The oil, covered with dry methanol, was allowed to remain in a refrigerator for one Tvcek. The mixture of crystals and oil was filtered through a fritted-glass funnel surrounded by ice. -4fter thorough trituration with cold methanol, the crystals melted at 49-51 '. dnat. Calcd. for C1IH130?SHr: S, 9 SG; R r , 24.57, Found: S, 9.63; Br. 24.53.
When either the oily product or the crystalline material was aminated with diethylalnine, the 4-diethylaminornethyl
(1ioxolaile obtailied boiled at 136-139" (n.ni mm.'i. d,l,lal, calcd,for c ~ N, 1,11 ~ s, Four1d:
s, 10.24.
s, 4.24;
A N N A R B O R , R/IICWIGAP;
,,,
~
RECEIVED OCTOBER11, 1951
/CONTRIBUTION FROM THE PlYRDUE ITNIVERSTTY D R P A K T M B N I OF CJIEMISTRY ASI) THE PTlRl>UE
RESEARCH FOtJSDATI0S ]
The Reducing Action of Grignard Reagents on Fluorinated Carbonyl Compounds1,2 HY
E.
rr. Z I C B E R , 0 . K.PIERG;
.\NU
J.
HIGGINS
I;.
The reaction of Grignard reagents with trifluoroacetaldehyde, pentafluoropropionaldehyde, heptafluorobutyraldehyde, the esters of trifluoroacetic, pentafluoropropionic, and heptafluorobutyric acids, l,l,l-trifluoroacetone, 3,3,4,4,4-pentafluoro-2butanone and 3,3,4,4,5,5,5-heptafluoro-2-pentanone were studied in an effort to delineate the extent of the reduction observed. In all Grignard reagents containing fl-hydrogens reduction was obtained, which may be attributed to the large inductive effect of the fluorinated alkyl group attached to the carbonyl grouping in these materials.
In a previous paper,3 mention was made of the TABLE I reduction of pentafluoropropionaldehyde and 3,3,K E A V T I O N S WITH FLUORINATED ALDBFWDES 4,4,4-pentafluoro-2-butanoneby ethyl and iso(:rignard CY;CFLHO CF~C kr o reageril liedn., ,, .iddu., Iledn., T;, Arldn., (';, propyl Grignard reagents. In order to investigate Met 11 y 1 57.0 0 07,O" 0 this reaction further, the action of six Grignard Ethyl ,it?, 5 3 3 , (i 20.0 DO, 0 reagents on both trifluoroacetaldehyde and pentaIsopropyl no. 0 0 87.0 0 fluoropropionaldehyde was compared to determine [-Butyl If),? 14.3 84.0 7.0 if the amount of fluorine present affects the degree Phenyl I) 80.0 0 xx.0 of reduction and to evaluate the effect of the Benzyl 0 87 0 0 81 0 structure of the alkyl group of the Grignard reagent 'I'his rw(.tioti \vas c'ontluctcd b y I k . J. .4.R:irone. on the product obtained. In addition, the study was extended to the action of ethylmagnesium ioTABLE 11 dide on esters of trifluoroacetic, pentafluoroproREACT~OXS WITH ETHYL GR~CNARD pionic and heptafluorobutyric acids as well as 1,1,1Compound Redn., ')h Addn., '7. trifluoroacetone, 3,3,4,4,4-pentafluoro-2-butanone, CFaC0:CH.S" 36.0 56.0 3,3,4,4,5,5,5-heptafluoro-2-pentanone and heptaC~FSCO~CH~ 68.0 29.0 fluorobutyraldehyde. The comparative amounts C~F~CO~CH~~' 08.6 12.5 of addition and reduction products are summarized CFZCOCH, 13.9 78.9 in Tables I and 11. CaFsCOCHa 44.5 41.6 Generally, reduction of carbonyl compounds by C~F~COCH.I 61.6 18.0 Grignard reagents has been observed in instances CaF7CHO til, 0 19.0 in which the addition reaction may be hindered ~ t e r i c a l l y . ~Hence the reduction previously oba Campbell, ref. 5 , synthesized the addition and reduction served3 with fluorinated derivatives of propion- products obtained iii this reaction from ethyl Grignard and trifluoroacets te and lxityl trifluoroacetate, respectively. aldehyde and 2-butanone was unexpected because I,ethyl Private cornniunicatio~~. of the absence of large groups and hence any significant steric factor. The results of this investiga- with a carbonyl group is particularly apparent i n tion indicate that an inductive effect, clue to the the reaction of trifluoroacetaldehyde with isoclose proximity of a highly electronegative fluori- propylmagnesium iodide. Although the principal, nated group to the carbonyl group, is affecting the if not exclusive, reaction of acetaldehyde with a course of the Grignard reaction to cause an ab- Grignard reagent is addition, trifluoroacetaldehyde normal amount of reduction. Recent work by undergoes 87y0 reduction to trifluoroethanol and Campbell and co-workers5 shows that reduction none of the expected adduct was isolated. Since a also occurs in the reaction of esters of trifluoro- fluorine atom is only a little larger than a hydrogen acetic acid with Grignard reagents. atom and hence a trifluoromethyl group is about the The pronounced effect of fluorine substitution on same size as methyl, this reducing, action cannot he the nature of the reaction of a Grignard reagent readily attributed to steric factors. The experimental results indicate (Tables I and (1) T h i s paper represents p a r t of a thesis submitted by 1. I?. Higgins t o t h e Graduate School, Purdue University, in partial fiilfillment of the TI) that as the length of the perfluorinated chain requirements of t h e degree of Doctor of Philosophy. This work waincreases, the amount of reduction increases with a supported by the Westinghouse Electric Corporation. corresponding decrease in addition. This was (2) Presented before the Organic Section, XIIth International Confound to be most significant when using ethyl gress of Pure and Applied Chemistry, New York. X . T.. September, 1951. Grignard reagent with trifluoroacetaldehyde and (3) E. T. McBee, J . F. Higginsand 0. K.Pierce, in press. pentafluoropropionaldehyde. In the case of tri(4) J. B. Conant and A. H. Blatt, ibzd., 51, 1227 (1929). fluoroacetaldehyde, the yield of reduction and (5) K. N. Campbell, 1. 0 Knobloch and R . K . Campbell, h i d . , 72, addition products were 20 and SO%, respectively, 4380 (1950). i
s
~
April 5, 1952
GRIGNARD ACTIONON FLUORINATIU-I CARBONYL COMPOIJNDS TABLE I11 NEW COMPOUNDS Analyses,
Compound
B.p.
