3Q24
ALLENS. HUSSEYAND MELVINS. NEWMAN
[CONTRIBUTION FROM THE CHEMICAL
Vol. 70
LABORATORIES OF NORTHWESTERN UNIVERSITY AND THEOHIO STATE UNIVERSITY ]
Some Observations on the Reformatsky Reaction BY ALLENs. HUSSEPBND
klELVIN
s. NEWMAN
In previous work, i t has been shown that low isobutyrate were isolated from reactions involving yields in the Reformatsky reaction may be caused an excess of the respective bromoe~ters.~Espeby the side-reaction of enolization. The recovery cially noteworthy is the fact that while ethyl broof unreacted ketone and reduced ester, I, from re- moacetate reacts with zinc very slowly in the abactions in which a mole of zinc and a mole of sence of carbonyl compounds,l ethyl a-bromoprobromoester are consumed has been explained as pionate reacted vigorously with zinc in the absence of ketone to give 16% of I and 39% of 11. shown below1: [ R-CH-COOEtIZnBr + R-C-CH+ -+ [R-COCHRIZnBr RCH2COOEt (1) Under the same conditions, ethyl I a! - bromoisobuteate gave traces of I However, the yield of Reformatsky product and 65% of II.8 The results are summarized in may often be greatly increased by an excellent Table I. The formation of non-halogenated j3-ketoesters, procedure involving the use of large excesses of zinc and b r o m o e ~ t e r . ~ The - ~ side reactions of 11, is quite interesting. There are many reports bromoester with zinc to form halogenated ,&keto- of the formation of such compounds, usually in ester and coupling products have been suggested4 low yield, from reactions of a-haloesters with mag. ~have determined that the in explanation of the improved yield of Refor- nesium and z i n ~ . ~We matsky product under the above2conditions. We over-all stoichiometry is as given by equation 2. have undertaken a study of the Reformatsky re- 2(R)zCBrCOOEt + 2Zn + action using 5,S-dimethyl-l-tetralone6 with ethyl 0 bromoacetate, a-bromopropionate,6 and a-bro1; moisobutyrate and have examined the reaction [ ( R ) ~ C = ~ ( R ) Z C O O E ~ ]+Z BrZnOEt ~B~ (2) mixtures for end-products of side-reactions involvV ing bromoester. In most experiments 60-SOy0 of One possible reaction path is indicated below. the bromoester and 85-957, of the ketone have been accounted for. We have found that a com[(R)zCCOOEt]ZnBr (R)2CBrCOOEt+ plex self-condensation of bromoesters to form nonOEt halogenated j3-ketoesters, (R),CHCOC( R)2-EtOZnBr I COOEt, 11, often occurs but we were unable to de(R)zCBrCC(R)zCOOEt I __ tect any halogenated j3-ketoester or coupled prod-
+
+
UCt.4
When an excess of bromoester and zinc was used, the yield of Reformatsky product, based on ketone, was increased from 25Y0 to S5y0 with ethyl bromoacetate and from 17Y0 to 827, with ethyl a-bromopropionate. No Reformatsky product was obtained with ethyl a-bromoisobutyrate. One mole of zinc was consumed for each mole of bromoester used and approximately the same amount, 1 0 - 1 5 ~ ~ ,of7 reduced ester, I, was isolated with all three bromoesters. In addition, 15% of ethyl acetoacetate, :35% of ethyl a-propionylpropionate and 69% of ethyl a-isobutyryl(1) Newman, THISJOURNAL, 64, 2131 (1942). (2) Bachmann, Cole and Wilds, ibid., 611, 824 (1940). (3) That large excesses of zinc and bromoester do not always give better yields is shown by the fact that with 4-keto-1,2,3,4-tetrahydrophenanthrene a single addition of a slight excess of zinc and methyl or ethrl hromoacetate gives a s good a yield as that reported by Bachmann and Edgerton, ibcd, 62, 2970 (1940). Newman, unpublished observations. (4) Shriner, “The Reformatsky Reaction” in “Organic Reactions,” Vol. I , John Wiley and Sons, Inc., N e w York, N. Y., 1942, p. 4. (5) Ruzicka and Waldmann, Helu. Chitn. Acta, 15, 907 (1932); Barnett and Sanders, J . Chem. Soc., 434 (1933). (6) Newman and Hussey, THISJOURNAL, 69, 3023 (1947) ( 7 ) t-ield based on bromoester used.
OZnBr Zn (R)pCBrCOC(R)zCOOEt + [ (R)XCOC(R)zCOOEt]ZnBr
The importance of this self-condensation reaction increases in the order CHzBrCOOEt < CH3CHBrCOOEt < (CHa)2CBrCOOEtas shown by the reactions of the esters in the absence of ketone. In view of the improved yield of ethyl apropionylpropionate in the presence of acetomesitylene (compare experiment 12 with 6 and i , Table I), even though the latter seems to play n o part in the reaction, further studies are in order. The ways in which reduced ester, I, may be formed are also of interest. Enolization, equation 1, offers one explanation. However, in view of the fact that appreciable amounts of ethyl propionate are formed in the reaction of ethyl CYbromopropionate with zinc in the absence of ke( 8 ) Zeltner, Ber., 41, 589 (1908), obtained 677, of ethyl a-isobutyrylisobutyrate from the reaction of magnesium with ethyl abromoisobutyrate. (9) Fittig, Daimler and Keller, A n n . , 249, 184 (1888); Hann and Lapworth, Proc. Cham. Soc., 19, 189 (1903); BLaise and Marcilly, Bull. SOL’. chim., [3] 81, 110 (1904); Stolle, Her., 41, 854 (J!208); Kottinghen and W’enzel, Monofsh., 84, 1867 (191.3
SOME OBSERVATIONS ON THE REFORMATSKY REACTION
Sept., 1948
3025
TABLE I
1 2 3 4 5 6 7 8 9 10 11 12
Procedure I
1 I1 I1 I 1 1 I1 I I I I
Ketone used g. moles 40.0 0.23 21.0 .12 17.7 .10 30.0 .I7 50.0 .29 97.7 .56
...
..
165 40.0 32.6
.95 .23 .19
...
..
44.4'
.27
Zinc consumed g. moles 45 0.69 24 .37 6.5 .10 10.6 .16 57 .87 107 1.63 27 0.42 69 1.05 46 0.70 37 .56 44 .67 46 .70
Bromoester" used g. moles 115 (A) 0.69 60 (A) 0.36 16.7 (A) 0 . 1 0 28.7 (A) 0 . 1 7 160 (P) 0.83 300 (P) 1.65 80 (P) 0 . 4 4 190 (P) 1.05 135 (B) 0.69 110 (B) 0.56 135 (B) 0 . 6 9 150 (PI 0.83
Ketone recovered g.
%
2.3
6
0
0
Reformatsky product g. %b 48.2 86 24.8 85 7.0 28 9.9 24 60.4 81 116 82
11.2 20.8 4.0 9.6
63 67 8 10
...
..
108 36.1 27.0
66
40.6
90 83
0
..
...
0
17 0 0
40.6
92
0
0
...
...
..
..
Reduced ester g. %" 6.3 10 4.1 13
