[CONTRIBUTION FROM TEE CHEMICAL
LABORATORY OF IOWA STATE
COLLEGE]
T H E REDUCTION OF CHLORAL BY ORGANOMETALLIC COMPOUNDS. 1-TRICHLORO-2-BUTANOL‘ HENRY GILMAN
AND
R. K. ABBOTT, JR.
Received November 98, 19&
As a broad generalization, it may be stated that organometallic compounds show essentially the same reactions, but a t different rates. On such a basis it is possible that organolead compounds, although quite low in the reactivity-series of organometallic compounds, will add to some typical functional groups like the carbonyl group, In connection with a comprehensive study on the reducing action of alkylmetallic compounds, Meerwein and co-workers (1)called attention in a footnote to a reaction between chloral and tetraethyllead. They reported a 20% yield of 1-trichloro-2-butano1, which may have resulted from the following addition reaction ; H H CCbCHO
f (CzH6)dPb
-
I I
CClsCC2H6 OPb(Cs&)o
I I
% CCbCC2H6 OH
They found no trichloroethanol, a product of reduction isolated when some other ethylmetallic compounds were used. Under corresponding conditions, they noted that no reaction took place between chloral and tetraethyltin, an observation that is quite reasonable in view of the known significantly lower reactivity of RhSn compounds as compared with the corresponding R4Pbtypes. However, we were unsuccessful in obtaining any 1-trichloro-2-butanol from the reaction of chloral with tetraethyllead. Subsequently we were informed2 that the 1-trichloro-2-butanol distilled a t 68-70”/13 mm. ; contained 60.19% chlorine (calc’d 60.0%); but that no derivatives of the alcohol were prepared. As an aid to the isolation and characterization of the 1-trichloro-2-butanol that might be contained in some of our reaction products, we set out to prepare the alcohol from chloral and an ethylmagnesium halide. Iotsitch (2) investigated the action of ethylmagnesium bromide on chloral and obtained two fractions: one, distilling a t 149.5-150.5’/765 mm., which was identified as trichloroethanol; the second, distilling a t 77-80°/10 mm., which was obtained in 15% yield and assumed to be 1-trichloro-2-butanol. We investigated this reaction under a variety of experimental conditions and likewise obtained trichloroethanol, in yields as high as 65%. We did not obtain a definite high-boiling fraction; the material boiled over a wide range, depending on the experimental conditions used, and showed varying halogen content. Then H6bert (3) treated chloral with ethylmagnesium iodide and, like Iotsitch, obtained trichloroethanol as the principal reaction product. He reported also 1 Paper L in the series “Relative Reactivities of Organometallic Compounds”; the preceding paper is J. Am. Chem. Soc., 66, 435 (1943). * Communication from Professor Meerwein. 224
225
REDUCTION OF CHLORAL
a 16% yield of 1-trichloro-2-butanol, distilling at 82-84"/22 mm. Identification was established by sodium carbonate hydrolysis to give propionaldehyde and a-hydr'oxybutyric acid. From several experiments we did not observe any apprec:iable quantity of material distilling higher than 72"/22 mm., and the amount of tarry products was increased when ethylmagnesium iodide was used insteadl of ethylmagnesium bromide. Later, Howard (4)reported 1-trichloro-2-butanol as the principal product of the reaction between chloral and ethylmagnesium bromide. His reported boiling point (99"/680 mm.) may be a typographical error.3 Although it does appear that HBbert (3) had 1-trichloro-2-butanol in hand, our experiments with ethylmagnesium chloride, bromide, and iodide indicate that no appreciable quantities of the alcohol were formed. It is possible that special catalytic influences may account for the variations in results. Incidentally, the reaction with ethyllithium appeared to be complicated by secondary transformations with the chlorine in chloral. We prepared 1-trichloro-2-butanol by the following sequence of reactions : CCbCHO
+ CHzNz + CChCH-CHz \ / 0 H
CClaCH-CH2
\ / 0
I + CH3Li 3CClaCCH2CHs I
OH
1-Trichloro-2-butanol gave a-hydroxybutyric acid on treatment with sodium carbonate solution. New derivatives are described both for trichloroethanol and l-t,richloro-2-butano1. Met hylmagnesium iodide could not be used in this synthesis because the magnesium, iodide contained in the complex reacted as follows to give l-trichloro-3iodo-2-propanol:
H
CC13CH-CH2
\ / 0
I + MgL 2 CC4CCHJ I
OH
Reaction of chloral with benzylmagnesium chloride. The reduction of chloral by nurnerous Grignard reagents and other R M compounds is one of a series of competitive reactions shown with a variety of carbonyl group^.^ In general, if simple oxidation of the RMgX compound is possible (accomplished by the essena In a private communication Professor Howard mentioned that a repetition of his reaction showed the boiling point to be about 150". This is the boiling point to be expected of trichloroethanol. His boiling point of trichloromethylbenzyl carbinol (from chloral and benzylmagnesium chloride) is undoubtedly in error, for one would not expect i t to be almost the same as his reported boiling point for 1-trichloro-2-butanol. 4 For a general discussion and some leading references see Gilman, "Organic Chemistry", John Wiley and Sons, New York (1943),Second Edition, Chapters 5 and 7.
