382
KEVILL,COPPENS, COPPENS, AND CROMWELL
Experimentalg Phenyl Glycidyl Ether.-To a mixture of 84 g. (1.0 mole) of phenol and 370 g. (4 moles) of epichlorohydrin was added dropwise with stirring during 1 hr. a t room temperature 54 g. (1.0 mole) of sodium methylate in 400 ml. of methanol, and the mixture was stirred for an additional 1 hr. After removal of epichlorohydrin, the residue was distilled under reduced pressure to obtain 115 g. (777,) of phenyl glycidyl ether, b.p. 102' (5mm.). Urethanes.-Urethanes were prepared by two methods: (A) an addition reaction of the corresponding isocyanates and alcohols, and (B) a condensation reaction of the corresponding amines arid ethyl chlorocarbonate. Examples follow. N-Phenylmethylurethane (Methyl Phenylcarbamate) .-To a solution of 32.0 g. (1.0 mole) of methanol and 0.1 g. of triethylamine in 100 ml. of benzene was added dropwise with stirring during 1 hr. a t 50" 59.5 g. (0.5 mole) of phenyl isocyanate in 300 ml. of benzene; the mixture was heated for an additional hour. After removal of benzene, the residue was recrystallized from ether-petroleum ether (b.p. 30-60") to give 68.5 g. (90yo) of phenylmethylurethane, m .p. 48-49 O . N-p-Chlorophenylethy1urethane.-To a solution of 21.7 g. (0.2 mole) of ethyl chlorocarbonate in 150 ml. of benzene was added with stirring a t 10" 25.5 g. (0.2 mole) of p-chloroamiline and 20.2 g. (0.2 mole) of triethylamine in 200 ml. of benzene, and the mixture was allowed to stand for 3 hr. After filtering the triethylamine hydrochloride and removal of the benzene, the crystalline solid was recrystallized from cyclohexane to give 30.5 g. (76%) of p-chlorophenylethylurethane, m.p. 67-69'. (9) Melting points and boiling points are uncorrected. Microanalyses were performed in the Laboratory of Organic Chemistry, Tokyo Institute of Technology.
VOL.29
Ureas.-Ureas were prepared by addition reactions of corresponding isocyanates and primary or secondary amines. N-Phenyl-N',N'-diethy1urea.-To a boiling solution of 23.9 g. (0.2 mole) of phenyl isocyanate in 100 ml. of benzene was added dropwise with stirring 14.6 g. (0.2 mole) of diethylamine in 100 ml. of benzene; this was heated under reflux for an additional hour. After removal of benzene, the residue was recrystallized from ether to give 30.2 g. (79%) of N-phenyl-","-diethyl urea, m.p. 86-88'. 3-Phenyl-5-phenoxymethyl-2-oxazolidone. A. From Phenylmethylurethane and Phenyl Glycidyl Ether.-A mixture of 15.1 g. (0.1 mole) of phenylmethylurethane, 15.0 g. (0.1 mole) of phenyl glycidyl ether, and 0.1 g. of triethylamine was heated a t 90" for 15 min. After cooling, the adduct was recrystallized from acetone to give 24.5 g. (91%) of 3-phenyl-5-phenoxymethyl2-oxazolidone, m.p. 139-140". A mixture melting point with an authentic sample showed no depression. I n the infrared spectrum there was found an absorption band a t 1740 cm.-' for C=O and no absorption band arising from N-H, 0-H, and an epoxy group was recognized. Anal. Calcd. for ClsHlsOJN: C, 71.38; H, 5.58; N, 5.20; mol. wt., 269. Found: C, 71.34; H, 5.54; N , 5.47; mol. wt., 258. B. From N-phenyl-N',N'-diethylurea and Phenyl Glycidyl Ether.-A mixture of 9.6 g. (0.05 mole) of N-phenyl-","diethylurea, 15.0 g. (0.1 mole) of phenyl glycidyl ether, and 0.1 g. of triethylamine was heated a t 90' for 1 hr. , The resulting oily viscous substance was recrystallized from acetone to give 11.0 g. (81%) of 3-phenyl-5-phenoxymethyl-2-oxazolidone.After removal of acetone from the filtrate, the viscous oily residue was a mixture of 3-phenyl-5-phenoxymethyl-2-oxazolidone and N,Ndiethyl-2-hydroxy-3-phenoxypropylamine,the infrared spectra of which was identical with that of an authentic sample.
