NOTES
Srptember 19B.j
699
TABLE I Yield,
B.p. (mm.) or m.p.. O C .
Formula 7c 81" 72-75(0.08) CI?H?IN?
Compd.
a ,a-l)iisopropyl-a-( 2-dimethylamino-
ethy1)acetonitrile ( I ) 82' a-Diisopropyl-a-( 2-dimethylaminoethy1)acetamide (11) a-Isopropyl- a-(2-dimethylaminoethyl)-l- 62" naphthylpropionit.rile (111) (jib a-Isopropyl-a-( 2-dimethylnminoethyl)-Inaphth?.lpropionamide (IT) -.>a i.> a-( 2-Dimet hylaminoet hyl)-2-naphthylacetonitrile (T) 81" a-Isopropyl-e-( 2-dimethylaminoethyl-2naphthylacetonitrile ( V I ) 63' a-Isopropyl-a-( 2-dimethylaminoet hy1)-2naphthylacetamide (VII) a-Isopropyl-~-(2-dimethylaminoethyl)-l96' naphthylacetamide methobromide (1'111) I-Dimethylamino-3-phenyl-4-hexanoneC 61" (IX) c Reported by a Once distilled. b Crltde produrt. mm.), yield 51.2%.
1 1 1-1 12
.I. A m . Chrm. S o r . , 36, 800
(1913).
--
Found,
%--7
x C H N 73.41 12.32 14.27 73.51 12.36 14.13 67.24 12.23 13.07 67.29 12.33 12.91
81.58 8.90 9.58 81.74 8.87 9.40
128.5-129.5 C,oH?,N?O
76.88 9.03 8.97 76.i4 8.94 8 . 9 3
154-155 (0.3) Cie,HisN?
80.63 7.61 11.76 80.69 7.65 11.64
142-144(0.1)CigH?4N?
81.38 8.63 9.99 81.25 8.56 10.05
122.5-123.5 C19H26K20
76.47 8.78 9.39 76.38 8.85 9.32
171-173
CnoH29Br?;20 61.06 7.43 7.12 61.12 7.33 7.08
97-99 (0.5)
C14H?ISO
76.66 9.65 6.39 76.78 9.73 6.39
F. F. Blicke and E.-P. Tsao, J . .Zm.Chern. Soc., 75, 5587 (1953),b.p. 90-92O (0.n
a-Carbethoxv-a-isooroovl-1 -. -naohthvlorooionitrile.-Ethvl - -- ~-isopropylcyanoacetate5 (155.2 g., 1 mole) was added with stirring to a solution of sodium (25.3g., 1.1 g.-atoms) in anhydrous ethanol (600 ml.). After the exothermic reaction had subsided, the mixture was refluxed overnight, and then cooled. The NaCl was filtered off, and the solvent was removed under reduced pressure. The oily residue was dissolved in ether, and the solution was washed with water and dried (Na~S04). The solvent was removed under reduced pressure and the residue was distilled a t 162-164"(0.3mm.) to give 233.4g. (79%) of a viscous colorless oil. Anal. Calcd. for C,sH21N02: C, 77.26;H, 7.17;N, 4.74. Found: C, 77.32;H, 7.23;N, 4.80. a-Isopropyl-l-naphthylpropionitrile.-a-Carbethoxy-a-isopropyl-1-naphthylpropionitrile(233.4g., 0.79mole) was hydrolyzed by refluxing for 32 hr. with ethanol (70ml.) and 35% KOH (565g.). The mixture was then diluted with water (500 ml.), washed with ether, and acidified with 1 : 1 HC1. The precipitated pasty product was extracted a i t h ether, and the extract was washed with water and dried ( l I g S 0 4 ) . Removal of the solvent under reduced pressure yielded 191 g. (90.6TC) of crude a-carboxy-a-isopropyl-1-naphthylpropionitrile, which was decarboxylated without purification by heating at 200' in the presence of powdered copper (1 g.). After about 10 hr. the evolution of CO2 practically ceased; the residue was distilled a t 134-135' (0.15mm.) to give 149.2g. (93.4%) of a viscous colorless oil. Anal. Calcd. for C16H17N: C, 86.05; H , 7.67; X, 6.27. Found: C,86.16;H, 7.70;N, 6.24. a-Isopropyl-a-(2-dirnethylaminoethyl)-l-naphthylpropionitrile (III).-a-Isopropyl-1-naphthylpropionitrile (149.2g., 0.668 mole) was alkylated with 2-( N,N-dimethylamino)-1-chloroethane (143.6g., 1.336moles) in the presence of sodium (30.7g., 1.336 g.-atoms) dissolved in liquid ammonla (1.2l.), following a procedure quite similar to that described for I. The reaction time was 30 hr., and the product obtained was a colorless oil, b.p. 151-153' (0.15mm.). a-Isopropyl-a-(2-dimethylaminoethyl)-1 -naphthylpropionamide (IV).--Hydrolysis of I11 (29.4g., 0.1mole), accomplished ( 5 ) .T. C, HesslPr,
%---
H
161-153 (0.15)C,oH,,X?
The ethereal layer was extracted a i t h 105 HCI, the acid solution was treated with charcoal, filtered, made basic t o phenolphthalein with 30% NaOH, and the separated oil was extracted with ether. The ethereal solution was dried (MgSOd), and the solvent mas removed under reduced pressure. Distillation of the residue at 72-75' (0.08mm.) yielded a colorless liquid. ~,~-Diisopropyl-~-(2-dimethylaminoethyl)acetamide (111.Hydrolysis of I (23 g., 0.11 mole), accomplished by heating for 18 hr. at 90-95" with 85% H2S04(70 ml.), yielded a solid which after crystallization from ethyl acetate gave colorless crystals, m.p. iii-112°.
-
C,?H?6K?0
--Calcd., C
.\pproa.
Compd.
I I1 I11 IT
ITI 1-11 VI11 IX llorphine .HC1 Phenylbutazone
LDsu (mouse), mg./kg. i.p.
120-150 380-400 250-300 120-140 130-160 110-140 40-70 100-130 110-140
Analgesic act. (moiise) Reaction time, inc., mg./kg. % i.p.
18 48 160 109 47 61 30 17 36 67
dntiinflammatory act. (rat) Edema inhib., mg./kg.
%
P.O.
25 39 25 200 34 200 50 30 50 100 42 100 25 18 25 25 21 25 25 20 25 2.5 Inactive 2