226
H E N R Y GILMAK A N D R . K . ABBOTT, JR.
tial loss of two hydrogen atoms and the formation of a carbon-carbon double bond), the preponderant reaction will be the reduction of chloral to trichloroethanol. With RMgX compounds having groups like methyl, benzyl, and phenyl, the main reaction is addition to the carbonyl group. This is strikingly illustrated by the formation of the secondary alcohol with benzylmagnesium chloride,
whereas other related phenyl-substituted alkylmagnesium halides like @-phenylethylmagnesium bromide, 7-phenylpropylmagnesium bromide, and b-phenylbutylmagnesium bromide reduce chloral to trichloroethanol ( 5 ) . The availability of suitable derivatives for the characterization of trichloroethanol suggested a re-examination of the reaction between chloral and benzylmagnesium chloride. We have found that a small quantity of trichloroethanol is produced in this reaction, and the filtered, clear solution of Grignard reagent that was used decreases the possibility that this reduction was due to unused magnesium (6). EXPERIMENTAL
Chloral and ethylmagnesium bromide. To the Grignard solution prepared from 24 g. (1.0 g. atom) of magnesium and 120 g. (1.0 mole plus 10%) of ethyl bromide in 40Qml. of absolute ether and cooled to -25" was added 140 g. (0.95 mole) of chloral in 100 ml. of absolute ether. The addition was performed dropwise over the course of one hour; a steady gas evolution was observed, and a white precipitate separated. The reaction mixture was allowed to warm up to room temperature, where i t was held under continuous stirring for one hour. Hydrolysis was then effected by the gradual addition of 300 ml. of iced 2 N hydrochloric acid to the reaction mixture held a t 0". The ether layer was then separated, washed with water, and dried over anhydrous sodium sulfate. After removing the ether under reduced pressure, the residue was distilled under 11 mm. pressure, the temperature of the bath being allowed to rise constantly until no more material would distill. Thus 102 g. of distillate boiling a t 48-69' was collected as a slightly yellowish oily liquid with a sharp odor. When shaken with water it imparted an acid reaction to the aqueous layer. The residue in the distilling flask was a dark thick tar. The distillate was refractionated a t 6 mm. pressure, and three fractions were collected which showed the following properties: 25 TEMP. WEIQHT nD d M.R. (7) 1.5033 33.8 1.4848 58 g. I 43-45" I1 45-47" 23 g. 1.4847 1.4945 34.0 I11 47-49" 19 g. 1.4838 1.4528 34.9
::
All fractions acquired a violet color upon standing overnight. The last two fractions were recombined and distilled under 0.6 mm. pressure into three fractions with the following properties: I I1 I11
TEMP.
WEIGHT
32-33' 33-34" 3437"
20 g. 9 g. 7 g.
