Translated b y
Paul R. Jones a n d Everelt Southwick University
of
N e w Hampshire Durham, 03824
I
V. Grignard: "Concerning Organomagnesium Compounds in Solution and their Application to the Synthesis of Acids, Alcohols, and Hydrocarbonsv
Of
all the organometallic compounds actually known, the only ones which have served up until now as a basis for methods of synthesis are those of sodium, mercury, and especially zinc. Furthermore, it has been possible to use the first two classes of compounds only in a small number of cases, none of which constitutes a widely applicable method (2). This is certainly not the case for organozinc compounds, which, since the outstanding research of Frankland, have constituted a marvelous device for synthesis in the hands of chemists for nearly a half century. As testimony, i t suffices to recall the names of Wurtz, Frankland and Duppa, of Freund, Boutlerow, Reformatsky, of Wagner and of Saytzeff who, listed in the order of their idcas, have remained associated with the classical methods. Whatever may be the importance of the results acquired, however, these methods are not free of rather serious disadvantages. It can be predicted in a general way, in fact, that when one avoids the preliminary Laboratory of General Chemistry of the Institute of Chemistry, Lyon (1).
preparation of the organozinc compounds, the yields are mediocre, if not ridiculously low (exception made, however, for application of the Saytzeff method with allyl iodide or bromide); in the cases where this preparation is necessary, it entails, as is known, a rather tedious manipulation, difficult and even dangerous, because of the facility with which organozinc compounds burn. Thus it was of great interest to replace these compounds by others, prepared directly with facility, more easily handled,, and possessing at least comparable reactivity. But a number of research endeavors concerning organic compounds with different metals have not furnished any encouragement along these lines, and zinc seemed destined to remain without challenge the metal of choice for synthesis by means of organometallic compounds. I n 1898,M. Ph. Barbier (S), employing the method of Saytzeff, carried out the reaction of natural methylheptenone (sic) with methyl iodide in the presence of magnesium. He obtained a tertiary alcohol, 2,6-dimethylhept-2-en-6-01, after the usual work up. Yet this
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,
,
,.
..,,.z'v"
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A Translation of Victor Grignard's First Full-Length Paper
A major area of organic chemistry of continuing importance is based on the gargantuan accomplishments beginning in 1900 of Victor Grignard, whose reagent has become a familiar byword in the vocabulary of most students and researchers of chemistry. The significance of the Grignard reagent is apparent in the extensive treatise compiled hy Xharasch and Reinmuth in 1954.' This has been followed regularly by the publication of an untold uuinher of related papers which promptly caused the treatise to become an outdated compendium The first full-length publication by Grignard containing experimcntal details, based on his doctoral dissertation a t Lyon, was issued in 1901.2 Alt,hough allusions to this prime document are prevalent in the literature, the contents have remained unfamiliar because of its location in a lesser known French journal. No translation into English has been provided heretofore, merely a brief excerpt of an introductory section having been rendered in English by Iiharasch and R e i n m ~ t h . ~ A terse preliminary communication4 by Grignard in 1900, in which he annouuced for the first time the formation of alkylmagnesium compounds in ether, was recently trauslated into English6 but wit,h omission of dny experimental details.
The authors have undertaken a complete translation6 of Grignard's original full paper with the inclusion of pertinent experimental descriptions considered to be of wide interest. Omitted were all numerical and analytical results following the first set included as an example. Effort has been made purposely to retain the flavor of Grignard's narrative--personal, critical, mildly humorous in spots-rather than to modernize the language according to present day usage. Although this paper would in any case have survived as a record of one of the classical pieces of organic chemical research, it is hoped that present and future chemists through this translation will come to know more direct,ly of the all encompassing pioneering experiments t,l~atproduced the Grignard reagent. 'KHARASCH, M. S., AND REINMUTIT, O., "Grigna~dReactions of Nonmetallic Substances." Prentice-Hall. New York. 1954. a GRIGNARD, V., Ann. ~ h . i m .(7) , 24,433-90 (1901). a Foot,notr 1. 5. -,n r . .. ~ m o m m V., C m p l . Rend., 130, 1322 (1900). LI:ICESTI:R, H. M., "Source Book in Chemistry 1900-1950," Rarvard Universit.~ Press, Cambrid~e, - . M~asachusetts, 1968, pp 254-6. 0 Wit,h amistance by: E. J. Goller, R. E. Burnett, S. J. Costaneo, W. J. Kauffman, R. W. Ridgway, J. E. Tomsjzewski, and ST.Sylvia Grassie.
was a novel result. In the first place, organozinc compounds, in reacting with ketones, do not give tertiary alcohols (4); and secondly, the Saytzeff method does not apply to methyl ketones, which generally condense with loss of water (5); there is but one exception, when the alkyl halide introduced into the reaction is allyl bromide or ally1 iodide. I t was therefore of particular interest to investigate to what extent this reaction could be generalized; to study, in a word, what advantages might result by substituting magnesium for zinc, and, upon the advice of my professor, I undertook this project. I recognized shortly that magnesium exhibited a reactivity superior to that of zinc. This allowed its use in many cases where zinc did not react, but on the other hand, rendered the reaction frequently difficult to regulate and almost always led to an abundance of polymerization products. I then considered returning to the method of Wagner, that is, to isolate the organomagnesium compounds. The facts already known about this matter were, however, scarcely encouraging. The most recent studies concerning organometallic compounds of magnesium are those of Lohr ( 6 ) , of Fleck (7),and of Waga (8). These workers have shown that the compounds are solid materials, extremely unstable, reacting with incandescence with water and alcohol, flammable in air and even in dry carbon dioxide, and insoluble in neutral solvents, except in a mixture of anhydrous ether and benzene. Even in this medium they reacted poorly and did not appear to be substitutes for organozinc compounds; moreover, one could only obtain them conveniently by heating alkyl iodides with amalgamated magnesium in a sealed tube, which singularly limited their use. At a previous time, however, Frankland (9) and Wanklyn (10) had attempted, for the preparation of organozinc compounds, a particular method which consists in heating in a closed vessel the zinc and alkyl iodide in the presence of anhydrous ether. They obtained in ether solution the compounds Zn(CHs)2, O(C2H5)1and Zn(CzH5)2,O(C2HJ2 which exhibit very obviously the usual properties of Zn(CH& and Zn(CnH&; but, unfortunately, this reaction was incomplete; and there remained a large mass of solid, which required distillation in the usual way in order to achieve separation of the organometallic compounds. With a metal such as magnesium, more electropositive than zinc and more reactive, one could expect that the preceding reaction would proceed more easily and more completely. This is, in fact, what experience has shown, since I have ascertained that, in the presence of anhydrous ether, magnesium attacks methyl iodide a t ordinary temperatures and that this reaction, which is quantitative, leads uniquely to a product soluble in ether. I have thus been prompted to prepare a certain number of new organomagnesium compounds, which, along with some of their uses, are to be made known in the present memoir. For convenience I shall divide the treatise into five chapters. I n the first, I shall present the actual account of my research on the organomagnesium compounds; in the second, third, and fourth. I shall survey
the action of these compounds on aldehydes, ketones, and esters; finally the fifth chapter will be concerned with a study of some hydrocarbons obtained in the course of the preceding investigations. Chopter I. Orgonomagnesium Compounds in Solution
