Synthesis of N,O- and N,S-heterocyclic compounds by condensation of fatty acid alkylolamides with carbonyl compounds and phosphorous pentasulfide, respectively.

Abstract

Fatty acid N-alkylolamides were prepd. from the acid heated with an excess of amino alc. at 160-80° until the theoretical amt. of water had been distd. and recrystn. of the product from benzene or benzene-acetone, or by distn. The compds. were obtained in 85-98° yields (N-alkylolamide and b.p./mm. or m.p. given): N-(2-hydroxyethyl)propionamide (I), 134-7°/0.4; N-(2-hydroxyethyl)capronamide, 164-6°/1.3 (m. 44°); N-(2-hydroxyethyl)cyclohexanecarboxamide, 77.5-8.0°; N-(2-hydroxyethyl)benzamide, 189-91°/1.0 (m. 50°); N-(2-hydroxyethyl)-enanthamide, 174-6°/1.4; mono-Et ester of N-(2-hydroxyethyl)-monoadipamide, 130-1°; N - (2-hydroxyethyl)hexahydroterephthalamide, 235-8°; N,N'-bis(2-hydroxyethyl)terephthalamide, 231.3.5°; N-(2-hydroxyethyl)caprylamide, 68-71°; N-(2-hydroxyethyl)undecenamide, 60-2°; N-(2-hydroxyethyl)-lauramide, 84-5°; N-(2-hydroxyethyl)myristamide, 93-4°; N-(2-hydroxyethyl)stearamide, 101-3°; N-(2-hydroxyethyl)-oleamide, 57-8°; N-(2-hydroxypropyl)propionamide, 144-7°/0.8; N-(2-hydroxypropyl)capronamide, 155°/1.0 (m.p. 30-3°); N-(2-hydroxypropyl)caprylamide, 47-8°; N-(2-hydroxypropyl)-capramide, 58-9°; N-(2-hydroxypropyl)lauramide, 65-6°; N-(2-hydroxypropyl)myristamide, 70-2°; N-(2-hydroxypropyl)-undecenamide, -; N-(2-hydroxypropyl)oleamide, 155-60°/0.8; N,N'-bis(2-hydroxypropyl)adipamide, 118-19°; N-(2-hydroxypropyl)benzamide, 91-2°; N-(3-hydroxypropyl)propionamide, 143-9°/0.9; N-(2-hydroxypropyl)capronamide, 165°/0.2; N-(3-hydroxypropyl)enanthamide, -; N-(3-hydroxypropyl)caprylamide, 39-40°; N-(3-hydroxypropyl)capramide, 62-3°; N-(3-hydroxypropyl)lauramide, 75-6°; N-(1-hydroxy-2-butyl)propionamide, 130-1°/0.7; N-(1-hydroxy-2-butyl)-capronamide, 165°/1.0; N-(1-hydroxy-2-butyl)caprylamide, -; N-(1-hydroxy-2-butyl)capramide, 50.5-3.0°; N-(1-hydroxy-2-butyl)lauramide, 65-7°; N-(4-hydroxybutyl)propionamide, -; N-(4-hydroxybutyl)capronamide (II), 54-7°; N-(5-hydroxypentyl)propionamide, 173-5°/1.0. The N-(β-hydroxyalkyl) compds. were condensed with aldehydes and ketones in xylene soln. in the presence of acid catalysts such as p-toluenesulfonic acid, Bu4TiO4, or dry HCl, to give N-acyloxazolidines (III). In a typical prepn., 0.1 mole I was condensed with 0.22 mole BzH to give 41% III (R = EtCO, R1 = Ph, R2 = R3 = H), b0·1 125-7°. Other III prepd. by this method were (R, R1, R2, r3, b.p./mm. or m.p., % yield, and n20D given): caproyl, H, H, H, 101-3°/1, 70, 1.4688; caprylolyl, H, H, H, 126°/1, 75, 1.4679; caprinoyl, H, H, H, 145-6°/1, 74, 1.4651; lauroyl, H, H, H, 49-50°, 42, -; tetradecanoyl, H, H, H, 52-3°, 60, -; cyclohexylcarbonyl, H, H, H, 51-2°, 33, -; capryl, Me, H, H, 96-8°/1, 54, 1.4526; caprinoyl, Et, H, H, 156-8°/2, 63, 1.4648; capryl, Pr, H, H, 110-15°/1 0.0001, 48, 1.4680; capryl, iso-Pr, H, H, 180-1°/1.5, 44, 1.4661; octanoyl, iso-Pr, H, H, 125-6°/0.2, 48, 1.4669; caproyl, Pr, H, H, 105-6°/0.1, 75, 