25
4;
M. R.
1.4849 1.4848 1.4826
1.4920 1.4712 1.4490
34.0 34.4 34.9
nD
REDUCTION OF CHLORAL
227
All three fractions gave a p-nitrobenzoate, the last two fractions, however, in poor yield. Recrystallized twice from petroleum ether (b.p. 68-70'), i t melted at 71" (8) and showed no depression in a mixed melting point with the p-nitrobenzoate prepared from an authentic sample of trichloroethanol.6 None of the above fractions gave a positive Lucas reaction (9). For additional confirmation the 3,5-dinitrobenzoate was prepared from each fraction. Recrystallized three times from petroleum ether (b.p. 68-70'), in which i t is not very soluble, i t melted a t 142-143'. Further recrystallization failed to raise the melting point. There waa no depression in the mixed melting point with the 3,5-dinitrobenzoate prepared from the authentic sample of trichloroethanol. Anal Calc'd for C Q H ~ C I ~ NC1,31.0. ~ O ~ : Found: C1,31.1. The last gram of the highest-boiling fraction was analyzed with the following results: Anal Calc'd for CdH+&O: C, 27.07; H, 3.98; 0, 9.02; C1, 59.94. Found: C, 22.41; H, 3.47; 0, 8.80; C1,65.32. By fractionating under normal pressure and collecting the fraction boiling a t 148-152" i t was possible to obtain trichloroethanol in 54% yield. Various modifications of the above reaction have been tried, including the use of ethylmagnesium chloride, ethylmagnesium iodide, and ethyllithium. A total of seventeen different runs were made, employing temperatures from -75" to 34", inverse order of the addition of the reactants, reaction times from 15 minutes to 24 hours, etc., without essential deviation from the above results. Chloral and tetraethyllead. To 32.3 g. (0.1 mole) of carefully purified tetraethyllead was added 14.7 g. (0.1 mole) of chloral which had been freshly distilled from phosphorus pentoxide and carefully fractionated from low-boiling material. Upon mixing there was no evidence of reaction. Heated under nitrogen, the solution became slightly greenish-yellow a t 130", and a small amount of white solid deposited. At 145' the solution turned slightly brown; a t 150" dark brown. A t 165" gas evolution was noticed. In another experiment the addition of a small amount of silica-gel produced no perceptible difference in these phenomena. Heating was continued for one hour a t 170", after which time there was no appreciable gas evolution. After the reaction mixture had cooled, i t was hydrolyzed with water and then with dilute acetic acid. Large quantities of triethyllead chloride remained undissolved. The dark red ether layer was dried with anhydrous sodium sulfate, and the ether was carefully removed on a water-bath a t 60". Further separation of triethyllead chloride took place, and the solution was filtered into a distilling flask. Two fractions of approximately equal size were cut a t 63-64' and 65-66' a t 14 mm. pressure. Material boiling lower than this was found to be principally tetraethyllead. The two fractions together weighed 3.5 g.; this would be a 19.8% yield of 1-trichloro-2-butanol, but the following physical constants for the two fractions show, together with the chlorine analysir; and the fzilure of the product to give the Lucas reaction for secondary carbinols, that the material was not the desired product: n::
I 11
1.4788 1.4822
45, 1.382 1.404
These two fractions were free of lead and contained 65.6% chlorine. Comparison should be made with the authentic properties of 1-trichloro-2-butanol described below. Repeated variations in other experiments of the quantities, time of heating, and temperature failed t o give fractions approximating more closely the properties of the veritable carbinol. Trichloropropylene ozide. This compound was prepared in essential accordance with the directions of Arndt and Eistert (10) from chloral and diazomethane. I n a typical run employing 44.0 g . (0.3 mole) of chloral, the yield was 23.2 g. (48%). Trichloropropylene oxide was found to boil a t 39-40" under 11 mm. pressure, and to have these constants: ?a: 1.4737, d z 1.4921. . 6
Kindly provided by Dr. C. S. Marvel.
228
HENRY GILMAN AND R. K. ABBOTT, JR.