Prepavation. Let us suppose, for example, that we wish to carry out the reaction of methyl iodide with magnesium. The apparatus simply consists of a flask of about 1-liter capacity, fitted with a two-hole stopper which holds a small dropping funnel and an elbow which may be connected to a good ascending reflux condenser. All of the system being well dried, one places in the flask a gram atom (24 g) of magnesium turnings (11) and assembles the rest of the apparatus. I n the meantime, a solution of equal volumes of one mole of the alkyl halide and perfectly dried ether has been prepared; 40-50 cc of the solution are placed over the magnesium from the dropping funnel. Almost immediately one notes the appearance a t different points around the magnesium of brownish turbidity (white in the case of alkyl bromides), accompanied by a very feeble effervescence. Then the reaction spreads rapidly; white floccules appear, and the liquid begins to boil vigorously. Then one adds 250-300 g of anhydrous ether in two or three portions and a t the same time cools the flask, if it is necessary, in a stream of cold water. The boiling subsides; the white floccules increase again briefly, then disappear almost instantaneously, the liquid again becoming clear and the reaction resuming with renewed vigor. Then one simply maintains the dropwise addition of the remainder of the reactant; under these conditions, t h dissolution of magnesium proceeds regularly, and exactly one gram atom disappears per mole of methyl iodide introduced. For completion of the reaction, it suffices to heat for a half hour on a water bath; and all that remains in the flask is a very fluid, slightly colored solution in which is suspended a very fine black dust formed by a trace of iron which exists as the sole impurity in the magnesium employed (1B). I have observed that the same reaction takes place, and under essentially the same conditions as for methyl iodide, with isopropyl, t-butyl, and sec-hexyl iodides, and with ethyl, propyl, isobutyl, isoamyl, and benzyl bromides; and i t most likely occurs with many other alkyl halides. Moreover, I have found the same results are obtained with bromobenzene and bromonaphthalene, which seems to indicate that the aryl halides can also react with magnesium in a general manner. I am actually studying this novel series of compounds in collaboration with IVI. Tissier; I shall not deal with these here. The ethereal solution obtained as described changes in moist air and reacts violently with water, with formation of magnesium oxide; dry carbon dioxide gas reacts with it to give a crystalline precipitate; finally, it reacts vigorously with aldehydes, ketones, esters, acid chlorides, anhydrides, etc. With the ether vapor as sufficient protection against the return of external air, it is unnecessary to operate in an inert atmosphere; and one can subject the reagent as it is, without modiVolume 47, Number 4, April 1970
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291
fying the generating apparatus, to different reactions effected up until now with organozinc compounds. But before we enter into the details of uses of organomagnesium compounds, one matter above all comes to mind: this is a study of the many properties of these novel compounds and research into their constitution. Let us see in the first place what the formulas are which permit one to explain the preceding reaction between one atom of magnesium and one molecule of alkyl halide. There are two
It is evident that in the second reaction we cannot have (CH&Mg MgL; the investigations of Lohr (6) and of Fleck (7) have demonstrated that dimethylmagnesium is a solid material insoluble or very slightly soluble in ether; on the other hand, magnesium iodide is itself extremely slightly soluble in anhydrous ether (I have found the solubility to be 0.198 parts in 100 a t 17"); for all of these reasons we should have a precipitate. We are thus left with two formulas as in the case of organozinc compounds; the formula of Frankland and that of Gladstone and Tribe (IS). Whichever of these we adopt, one fact is certain: both of these lead to the result that, by the action of water, we must collect one mole of saturated hydrocarbon (methane in the case being considered) per mole of halide employed
+
It was advantageous to verify this first. Action of water. fior a study of the action of water, I allowed 2 g of magnesium turnings to react with methyl iodide, in slight excess, in such a way that the metal was completely dissolved. I carried out the operations in the apparatus previously described; and, when the reaction was terminated, I removed, as well as possible, the vapor which could have remained in a rapid distillation of a certain amount of the ether employed, without cooling the condenser. Secondly, I had arranged in series two bottles, the first empty, the second containing a bubbler in sulfuric acid, the exit tube being fitted to a potassium hydroxide trap of a nitrogen analyzer. Into the system thus constructed, I introduced a current of carbon dioxide gas until all the air had been displaced; then I connected the empty container to the open end of the condenser which was attached to the flask containing the organometallic compound. My apparatus was thus assembled in the following manner: (1) the flask where the reaction was carried out; (2) an ascending condenser; (3) a cold, empty flask serving as a safety flask and condenser for entrained ether; (4) a wash flask charged with sulfuric acid to trap the last traces of ether; (5) a potassium hydroxide trap. This latter attachment, because of its well known design, made it possible for me to control the pressure in the entire system very easily and consequently to introduce water into the organometallic compound and to collect the gas evolved. I thus added the water little by little by means of a dropping funnel; and when the decomposition was 292
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Journal of Chemical Education
terminated, I swept the entire apparatus with a stream - of carbon dioxide. I n this way I collected 1690 ml of gas, theory requiring about 1850 ml (91%). It is essentiallv " Dure . methane. Actually, absorption by amyl alcohol, carried out according to directions of Friedel and Gorgeu (14), gives a coefficient close to (0.45); and a nonabsorbable residue of about 2.5% remains. Xudiometric analysis of the gas regenerated from the amyl alcohol solution gave the following results:' volume of gas, 2.22; oxygen, 9.60; after combustion, 7.69; after potassium hydroxide, 5.66; hence: volume lost V = 4.13; CO; =2.03; H,O = 3.82; all of which leads to the formula Cl.olsHa.sz, or, more sensibly, CHh. Further, one has ~
Calculated
V/C02 = 2.03:. V/HpO = 1.08 V/R%? , . - volume = 1.86 for CH,
2.00
1.00
2.00
I n the same way ethylmagnesium bromide gives pure ethane. The action of water thus proceeds in accord with projected theory. Pure State. Let us now consider the isolation of methylmagnesium iodide. If one distils the ether on a water bath, there remains a gray, highly viscous mass which retains ether tenaciously. Heating for two hours a t 50°/10-12 mm does not alter its appearance appreciably; I thus raised the temperature to 80' and continued to heat for three hours with frequent agitation in order to renew the surface. Under these conditions the light yellow portion distributed on the walls of the flask in a thin layer is dry, but the lower layer still resembles cement and is impossihle to remove without breaking the flask. The dry portion is changed rapidly and very exothermically in air and reacts violently with water. Anal. Calc'd for CHJIgI 2/3 [C~HSI~O: Mg, 11.14; I, 58.99. Found: Mg, 11.03; I, 60.17. Ethylmagnesium bromide, heated on a steam bath for 12 hr a t 12 mm, gave analogous results. . . . It was necessary to heat these compounds i n vacua for several days a t about 150" in order to remove the ether completely. I n the dry state they are in the form of a grayish, oorous mass which resembles barium oxide. As I have already stated, they decompose rapidly and exothermically in air and violently with H20, but without igniting, even if one introduces several drops of concentrated HCl on their surface. They are no longer appreciably soluble in anhydrous ether. I n this form, these compounds appear identical to those obtained by Lohr (15) by the reaction of methyl or ethyl iodide with magnesium in a sealed tube. Actually, as we shall see presently, they are less resistant to the action of heat, but this can reasonably be attributed to their porous structure caused by the removal of ether during drying. The tenacity with which the preceding compounds retain ether leads to the supposition that they contain one molecule of ether, which plays the role of water of crystallization. This is not too surprising if one notes the similarity in structure between these compounds and ether.
+
'The characteristic experimental results are included in the translation only for this first experiment. Reference to the original paper would provide additional experimental detail.
