Gurnos Jones
University College of
The Markovnikov
North Staffordshire Keele, Staffordshire, England.
[he Markovnikov Rule is one of the best-known of the empirical rules of organic chemistry. It is encountered at an early stage in the teaching of organic chemistry; it is comprehensive and easy to remember and it is capable of clear theoretical explanation even at an elementary level. Yet it is often stated in a form appreciably different from that in which it was enunciated by Markovnikov, and it was the subject of an interestina - controversy between Markovnikov and L. Henry. The first statement of the Rule in an accessible journal seems to have been in Liebig's Annalen in 1870 ( 1 ) under the somewhat uninformative title "Communications from the Chemical Laboratories a t Kazan" [where Markovnikov was at that time a professor ($)I. A large section of the communication was devoted to a study of the isomeric hydroxybutyric acids; the intermediate for the synthesis of one of the isomers was propylene chlorhydrin, derived from propylene by direct addition of hypochlorous acid. After some discussion of the apparently contradictory modes of addition of hypochlorous acid to propylene and to "butylene" (by which Markovnikov meant iso butylene from the formula given) Markovnikov decided that it was not possible to propose a general rule for the addition of "(0H)CI" to unsaturated hydrocarbons. He went on to say that such a rule could be formulated for the addition of hydrogen halides to unsaturated compounds; then followed the original statement of the Markovnikov Rule: When a hydrocarbon of unsymmetrical structure combines with a halogen hydracid the halogen adds itself to the less hydrogenated carbon atom, i.e. to the carbon whioh is more under the influence of other carbon (atoms).
As examples of the Rule relating to hydrocarbons Markovnikov quoted the addition of hydriodic acid to propylene, to two butylenes, and to an amylene: (1)
CHs CH CHI
(3)
CHa CH CzHs
CH* + HJ = CH, CHJ
+ HJ =
CH. CHs CHx
(2) C
CHa CHJ C2Ha
(4)
CH* CH CH2 CaH,
CHa + H J = JC CHa CH1
CHI + HJ = CHJ
C& CzHr
and of hydrogen chloride to another amylene CH, CH CH CHa
+ CH1
HCI
=
CHz
CHI CHCI CH
CHa
Markovnikov then extended the Rule to include unsst,urated cornponnds having a halogen atom already attached to one of the carbon atoms forming the double bond :
I n the addition of hydrochloric, hydrobramic, or hydriodic acids to vinyl chloride, chlorinated propylene and other analogues, the halogen adds to the carbon atom which is already hound to a halogen (stom).
The examples quoted for this extension of the Rule are interesting because less obvious (apart from the addition of hydrobromic acid to vinyl bromide to give ethylidene bromide and not ethylene dibromide: CHa
CHa + HBr = CHBr CHBr,.
Thus, Pfaundler had reported (3) that the product of addition of hydriodic acid to vinyl bromide gave, on treatment with silver oxide and acetic acid, aldehyde (acetaldehyde). Markovnikov interpreted this reaction as follows: CHs CHBrJ
+ 2C2H3O2Ag=
CHa
C3Ha0 AgBr + 0 + CHO CzHIO AgJ
Using more highly unsaturated compounds as examples Markovnikov noted that acetylene adds on two molecules of hydriodic acid (a process used in its purification) to give "an isomer of ethylene iodide." CH CH
+ 2HJ
CH, =
CHJ
+ HJ =
CH, CHJ,
and allylene
Nothing further was added to these first simple statements of the Markovnikov Rule until 1871, when L. Henry, already well-known for his work on allylic compounds, published a paper "On the products of addition of propylene to hypochlorous acid" (4). This paper commenced with a statement of a general law hearing a considerable resemblanre to Markovnikov's Rule, hut with no mention of Markovnikov in this connection. The general lam was When a molecular system XX', madeup of simple or compound radicals, different in nature, quality, and chemical energy approaches an unsaturated .compound C"Hm, . . . , I- containing unsaturated carbon atoms unequally hydrogenated, such as CHP, CH, and C, the radical X, negative or more negative, attaches itself to the least hydrogenated carbon atom, and the radical X', loss negative, the 'positive' radical either absolutely or by comparison, attaches itself to the more hydrogenated carbon atom.