I-Trichloro-3-iodo-$-propanol. T o 21.0 g. (0.13mole) of trichloropropylene oxide in 75 ml. of ether a t -15" was added 0.13 mole of methylmagnesium iodide in 125 ml. of ether. A white solid rapidly separated. The reaction mixture was allowed to warm up to room temperature. I t was then stirred for one-half hour, when i t was hydrolyzed by the addition of 100 ml. of 2 N hydrochloric acid. There was a vigorous gas evolution. The ether layer was washed with 5% sodium bicarbonate and dried over sodium sulfate. The ether was removed under reduced pressure, and the residue dried a t 2 mm. and 30' overnight. Oily crystals formed which weighed 31.1 g. Pressed out to dryness on a clay plate, the crystals weighed 22.2 g., which represents a 59% yield. After three recrystallizations from petroleum ether (b.p., 68-70'), the hard white crystals melted a t 54-55'. Qualitative analysis showed both chlorine and iodine to be present. The Lucas test for a secondary carbinol was positive. A similar reaction is known between epichlorohydrin and methylmagnesium iodide (11). Anal. Calc'd for CaH&llIO: I, 43.8. Found: I, 43.6. l-Trichloro-b-butanol. T o 22.0 g. (0.14mole) of trichloropropylene oxide in 75 ml. of ether a t -75' was added 140 ml. of 1.0 N methyllithium. The solution turned slightly yellow, and the color darkened as the reaction was allowed to warm up to room temperature. No precipitate separated. The reaction product was worked up by conventional procedures and distilled under 3 mm. pressure: 21.0 g. (85%) was collected boiling a t 44-46'. The boiling point under 738 mm. pressure was found to be 169-171". Physical constants taken on the liquid were nt 1.4901,d$ 1.3760. Anal. Calc'd for C4H7ClrO:C1,59.9;M. R., 36.9. Found: C1, 59.8;M. R., 37.3. The compound readily formed a p-nitrobenzoate, which after two crystallizations from petroleum ether (b.p. 68-70') melted a t 70-71.5". Anal. Calc'd for Cl1Hl&l3NO4: C1, 32.6. Found: C1, 32.6. Two isomers are possible: 1-trichloro-2-butanol and 3-trichloro-2-methyl-1-propanol. The above compound responds readily to the Lucas test for secondary carbinols. It also was readily oxidized: a mixture of one part carbinol, 1.3 parts of potassium dichromate in 8% aqueous solution, and 2.0 parts of conc'd sulfuric acid yielded a product which readily gave an addition compound with saturated sodium bisulfite solution, but which gave a negative reaction with Schiff's reagent. Conversion into a known compound as more definite proof of structure was accomplished by refluxing 17.7g. (0.1 mole) of the compound with 100 ml. of 5% sodium carbonate in 50% aqueous alcohol for ten hours. The acid was isolated as the zinc salt which, when decomposed with dilute hydrochloric acid, gave an acid boiling a t 138-141"/11 mm. The distillate solidified to light colored crystals which melted a t 41-43'. Sublimation was noticed in the vicinity of 70'. The anilide melted a t 89-90". The yield was 3.4g. or 46.2%. A mixed melting point of the acid with a-hydroxybutyric acid, and of the respective anilides showed no depression. I-Trzchloro-9-chlorobutane. In the Lucas reaction a hydroxyl group is replaced by a chlorine atom. The alkyl halide separates gradually as the upper layer. In our abovementioned test the reaction was allowed to stand for one hour, and then the upper layer was separated, dried, and distilled. It boiled a t 134-135"/742 mm. and showed these physical constants: nbJ 1.4920,& 1.3932. Anal. Calc'd for C4HllC14:C1, 72.5;M. R., 40.4. Found: C1, 72.4;M. R., 40.7. Chloral and benzylmagnesium chloride (I). To a Grignaxd solution, prepared from 48.6 g. (2.0g. atom) of magnesium and 253 g. (2.0 moles) of benzyl chloride in 1200 ml. of ether and cooled to -20°, was added dropwise over a period of three hours 250 g. (1.7moles) of chloral in 750 ml. of ether, The reaction mixture was then allowed to warm up to room temperature and stand overnight. Hydrolysis was carried out a t 0' by the addition of lo00 ml. of 5% aqueous acetic acid, cooled to OD. The ether layer was washed twice with 100-ml. portions of water, dried over anhydrous sodium sulfate, and the ether was then removed on the steam-bath. The dark fluid remaining was distilled under 10 mm. pres-