An analogous case has been observed by Frankland (9) who, in preparing dimethyl zinc in the presence of
ethyl ether. and also methyl ether, obtained the compounds Zn(CH&, O(C2H& and Zn(CH,),, O(CHa)%. The constitution of these etherates is not without importance in the reaction which we are studying; in fact, in the presence of other neutral solvents such as benzene or ligroin, the alkyl halides do not attack magnesium, whereas, on the contrary, the reaction proceeds very well in various ethers, as I have verified with isoamyl methyl ether and with anisole. I n addition, this molecule of ether of crystallization appears to play an important role from the point of view of physical properties; it is this which gives the complex its solubility in ether. We have seen, in fact, earlier, that the organometallic compound freed from the ether is not noticeably soluble in this solvent. But the ether of crystallization does not interfere a t all in the chemical reactions, and we shall not concern ourselves with this subject. Action of Heat on Organomagnesium Compounds. Lohr (15) was able to heat methylmagnesium iodide or ethylmagnesium iodide up to 330" without decomposition. This is not the case here. Heated progressively in an oil bath, methylmagnesium iodide decomposes abruptly around 255' while evolving white fumes and abundant violet vapors of iodine; a very small quantity of viscous liquid contaminated with iodine is distilled a t this same temperature. The vapors which were released and which I could not recover, because of the violence of the decomposition, give an acid reaction; they contain without doubt hydriodic acid. I have been more fortunate with ethylmagnesium bromide. This compound, dried on a water bath in vacuo, and then heated gradually gives off, beginning at about ZOO0, a gaseous mixture of a little ether and a trace of fumes which I recovered over mercury. At 300°, a violent decomposition takes place, exactly as in the preceding case, with copious acidic fumes and distillation of several drops of a brown liquid. When this decomposition ceased, I again heated the flask up to 350"; but no more gas evolution occurred. The contents of the flask were not changed. The gas recovered between 200' and 300" was subjected to analysis. The absorption by amyl alcohol is very irregular; the coefficient, which is 2.28 for the first cc, drops to 0.2 beginning with the eighth and then remains constant. Water absorbs nearly a third (33.9/99.8) which must consist primarily of ether. The residue treated with bromine gave the following results. . . . For eudiometric analysis I have absorbed the gas in excess absolute ethyl alcohol and regenerated i t from this solution. . . . This leads to the formula CMHMO or reasonably CaHlo or CzHs. But in considering the relation of volumes involved, one recognizes immediately that the molecule must be represented by CIHj and not by CaHlo.. .. The gas
analysis shows it to be a mixture of equal volumes of ethane and ethylene. For confirmation of this fact, I have regenerated a new portion of gas from its alcohol solution and treated it with bromine, From 27 cc, 13.3 cc were absorbed; that is, slightly less than half. But i t is not surprising that thin proportion varies with the quantity of water introduced, ethylene being about twice as soluble in absolute alcohol as ethane and three times as soluble in water. I have verified finally that the residue which was obtained by treating the gas, simply washed, with bromine, was entirely ethane. I have found that this residue contained about one-third of its volume as ethane and that the rest was a nonhydrocarbon gas, probably air. It did not appear to be liberated hydrogen. I n summary, the gas evolved from ethylmagnesium bromide between 200' and 300" consists essentially of 7 parts ethylene and 1 part ethane. Now it seems that for each C2H6residue transformed into ethylene there ought likewise to be another reduced to ethane, since one does not find hydrogen liberated; this is far from the case, and a considerable amount of hydrogen is lacking, as one can see. I have not as yet discovered the reason for this phenomenon. The solid product which remains in the flask and which, as I have already stated, maintained its original appearance, reacts vigorously with water to give a copious precipitate of magnesium oxide colored gray by strongly adsorbed black particles, insoluble in acid, which are apparently carbon. They are present in a very small quantity, generally less than O.l'%. With respect to the portion soluble in aqueous acid, the following analytical results were obtained. . . . The deficit of magnesium in relation to the formula MgBrz MgO can validly be attributed to a small amount of moisture absorbed by these hygroscopic materials, and to the entrainment of a little magnesium oxide by the gas at the moment when the decomposition is most violent. I n fact, the delivery tube is coated by a light, white deposit. The action of heat on ethylmagnesium bromide could then be explained, in part at least, by the reaction
+
ZEtMgBr or M g E h MgBrz
1-
CxHe
+ CIH. + MgBn + M g
The magnesium liberated, finely divided in this very porous mass, is oxidized immediately in the presence of air in the flask or on decantation to give MgO. I n fact, when one decomposes the remaining product with water under a bell jar of mercury, one recovers only an absolutely negligible quantity of gas, which demonstrates that no metallic magnesium remains. But the two recovered gases are far from being equimolar in quantity; thus other reactions certainly occur as is demonstrated further by the presence of carbon. I n any case, i t is evident from this study that the alkylmagnesium bromides or iodides are completely decomposed by heating, and consequently they behave very differently from zinc compounds of the same type. Constitution of O~ganomagnesiumCompounds. We have already seen that organomagnesium compounds are formed without any precipitate in ether, that in the Volume 47, Number 4, April 1970
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free state they do not ignite in air, that they react with water and likewise with acid without burning, which leads one to doubt the presence of the group Mg(CH3)z or Mg(CrHr)z. The analvsis does not nrovide anv indication since it obviously agrees with both formulas. To complete the analysis it is necessary to determine the molecular weight because the second formula represents a double molecule of the first. I have not been able to pursue this particular point, but I propose to try the ebullioscopic method by preparing the organometallic compound in ordinary ether or in another oxygen ether for which I shall have previously determined the ebullioscopic constant. I n the absence of positive experiments I will rely on various theoretical considerations deduced from the circumstances of formation and the mode of reaction with different functions, in particular with aldehydes and ketones. With the mode of formation in mind, let us study now the action of an aldehyde, for example, on methylmaenesium iodide. If into the ether solution, formed -by the reaction of one mole of methyl iodide with one gram-atom of magnesium, one adds dropwise one mole of aldehyde, a compound forms which, when treated with water, yields 0.6 to 0.8 mole of the expected secondary alcohol. If this molecule of organomagnesium compound is (CHZ)2Mg.MgI2it is evident, according to what is already known about organometallic compounds, that the active part will be simply (CHa)tMg; and consequently, to express the preceding results according to the two hypotheses we are discussing, we will have the following two pairs of equations
-
OMgCHa
Simple inspection of the formulas shows that 1) the first case onlv. -, In " , treatment with water should cause gas evolution. 2) I n the second case, the compound which forms originally contains all the halogen introduced; in the first case, on the contrary, it contains no trsce because it seems very reasonable to assume that, if the group MgI. pre-exists in the organomagnesium compound, it precipitates at the moment of condensation with the aldehyde or ketone. 3) The theoretical yield is, with the first formula, 0.5 mole per mole of alkyl halide used; whereas with the second formula it is 1.0 mole.
Now, here are the obsewations 1) On treatment of the compound obtained from aldehydes or ketones with water, there is never any gas evolution. 2) Certain of these compounds are entirely soluble in ether; there is no MgIl liberated. Others, a n the contrary, are perfectly crystalline, and one does not see a. single crystal system; it does not appear to deposit magnesium iodide a t the same time.
I h v e elsewhere chosen from among these compounds those which appear the most crystalline, obtained by the action of 294
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acetone on methyl magnesium iodide, and have analyzed them after standing 24 hr in a dry vacuum; here are the results obtained. This combination should u'ystdlize, therefore, with one mole of ether and correspond to the formula
.. .
\ /
C
bHZ
+ O(C,Hd*
C H ! Finally, the excellent yields obtained, which vary generally 3) from 0.6-0.8 mole of alcohol per mole of alkyl hdide snd often exceed the latter value significantly, leave no doubt that only the second hypothesis is acceptable.
It is almost unnecessary to add that all other reactions of organomagnesium compounds with esters, acid chlorides, acid anhydrides, etc., are perfectly in accord with this point of view. I n summary, the organomagnesium compounds prepared in anhydrous ether exhibit the following properties 1) They are solids and do not ignite spontaneously in air. 2) They form without liberating magnesium iodide or bromide. 3) Their combination with aldehydes or ketones does not cause any deposition of these same salts; the compound formed contains all of the halogen introduced and decomposes on reaction with water to yield a secondary or tertiary nlcohol without evolution of any gas. 4) The yield in these reactions based on alkyl halide employed is greater than 50%.
