Allylamines

Butylamines have played a versatile role in the manufacturing industries of different day-to-day products. These include industries associated with textiles, leather tanning, pesticides, antioxidants and pharmaceuticals, photography, plastics, dyestuffs, and many other emulsifying agents. 

Toxicity Studies by Cheever et al.31,41,45 have indicated that n-Butylamine has caused toxicity to animals. The acute oral LD50 of male and female Sprague Dawley rats is 371 mg/kg. The vapors of n-Butylamine cause irritation to eyes and mucous membranes, as well as irritation and blistering effects to the skin of animals and humans.31,41,45 Workers exposed by direct skin contact to the liquid form demonstrated severe irritation of the skin in addition to deep second-degree bums and blistering. 

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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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