino-glutarate 87%, /3-aminopropionitrile 58%, and 2,5-diamino-3,4-dicyanothiophene 22%. 

A bacterial isolate APN has been shown to convert a-aminopropionitril enantioselectively to L-alanine (94% yield, 75% e e). However, the major disadvantage of this approach, is the low stability of most aminonitriles in water (for example a-aminophenylacetonitrile in water of pH 7, degrades completely within 48 hours). The aminonitriles are always in equilibrium with the aldehyde or ketone and ammonia/HCN. Polymerisation of hydrogen cyanide gives an equilibrium shift resulting in the loss of the aminonitrile. Therefore, a low yield in amino adds is to be expected, which makes this method less attractive for the industrial synthesis of optically active amino adds. 

With 3-aminopropionitrile hydrochloride, phosphorus pentachloride produces phosphazene linkages at both ends of the alkyl chain, as might be expected from the foregoing discussion ... 

Stereochemistry has also been used as a diagnostic tool. If an Sr I reaction occurs at an optically active sp carbon centre, racemization should take place. This has indeed been observed in the reaction of 2-(4-nitrophe-nyl)-2-nitrobutanewithbenzenethiolate,benzenesulphinate,2-nitropropanate and also nitrite ions (Kornblum, 1975 Kornblum and Wade, 1987) as well as in the reactions of 2-(4-nitrophenyl)-2-chloroethane with the V,V-diethyl-a-aminopropionitrile and phenlyacetonitrile anions (Cabaret et al., 1985). 

Selenocystathionin occurs in seeds of the Central and South American Lecythis ollaria. It causes abdominal pain, nausea, vomiting, and diarrhea. Lathyrus odora-tus contains aminopropionitrile (Rosenthal and Bell, 1979). 2,4-Diaminobutyric acid (Fig. 11.10) in Lathyrus latifolius and Lathyrus sylvestris causes muscular weakness, paralysis, and death in humans and other mammals. In India, 25000 cases of this neurolathyrism were reported in a population of 634000 people (Rosenthal, 1991). 3-Cyanoalanine (Fig. 11.10) from Vivia sativa and 15 other Vivia species causes convulsion, rigidity, and death. 

CA 72, 14387c (1970) (Plastic expl eompns prepd by mixing TNT AN with acrylamide gel, /3-dimethy 1 aminopropionitrile and Amm persulfate. Their densities were 1.36—1.48 aud deton velocity 5100—6300m/sec)... 

The biochemical problem has been traced to the presence in the seeds of P-cyanoalanine and of its decarboxylation product P-aminopropionitrile. 

Aminomutases (vitamin B12) 872, 874 8-Amino-7-oxo-nonanoate 718, 742 Aminopeptidase(s) 117, 609, 627 p-Aminopropionitrile 438 Aminopterin, inhibition of dehydrofolate reductase 805... 

Osteolathyrism is a disease characterized by lameness, skeletal deformities, aortic aneurysms, and slowing or cessation of body growth. Certain aminonitriles are known to cause osteolathyrism in several animal species aminoacetonitrile, 3-aminopropionitrile, and 3-amino-2-methylpropionitrile are potent inducers of this disease. It is believed that the basis of their ability to cause osteolathyrism is due to their ability to inhibit lysine oxidase, an enzyme important in cross-linking of collagen and formation of connective tissue. While no reports of these substances causing osteolathyrism in humans have appeared, it seems plausible that these substances could cause this disease in humans because they are known to cause it in a variety of experimental animals. 

Direct reaction of hydrocyanic acid with ethyleneimine does not yield the desired p-aminopropionitrile (68). However, ring opening of tosylated aziridines to give the corresponding tosylated p-aminopropionitriles is possible using trimethylsilyl cyanide [7677-24-9] with lanthanoid tricyanide catalysis (69,70). 

Covalent cross-links both between and within the tropocollagen molecules confer strength and rigidity on the collagen fiber. These cross-links are formed between Lys and its aldehyde derivative allysine. Allysine is derived from Lys by the action of the copper-containing lysyl oxidase which requires pyridoxal phosphate for activity. The disease lathyrism is caused by the inhibition of lysyl oxidase by the chemical (3-aminopropionitrile in sweet pea seeds, and results in defective collagen due to the lack of cross-links. 

D. Kumar, et al., Allylamine and beta-aminopropionitrile induced vascular injury An in vivo and in vitro study. Toxicol. Appl. Pharmacol. 103 288-302, 1990. 

Alanine has been prepared by the catalytic reduction of cyanoacetic esters 1 or salts 2 by heating acrylonitrile,3 /3-amino-propionitrile,4 iw-(/3-cyanoethyl)-amine,5 /3-hydroxypropionitrile, /3-alkoxypropionitriles,7 u.s-(/3-cyanocthyl) ether,8 or bis-(fi-cyano-ethyl) sulfide 8 with aqueous ammonia at 150-225° by the hydrolysis of /3-aminopropionitrile with concentrated hydrochloric acid and subsequent removal of the acid with anion exchange resins.9 The method as described above has been published.10 Additional references to methods of preparation are given in connection with a procedure for the making of /3-alanine from suc-cinimide through the action of potassium hypobromite.11... 

Aminopropionitrile and bis-(fi-cyanoethyl)-amine have been made by the addition of anhydrous 2-3 or aqueous4 ammonia to acrylonitrile. 

In lathyrism, the /3-aminopropionitrile inhibits cross-linking generated by lysyl oxidase. 

Cotter MA, Policz DL, Poch G, Dawson DA. 2000. Analysis of the combined osteolathyritic effects of beta-aminopropionitrile and diethyldithiocarbamate on Xenopus development. Toxicol Sci 58 144-152. 

These "suicide reagents" will be described in detail elsewhere in this volume (44), so only one phase will be briefly mentioned here. Of particular interest to food and nutrition researchers are the naturally occurring toxins which involve a "suicide" mechanism (42). Some of these can be consumed in foods or feeds and commonly occur in a number of different plant sources. A very common toxin is the beta-aminopropionitrile present in lathyritic legumes, and another is the wildfire toxin (42) (Figure 21). 

Figure 3. Lysyl oxidase. The enzyme, lysyl oxidase, appears to seek out lysyl residues in alanyl- and lysyl-rich regions in the pro fibrillar forms of elastin. The presence of an aromatic amino acid residue adjacent to lysine appears to block its oxidation. The product of oxidation is peptidyl a-aminoadipic-S-semialdehyde. Assays for the enzyme against elastin involve first the preparation of an elastin-rich pellet containing 3H-lysyl residues labeled in the 6 or 4,5 position. This is usually accomplished by incubating embryonic chick aortas in medium containing 3H-lysine plus f3-aminopropionitrile (BAPN) to inhibit endogenous lysyl oxidase activity. BAPN is then removed leaving behind an elastin-rich residue in which the profibrillar forms of elastin labelled with 3H-lysine are only partially crosslinked. When lysyl oxidase preparations are added to this residue the release of tritium represents the assay for activity. It has also been demonstrated that tropoelastin, when incubated with lysyl oxidase, forms a-aminoadipic-S-semialdehyde and eventually crosslinks as shown in Figure 4.

Meyers and co-workers141 have recently reported an improved method for obtaining enaminoketones from j8-aminonitriles instead of j8-amino esters (Scheme 8). The enamines, which are easily obtained from ]8-aminopropionitriles, yield the amino dihydropyrindinium salt (210) on warming with anhydrous magnesium perchlorate or magnesium iodide in benzene or toluene. It was proposed that the role of magnesium... 

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