All of these reasons lead us to adopt for these compounds the general formula RMgI or RMgBr, in which R represents a saturated aliphatic, aralkyl, or even an aryl residue, in accord with the results of my most recent research in collaboration with M. Tissier (16). Action of Unsaturated Aliphatic Halides on Magnesium i n the Presence of Anhydrous Ether. Until now I have considered only the case of the saturated alkyl halides; actually i t would not be expected a priori that the unsaturated halides would behave very differently toward magnesium. When one allows allyl bromide or iodide to react with magnesium in the presence of anhydrous ether, the reaction, initiated by gentle heating, is more vigorous in the beginning, but quickly subsides because the compound formed is only slightly soluble in ether and is deposited on the bottom of the flask with formation of a somewhat viscous brown layer. Therefore, to complete the reaction, i t is necessary to heat for a few hours on a water bath. When allowed to cool, the allyl bromide compound deposits only a few small crystals on the surface of the ether, but the portion of the allyl iodide compound dissolved in ether crystallizes in large flat needles, colorless and very unstable, not only in air, but also in the mother liquor. Furthermore, one notes that this reaction requires only about 0.5 gram atom of magnesium per mole of halide. The crystals mentioned above decompose on the surface when washed with anhydrous ether; it is therefore preferable for isolation to place them immediately in a vacuum over sulfuric acid. Their analysis gave the following results.. .. Thus the compound formed appears to correspond to the formula CaH5MgI, CIHJ which agrees well with the observation that the reaction consumes only 0.5 gram atom of magnesium
per mole of allyl halide. There is no ether of crystallization, and i t is allyl iodide that takes its place. If this compound were simply a molecular combination of CaHsMgI and C3HsI,it should react in the same manner as the saturated compounds already described; besides, the ally1 iodide that would be liberated probably would attack the unchanged magnesium (in that case where one has used one gram atom of magnesium per mole of allyl iodide) to regenerate the organometallic compound, so that the reaction could continue to completion between one mole of allyl iodide and one mole of aldehyde, for example. I n practice this is not the case, the results obtained h e n being generally mediocre and inferior to those with zinc in the Saytzeff method. I t is therefore probable that the organometallic compound formed has a more complex constitution than that indicated above. I have studied no other unsaturated alkyl halides except the preceding ones; but there is good reason to believe that we are not dealing here with an exceptional case, and that the reaction will proceed analogously, a t least whenever the double bond is sufficiently close to the halogen atom. Secondary Reactions in the Preparation of Organomagnesium Compounds. I have assumed until now that the reaction between saturated alkyl halides and magnesium proceeds entirely according to the equation RBr
+ Mg
+ RMgBr
I n practice this is not at all the case. A primary side reaction, which is present in a11 of the cases, is due to inevitable traces of moisture, which, a t the beginning of the reaction, produce cloudiness and flakes of magnesia that one observes. Thus in a reaction with one mole of ethyl bromide, I have been able to collect up to 100 ml of ethane formed by the following
This is, as one can see, an absolutely negligible source of error not exceeding 0.5%. Another side reaction a great deal more important, which I have already mentioned a t the beginning of my research in connection with benzylmagnesium bromide (17), results from the fact that magnesium possesses a certain tendency to play the same role as sodium in the Wurtz reaction by combining with the halogen and consequently permitting the joining of the two hydrocarbon residues 2RBr
+ Mg
-
MgBn
+ R-R
This reaction is unappreciable with the methyl halides, but its importance increases rapidly with substitution a t carbon. With isobutyl bromide, one obtains a little diisobutyl but generally in an amount too small to isolate in a pure state. With isoamyl bromide, one can collect 10 to 15y0 of diisoamyl; with benzyl bromide, the amount of bibenzyl increases to 30 to 35%, and with 2-iodohexane (18) the dihexyl is ohtained in about 50% yield (19). I n comparing the preceding reaction to the normal reaction, written above, one sees that the latter requires one gram atom of magnesium per mole of the alkyl halide, whereas the former utilizes only 0.5 g atom.
Consequently, I wondered whether by using much finer magnesium turnings, thus providing a larger reactive surface, one might not succeed in diminishing the side reaction with enhancement of the principal one. The result obtained with benzyl bromide confirmed my predictions, but to a negligible extent. As for employing magnesium powder, one can scarcely consider this inasmuch as it is always more or less oxidized. Finally, a last point to mention on this subject is that the normal reaction does not proceed as well with secondary alkyl halides as with the primary ones and even less so with tertiary halides. Admittedly, I have only examined t-butyl iodide in this last category. During the course of the reaction, a gas is liberated that consumes bromine and is absorbed by sulfuric acid; this is certainly isobutylene. Besides, there always remains about half of the magnesium which was introduced. This explains why I have not obtained appreciable results with this compound. But if one considers the ease with which t-hutyl iodide decomposes, under the influence of alkali or certain metals such as sodium and zinc, into hydriodic acid and isobutylene (do), one will understand that i t would be premature to generalize. Action of Carbon Dioxide Gas on Organomagnesium Compounds in Solution. A New Method of Synthesis of Monobasic Organic Acids. Lohr (6), Fleck (7), and Waga (8) have observed that symmetrical organomagnesium compounds ignite in carbon dioxide. I have discovered on my own that the gas reacts likewise with organomagnesium compounds in solution but in a moderate fashion, which has allowed me to study the reaction. If one passes a stream of carbon dioxide gas into an ether solution of methylmagnesium iodide, one notes there is formed immediately a crystalline deposit that quickly causes all of the liquid to become pasty. When this reaction is completed, one adds crushed ice and makes the mixture strongly acidic with sulfuric acid; extraction with ether permits easy isolation of acetic acid, which I characterized by its acidic properties, its odor, its boiling point, and its conversion to ethyl acetate. I n the same way I have verified the formation of isovaleric acid from isobutylmagnesium bromide. The reaction thus appears to be general; I then studied quantitatively a still higher member of the series, isoamylmagnesium bromide. I prepared 0.5 mole of this compound in the usual manner and then bubbled into the ether solution a stream of dry carbon dioxide gas, introduced through a rather large tube. Little by little there was formed a crystalline deposit which partially obstructed the addition tube; then a gray, slightly viscous layer separated, in which a small quantity of crystals was deposited. At the end of five hours there did not appear to be any further change. Then I decomposed i t with ice; only a relatively small quantity of magnesia precipitated, which one dissolves by adding 25% sulfuric acid drop by drop, so that the liquid remains rather slightly alkaline (81). One decants the ether layer, washes it with a little distilled water and distills the ether; there remains a residue of 5 g, which is distilled almost completely at Volume 47, Number 4, April 1 9 7 0