CFsCHOHCeH6 CFaCFaCOH(C2H6)2 CF3CFzCHOHCJIi CFsCFzCFaC(OH)( CHa)CzHb CFaCHOHCH2CJ36 CSC(OH)(CHs)GH, CFaCFzCHOHCHGH5 CFsCHOHC(CHs)s CF3CFzCHOH C( CHs), 0 5 m m . b3mm. c5mm.
64-65" 127 52' 125 74-76c 98.3 79" 110.5 120
n%
1.4610 1.3590 1.4340 1.3395 1.4662 1.3540 1.4430 1.3670 1.3578
while with pentafluoropropionaldehyde they were 55.5 and 33.6y0. This increase in the relative amount of reduction obtained, as the amount of fluorine in the carbonyl compound is increased, may be attributed to the increasing positive charge on the carbonyl carbon atom, resulting from the increased inductive effect. A possible explanation for the reduction reaction can be found in the work of Whitmore6 who postulated a cyclic process involving formation of a sixmembered ring followed by a shift of a hydride ion from the Grignard reagent. I n the case of fluorinated aldehydes, ketones and esters, the inductive effect of the fluorine atoms should provide an increased driving force for the hydride ion shift and thus accelerate the reduction process relative to the competitive addition reaction. In support of this postulate, i t was found that the reaction of ethyl Grignard with pentafluoropropionaldehyde, which usually gives about 33y0 addition and 55% reduction products, gave 5801, addition and 36.4% reduction when the aldehyde was added to a solution of magnesium bromide before addition of the Grignard reagent. This parallels the results of Swain7and is cited as additional evidence for a cyclic reduction process. The increase in the relative amount of reduction obtained as the Grignard reagent is varied from ethyl to isopropyl can be explained by the increasing number of 0-hydrogen atoms in the alkyl group of the Grignard reagent. The addition of tertiary butyl Grignard to the aldehydes in low yields, as contrasted with no addition with isopropyl Grignard, might result from a lesser tendency for the tertiary butyl Grignard reagent to coordinate with the carbonyl group of the aldehyde because of the (6) F. C. Whitmore, paper presented helore t h e Atlantic City Meeting of the American Chemical Society, April, 1943. (7) G.Swain and H . B. Boyles, THIS J O U R N A L ,73, 870 (1951).
c.
d '04
1.293 1.259 1.366 1.396 1.234 1.161 1.330 1,118 1.105
Carbon Calcd.
Found
54.54 40.78 47.79 34.71 56.84 42.25 50.00 40.78 46.15
54.55 40.78 48.00 34.85 56.80 42.20 50.10 40.71 45.95
%
I737
-.
Hydrogen Calcd. Found
3.97 5.34 3.10 3.72 4.74 6.34 3.75 5.34 7.05
4.02 5.30 3.12 3.75 4.64 6.33 3.85 5.45 6,9F,
increased electron density on the magnesium which results from the electron donating property of the methyl groups. Thus, the rate of reduction would not overshadow the rate of addition as completely. This is similar to the behavior of t-butyl Grignard with benzophenone in which case exclusive addition is obtained as contrasted to isobutyl Grignard which reduces benzophenone exclusively.s No reduction was noted with methyl, benzyl or phenyl Grignard reagents, which was expected since they lack a 0-hydrogen atomsg
Experimental The Grignard reagents used were prepared by standard methods from the alkyl iodides in the case of methyl and ethyl, the alkyl bromides for isopropyl and phenyl and the alkyl chlorides for t-butyl and benzyl. After preparation, they were filtered through glass wool, using nitrogen pressure, into a dropping funnel and added to the reaction flask. The latter was equipped with a Tru-boretype stirrer and a condenser attached to a Dry Ice cooled trap. A gas inlet tube reaching just over the surface of the liquid was used for introducing the aldehydes and l,l,l-trifluoroacetone. A dropping funnel was used for introducing the other ketones and esters. The reaction flask was stirred and cooled in an ice-bath while the carbonyl compound was introduced. After all the carbonyl compound was added the reaction mixture was hydrolyzed in the flask with 10% sulfuric acid, the ether layer separated, and dried with Drierite. The ether was removed by distillation and the remaining liquid rectified through a Todd column. Two- to three-tenths mole of carbonyl compound was used with approximately twice the theoretical quantity of Grignard reagent. The experiment using magnesium bromide was conducted as described by Swain,' but hydrolysis was effected with 10% sulfuric acid. The reduction products obtained with esters were secondary alcohols presumably formed by reductio11 of the intermediate ketone.s Physical constants and analyses are listed in Table 111. LAFAYETTE, INDIANA
RECEIVED SEPTEMBER 4, 1951
( 8 ) M. S. Kharaseh and S. Weinhouse, J . Org. Chcm., 1, (1936). (9) F. C. Whitmore and R. S. George, THISJOURNAL, 64, 1239 (1942).