Reactions of 2-Bromo-2-(a-halogenobenzyl)-l-indanones DENNISX. KEVILL,'~ GUILLAUME A. COPPENS,MIREILLECOPPENS,AND NORMAN H. CROMWELL'~ Avery Laboratory, University of Nebraska, Lincoln, Nebraska Received J u n e 27, 1963 Reactions of 2-bromo-2-( a-bromobenzyl)-1-indanone ( I ) and 2-bromo-2-( or-chlorobenzy1)-1-indanone (IV) have been investigated. With nucleophilic reagents, three types of reaction have now been established. The cis and trans isomers of 2-( a-chlorobenza1)-1-indanone (111) have been prepared and separated. Structural assignments have been strengthened by an examination of the proton magnetic resonance spectra of deuterated derivatives.
indanone. Reaction with piperidine in acetonitrile It has long been known that 2-bromo-2-( a-bromoleads to a product no part of which can be extracted by benzyl)-1-indanone (I) is readily debrominated to give acid and which on recrystallization gives a 5Oy0 yield 2-benzal-1-indanone (11).za Suitable reagents are, of 11. Reaction of I with N-methylpiperidine in benfor example, ethanolic solutions of sodium hydroxide, zene proceeds with precipitation of N-methylpiperidine sodium acetate, or potassium iodide. More recently hydrobromide and on work-up a good yield of 2-benzalconditions have been found which lead, in addition to 1-indanone is obtained. 11, to substantial yields of 2-benzal-1-indanones substituted in the 3-position; these products are formed Reaction of I with tetraethylammonium bromide in by endocyclic dehydrobromination followed by an acetonitrile at 75" leads to a 95% yield of the debromallylic s u b s t i t u t i ~ n . ~ ~ ~ ~ ination product, 11. Reaction of I with excess tetraFurther reactions of I have been investigated. In ethylammonium chloride in acetonitrile a t 90' differs most instances I1 has been found as the favored prodmarkedly from the bromide ion-promoted reaction in uct. In one instance a third type of product, involving that it leads to an 80% yield of a mixture of cis- and replacement of the bromine to the carbonyl group trans-2-(a-chlorobenzal)-l-indanone @lye IIIa and accompanied by exocyclic dehydrobromination, is 19% IIIb). Reaction for a longer period of time and formed in good yield. with a reduced chloride ion concentration leads to Reaction of I with piperidine in benzene is k n o ~ n ~ some ~ , ~ tar formation and to some accompanying 2to lead to a good yield of 3-piperidino-2-benzal-lbenzal-1-indanone (TI). The addition of bromine chloride to alp-unsaturated (1) (a) Department of Chemistry, Northern Illinois University, DeKalb, carbonyl compounds is established4 as proceeding via Ill.: (b) to a h o m communications concerning this paper should be ad1,4-addition with chlorine entering the 4-position. In dressed. (2) (a) F. S. Kipping. J. Chem. Soc., 66, 499 (1894) (b) N. H. Cromwell this way 2-bromo-2-(a-chlorobenzy1)-1-indanone (IV) ~
and R . P. Ayer, J. A m . Chern. S o c . , 81, 133 (1960). (3) B. D. Pearson, R . P. Ayer. and N. 13. C r o m a e l l . J . O w . Chem., 17, 3038 (1962).
(4) E. P. White and P. W. Robertson, J . Chem. Soc., 1509 (1939).