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155-160" and is not noticeably affected by sodium; this is diisoamyl. The aqueous portion remaining is acidified with 100-120 g of 25% sulfuric acid (a little more than 0.25 mole), then extracted three times with ether. All of the ether is washed three times with distilled water and then distilled. The residue purified at atmospheric pressure comes over entirely between 190-200'; from the second distillation I obtained 32 g boiling sharply a t 197" (750 mm). This colorless liquid, distinctly of acidic character, with an odor of perspiration and a t the same time of butter, is isocaproic acid (bp reported to be 199.7' for this acid). The yieldis 55%. I have identified this acid by its analysis and by its transformation to the ethyl ester. (C-H anal. given); ethyl isocaproate: bp 160-162'/747 mm (lit. bp 160.4"); C-H anal. Therefore, one sees that this is a practical method of preparing monobasic acids, probably applicable not only in the aliphatic series but also in the aromatic series, which should frequently be preferable to the potassium cyanide method. The theoretical interpretation of this reaction appears to be the following RMgBr RCONgBr
or else 2RCOJXgBr
+ GO. + H20
+ HnO
-
--
KGOnMgBr RCOIH MgBrOH
(RCOdsMg
+
+ MgBn + Hz0
This reaction of organomagnesium compounds resembles that of organosodium compounds, which also condense with carbon dioxide gas to produce the acid with one more carbon atom than that of the original alkyl radical ($2). Nevertheless, it is necessary to remark that it is sodium, not the method, that is of theoretical interest in most cases. I propose to study the action of a certain number of other gases on organomagnesium compounds; in particular sulfur dioxide, which will probably furnish, as with the organozinc compounds, sulfinic acids; and carbon monoxide which perhaps will lead to aldehydes or ketones ($3). Actual State of the Study of Organomagnesium Comnounds in Solution. While in their reaction with carbon dioxide gas the organomagnesium compounds are comparable to the sodium compounds, in other reactions they resemble organozinc compounds, but with' a considerably greater reactivity. I n order to demonstrate the considerable importance acquired by this major development, I am going to present a brief sketch of the research projects on this subject by other chemists and me since my discovery of organomagnesium compounds. 1. When organomagnesium compounds me treated with water, they decompose to giye the corresponding saturated hydrocarbon, and this reaction may be utilized for the preparation of certain hydrocarbons (18). 2. They combine with carbon dioxide gas, as I have shown, and thus furnish a novel method of synthesis of monobasic acids. 3. With aldehydes and ketones they give compounds that are decomposed by water with liberation of the corresponding seeondary or tertiary alcohol (17). These are two of the points I
likethe previous one, gives excellknt yields. This method has been extended to the fatty acid series hy M Masson (86)and to the aromatic series by MM. Behal, Tiffeneau,
296
/
Journal of Chemical Education
and Sommelet (26); the latter distinguished investigators obtained mainly the hydrocarbons resulting from dehydration of the expected tertiary alcohols. M. Valeur (ST), on studying the action of organomagnesium compounds on esters of dibasic acids, has found that they react s i m i l d y a t both ester functions, which is not the case, as is known, for the method of Frankland and Duppa. (oxdic ester and orgsnozino compounds). In addition, the method is not limited to oxalate esters hut is also applicable to their higher - homologs. 5. I n collaboration with M. Tissier (28), I have shown that acid chlorides and acid anhydrides are converted principally to tertiary alcohols. As a consequence of the very great reactivity of organomagnesium compounds, i t appears difficult to stop the reaction intentionally a t the first stage so as to obtain only the ketones, as in the method of Freund. 6. Earlier Frankland (29) had advanced the hypothesis that one could expect to obtain ketones from the reaction of nitriles with organozinc compounds; hut the efforts of Frankland and his students led to polymerization products of the nitriles. Taking up the ideas of Frankland on this subject, M. Bltlise (SO) carried out the reaction of nitriles with organomagnesium compounds and in fact obtained ketones. Cyanogen gave him symmetrical ketones and phenylisocyanate the anilides. Finally, in extending the method to the esters of eyano acids, M. Blaise has arrived a t s novel procedure for the synthesis of keto acids. 7. I n an aceaunt of the reaction of aldehydes with orgrtnozinc compounds, Wagner (32) concluded that the possibility of oxygenated organic compounds combining with organozino compounds depends upon the presence of a C=O group. M. Moureau (32) has shown that "carbon was not the indispensable element to which the oxygen must be hound in order that attt~ck x PII~I~IICP bj. orgxtrmagnesiun~ dcriva~ivev on o mwhr tw puss>l,lr." \Vith alkyl i.itrirrs. aIkvI ~a~tratrp, and rlitrnrr d~rivntiver,he ha>r h t n i n d , in i w t , diiul,rr~tutedl,\.droxvlamines. These results are moreover similar to those obt&nedby M. Bewad (33) somewhat earlier with organozinc compounds. 8. I had noted a t the beginning of my investigations that hromobenzene reacts in anhydrous ether as readily as methyl iodide. It was very important to verify whether this reaction could be generalized and would lead to the same type of compounds as the alkyl halides. This is, in fact, the case, as M. Tissier and I (16) have shown; thus there is available a novel, very practical procedure for the introduction of aromatic residues into organic compounds. 9. Finally, one other.extremely interesting question again arises. Are the halides derived from polyhydroxy alcohols, of glycols in particular, capable of reacting with magnesium, bonding with several atoms of this metal to give derivatives of the form MgBr
..
MgBr R" being a divdent residue containing a t least two atoms of carbon? The investigations on this point, which I have undertaken in collaboration with M. Tissier (IT), have not confirmed these predictions. A single atom of magnesium consumed t,wo atoms of halogen, and the R" residue was liberated.
All of this work, accomplished since I announced the organomagnesium compounds-that is to say in less than a year-affirms the marvelous facility with which these compounds are adapted to organic syntheses and permits one to hope that an additional number of important results will be forthcoming. I am continuing my investigations in these various areas. Chapter II. Action of Organomagnesiurn Compounds on Aldehydes With organozinc compounds the following reactions occur
With the organomagnesium compounds, the theoretical interpretation remains essentidy the same
+
R'MgBr RCHO Hz0 2RCH(R')OMgBr
+
--
RCH(R')OMgBr 2RCH(R')OH Mg(OHh
+
+ MgBh
