Allylamine

TABLE 9-3 Acute Toxicity of Allylamines in Rats and Rabbits 

Allylamine (Monoallylamine, 3-Aminopropylene, 3-Aminopentene) Molecular formula CH2=CHCH2NH2 

Uses Allylamine is applied in different industries as a solvent. It also is used in the preparation of diuretics, sedatives, and antiseptics.32 

Toxicity Allylamine has caused adverse effects in animals and humans with irritation to eyes, skin, and mucous membranes. Reports on cardiovascular toxicity due to allylamine exposure in species of animals is not confirmatory, 31,46 48 

Uses Cyclohexylamine is a strong inflammable liquid with a fish-like odor. It has many applications in both household and industrial processing (e.g., a corrosion inhibitor in water boilers, the synthesis of pesticides, dry-cleaning soaps, the manufacture of plasticizers, textile chemicals, cyclamates (artificial sweeteners), dyestuffs).41,49 

In a 5-I. round-bottomed flask, equipped with a reflux condenser connected to a gas trap (Note 1), are placed 2 1. (12.r moles) of 20 per cent hydrochloric acid and 500 g. (5.05 moles) of allyl isothiocyanate (Note 2). The mixture is refluxed over a free flame until the upper layer of allyl isothiocyanate has completely disappeared, about fifteen hours being required for the hydrolysis. When the reaction is complete, the solution is -poured into a 3-I. beaker and concentrated on the steam bath until crystals begin to form in the hot solution. This occurs when the volume is approximately 400 cc. (Note 3). 

The warm residue is then diluted with water to a volume of 500-550 cc. and placed in a 2-1. three-necked, round-bottomed flask equipped with a 500-cc. dropping funnel, a mercury-sealed mechanical stirrer, and a condenser arranged for distillation. The lower end of the condenser is fitted to a receiver consisting of a 500-cc. suction flask, whose side arm is connected to a reflux condenser (Note 4). The receiver is placed in an ice-salt bath and the three-necked flask in a water bath. The temperature of the water bath is raised to 95-98°, the stirrer is started, and a 

The distillate is then dried over solid potassium hydroxide for twenty-four hours and finally over metallic sodium (Note 5). The allylamine is distilled from a water bath held at 70-78°, through a 12-in. fractionating column, and into a receiver immersed in an ice bath, the following fractions being collected up to 54°/746 mm., and S4-S7°/746 mm. The lower fraction amounts to 14-16 g., and on redistillation yields 6-8 g. of pure material. The total yield of pure aEylamine boiling at 54—570/ 746 mm. is 200 -210 g. (70-73 per cent of the theoretical amount). 

It is desirable to use a gas trap in order to prevent vapors of allyl isothiocyanate from escaping into the room. The gas trap described in Org. Syn. Coll. Vol. 1, 91, is suitable. 

Eastman s practical grade (b. p. 150-152°) of allyl isothiocyanate was used in this preparation. 

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The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

The facile cyclopalladation of allylamine proceeds due to a chelating effect of the nitrogen. In MeOH, methoxypalladation take.s place to give the five-mem-bered chelating complex 507[460). The CO Insertion takes place readily in EtOH, giving ethyl 3-methoxy-4-dimethylaminobutyrate (508) in 50% yield[461). The insertion of alkenes also proceeds smoothly, giving the ami-noalkenes 509[462],... 

The carbopalladation of allylamine with malonate affords the chelating complex 510, which undergoes insertion of methyl vinyl ketone to form the amino enone 511[463]. The allylic sulfide 512 has the same chelating effect to give the five-membered complex 513 by carbopalladation[463.464]. 

Allylic amines are coupled to halides giving either allylic amines or enamines depending on the reaction condition. Reaction of steroidal dienyl triflate with Boc-diprotected allylamine affords allylamine. Use of AcOK as a base is crucial for the clean coupling[102]. The tert-allylic amine 123 reacts with an aryl halide to give the enamine 125 in DMF and allylic amine 124 in nonpolar solvents[103]. 

Preparation of primary allylamines by the selective monoallylation of ammonia is not possible and they are prepared by indirect methods. The monoallylation of Li and Na amides of di-/-butoxycarbonyl (Boc) (305), followed by hydrolysis, affords a primary allylamine (306)[184],... 

The secondary allylic methylamine 324 can be prepared by the allylation of A -methylhydroxylamine (323), followed by hydrogenolysis[201], Monoallylation of hydroxylamine, which leads to primary allylamines, is achieved using the jV,0-bis-Boc-protected hydroxylatnine 326. N -... 

Allylamines are not easily cleaved with Pd catalysts, but the carbonylation of the allylic amine 395 proceeds at 110 C to give the /3,7-unsaturated amide 396 by using dppp as a ligand[252], Dccarboxylation-carbonylation of allyl diethyl-carbamate under severe conditions (100 C, 80 atm) affords /3,7-unsaturated amides[2531. The 3-vinylaziridine 397 is converted into the a-vinyl-J-lactam 398 under mild conditions[254]. 

Allylamines are difficult to cleave with Pd catalysts. Therefore, amines are protected as carbamates, but not as allylamines. Also, allyl ethers used for the protection of alcohols cannot be cleaved smoothly, hence alcohols are protected as carbonates. In other words, amines and alcohols are protected by an allyloxycarbonyl (AOC or Alloc) group. 