FEBRUARY, 1964
REACTIONS O F %BROMO-%( a-HALOGENOBENZYL)-l-INDANONES
was prepared from 2-benzal-1-indanone (11). Compound IV reacted with tetraethylammonium chloride in acetonitrile to give, after recrystallization, a 78% yield of IIIa. When the reaction was repeated using tetraethylammonium radiochloride (NEt4ClaS), the product I11 isoIated showed a quantitative uptake of Class The cis and trans isomers of 2-(a-chlorobenzal)-lindanone (111), as formed from I, were separated by column chromatography. The proton magnetic resonance spectra of IIIa and IIIb differ, among other aspects, in the position of the signal for the methylene protons, 7 6.03 for IIIa and 6.23 for IIIb. Ultraviolet irradiation of a deuteriochloroform solution of IIIa followed by analysis of the proton magnetic resonance spectrum showed an equilibrium mixture of 75% IIIa and 25% IIIb. Similarly, equilibration by hydrogen chloride in deuteriochloroform leads to 83% IIIa and 17% IIIb. The acid-catalyzed equilibration concentrations are almost identical with the product ratios obtained under the acid conditions in which 111 is formed from I. It appears that the product ratio of IIIa to IIIb, as formed from I, is governed by thermodynamic and not kinetic control. The ultraviolet spectrum of IIIa includes Amax 301 mp ( e 17,900), corresponding to a Amax 314 mp ( 6 34,900) for IIIb. On this basis I I I b is tentatively assigned the trans arrangement of phenyl and carbonyl groups and IIIa the corresponding cis arrangement. The higher melting point of IIIb (105-106.5') relative to IIIa (7&71.5') is consistent with this assignment.6 Treatment of 2- (a-chlorobenzal) - 1-indanone (IIIa) with piperidine in benzene leads to an oil, probably a mixture of cis- and trans-2-( a-piperidinobenza1)-1indanone. The oil, unstable to heat, was hydrolyzed instantaneously by 20% sulphuric acid to give 2benzoyl-1-indanone (V). C1
20%
I
nm,
v Features of the proton magnetic resonance spectra of several derivatives of 2-benzyl-1-indanone are reported in Table I. Of particular interest is the fact that the product resulting from bromine addition to 2-(adeuteriobenza1)-1-indanone gives two doublets, corresponding to two methylene protons, with J a b = 18 C.P.S. Such a proton magnetic resonance spectrum is consistent only with formulation as Ia and not with the alternative Ib.3 Both Ia and Ib are feasible structures for explanation of the proton magnetic resonance spectrum of the nondeuterated dibromocompound since a methylene group of type CeH6( 5 ) For an excellent discussion of &-trans isomerism in a,@-unsaturated carbonyl compounds. see E. L. Eliel, "Stereochemistry of Carbon Compounds," McGraw-Hill Book Co., Inc., New York, N. Y . . 1962, Chap. 12.
383
TABLE I FEATURES OF THE PROTON MAGNETIC RESONANCE SPECTRA OF SEVERAL DERIVATIVES O F 2-BENZYLl-INDANONE' H a ,Hb
Yz
-?-Values Substituents
Hg .
relative t o tetramethylsilaneHaor H b Yi, Ya
X = Yi = Yg = Db X = Br,Y1 = Yz = H* X = Br, Y1 = Yz = Dc X = YI = Br,Yz = H e X = Y1 = Br, Y, = Dc
2.37 6.98,7.24 2.25 6 . 4 0 , 6 . 5 3 Y1 = YZ= 6 . 5 1 2.17 6.33,6.45 2 . 0 3 5 . 4 0 , 6 . 3 7 YZ = 4 . 2 0 2.03 5.40,6.33 X = B r , Y 1 = C 1 , Y 2 = H c 2.08 5.55,6.55 Y 1 = 4 . 3 0 a J a b = 18 C.P.S.(except X = B, Y, = Yz = H when J a b = 14 c.P.s.), Jar = 7 C.P.S. ( b ) Determined in carbon tetrachloride. (e) Determined in deuteriochloroform.
H Br
Br 0 Ia
Ib
CH2CR1R2R3, where R1# Rz # R3,can show a splitting pattern similar to the methylene group of Ia. Experimentale Reaction of I with Piperidine in Acetonitrile.-A solution of 0.50 g. of I and 3.0 g. of piperidine in acetonitrile was maintained, in a sealed tube, at 90' for 24 hr. Evaporation and extraction with benzene-isopropyl ether was followed by water washing. The solution was extracted with 1 N hydrochloric acid. Neutralization of the hydrochloric acid solution by sodium carbonate did no+lead to any precipitation. Evaporation of the benzene-isopropyl ether solution gave a product which on recrystallization from methanol gave 0.15 g. (50% yield) of 11. It was identified by mixture melting point with an authentic sample .7 Reaction of I with N-Methylpiperidine in Benzene.--,4 solution of 2.5 g. of I and 4.1 g. of N-methylpiperidine in 25 ml. of benzene was allowed to stand a t room temperature. After the solution had stood for 2 days, 0.2 g. of hygroscopic precipitate was filtered off and dried in z)acuo, yielding a product with m.p. (determined in sealed tube) 179- 181", m.m.p. (with N-methylpiperidine hydrobromide) 179-180". After 6 weeks, further precipitate was filtered off and the benzene solution extracted with 1 N hydrochloric acid. Neutralization of the hydrochloric acid solution with sodium carbonate did not lead to any precipitation. The benzene solution was evaporated to dryness to give a dark brown product whose proton magnetic resonance spectrum indicated it to be largely 2-benzal-l-indanone, accompanied by unidentified impurities. RecrystalIization from methanol-water gave pure 2-benzal-l-indanone, identified by infrared and ultraviolet spectra and mixture melting point. The proton magnetic resonance spectrum of 2-benzal-1-indanone shows the aromatic proton @ to the carbonyl a t 7 2.08 ( J = 7 c.P.s.), eight aromatic and the vinylic proton represented by peaks in the range 7 2.2-2.8, and the methylene protons (6) Melting points were read with a calibrated thermometer. Ultraviolet spectra were determined with a Cary Model 11-MS recording spectrophotometer using reagent grade methanol solutions. Infrared spectra were determined with a Perkin-Elmer Model 21 double beam recording instrument employing sodium chloride optics and matched sodium chloride cells with carbon tetrachloride solutions. The proton magnetic resonance spectra were obtained with a Varian A-60 instrument using a trace of tetramethylsilane ( T 10.00) as internal reference. (7) A. Hassner and N. H. Cromwell, J. Am. Chem. Soc., 80,893 (1958).