The reaction therefore always proceeds in two steps: equimolar coupling of the aldehyde with the organometallic derivative, then decomposition of the complex with water and generation of the secondary alcohol. There is only one case where this method can lead to primary alcohols: that in which one employs formaldehyde which can undoubtedly be replaced by its trimer, trioxymethylene, as in the case of the organozinc compounds (54). I have not yet studied this particular ease. I shall not reiterate the advantages of olganomagnesium wmpounds from the point of view of the method of prepsration; let us survey those which are offered in comparison to the method of Wagner. 1. The first stage in the method of Wagner requires extensive time for completion, one week to two months; on the contrary, a few hoursl~regenerallysufficient in the method with magnesium. of view of yields, in the first method one2. From the half of the elkyl halide is theoretically lost through formation of hydrocarbon R'H. The new method presents no such difficulty in view of the constitution of the organomagnesium compounds. 3. The method of Wagner, although slow, gives the best fesults with primary organosinc compounds, but from propylzlnc one observes secondary reactions, among which the most common is the simple reduction of the aldehyde to the corresponding alcohol (%), which lowers the yield considerably. We shall see, on the contrary, that one can proceed with magnesium a t least to the amyl derivative before this phenomenon occurs. Finally, I must point out in favor of sine that Wagner (36) and especially Fournier (37) have been able to apply the method of Sxytzeff to a certain number of aldehydes, but only for the formation of allylic secondary dcohals. This is a point to remember for, as I have already indicated, i t is precisely the allylic com~ o u n d sof mamesium which lend themselves very badly to synthesis. Ezperimental Method. The experimental method-bringing abont the reaction of the organomagnesium compound with an ddehyde, ketone, or ester--being always essentially the same, I will describe it once for all cases so as not to be repetitious. After one mole of organomotallic compound has been prepared in anhydrous ether solution, as I have previously described, one recools the flask under a stream of water and introduces drop by drop, by means of an addition funnel like that already used, a. mixture of equal volumes of anhydrous ether and the qusntky of aldehyde (one mole), ketone (one mole), or ester (one-half mole) (88) which is expected to react.. In the majority of cases, this reaction is very vigorous, s t least s t the beginning; each drop produces a decreasein the exothermic nature of the reaction and gives rise generally to a white or yellow flaky solid which sometimes redissolves immediately, sometimes deposits in the form of a crystalline mass, and finally forms a more or less fluid, grayish layer in the bottom of bheflask. When all the mixture has been introduced into the flask, one can heat it a few hours on a steam bath a t gentle reflux, and this works very well when the compound formed is soluble in ether; but, in other cases, to avoid local superheating, i t is preferable to allow the flask to stand one day a t laboratory temperature. The contents of the flask are then poured gradually onto ice, after which one dissolves the msgnesium by ndding in small portions hydrochloric acid or, better, aeetio acid in dilute solution. Theoret,ically, one mole is required; i t is necessary in reality to introduce s little excess; in any case, one stops when the liquid becomes clear and slightly acidic. One then decants the ether layer and, in the case when the alcohol formed is soluble in water, one subjects the aqueous portion to steam distillation and then separates the alcohol from the distillate with potassium carbonate. The ethereal solution is washed with sodium bicarbonate rather than carhonete to avoid precipitation of magnesium salts, which are slightly soluble in ether. I t is necessary to follow this by treatment with sodium bisulfite to remove the aldehyde or ketone which hsa not reacted and then to finish with a fresh bicarbonate wash. One distils the ether with suitable precautions, depending on
the volatility of the dissolved alcohol, and purifies the residue a t ordinary pressure or reduced pressure according to the circum~tances. After distillation of the alcohol there generdly remains in the flask a very small quantity, sometimes none, of polymerization products which decompose when distilled. As for the alwhol, a second purification suffices in most cases to obtain i t very pure and absolutely free of halide. I hsve applied this method to the following aldehydes: In the aliphatic series, ethanal and valeral (sic) which are saturated; crotonaldehyde, methylethylacrolein, citronellal, and lemonal, which are unsaturated; in the aromatic series, benzddehyde and :furfural. Lemonal provided a hydrocarbon which will be taken up in Chapter 5. [Preparation of the following compounds is then described individually. For reasons of brevity here, the name of each product is followed by the reagents used in its preparation; (yield); boiling point; and indication of other information included (density, refractive index, elemental analysis).] Isopvopyl Alcohol: CHGHO CHsMgI(67'%) (The reaction failed when ethanal was replaced by paraldehyde (59)) (CHs)&HCH2MgDiisobutylearbinol: (CHs)2CHCHnCH0 Br(650/,) bp 172-174'C/750 mm; d, n, C-H anal. acetate: bp 183'/750 mm CHaMgI(-) bp 1205-Paten-$-01: C H G H = CHCHO 12Z9/735 mm; d, n, C-H a n d . acetalc: hp 136-137"/ 751 mm CHs5-MethybPhezen-8-01: CHsCHzCH = C(CHa)CHO MgI(65%) hp 8g0/55 mm; d, n, C-H anal. acetate: 9597'/50 mm (CH&CHCHr 7-Methyl-8-oden-4-01: C H C H = CHCHO CH2MgBr(48%) bp 89-9l0/11 mm (Trace of hydrocarbon obtained as well) acetatc: bp 96-98"/13 mm 5,9-Dimethyl-8-decenY-01:citronellel C2H5MgBr(65-70%) bp 113-116"/8mm; d, n, C-H anal. acetatc: bp 120-123"/ 8 mm
+
+
+
+
+
+
Aromatic Series. By reaction of henzaldehyde with methylmsgnesium iodide and ethylmagnesium bromide I have obtained in excellent yield8 (78%) phenylmethylcarbinoI and phenylethylcarhinol. Phaylpropylea~binol: (40) bp 113-115°/10 mm; d, n, C-H anal. aeelate: hp 117-11S0/8 mm Phaylisop~opylearbinol: (41) CsHaCHO (CHa)>CHMgI(51%) b~ 112-113°115 mm:. d,. n.. C-H anal. acetate: bp i?-1i5"/20 mm (CH8)~CHCHzMgBr(-) Phenylisobutylcarbinol: CsHsCHO bp 12Z0/9 mm; d, n, C-H anal. acetate: bp 125-126"/9 mm (CHa)GHCH%CHxMgPhenyliswmylcarbinol: CaHaCHO Br(56%) bp 13Z0/8 mm; d, n, G H anal. acetate: bp 137139"/9 mm (Traces of diisoamyl snd beneyl alcohol were also produced.) Isoamylfurfurylcarbinol: fnrfural (CH3)&HCH2CH.MgBr (43%) bn 118'114 mm: d. n. C-H anal. acetate: b~ 123-
+
+
+
+
Bensylmagnesium bromide did not give good results with aldehydes but, appeared to polymerize; but we shall see presently that i t reacts smoothly with acetone. One can see that aliphatic organomagnesium compounds react very satisfactorily with a variety of aldehydes in yields equal if not superior to those from the Wagner method, when the latter is applicable. For the preparation of one mole of alkylmagnesium hdide only one mole of alkyl halide is needed, whereas two molm are required for orga-nozincs. Thus one om say that the new method, besides being general, gives yields based on alkyl halide s t least double those from the method of Wagner.
Chapter Ill. Action of Organomagnesium Compounds on Ketones The theoretical interpretation is the same as in the case of the Saytaeff method where ally1 iodide or bromide is used
+
R'MgBr RRICO 2H2O ZRR,C(R')OMgBr
+
--
RR,C(R')OMgBr RR,C(R')OH MgBrs Mg(OH)*
+
+
The major advantage of organomagnesium compounds is their normal reaction with methyl ketones, which is the case in the Saytseff method only for allylzinc compounds. Volume 47, Number 4, April 1970
/
297
I shall consider in this c h p t e r the ketones which have afforded stable tertiary alcohals.
+ + +
CH~MgI(700/o)mp 25' Trimdhylearbinol: (42) CHsCOCHa Pntamrlhylelhonol: (43) CHsCOCH3 (CHa)GMgI (trace of hydrate) Dimcthylisoamylucvbinol: CHsCOCHs (CHI)~CHCH~CHIM~Br(46%) bp 150-153'/756 mm; d, n, C-H snal. acetate: bp 171-173°/745 mm (Traces of mesityl oxide and phorone are also produced.) CHaMgI(65'%) bp Phenyldimdhylcarbhol: CsHsCOCHz 91°/X mm; mp 23'; C-H anal. (Previous attempts to synthesize t,his alcohol with organozinc reagents failed (44, 45).) The dehydration product was formed in 21yo vield dmine the resetion and ouantitativelv when acetvlaiion of the &ohol was a t t e m ~ t e d . Bnzyldimethylearbinol: (46) CHaCOCH$ CsHsCH2MgBr(33%) bp 103-105"/10 mm; mp 0"; d, n, C-H and. (A l u g e amount of bihenzyl was formed; the alcohol was de-
+
+
.
,
.
