26'3s
CALVIN
L.
STEVENS, MILTON
L.
flux temperature in a solution of 10 ml. of acetone, two drops of hydrochloric acid and enough water t o make the solution turbid. Evaporation of the solvents left the product as white crj-stals. Recrystallization from an ether-petroleum ether mixture gave 0.55 g. (62%) of a-hydroxyheptaldehyde dimer, m . p . 120-122". Anal. Calcd. for C7H1402: C, 64.57; 1-1, 10.84. Found: C, 64.09; H, 10.81. Reaction of the Epoxyether XI with Organic Acids.-A solution of 4 g. (0.03 mole) of the epoxyether XI in 20 ml. of anhydrous ether was cooled in an ice-bath and 6 g. (0.03 mole) of 3,5-dinitrobenzoic acid added slowly. The reaction mas allowed t o stand overnight a t room temperature. The ether solution was then quickly washed with 10% cold aqueous bicarbonate solution, dried with sodium sulfate aiid the ether removed with a water aspirator. The resultitig solid was recrystallized from an ether-petroleum mixture to give 7.85 g. (79%) of white crystalline acylal, l-methosy-
WEINER AND CARL
'r. LENK
Vol. 76
2-hydroxyheptyl 3,5-dinitrobenzoate (XIV), m.p. 86-87". Anal. Calcd. for C I ~ H ~ O O ~C, N ~50.56; : H, 5.W. Found: C, 50.16; H, 5.60. This pseudoester decomposed when heated above the melting point. From 4 g. (0.03 mole) of cposyether and 1.7 g. (0.0;j mole) of acetic acid bv a similar Drocedure was obtained 1 . 1 g. (73%) of the corresponding acylal, 1-methoxy-2-hydroxyheptyl acetate (XV), b.p. 73-77" (2 mm.), ?z% 1.4282. Anal. Calcd. for CtoHlOO4: C, 58.79; H, 9.87; OCI-I., 15.2. Found: C,58.23; H,9.62; OCH,, 14.8.
Acknowledgment.-The authors wish to thank Miss Phylis Tocco and Mr. Michael Papo for the microanalyses. DETROIT 1, MICHIGAN
[ C U N T K I U U I I U N FROM T l l E U E P A R T M E Y r OF CHE.MISI.RY U F \\IAYNE ~ N l V E R S lYl l
Epoxyethers. VIII. The Reaction of Epoxyethers with Grignard Reagents BY CALVIN L. STEVENS, MILTONL. W E I N E RAND ~ C.IRLT. LEXK? RECEIVED DECEMBER 8, 1053
/O\
Tlic reaction of a Grignard reagent with certain epoxyethers, which have the characteristic structurc Ar-C-CII--, OCHs has been shown to proceed to give two types of products. One product was a monomethyl ether of a substituted ethylene glycol that resulted from the attachment of the organic radical of the Grignard reagent to the carbon of the epoxide that contained the methoxyl group. The other product was an isomeric monomethyl ether of an ethylene glycol t h a t resulted first from rearrangement of the epoxyether to the methosyketone, Ar-CHOCH,-CO-, followed by addition of the Grignard reagent to the carboxyl group of this ketone.
Ordinary l12-epoxides are known to undergo 427* yield of l1l-diphenyl-l-methoxy-2-propanol ring-opening reactions with Grignard reagents. (111) could be separated. The structure of I11 was These ethylene oxides react less readily than car- proved by independent synthesis from 1,l-diphenylbony1 compounds with the Grignard reagent, and 1-methoxy-2-propanone4 (IV) by reduction with in many instances OH the reaction must be heated above the reCoI16Mg13r ~ ~ H c c H I , C--CI-I--CH, flux temperature of o - f 3 c ~ c l l 3 I ether. The most imOCII3 nortant comdication in this reaction is the rearrangement of the I ethylene oxide prior ./,hIgUry to addition of the Grignard reagent. 0 Epoxyethers have It LCH-C-C-CH~ k-C-CH, been shown in this in- ~ - ~ F I - - C - C H , + vestigation to react readily with Grignard OCHI reagents a t the reflux 1' teinperaturc of ether or below, but iii the examples stutlictl thc reaelioiis lithiuiii aluiiiiiiuin hydride iii 78% yield. 'lie arc coniplicntccl by rearrangcment of thc epoxy- formation of I11 from the epoxyether and tlic Grignard reagent is comparable to the normal ring-openetlicr. The epoxyether, 1-phenyl-1-methoxy-1 ,%epoxy- ing reactions with ethylene oxides. In this in~iropane(I) reacted readily with phenylmagnesium tance the carbon of the epoxide t h a t contains the bromide a t room temperature t o give 86% of a mix- methoxy group is most susceptible to attack by the ture of isomers from which a 24yo yield of crystal- nucleophilic reagent. (11) and a line 1,2--diphenyl-l-niethoxy-2-propanol The structure of I1 was proved by synthesis from ( I ) 4 t o m i c Energy Predoctoral Fellow, 1950-1932. Abstracted in 1-methoxy-1-phenyl-2-propanone (V), V could be part from t h e Doctoral thesis of 11. L. Weiner, W a y n e Univrrsity, prepared by the alcoholysis of the corresponding I'L;?.