384
KEVILL,COPPENS, COPPENS,A N D CROMWELL
as a characteristic doublet at T 5.96 ( J = 2 c.P.s.). The splitting is due to a long-range coupling with the vinylic proton. Consistent with this explanation, the methylene protons of 2-(adeuteriobenza1)-1-indanone are represented by a sharp singlet corresponding in intensity to two protons at T 5.97. This presents additional evidence that 2-benzal-1-indanone does not possess the alternative 2-benzyl-1-indone structure.8 I n the presence of a deuterium substituent in the ezo-benzylic methylene group, the prot'on magnetic resonance spectrum of 2-benzyl-llncione would show two nonequivalent protons, one vinylic and one methylenic. Reaction of I with Tetraethylammonium Bromide in Acetonitrile.-A solution of 2.5 g. of I and 4.0 g. of tetraethylammonium bromide was maintained, in a sealed tube, a t 75" for 2 hr. Evaporation to dryness, extraction with benzene, and evaporation of benzene leaves a product whose proton magnetic resonance spectrum indicates it to be almost pure Zbenzal-1-indanone (11). After recrystallization from methanol the identity was confirmed by mixture melting point. Reaction of I with Tetraethylammonium Chloride in Acetonitrile.-Asolutionof 6.1 g. of I and 4.0 g. of tetraethylammonium chloride in 30 ml. of acetonitrile was maintained, in a sealed tube, a t 90" for 60 hr. Evaporation to dryness, ether extraction, and evaporation of the ether layer left a brown oil which was chromatographed on alumina using benzene-petroleum ether (b.p. 60-70") as eluent. Obtained was a 50% yield of IIIa, followed by about 5% of IIIb, followed in turn by about 1870 of I1 (identified by mixture melting point). The cis(?)-2-(a-chlorobenzal)-l-indanone(IIIa) was recrystallized from methanol-water; m.p. 70-71.5'; A,, 301 mp (e 17,90Oj, 278 (sh, 14,900), 226 (8800); Ami, 243 mp (E 6000); YC-o 1711 (vs); YC-C 1620 (9) em.-'. The proton magnetic resonance spectrum shows the aromat,ic proton fi to the carbonyl at T 2.28, eight protons in the range T 2.3-2.8, and two methylene protons at T 6.03. Anal. Calcd. for ClsHi1OCl: C, 75.49; H, 4.36; C1, 13.93. Found: C, 75.56; H , 4.36; CI, 14.02. The trans(?)-2-(a-chlorobenza1)-1-indanone, m .p. 105-106.5', has, , ,X 314 mp (e 34,900), 227 (14,500); Amin 247 m p (e 8200); The proton yc-0, 1707 (vs); yc=c, 1637 (s), 1617 (8) em.-'. magnetic resonance spectrum shows the aromatic proton fi to the carbonyl group at T 2.13, eight aromatic protons in the range T 2.3-2.8, and two methylene protons at T 6.23. When, in a sealed tube, 1.0 g. of I was heated for 2 hr. a t 90' with 10 g. of tetraethylammonium chloride and the solution evaporated t,o dryness, extracted with benzene, and the benzene solution evaporated to dryness, a crude product constituting an 807, yield of a mixture of cis and trans 111 waa obtained (81% IIIa and 19yc IIIb). Equilibration of cis- and trans-2-(~-Chlorobenzal)-l-indanone (IIIa and IIIb) .-Irradiation of a solution of IIIa in deuteriochloroform, contained in a Pyrex flask, by a B100-A "Blakray" ultraviolet source (Ultra-Violet Products, Inc.) over a period of 20 hr. leads to an equilibrium mixture of 75% of IIIa and 25% of I I I b as determined by a consideration of the relative intensities of the peaks in the proton magnet'ic resonance spectrum a t T 6.03 and 6.23. Similarly, when IIIa is allowed (for 7 hr.) to equilibrate in deuteriochloroform containing a trace of hydrochloric acid, the proton magnetic resonance spectrum indicates a mixture of 83% of IIIa and 1776 of IIIb. Conversion of 2-(a-Chlorobenzalj-1-indanone(IIIa) to 2Benzoyl-1-indanone (Vj.-A solution of 1.O g. of piperidine and