REDUCTION OF CHLORAL
229
sure, and the cut was taken between 30" and 80". This cut was then refractionated under normal pressure and the fraction 148.152' taken; weight 2.7 g. This small fraction formed a fairly pure p-nitrobenzoate which after two recrystallizations from petroleum ether (b.p. 60-68")melted a t 70-71' and showed no depression in a mixed melting point with the p-nitrobenzoate prepared from an authentic sample of trichloroethanol. The yield, assuming purity of the small fraction, was 1.06%. This would require 0.44 g. of magnesium, as colloidal magnesium, to perform the reduction. A second cut was made a t 18 mm. pressure and 157-161'. The yield was 110 g. or 26%. The acetate was prepared with acetic anhydride and crystallized from alcohol, m.p. 109-110' (12). This indicated trichloromethylbenzyl carbinol. Chlorcil and benzylmagnesium chloride (11). The Grignard solution prepared from 50.0 g. (2.06 g . atom) of magnesium and 253 g. (2.0 moles) of benzyl chloride was allowed to settle overnight. The clear supernatant liquid was carefully decanted and filtered through an "Ace C" sintered-glass filter to give an absolutely clear solution with a slight yellow-green color. The solution was cooled to -20' (further cooling causes a separation of solid on the walls of the flask) and 250 g. (1.7 moles) of chloral (dried over phosphorus pentoxide arid freshly distilled with careful fractionation) in 700 ml. of ether was added dropwise. The reaction was extremely vigorous. The adduct was quite insoluble and soon separated as a heavy white precipitate; accordingly, the stirring must be efficient. After addition was completed (four hours), the mixture was allowed to warm up to room temperature, and then stirred for one hour. It was then cooled to 0" and hydrolyzed by iced ammonium chloride (300 g. in lo00 ml. of water). The ether layer w m separated, washed with water three times, dried over anhydrous sodium sulfate, and the ether was removed on a bath a t 60'. Distillation was carried out a t 10 mm. pressure, and the fraction boiling between 30' and 80" collected. This was refractionated at normal pressure and the fraction boiling 148.152" collected. The yield was 2.1 g. or 0.82%. The p-nitrobenzoate melted a t 71" and showed no melting point' depression in mixture with an authentic sample. SUMMARY
I n the reaction between chloral and ethylmagnesium halides, no significant quantities of 1-trichloro-2-butanol were isolated. The chief product is trichloroethanol, formed by reduction. 1-Trichloro-2-butanol has been synthesized, and suitable derivatives are described for this alcohol and for trichloroethanol. A small quantity of trichloroethanol is formed by interaction of chloral with benaylmagnesium chloride. AMES, IOWA REFERENCES (1) MEERWEIN, HINZ,MAJERT,A N D SBNICE,J. prakt. Chem., (2), 147, 234 (1936). (2) IOTSITCH, J . Russ. Phys.-Chem. SOC.,36,445 (1904); Bull. soc. chim., [3] 134, 329 (1905). (3) H ~ I B E RBull. T , SOC. chim., [4] 27, 45 (1920). (4) HOWARD, J . Am. Chem. SOC.,48, 774 (1926). (5) DEANAND WOLF, J . Am. Chem. SOC.,68, 332 (1936). (6) KILPATRICK AND BARR,J. Am. Chem. SOC.,62, 2242 (1940). (7) GILMAN,"Organic Chemistry", John Wiley and Sons, Xew York (1943), Second Edition, Vol. 11, p. 1751. (8) WILLSTATTER AND DUISBERQ, Ber., 66, 2283 (1923). (9) LUCAS, J. Am. Chem. SOC.,62,803 (1930). See also SHRINERAND FUSON, "The Systematic Identification of Organic Compounds", John Wiley and Sons, New York (1940), Second Edition, pp. 55-56. (10) ARP~DT A N D EISTERT,Ber., 61, 1118 (1928). (11) KLING,Compt. rend., 137, 756 (1903); Bull. soc. chim., I31 31, 14 (1904). (12) HhERT, Bull. SOC. chim., [41 27, 54 (1920).