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( 2 ) I'arke, I h v i s a n d C o m p 1 1 y Fellow, l!~.jl-lCl.j?. ( 3 ) Recently t h e literature concerned with t h e reaction of Grignard reagents with t h e oxirane ring has heen e x h a n s l i v r l y reviewed bv N ( > Gaylord a n d I?, I . Ijecker, C h i n lic;'r , 4 9 , 11:1 (t!lt51).
+
(4) T h e s t r u c t u r e of 1V has recently been proved in this L a b o r a t o r y b y synthesis from rr-methoxydiphenylacetonitrilea n d methylmacnesium iodide arid b y alcoholysis of the corresponding brornokctone. C . I,. Stevens a n d C. T . I m i k . J O Y # C h c m . . in press.
hray 20, 1054
REACTION OF EPOXYETHERS WITII GRIGNARD REAGENTS
2699
bromoketone and when treated with phenylmagne- ing of the epoxide ring with nucleophilic attack a t the carbon atom bearing the niethoxyl group. VI11 sium bromide gave a 63y0yield of II.5 The only reasonable route for the formation of I1 results from rearrangement of the epoxyether6 bein the original reaction mixture involves rearrange- fore addition. The rearrangement can be prement of the epoxyether I to V by the magnesium vented by allowing the epoxyether VI1 to react bromide of the Grignard reagent followed by con- with diphenylmagnesium, from which reaction pure version of V to 11. The fact that the epoxyether I IX can be isolated in 3Oy0yield. gave an 80% yield of the methoxyketone V when Experimental treated with an ethereal solution of magnesium Reaction of l-Methoxy-l-phenyl-l,2-epoxypropane(I) bromide supports this view. Further, when the with Phenylmagnesium Bromide.-A solution of 12.5 g. epoxyether was treated with a solution of diphenyl- (0.07G mole) of the epoxyether7 ( I ) in 30 nil. of dry ether magnesium, only the normal product and none of was added slowly t o the Grignard reagent prepared froin 14.6 g. (0.093 mole) of bromobenzene, 2.2 g. (0.091 g. II could be isolated. a t o m ) of magnesium and GO ml. of dry ether. T h e reaction When the epoxyether I was treated with a hind- mixture was stirred vigorously for three hours and then hyered Grignard reagent such as t-butylmagnesium drolyzed with a saturated ammonium chloride solution. chloride, only the product that resulted from rear- The ethereal layer was washed with water, dried and the rangement of the epoxyether followed by addition ether evaporated. The residual oil was distilled to give 15.7 g. (86%) of a mixture of isomers, b.p. 128-136" (0.8 of the t-butylmagnesium chloride could be isolated. mm.). After the distillate had remained a t room temperaThis product, l-methoxy-2,3,3-trimethyl-l-phenylture overnight, partial solidification occurred. T h e solid 2-butanol (VI), was prepared independently by al- was seDarated and recrvstallized from aetroleum ether to lowing the methoxyketone V to react with t-butyl- give 4:4 g. (24%) of ~1,2-diphenyl-l-methoxy-2-propanol magnesium chloride under the conditions of the ini- (11), m.p. 66-68". Anal. Calcd. for C16H1309: C, 79.34; H , 7.44. Found: tial reaction. C, 79.01; H, 7.65. The mother liquor gave no further solids and was distilled to yield 7.7 g. (42%) of l,l-diphenyl-l-methoxy-2propanol (III), b.p. 127-131' (0.7 mm.), ? z 3 1 ~1.5721. Anal. Calcd. for C16H1802: C, 79.34; H, 7.44. Found: C, 79.19; H, 7.52. The benzoate derivative of I11 was prepared in 50% yield using benzoyl chloride and pyridine. T h e melting point was 104-106°. Anal. Calcd. for C2aH?203: C, 79.77; H , 6.36; C&O, 8.96. Found: C, 80.00; H, 