VOL. 29
0.50 g. of IIIa in 10 ml. of benzene was allowed to stand for 38 hr. and then refluxed for 4 hr. Addition of isopropyl ether precipitated 0.23 g. (96% yield) of piperidine hydrochloride. Evaporation to dryness gave an oil, unstable to heat, which was instantaneously hydrolyzed by 20% sulfuric acid to give 2-benzoylindanone,2bidentified by mixture melting point with an authentic sample and by ultraviolet spectrum. The oil, presumed to be 2-(a-piperidinobenzal)-l-indanone, has an ultraviolet spectrum in methanol with major peaks a t 263 and 392 mp and with minor peaks a t 292 and 301 mp. The positions of the major peaks are very similar to those for the known 2-(a-piperidinobenza1)-3,3dimethyl-1-indanone.3 2-Bromo-2-(a-chlorobenzyl)-l-indanone(IV).-To a solution of 1.1 g. of 2-benzal-1-indanone (11)in 10 ml. of acetic acid, maintained a t 50', was added dropwiae and with stirring about 5 ml. of a solution containing 26 g. of BrCl in 200 ml. of acetic acid. When a slight red color remained, addition was curtailed. Evaporation to dryness gave a yellow oil which on recrystallization from methanol gave 0.60 g. of crude product. A further recrystallization (from benzene-petroleum ether, b.p. 6&70") gave pure IV, m.p. 127-128'. Characteristics of the proton magnetic resonance spectrum of IV are included in Table I. Anal. Calcd. for C18H120BrCI: C, 57.25; H, 3.61; Br CI, 34.37. Found: C, 56.90; H, 3.86; Br C1, 34.61. Reaction of IV with Tetraethylammonium Chloride in Acetonitrile.-A solution of 0.50 g. of IV and 3.3 g. of tetraethylammonium chloride in 25 ml. of acetonitrile was maintained, in a sealed tube, a t 90" for 3 hr. Evaporation, extra'ction with benzene, and evaporation of the benzene gave a yellow oil. Recrystallization from methanol-water gave 0.30 g. (78QI, yield) of IIIa, identified by mixture melting point and proton magnetic resonance spectrum. A solution of 0.30 g. of IV and 0.80 g of NEt4C13ein 15 ml. of acetonitrile waa maintained, in a sealed tube, a t 90' for 3 hr. Evaporation to dryness, benzene extraction, several washings of the benzene layer with water, drying of the benzene layer over anhydrous magnesium sulfate, and evaporation to dryness gave a yellow oil. A 1.00-mi. portion of a 0.0286 M solution of the NEtaC1" in acetonitrile gave 3075 counts per minute, corresponding to 2150 counts per minute for a 0.0200 M solution. A solu-' tion of 5.1 mg. of product in 1.00 ml. of acetonitrile (0.0200 M ) gave 1567 counts per minute. For statistical distribution of Cl88 the predicted count is 1810 counts per minute and, since the product was counted in a crude condition, the agreement is fairly good. The counting technique has previously been described.8 Preparation of Derivatives Containing Deuterium.-Condensation of 1-indanone and deuteriobenzaldehyde (CeHsCDO) in the usual manner' gave 2-(a-deuteriobenzal)-l-indanone. A portion of this product waa deuterated a t atmospheric pressure using 10% palladium on charcoal as catalyst in carbon tetrachloride as solvent. A portion of this product waa then brominated in the position a to the carbonyl by the method of Leuchs.9 A further portion of 2-(a-deuteriobenzal)-l-indanone was treated with an equimolar amount of bromine in carbon tetrachloride and the bromine addition product was obtained.
+
+
Acknowledgment,-This work was supported in part by Grants G-14469 and G-20149 from the National Science Foundation. (8) D. N. Kevill, G A. Coppens, and N. H. Cromwell. J . Ow. Chem., (1963). (9) H. Leucha, J. Wutke. and E. Giealer, Ber., 48, 2200 (1913).
as, 567