.
u
,,
snsl. (The slcohal was dehydrated completely under scetylation conditions.) The preceding syntheses demonstrate that organomagnesium compounds react very satisfactorily with methyl ketones. Furthermore, this method requires only one mole of halide per mole of ketone. In the Sayteeff method, excepting the synthesis of tertiasv allvl alcohols. two to three moles of halide are reauired
Chapter V. Some Hydrocarbons Obtained During the Preceding Studies Of the alcohols that I have tried tb prepare by the previous methods, a certain number (especially tertiary alcohols) were not sufficientlv stable for isolation. In these cases the corremondine" dehydratkn products were obtained. I have observed this in t,he aliphatic series only where dehydration of the alcohol formed a conjugated double bond; bhus lemgave the hydrocarbon while anal (2,6-dimethyl-2,6-octadien-8-al) citronellal (2,6-dimethyl-2-octen-X-al) gave a. stable alcohol; eynthetic methylheptenone (2-methyl-l-hepten-6-ane) gave the hydrocarbon while natural methylheptenone (%methyl-2-hepten-6-one) led to a stable alcohol (58). There is no general rule, however, dehydration in the case of aldehydes apparently being the exception. Even though dehydration occurred with every unsaturated ketone I have studied, nevertheless tertiary 2,8-en018 are known to exist; for example, dimethylisoallylcarbinol (57) (4-methyl-2-penten-4-01) and dimethylisopropenylcarbinol (58) (2,3-dimethyl-1-huten-3-01), I n the aromatic series this instability was much more common and there was no requirement for an adjacent double bond; thus cinnamddehyde, anisaldehyde, piperonal, henzylidene acetone and naphthyl methyl ketone gave hydrocarbons. With tertiary dcloohols derived from aromatic mid esters, this dehydration appears to be almost a general rule (26). Finally in the terpene series I have worked with carvone, pulegone, and menthone, all of which affordedhydrocarbons. I n this chapter I will describe few of these compoundsand a. few other hydrocarbons (59) t,hat were obtained by dehydrating dcohols studied previously. 2,4-Dimelhyl~1,3-pntadin~: Mesityl Oxide CH~Mgl(707~) bp 92-93'/750 mm; d, n, C-H anal. letmbromide (unstable), dibromide: bp 83-84"/7mm, dimer: bp 98-100°/12 mm; d, n 8,8-Dimethyl-1,s-heptadiene:Methylheptenone (48) CHsMgI(-) bp 143-145"/755 mm; d, n, C-H anal. bis-hydrobromide: h p (dec) 110-1129/10 mm 4,8-Dimethyl-1,S,7-nmatrine: Lemonal or Citral CH3MgI ( - ) bp 193-197'/750 mm, 76-78'/8 mm; d, n, C-H anal. tris-hydrobromide (probably a mixture): Br anal, cyclic isomer: hp 67-69"/9 mm; 183-185"/744 mm, di-hydrobromide: hp 130-135'/10 mm; d, n [The cyclic isomer, shown to he the same (bp, d, n) as that from dehydration (49, 50), was assigned the of 4,8dimethyl-1,7-nonadien4-ol structure: 1,3-dimethyl-1-allyl-3-cyclohexenel 3-Methylme-A-menthem (4, 8): Pulegone CHaMgI(-) bp 64-65'/9 mm, 177-17g0/744 mm; d, n, C-H anal. dihudrobromide: Br anal. CHaMgI(-) bp 72-74'/ 3-Mel~ylenementhane: Menthone 10 mm; d, n, C-H anal. (CHp 8,6,8-Tvimethyl-4mme: Methyldiisoamylcarbinol CO)20(-) bp 74-76'/9 mm; d, n, C-H anal. (Oxidation gives only acetic and isavalerie acids) (CHaCO)rO, C H r a-Methylstyrene: Phenyldimethylcarbinol COCl or HI(-), bp 158-16O0/748 mm (51 ), d, n, C-H anal (~olvmerizes~artiallvon distillation and little bv little a t room temperature) &ibromide: bp 111-114"/7 m i , dimer: mp 52-53' (triclinic prisms) (58); bp 158-1.59°/8 mm (CHT 1-Phayl-2-Melhylp~opne: Beneyldimethylcarbinol CO).O(-) bp 183-18.i0/748 mm, 76-77"/11 mm; d, n, C-H a n d (Oxidation gives acetone, benaoic acid. and a trace of benzaldehyde, in accord with the hydrocarbon already obtained by Perkin (5S), Fittig and Jayne (54), and Liebmann (55).) 1-Phenyl-3-methyb1,S-butadiene: Benealacetone CH3MgI (-) bp 115'/18 mm, mp 27"; C-H anal (polymerizes rapidly) (CHI2-a-Naphthylp~opac: a-Naphthyldimethylcsrbinal C0)*0(-) bp 125'/8 mm; d, n, C-H aual. picrate: mp 91"; Nsnal CHIM~I 2-b-Naphlhylpropene: 8-Naphthyl Methyl Ketone (80%) mp 46-47'; C-H anal, picrole: mp 88'; N anal 2-(4-Naphthy1)-5-methyl-(?I-hexene: p-Naphthyl Methyl Ke(CH3)1CHCH1CHzMgBr(75Yo)bp 17.5-178"/10 tone mm:~ d., 11., C-H anal. oicrate; mD 46-47idl: . ., N anal. (1 have not prepared the hydrocarbon in sufficient quantity to carry out an oxidative degradstion.) I n summary, i t can be seen that organomagnesium compounds ~ r o v i d ea convenient route to the svnthesis in excellent vield of
+
mule. I hope soon to study bhe application of this method to diketones.
Chapter IV. Action of Organomagnesium Compounds on Esters The reaction occurs in three steps, as in the Wagner-Saytzeff method RCOOC,H,
+ R'MgBr
-
RR'C(OIMgBr)OCaHs
(1)
+
+
+
A8 one can see, two males of alkyl halide per mole of ester were employed, whereas in the Wagner-Sayt,zeff method four moles of halide are required, for reasons already given in Chapter 11. Furthermore, the Wagner-Saytneff method appears to be of practical use only for formate ester with saturated alkyl iodides. Other esters react only with ally1 iodide. On the other hand the method is quite general with the organomagnesium compounds, as shown by investigations (84), followed by those of Masson (25) in the aliphatic series of Behal, Tiffeneau and Sommelel (26) in the aromatic series, and of Valeur (67)wit,h esters of dicarboxylic acids.
+
C.HsMgBr(73%) bp 114Dielhylearbinol (4): HCOOCIHs 115"/749 mm; d, n Diisoamylearbinol: HCOOC2Hc (iso)CoHlrMgBr(-). The initial major product was the formale ester (hp 100-10Ia/8 mm; C-H anal.), which could be saponified to the alcohol: bp 105"/9 mm; d, n, C-H anal. (iso)C4HqMgBr(-). The Diisobulylearbinol: HCOOCIHs init,ial product was a mixture of free alcohol a n d f m a l e ester, hv 173-1759/750 mm. The alcohol was obtained bv . sanoni. fication. Trimethylcarbinol: CHaCOOCHs CHaMgI(82%) Mrthyldiisoamylcarbinol: CHICOOCHJ (iso)CsH~~MgBr(45%) bp 108-109°/10 mm; d, n, C-H anal. acetate: bp 1209/16 mm. Phenyldimethylcarbinol: CrHsCOOCHa CHaMgI(78%)
+
+
+
+
+
These results in combination with the information shown a t t,he beginning of this chapber clearly demonstrate the superiority of this new method to that of Wagner and Saytzeff. I am contin,ling l o st,rtdy the ester group in f~tnctionallymbstitnted esters, especially that in keto esters.