6.50; CHaO, 8.93. I n another experiment the Grignard reagent was prepared by 33.0 g. (0.21 mole) of broinobenzene and 5.3 g. (0.22 g. atom) of magnesium in 200 ml. of dry ether. A mixture of 80 ml. of purified dioxane and 50 ml. of dry ether was slowly added while the solution was heated t o the reflux temperature. T h e mixture was stirred and heated for one-half I X hour and then allowed t o cool t o room temperature, after which 18.5 g. (0.113 mole) of epoxyether ( I ) in 50 ml. of The epoxyether, 1,2-diphenyl-l-methoxyethyl- dry ether was added. T h e mixture was then stirred and ene oxide (VII), gave similar results when treated heated t o the reflux temperature for one hour, after which with Grignard reagents. VI1 reacted readily with the isolation procedure described above was used. After a low-boiling fraction of 1.85 g. was removed by distillation, phenylmagnesium bromide a t room temperature 22.6 g. (83%) of I11 was collected, b.p. 122-126' (0.7 mm.), and gave G3Y0 of a crystalline mixture of isomers. Z3'D 1.5714. The isomers were difficult to separate, but after reA mixture of 0.0248 g. of 11, m.p. 66-68", and 0.1640 g. peated recrystallization 11% of pure 1,1,2-tri- of pure 111, n 3 I ~1.5743 (made by independent synthesis), ' 11, corresponded to the percentage composition of 13.1% phenyl-2-methoxyethanol (VIII) and 8% of pure and 86.9% 111, and was found to have ? z 3 I ~1.5723. 1,2,2-triphenyl-2-methoxyethanol(IX) could be Assuming that a change in the composition of the binary isolated. The structure of IX was proved by inde- system 11-111 will cause the refractive index to change in a pendent synthesis from a,a-diphenyl-a-methoxy- linear fashion, and that the 111 isolated above is contaminated only with 11, the n 3 I ~value of 1.5714 corresponds to a acetophenone (X). X was prepared from a-meth- mixture of 80.4% I11 and 19.6% 11. oxydiphenylacetonitrile and phenylmagnesium broRearrangement of the Epoxyether I.-Anhydrous magmide and when treated with lithium aluminum hy- nesium bromide was prepared by the action of magnesium dride gave IX in 69y0 yield. VI11 could be pre- on propylene bromide. T o a solution of 16.5 g. (0.09 mole) of anhydrous magnesium bromide in 150 ml. of anhydrous pared independently in 71y0yield from the methyl ether was added 15 g. (0.09 mole) of epoxyether I in 50 ml. ether of benzoin and phenylmagnesium bromide. of ether. After 15 minutes a t the reflux temperature a In this series, IX corresponds to the product thick brown insoluble paste formed, the character of which formed from the epoxyether VI1 by normal open- changed very little during 5.5 hours a t the reflux temperature. After 23 g. (0.26 mole) of dioxane was added the (R) According t o t h e rules proposed by Curtin (THISJOURNAL, 74, character of the precipitate changed t o a white granular ?!IO1 (1952)) a n d C r a m (ibid, 74, 5828 (1952)) I1 should have t h e solid. After the mixture had been heated t o reflux overf o l l o w i n g rliastereomeric formula night, the solid was filtered and the filtrate distilled to give 12 g. (80%) of 1-phenyl-I-methoxy-2-propanone (V)3 OH b.p. 82-84' (0.8 mm.), n Z L1.5080. ~ A semicarbazone de.
"/ I
( 6 ) T h e rearrangement of this epoxyether in an ethereal solution of niagnesium bromide has been reported previously in ibid., 76, 3977 (19.53). ( 7 ) C. I.. Stevens, U'. Malik and R . P r a t t , ibid., 79,4758 (1950). ( 8 ) K. v. Auwers. 11. 1,ridewig an(l A . hliiller, A n n . . 626, 113 il93G).