Synthetic Polymers. Examples of polymers in this class include acrylamide—acryHc polymers and their derivatives, polyamines and their derivatives, poly-(ethylene oxide), and allylamine polymers. 

Use of HRh(CO)[P(CgH )2]3 as the catalyst and an excess of triphenylphosphine improves the y P ratio. For example, reaction of triethoxysilane with allylamine of equivalent moles at 150°C for 10 h, yields the y-form product ia more than 70% and the y P ratio is 26. Compared with this, when H2PtCl3 is used as the catalyst, the y P ratio is 4 (41). Furthermore, when Rh[(p.-P(C3H3)2-(cyclooctadiene)]2 is used as the catalyst, the yield of y-form product is selectively increased to 92% and that of P-form product is decreased to 1.1% (42). 

Allylamine. This amine can be synthesized by reaction of aHyl chloride with ammonia at the comparatively high temperature of 50—100°C (49), or at lower temperatures using CUCI2 or CuCl (51) as the catalyst. In aH such methods, a mixture of monoaHyl, diaHyl, and triaHyl amines is obtained. 

Pyrrohdinone (2-pyrrohdone, butyrolactam or 2-Pyrol) (27) was first reported in 1889 as a product of the dehydration of 4-aminobutanoic acid (49). The synthesis used for commercial manufacture, ie, condensation of butyrolactone with ammonia at high temperatures, was first described in 1936 (50). Other synthetic routes include carbon monoxide insertion into allylamine (51,52), hydrolytic hydrogenation of succinonitnle (53,54), and hydrogenation of ammoniacal solutions of maleic or succinic acids (55—57). Properties of 2-pyrrohdinone are Hsted in Table 2. 2-Pyrrohdinone is completely miscible with water, lower alcohols, lower ketones, ether, ethyl acetate, chloroform, and benzene. It is soluble to ca 1 wt % in aUphatic hydrocarbons. 

Formation of Amines. Mono-, di-, and triaEyl amines are prepared by reaction with ammonia. The ratio of reagents determines product distribution with sufficient time and excess of aEyl chloride, tetraaEylammonium chloride [13107-10-3] and triallylamine [102-70-5] predominate. Mixed amines are prepared in similar fashion by using a substituted amine in place of ammonia they may also be prepared with allylamine [107-11-9] and a suitable organic chloride. 

Hexaazadecalin PE, 3, 543 <75CB1557> Hexakis(benzotriazolyl)hexakis(allylamine)-trisnickel(ll) triphenylphosphine oxide X-ray, 5, 675 <76AX(B)714>... 

Synthesis of E allylamines from vinylphosphomum saRs and aldehydes (via WRtig reaction)... 

Allylamines have been used as nitrogen protective groups. They can be removed by isomerization to the enamine (t-BuOK, DMSO) or by rhodium-catalyzed isomerization. ... 

Several chemical compounds may cause inflammation or constriction of the blood vessel wall (vasoconstriction). Ergot alkaloids at high doses cause constriction and thickening of the vessel wall. Allylamine may also induce constriction of coronary arteries, thickening of their smooth muscle walls, and a disease state that corresponds to coronary heart disease. The culprit is a toxic reactive metabolite of allylamine, acrolein, that binds covalently to nucleophilic groups of proteins and nucleic acids in the cardiac myocytes. 

Figure 6.29 (page 205) shows the ehromatogram of poly(allylamine hydro-ehloride) using the Asahipak GF-HQ series. The peak shape is affected by ehanging the ionie strength. It was eonfirtned that the best peak shape is obtained when the eoneentration of LiCl in the eluent is 250 mM. 

FIGURE 6.29 Poly(allylamine hydrochloride). Column Shodex Asahipak GF-7I0 HQ + GF-5I0 HQ + GF-310 HQ. 7.6 mm i.d. x 300 mm x 3. Eluenc LiCI aqueous solution. Flow rate 0.6 mL/min. Detector Shodex Rl. Column temp. 50°C. Sample I %, 50 /cL Poly(allylamine hydrochloride). 

More commonly a combination of techniques is used as illustrated by the following study. The reaction is the acylation of allylamine by rrans-cinnamic anhydride, Eq. (2-34). 

The initial anhydride concentration was about 3 x 10 M, and the amine concentration was much larger than this. The reaction was followed spectrophoto-metrically, and good first-order kinetics were observed hence, the reaction is first-order with respect to cinnamic anhydride. It was not convenient analytically to use the isolation technique to determine the order with respect to allylamine, because it is easier to observe the cinnamoyl group spectrophotometrically than to follow the loss of amine. Therefore, the preceding experiment was repeated at several amine concentrations, and from the first-order plots the pseudo-first-order rate constants were determined. These data are shown in Table 2-1. Letting A represent... 

Treatment of allylamines with potassium amide on alumina causes their isomerization to enamines in good yields (124b). When allylamines are heated to about 55° the same type of isomerization takes place (I24c). 

Allyl groups are subject to oxidative deprotection with Chromiapillared Montmorillonite Clay, -BuOOH, CH2CI2, isooctane, 85% yield. Allylamines are cleaved in 84—90% yield, and allyl phenyl ethers are cleaved in 80% yield. 

Pd(Ph3P)4, RS02Na, CH2CI2 or THF/MeOH, 70-99% yield. These conditions were shown to be superior to the use of sodium 2-ethylhexanoate. Methallyl, crotyl, and cinnamyl ethers, the Alloc group, and allylamines are all efficiently cleaved by this method. ... 

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