Synthesis of some 2-imino-4-oxazolidinones. VI. 5-Phenyl-2-cycloalkylamino-4-oxazolinones. Najer, Henry; Giudieelli, Rene; Menin, Jacques.
Bull. Soc. Chim. France (1963), (8-9), 1810-13.
Abstract
cf. CA 59, 589b. PhCHClCOCl (I) condensed with a cycloalkylurea gave N-cycloalkyl-N°-(a-phenyl-a-chloroacetyl)ureas, which cyclized in the presence of Na alcoholate to 5-phenyl-2-cycloalkylamino-4-oxazolines (II). The ultraviolet and infrared spectra of the II showed that the amino form predominates in the existing amino-imino tautomer equil. II (n = 1) (III) is a
much more active central nervous system stimulant than the most active 5-phenyl-5-alkylamino-4-oxazolinones. This activity disappears completely as soon as the cycloalkyl group contains more than 3 C atoms; it depends, therefore, partly on the no. of C atoms in the N-substituent and partly on its aliphatic or alicyclic character. Cyclopropylurea (17.6 g.), m. 124-5°, 21.3 g. Me2NPh, and 310 cc. dry C6H6 treated during 45 min. with stirring with 33.3 g. I in 130 cc. dry C5H6, kept 1 hr. at room temp., refluxed 5 hrs., cooled, and evapd., and the residual oil triturated 3 times with Et2O and then with 250 cc. H2O gave 24.7 g. N-cyclopropyl-N°-(a-phenyl-a-chloroacetyl)urea (IV), m. 134-5° (1:4 EtOH-hexane). Similarly prepd. were the following analogs of IV (N-substituent, % yield, and m.p., and m.p. of N-substituted urea used as starting material given): cyclobutyl, 55, 130-1, 173-4.degree.; cyclopentyl, 56, 133, 198-200°; cyclohexyl, 55, 160-1°, 200-2°; CH2CN2CH2, -, 84°, 149°; all recrystd. from EtOH. IV 16.6 g.) and 1.5 g. Na in 330 cc. abs. EtOH refluxed 2 hrs., filtered, and evapd., and the gummy residue triturated with 150 cc. H2O yielded 11.4 g. III, m. 139-40° (1:4 EtOH-hexane). Similarly prepd. were the following II (n, % yield, and m.p. given): 2, 61, 155-6°; 3, 50, 159-60°; 4, 70, 178 80°; all recrystd. from EtOH. 5-Phenyl-2-allylamino-4-oxazolinone, m. 123-4.degree., 50%, was prepd. in the same manner.
5-Aryl-2-cycloalkylamino-4-oxazolinones.Patent NL6613484
(It has the deatails)
Abstract
The title compds. of the formula I (R = Ph or p-C6H4Cl and R1 = H or Me) were prepd. by treating p-ClC6H4CHClCO2Cl (II) or PhCHClCO2Cl (III) with cyclopropylurea (IV) or N-cyclopropyl-N-methylurea (V) and treating the product (VI) with Na alcoholate. I are useful in prepg. psychostimulant, anorexigenic, or sedative compns. Thus, 39 g. II in 130 cc. C6H6 was added through a dropping funnel over 45 min. to a mixt. of 17.6 g. IV, 21.3 g. PhNMe2, and 310 ml. C6H6, after 1 hr., the mixt. refluxed 5 hrs., the oily residue poured out, the C6H6 distd., the residue washed 3 times in 100 ml. Et2O, and the Et2O evapd. in vacuo to yield 28.6 g. N-cyclopropyl-N'-[a-(p-chlorophenyl)-a-chloroacetyl]urea (VII), m. 132° (H2O). VII (28.7 g.) was dissolved in a soln. of 2.3 g. Na in 500 ml. EtOH, the soln. refluxed 2 hrs., and NaCl and alc. removed to give 18 g. I (R = p-C6H4Cl, R1 = H), m. 211°. I (R = Ph, R1 = Me) was also prepd. by treating V with III to yield N-cyclopropyl-N-methyl-N'-(a-phenyl-a-chloroacetyl)urea (VIII), and treating VIII with Na alcoholate.
I had strong stimulant effects on the central nervous system, a strong anorexigenic activity, and negligible cardiovascular activity.Tautomerism of 5-phenyl-2-alkyl(or aralkyl)imino-4- oxazolidones with 5-phenyl-2-alkyl(or aralkyl)amino-4-oxazolinones. Najer, Henry; Giudicelli, Rene; Menin, Jacques; Loiseau, Jacques.
Compt. Rend. (1962), 254 2173-5.
Abstract
cf. CA 55, 27268i. Refluxing PhClCHCOCl over (MeNH)2CO in C6H6, with Et3N present, gave H. Heating Me2NH with 2-imino-5-phenyl-4-oxazolidinone in EtOH in a sealed tube at 120° gave III. Unexpectedly, III proved to be a central nervous system stimulant, as were I but II was not. Comparison of the ultraviolet and infrared spectra confirmed the suspicion that I exist predominantly in the tautomeric aminooxazolinone (IV) forms. In alcohol, the l and log e, resp., are: II, 209, 4.24; III, 228, 4.43. The series IV: (R .dbd. Me), 221, 4.48; (R .dbd. Et), 221, 4.42; (R .dbd. Pr), 222, 4.46; (R .dbd. iso-Pr), 221, 4.44; (R .dbd. Bu), 223, 4.34; (R .dbd. Bz), 225, 4.48; (R .dbd. phenylisopropyl), 225 mm, 4.46. The infrared comparisons, limited to the bands of valence vibrations of CO and C: N bonds, assign conjugated double bonds to the tautomers for which these frequencies are lowered (Bellamy, The Infrared Spectra of Complex Molecules, 1954 (CA 48, 12562c)). Found for CO, C:N, resp.: II, 1765, 1700; III, 1730, 1630 cm.-1. The same decrease (CO, 1720-1745 and C:N, 1645-1680 cm.-1) is noted on comparison of the infrared spectra of IV with that of II.
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