rivative,* m.p. 154-156", was prepared in 52% yield. Reformation occurred during addition of the last 10% of the crystallization raised the melting point t o 159-160". The cposyether. After the reaction was stirred for an adtliderivative contained 13.9yotnethoxy (calcd. 14.0). tiotial oiic-half hour, hytlrol~-sir\vas cffcctcd with S70 11yThe mcthoxykctonc 1' \i as prepared independcntly by drochloric acid solution. T h c ether layer was washed, alcoholysis of l-bronio-1-pheny1-2-propanoneg with a large dried and the ether evaporated. Heptane (10 nil.) was excess of methyl alcohol and three equivalents of calcium added t o the residual oil and crystallization was induced, carbonate at the reflux temperature for 30 days, b.p. 68The crude solid mixture of isomers was filtered and amounted 69' (1 m m . ) , nZ5D 1.5055. A semicarbazone, m.p. 154to 4.0 g. (63%). Recrystallization of the solid from hepl 3 O , did not depress the melting point of the derivative tane gave 2 g. of material, 1n.p. 112-119'. The ofiltratc prepared from 1. from the rearrangement of the epoxyether. from this solid gave 1.5 g. of material, m . p . 81-85 , aftcr. The semicarbazone of a-methoxypropiophenone,' which concentration. melted at 163-162', caused a large depression of melting Repeated recrystallization of the former material gave point when mixed with the semicarbazone of T'. 0.7 g. (11y0) of ~1,1,2-triphenyl-2-1nethoxyethanol( I ' I l I ) , 1,2-Diphenyl-l-methoxy-2-propanol(II).-An ethereal l1i.p. 138.5-139.5 . 5olution of 4.65 g. (0.028 mole) of V was added slowly t o a Anal. Calcd. for C ? I N ~ O OC, ~ :82.57; H, 6.58. Found: slight excess of phenylmagnesium bromide. After the C,82.78; H , 6.91. usual isolation procedure, 4.25 g. (63%) of 11, m.p. 67-70', Repeated recrystallization of the lower melting componeiit was obtained. The mixture melting point with I1 from the from a mixture of benzene and petroleum ether gave 0.50 g . epoxyether was not depressed. l,l-Diphenyl-l-methoxy-2-propanol(111).-An ethereal (8%) of 1,2,2-triphenpl-2-methoxyethanol(IS),ii1.p. 84 .&36.5". solution of 13.8 g. (0.057 mole) of 1,l-diphenyl-1-methoxyA n d . Calcd. for C?IH?~O?: C , 82.57; IT, 6.33. Founrl: 2-propanone4 (IV) was slowly added t o a suspension of 1.14 C, 82.132; H, 6.70. g . (0.03 mole) of lithium aluminum hydride in ether and the mixture stirred and heated a t the reflux temperature for six In another experiment, 30 ml. of purified dioxaric i n dry hours. After the reaction had been hydrolyzed with 5% ether was slowly added to an ethereal solution of phenylhydrochloric acid, the ether layer was washed, dried and magnesium bromide (from 0.075 mole of bromobcnzene 1 the ether evaporated. Distillation gave 3.7 g. of forerun, which had been heated to the reflux temperature. Aftcr b.p. 134-138", and 7.0 g. of l,l-diphenyl-l-methoxy-2- the addition, the mixture was heated an additional hour ant1 propanol, b.p. 138-139" (1 m m . ) , n 3 I ~ 1.5743. The total then cooled. A solution of 0.3 g . (0.028 mole) of the eposy3 ield of 111 was 78%. ether 1.11 in dry ether was then added and the stirring continued for one-half hour. From the same isolation proceAnal. Calcd. for CI6Hl8O2:C, 79.34; H,7.44. Found: dure described above was isolated 4.25 g. (50%) of I S , C,79.13; H,7.48. m . p . 83-85". A mixture melting point with authentic I S A benzoate derivative, m.p. 104-10G0, was prepared in 60% yield and was identical with the benzoate of I11 ob- was not depressed. S o n e of the more insoluhle isomer 1.111 was found in this experiment. tained from the epoxyether I as determined by mixture 1,1,2-Triphenyl-Z-rnethoxyethanol(VIII) .-Phenyltnagmelting point determination. nesium bromide was made from 4.86 g. (0.031 mole) of Reaction of the Epoxyether I with t-Butylmagnesium bromobenzene and allowed to react with 0.40 g. ( 0 Chloride.