1.4671; heptanoyl, iso-Pr, H, H, 125-7°/0.6, 66, 1.4660; heptanoyl, Et, H, H, 125-7°/0.8, 47, 1.4681; decanoyl, 3-pentyl, H, H, 102-5°/0.001, 61, 1.4630; hexanoyl, Et. Me, H, 120-2°/1.5, 23, 1.4614; hexanoyl, Me, Bu, H, 138-42°/1.5, 29, 1.4580; decanoyl, Me, Pr, H, 140-4°/0.4, 34, 1.4688; hexanoyl, H, H, Me, 121-2°/2, 76, 1.4640; octanoyl, Me, H, Me, 78-80°/0.1, 26, 1.4480; benzoyl, H, H, Me, 137-9°/0.8, 65, 1.5521; octanoyl, H, H, Me, 69-74°/0.001, 70, 1.4658; EtCO, pentyl, H, Me, 99-100°/0.5, 75, 1.4631; decanoyl, iso-Pr, H, Me, 142-5°/0.8, 50, 1.4590; caproyl, Pr, H, Me, 118-20°/0.3, 57, 1.4623; EtCO, hexyl, H, Me, 115-17°/0.4, 71, 1.4613; isononanoyl, (isomeric mixt.), H, H, Me, 130-3°/2.5, 79, -; decanoyl, H, H, Me, 138-40°/1.0, 76, 1.4673; caproyl, iso-Pr, H, Me, 109-11°/0.6, 48, 1.4592; decanoyl, Me, H, Me, 128-30°/0.6, 22, 1.4563; octanoyl, Et, H, Me, 96-100°/10-3, 54, 1.4609; caproyl, 2-pentyl, H, Me, 139-40°/1.0, 44, 1.4637; dodecanoyl, H, H, Me, 122-6°/10-3, (m. 27-9°), 67, -; tetradecanoyl, H, H, Me, 140-3°/10-4 (m. 41°), 57, -; caproyl, Ph, H, Me, 144-9°/0.1, 77, 1.5170; decanoyl, Ph, H, Me, 190-2°/1.2, 46, 1.5070; dodecanoyl, Pr, H, Me, 127-30°/10-3, 74, 1.4652; oleoyl, H, H, Me, 166°/0.2, 60, 1.4743; stearoyl, H, H, Me, - (m. 54-7°), 43, -; decanoyl, Me, iso-Bu, Me, 118-20°/1.0, 26, 1.4531. The N-(3-hydroxypropyl)amides were used similarly to prep. tetrahydro-1,3-oxazines of general formula IV (R4, R5, R6, b.p./mm., % yield, and n20D given): decanoyl, H, H, 140-4°/0.2, 88, 1.4739,; lauroyl, H, H, 116°/10-4, 82, 1.4755; EtCO, H, H, 77°/0.5, 14, 1.4765; caproyl, H, H, 100-2°/0.4, 88, 1.4756; EtCO, Pr, H, 114-34°/0.5, 32, -; octanoyl, H, H, 117°/0.4, 66, 1.4735; EtCO, Ph, H, 122°/0.08, 73, 1.5328; caproyl, Me, iso-Bu, 123-5°/0.4, 24, -; octanoyl, Ph, H, 110°/0.002, 71, 1.5022. N-Hexanoylhexahydro-1,3-oxazepine, b0·4 112-15°, n20D 1.4788, was prepd, in 45% yield from II and paraformaldehyde. N-Hexanoyl-1-oxa-3-azacyclooctane, b0·003 72-6° n32D 1.4714, was similarly prepd. in 9% yield from N-(5-hydroxypentyl)capronamide. The N-(2-hydroxyalkyl)-and N-(3-hydroxypropyl)amides were condensed with P2S5, giving 2-thiazolines of general formula V and 4,5-dihydro-6H-1,3-thiazines of general formula VI. Compds. of formula V prepd. were (R7, R8, b.p./mm., % yield, and n20D given): pentyl, H, 59-60°/1, 67, 1.4961; heptyl, H, 85°/0.6, 68, 1.4912; isoheptyl (isomeric mixt.), H, 117°/2, 86, -; isooctyl (isomeric mixt.), H, 88-90°/2.5, 65, -; nonyl, H, 115-16°/15, 45, 1.4880; isododecyl (isomeric mixt.), H, 163°/1.5, 63, -; pentyl, Me, 104°/10, 76, 1.4895; Ph, Me, 99-100°/0.8, 90, 1.6005; heptyl, Me, 85-7°/0.6, 95, 1.4872; nonyl, Me, 110-12°/0.6, 88, 1.4840. Compds of general formula VI prepd. were (R9, b.p./mm., % yield, and n20D given): nonyl, 124°/0.5, 62, 1.4990; pentyl, 77°/0.5, 88, 1.5092; heptyl, 107°/0.8, 70, 1.5031; undecyl, 160°/1.0, 51, 1.4958; octyl, 107°/0.9, 66, 1.4982; hexyl, 92°/.5, 70, 1.5050. A no of these compds. showed bacteriostatic and fungistatic activity. [on SciFinder(R)]