298
/
Journol of Chemicol Education
+
+
+
+
+
+
+
+
Conclusions
From the preceding research the following conclusions have been drawn. I. The saturated alkyl halides (bromides and iodides), both aliphatic and benzylic, react easily with magnesium in the presence of anhydrous ether to give organometallic compounds of the general formula RMgI or RMgBr. The' reaction is different with allyl bromides and iodides, which give compounds of the form C8H6MgI.C3HSI; hut these can become normal again when the double bond is removed from the halide. 11. The organomagnesium compounds, completely soluble in anhydrous ether, can be used directly in this solvent. I n a great majority of cases, these compounds can replace the organozinc compounds, with important advantages. (1) They are very easily prepared and handled without the slightest danger of igniting. (2) They exhibit a much broader reactivity, reacting more rapidly, more completely, and in a greater number of cases. (3) They are much more numerous and in particular can contain aromatic residues, which has not yet been realized with zinc. 111. Their decomposition by water gives saturated hydrocarbons, and this reaction can be utilized in a certain number of cases as a preparative method. IV. I n certain reactions, they resemble organosodium compounds. Thus they combine with carhon dioxide to give compounds which upon hydrolysis furnish, in good yield, a monohasic acid containing one more carbon atom than the original halide. V. With saturated or unsaturated aliphatic or aromatic aldehydes and with furfural these compounds generally give secondary alcohols and do not undergo side reactions, which do occur with propylzinc by the Wagner method. Furthermore, yields based on the alkyl halides employed are at least double those furnished by the Wagner method. VI. Upon reaction with aliphatic or aromatic ketones, saturated or unsaturated, they generally lead to 3" alcohols. Here they exhibit a reactivity distinctly superior to that of organozinc compounds, which do not react with ketones. I n addition they react at the carbonyl of methyl ketones, which are resistant to attack or are condensed by the method of Saytzeff (allyl compounds excepted). These properties have permitted the synthesis of 3' alcohols which could only be accomplished previously by the method of Boutlerow; the latter occasionally is found to be inadequate, as in the case of phenyldimethylcarbinol. Finally, the yields obtained here are a t least three times as high as those by the Saytzeff method. VII. By condensation with esters, organomagnesium compounds lead to symmetrical 2' alcohols from formates and symmetrical 3" alcohols from other esters. Because of the ease of execution and the excellent yields obtained, this method appears destined to replace Boutlerow's method whenever the ester can he used in place of the acid chloride. VIII. These investigations have shown, finally, that in general 3' alcohols and sometimes 2' a,8-unsaturated I ~houldbe able to include sec-butyl alcohoi, which I have not tried to make but which ought to be easily obtained by the action of propanai on methylmagnesium iodide or, better, by the action of ethand on ethylmagnesium brom~de.
alcohols are unstable and dehydrate on attempted isolation to give a 1,3-diene and not an allcne. I n addition, 3' alcohols derived from cyclic ketones and 3' 8naphthyl and carbinols are not stable or only slightly so. IX. The application of my method to aldehyden, ketones and esters provides a very practical preparation of certain alcohols, such as isopropyl- and trimcthylcarhin01.~ Its value is demonstrated by the synthesis of 29 new alcohols or hydrocarbons. Bibliography (1) . . Tins rooort has been nubiished with some additional details as Doctoral ~ h & (Lyon, ~uly; 1901). (2) I s m omittine here compounds of the sodioaostoaoetic eater and metal cyanide ty& whioh possess particular characteristics and are of coo-
siderable imwrtanoe. (3, B ~ n r n ~ n Ph., . Compt. Rcnd.. 128,110 (1899). (4) W ~ o ~ e G., n , A N D SAITZEFF. A , , Ann.. 175,351 (1875). A , , A N D S A T T Z EA,, > ~J . Prokt. Chcm., [21 34, 194 (5) TBCHEBOTAREFF, ,,P.s,I, \.--",.
(6) (7) (8) (9) (10)
P.,Ann..261,72(1891). W A ~ AF.., Ann.. 282,320 (1894). La"=.
FLECK.H., Ann.. 276,129 (1893).
F ~ A N X L A E., W DPhiloa. . T7ansoclianr. 149. 412 (1859). W A W X L ~JN. .A,, J . Chem. Sor., 13, 125 (1861). (n)The turnings \vhieh I prefer to nse are 3 mm wide and 0.6 mm thiok.
(12)
Cut to these dimensions, the metal is not in the iorm of ribbon but is torn by the cutting tool into shredded torninps, consequently providing a large surface. Themagnesium titrates99.%99.4%. G L A D ~ T O NJ. E ,H.. A N D TRIBE, A,, J. Chem. Soc.,26,445 (1873). FRIEDEL, C . . A N D GOROEU, A,. Compl. Rend.. 127,590 (1898). LSxn, P., Ann.,261,48 (1891). TISSIER, L., A N D GRIGNARD,V.. Corn$. Rend., 132,1182 (1901).
(13) (14) (15) (16) (17) G m o l r ~ n oV.. . Compl. Rend., 130. 1322 (1900). (18) Tzssmn L., AND O n r c n ~ n nV.. . Compl. Rend.. 132,835 (1901). (19) I n the reaction of magnesium with hiiyl bromide or iodide there is iikevise a oertain amount of biallyl formed. (20) B o u ~ ~ s n o w A,., Zeil. Chem.. 10, 362 (1867). Doanrs. L., J . Chem. Soc.. 37.236 (1880). (21) One C & also aoidifr in the presence oi ether, but the ether must be
extracted with hiasrhonate to remove theisoeaproic acid. (22) WANKLYN. J. A , , Ann., 107. 125 (1858); T i ' m ~ ~ r nJ ,. A,, ibid., 111, 234 (1859); KEXULE,A,. ;bid.. 137, 129 (1866): M u m . AND MULLEA.E.. 8 9 7 . . 15. 496. I903 (1882): .. . . TVAWKLIN J. A . A N D
698. S C X = N X , ' R . , ' AV I~, 120 ~ . (1868). S~~~I.
R..
(23) W m x ~ n r J. . A . [Ann.. 140, 211 (1866)l hss obtained diethyl ketone hy thesstiotl oi CO on a heated mixture of (C?Hs)zZn and Na. (24) Gmawno, V., Compl. Rend., 132,336 (1901). (25) M ~ s s o a H., . Corns. Rend.. 132,483 (1901). (26) BE%&, A.. Compt. Rend.. 132 480 (1901). (27) V ~ b e u n A . , . Compl. Rend.. 132,833 (1901). (28) Tmsrm, L., AND Gmamnn, V., Compt. Rend., 132, 683 (1901). (29) FAANXLAND. E.. PIOC.Rau. Soc. (London). 8.506 (1857).
TISCXTSOHENKO. B&.. ZOB.704 (1887). WAcsnn, G., Bcr., 17B.314 (1884). W A ~ N E RG.. . Bar., 21,3347 (1888). Founliren, Dootoral Thesis, Paris. 1898. This lholds only for esters of monohasio aoids; ior esters of dihhsio acids only 0.25 mole is rewired. This was already tentatively established for the organorinc compounds hy Wagner, G. and Wedinsky, TT. [J. Pmkt. Chem., (21 39, 538
(1889)l. (1891).
(40) M*nax*m, T . R., * s o Pmnum, W. H., Jn., J . Chem. Soe., 59, 853 (41) CTAUB,A,. J. Pmkt. Chsm., [2]46. 481 (1892). (42) B o u ~ ~ s n o A,, w , Bull. Soc. Chim. F~ance.[21 1, 106 (1864). o wAnn., , 177, 176 (1875): K*scmnsrr, J . Russ. Phva.(4%) B o n ~ ~ ~ n A,. . ~Ann., , 209, 70 (1881). Chem. Soc., 13, 86 (1881): I l o a a ~ o ~ pJ., (44) D=r.*cn~. M., Deilstein's Handbuch der oroanischen Chemie. 3, 119. 249 (1892). (45) B o u r ~ ~ n o A,, w , Bull. Soe. Chim. France, [2l 18 (1866). (46) W r m o ~ n o o C ~ ,. 11. C . , A N D GEN~LBEA, J. Prakt. Chem., [2l 37, 367
(1888).
(47) W ~ n r r e n G.. , A N D SATTZEFF, A. obtained this in only 24% yield (Ref. ,& , ~-,,.
B*nsren. Ph., A N D EOUVEAULT. L.. Compl. Rcnd.. 118,198 (1894). TIEMANN. F., ANDSCAMII)T, R., BcI., 29,691 (1896). B*nsrsn,Ph.. A N D BOUVEAULT, L., Compl. Rcnd., 122,842 (1896). The boilinp: point has been erronmusly reported aa 158-160e/8 mm
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