-An ethereal solution of the Grignard reagent mole) of the methyl ether of benzoin. After hydro was prepared from 2.43 g. (0.1 g . atom) of magnesium and and evaporation of the ether from the ether lnycr, the 9.26 g . (0.1 mole) of t-butyl chloride. The solution was cooled to 0" and 8.2 g. (0.05 mole) of the epoxyether I due solidified and amounted to 6.6 g. Rccrystallizntioii from a benzene-lieptanc mixture gave 6.1 g. (71%) of Y I I I , slowly added. After 15 minutes of O', 30 minutes a t 25" and 15 minutes at the reflux temperature, the reaction was m.p. 138.6-139.,5". A mixture melting point with I T I I I obtained from the epoxyether was not depressed. hydrolyzed with saturated ammonium chloride solution. 1,2,2-Triphenyl-2-rnethoxyethanol(IX) .--ol-MethoxycliThe ether layer was decanted, dried and the ether removed. phenylacetonitrile, m.p. 52-5c3.,50, WRS prepared from tliThe residue, 9.7 g., was dissolved in petroleum ether and cooled t o -60", a t which temperature 1 g . of product crys- phenylacetonitrile by chlorination with phosphorus chloritic to give ol-chlorodiphenT-lacetonitrile anti then nlcoholysii of tallized, m.p. 40-43'. The remainder was distilled t o give a fraction, 2.0 g., b.p. 58-68" (0.5 mni.), n z 5 ~1.5058. the chloronitrile to the methoxynitrile." A solution of 13.0 g. f0.058 mole) of a-methoxycliphenylThis fraction was composed mostly of 1. since the semicaracetonitrile in 40 mi. of ether was added to a n ethereal solubazone of V could be prepared in 50% yield. The second fraction, 2.65 g., b.p. 68-77" (0.5 m m . ) , tion of phenylmagnesium bromide made from 11.6 g. (0.074 mole) of bromobenzene. The mixture was stirred antl solidified. After this material was dissolved in petroleum heated to the reflux temperature for 18 hours, after which ether and the solution cooled t o --SO", 1.8 g . of crystalline time 100 ml. of 20y0 hydrochloric acid was atitled antl thc material was obtained. The total yield of solid was 35%. mixture stirred an additional three hours. The ether lavor. Recrystallization from a mixture of methanol and water gave pure l-methoxp-2,3,3-trimethyl-l-phenyl-2-butanol was separated and the aqueous layer stirred an at1ciitiou:il 20 hours and then extracted with ether. The cornbinetl (\.I), m.p. 48.5-49'. ethcr extracts mere washed with water, dried ant1 the ether A n d . Calcd. for C I ~ H Z Z OC, ~ : 75.63; H, 9.97; CH:IO, solution concentrated to give a n oil which slonlv cryst:iI14.0. Found: C,75.90; H, 9.95; CH30, 14.2. lized. The solid was recrystallized from a incthylcyclo. T'I also was prepared from 6.1 g. (0.037 mole) of V and hesane-petroleum ether mixture to give 4.6 g. (26%) of 0.07 mole of t-butylmagnesium chloride by the same procc- ~,cu-diphenyl-a-methoxyacetopheiione1* (S) , m . p . 90-93'. dure as used for the epoxyether. Distillation gave a foreX was reduced with lithium aluminurn hydride following run of 0.9 g., b.p. 68-84' (1 mm.), Z Z ~ D 1.5058, and then the procedure described for the reduction of I \ . . From 4.(i g . 3.7 g . (45%) of VI, b.p. 84-89" (1 mm.), which solidified. of X was obtained 3.2 g . (09%) of 1,2,2-triphenyl-2-metliRecrystallization of this fraction gave 2.75 g. of pure V I , oxyethanol ( I X ) , 1n.p. 8,5-87'. A mixturc melting point m.p. 47-48', A mixture melting point with T-I from the with I S from the epoxyethcr showed no d c p r e 4 o n . epoxyether was not depressed. DETROIT1, MICHIGAX Reaction of 1,Z-Diphenyl-1-methoxyethyleneOxide (VII) with Phenylmagnesium Bromide.;A solution of 4.7 g. of (11) T h i s procedure is described i n t h e article given in ref. 4. the epoxyetherlo V I I , m.p. 56-58 , in 30 ml. of dry ether (12) T h e melting p o i n t of X was n o t depressed when mixed w i f h was added t o an ethereal solution of phenylmagnesium t h e a,a-diphenyl-a-mcthoxyacetophenone m a d e previously i n tlii? bromide made from 3.6 g. (0.023 mole) of bromobenzenc L a b o r a t o r y by alcoholysis of t h e corresponding chloroketone or Iirornoand 0.55 g. (0.023 g. atom) of magnesium. Heavy salt ($3) E. If.Schultz a n d S. M i c k e y , Org. S y v l h e s e s , 29, B R (1949). ( I O ) C . L . Stevens, A I . I. TVeinrr a n d R C FrrrIT1