This was a much more general law than that statedby Markovnikov, and Henry went on to say that the law was confirmed, notably, by the mode of addition of hypochlorous acid; that there were numerous examples to prove this, but that he would deal only with the Volume 38, Number 6, June 1961
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297
allylic derivat,ives. I-Ie had previously ~eportedthat allylic derivatives (C3H5)X combine readily with a molecule of (0H)Cl to give glycerol chlorhydrins which are primary alcohols; hence they must be CHZX CHCl CH20H
Since allyl derivatives are merely primary derivatives of propylene, then propylene should add on (0H)Cl to give CH'OH CHCl CHa
But Markovnikov in his paper had stated that the chlorhydrin of propylene was a secondary alcohol, since on oxidation with dichromate and sulfuric acid it gave chloro-acetone. This, in Henry's opinion, constituted the sole exception to his law and he wrote In spite of all the esteem in which I hold the fine works of M. Mctrkovnikav, and the authority of his name, I cannot, after reflection, accept his opinion as the truth. I have re-read his work attentively; it is irreproachable as regards the facts, and I admit the reality of all the experimental details contained in it; but I reject the conclusion as to the nature of the addition product from propylone and hypoohlorous acid. This conclnsion is not justified, in a rigorous or certain manner, by any fact.
Henry pointed out subsequently that the structure of this product of addition could be proved either by reduction or by oxidation. On reduction one possible chlorhydrin would give normal propanol, and the other iso-propanol; on oxidation one would give chloroacetone (as Markovnikov had already reported) and the other chloropropionaldehyde. He also pointed out that the properties reported by Markovnikov for his 'chloro-acetone' were those to be expected for chloropropionaldehyde. Finally Henry announced that he had oxidized propylene chlorhydrin beyond the point reached by M. Markovnikov and that he would publish the results in a subsequent communication. Before this other evidence was forthcoming, however, Markovnikov had replied with three commnnications under the title "On the laws which govern direct addition reactions" which were submitted by Wurtz and published in Comptes rendus (6, 6, 7). I n the first of these Markovnikov's Rule was presented in its final and more general form, obviously much modified by Henry's intervention. Markovnikov commenced his paper with a re-statement of the Rule in its original form, "in which state the question has remained for more than five years," and noted that "among the studies concerning these laws were those of M. Henry." Further "that in studying derivatives of the allyl group this chemist has arrived at conclusions, of which the resemblance to those that I have advanced seems t,o have escaped his attention." He then discussed Henry's view of direct addition and decided that both Henry's law and his own Rule were too "absolute," and required qualification ("It seems to me that the form given by M. Henry is too absolute and does not always coincide with the views of other chemists"). The direction of addition is obviously dependent on the conditions of the reaction, of which Markovnikov mentions temperature. Reboul had shown that monobromopropylene added hydrobromic acid to give either 298 / Journal of Chemical Education
CHaCHBrCH2Br or Ci13CBr%H3 depending on the conditions used.* Markovnikov then proposed the linal form of his Rule: When a molecular system YZ approaches an unsaturated mole cule CnHmXa t low temperature, the more negative element or p u p Y combines with the less hydrogenated carbon atom, or with that which is directly attached to some negative element; but at compmittively higher temperatures, it is the element Z which combines with the less hydrogenated carbon (atom), that is to say that, for the same substances, the reaction takes a. direction exactly opposite from the first.
In his next paper, Markovnikov noted that the uniformity of addition is often masked, since ordinarily both possible products of addition occur together. The proportions of the isomers formed varies according to the conditions of reaction, and this led Markovnikov to the conclusion that it should be possible to control the direction of addition. On the structure of propylene chlorhydrin, Markovnikov's reasoning was less assured. He pointed out that Butlerov had reduced the chlorhydrin to 'pseudopropyl alcohol,' but then went on to discuss the formation of the dichlorhydrin of glycerol from epi-chlorhydrin CHzCl CH O+HCI+ CH'
CHZCl CHOH CHU
He concluded that attachment of the hydroxyl group to the less hydrogenated carbonatom during this reaction indicated that the hydroxyl group had a greater affinity for such a carbon atomnon sequitur that Henry was quick to point out in a subsequent paper. But Markovnikov ended his paper by stating once more that there were two contradictory lindings for the addition of hypochlorous acid to unsaturated hydrocarbons and hence no definite rule could be advanced for this addition. In his final paper (7) on this subject, Markovnikov gave experimental details of his oxidation of propylene chlorhydrin and his isolation of monochloro-acetone, pointing out that chloro-acetaldehyde is readily oxidized (in the air) and hence that chloropropioualdehyde was unlikely to be isolated from an oxidation mixture. This seems to have been Markovnikov's last word on his Rule, or on the oxidation of propylene chlorhydrin, but Henry produced two further papers (8, 9) also in 1876, on the oxidation experiments. Henry began (8) by stating that he had attempted to establish the law of addition of hypochlwous acid, and a t the same time to oppose M. Markovnikov's opinion on the particular structure of propylene chlorhydrin (Henry's law, reproduced above, was in fact quite general, and was not referred to as a law of addition of hypochlorous acid.) Henry also protested that Markovnikov had wed a different oxidizing agent (dichromate and sulfuric acid) and that in experimeots using nitric acid as oxidizing agent the major product from propylene chlorhydrin was chloropropionic acid, identical in "properties, analysis, and vapour density" with a sample derived from lactic acid. Furthermore, since Henry's oxidation product was chloropropionic acid, Markovnikov's
* An early example of the confusion that was to grow until the work of Kharasch in the 1930's.
must be chloropropionaldehyde. Henry then enunciated his law of addition of hypochlorous acid: In the addition of hypochlorous acid OH,CI to an unsaturated compound containing the system CH=CH', the hydroxyl attaches itself to the more hydrogenated carbon, and the chlorine to theless hydrogenated carbon.
He pointed out that there was no evidence to justify the extension of this law to the systems -C=C-, C s C H , or CH=CI-I, but that he proposed to fill in this gap in knowledge. He then advanced two reasons why the chlorine should be considered as the more electronegative part of (0H)CI: First, chlorine is more electronegative than oxygen; as for hydrogen it constitutes a positive element, following the happy expression of M. Dumas, s. gaseous metal, therefore the 0 , associ(OH) must be less negative than ated with an atom of hydrogen chlorine. Second, the hydroxy HO in the form HO-OH, easily expels iodine from alkaline earth iodides, hut not the Cl of corresponding chlorides. ~
Henry added a coda vith two main points-first, that he had considered only addition of hypochlorous acid to hydrocarbons (excluding cases where the unsaturated carhon atom bore a negative substituent) ; and second, that he had ignored the effect of temperature since all the experiments made with hypochlorous acid were in fact made in the cold. Finally, I do not hesitate to recognize that Mr. Msrkovnikov was the first to formulate a general law pertaining to the products of sdditian to unsaturated bodies. If I have not mentioned this, it was that I could not go into the history of the question in a Note, and that it seemed superfluous to mention faots known to d l chemists. Having taken the part of my savant eontradicteur, perhaps he will pennit me to claim for myself the law of addition of HOCI.
On this fairly amicable note the direct controversy between Henry and Markovnikov would appear to have ended. Markovnikov's experimental results were confirmed in 1895, by Michael (lo), who isolated chloroacetone (as its semicarbasone) from the oxidation products of propylene chlorhydrin; Michael' also showed that Henry's "chloropropionic acid" was very largely chloro-acetic acid. Subsequently Krassousky (11) re-examined the addition of hypochlorous acid to isobutylene (an addition which was thought by Markovnikov to be anomalous) and showed that in this case also the hydroxyl group becomes attached to the less hydrogenated carbon atom, giving a secondary alcohol. Finally, in 1902, Tiffeneau (18) published further evidence for 'Markovnikov addition' of hypochlorous acid to unsaturated hydrocarbons, but was unwise enough to begin his article: In 1875, Markovnikov had shown, entrary to the assertions of H e n ~ y that , in the addition of ClOH to propylene, the hydroxyl is attached to the less hydrogenated carbon atom giving the chlorhydrin CH8CHOHCH2C1.
Within a month a reply from Henry ( I S ) appeared, t,aking exception to this remark, and re-iterating his former arguments. Henry appeared to be in ignorance of Michael's paper, as he still maintained that the oxidation product was chloropropionic acid, although admitting that Markovnikov had isolated chloro-acetone. Henry ended by saying that he intended to re-examine the problem; the results of his re-examination were
embodied in two last papers on this addition. I n the first (14) he reported unambiguous syntheses of the two possible propylene chlorhydrins (called a- and B-) and an examination of their behaviour with the oxidizing agents nitric acid and acid dichromate: CHICHOHCHSC~
CHGHClCH?OH B
a
Nitric acid on the 'a-chlorhydrin' gaye first chloronitrosoacetone, and then a mixture of acetic and chloroacetic acids. Dichromate mixture with the a-chlorhydrin gave a poor yield of mono-chloroacetone. Oxidation of the 6-chlorhydrin gave a poor yield of a-chloropropionic acid, with no chloroacetaldehyde, but "it is not surprising that chloropropionaldehyde is not formed in the oxidation, as I have shown by direct experielice that a-chloropropionic acid itself is oxidized to acetic acid under these conditions." Henry's fiual words on the subject were contained in a lengthy snnlmary of the controversy (15) wherein he concluded that the product of addition of hypochlorous acid to propylene was a mixlure of the two possible chlorhydrins with Markovnikov's candidate ( a above) in the major proportion. However, he remained convinced that hypochlorous acid added to isohutene in the opposite sense, and he made a number of somewhat. slighting remarks about "un chimiste americain M. Arthur Michael" who held the opposing viewpoint. It is interesting to compare the current interpretation of electrophilic addition with Markovnikov's ideas. Thus, in the addition of HX to an ethylenic double hond, the proton adds on to give an intermediate carbonium ion. I t is supposed that the double hond is polarized on approach of the proton in a sense which is determined by hyperconjugation with alkyl groups attached directly to the ethylenic carbon atoms; it should also be noted that the more stable carbonium ion will be that which carries the largest number of alkyl groups around the positively charged carbon atom; thus CHa
I
CHrC==CH1
,
X P.
H+
CHa
I
CH3-C+-CHa
CHICH-CH?
+
Markovnikov's original Rule contained a statement that the halogen atom in HX will go to that "most influenced by surrounding carbon atoms" which is in close accord with current theory. It is also currently accepted that at higher temperatures the homolytic fissiou of the reagent becomes important with a concomitant change in mechanism, and hence in position of attachment of the halogen atom : CHsCH=CH2 CHsCHCH;Br
+ Bra + HBr
--
CHsCH-CH& CH&H&H3Br
+ Br., etc
The addition of hypochlorous acid is more interesting since Henry's views appear more logical and yet Markovnikov's were correct. The fallacy in Henry's arguments lay in his assumption that hypochlorous acid is (HO)CI, and was encouraged by the confusion in the literature-for example, by Butlerov's report that the addition of hypochlorous acid to isobutylene proceeded thus: Volume 38, Number 6, June 196 1
/
299
CHI C CHI C&
'
+ (0H)Cl-
CHa CIC CHB CHzOH
This addition has been studied by de la Mare (16) who reported that the product was mainly l-chloro-2methylpropan-2-01, confirming the generally accepted view that the initial addition is of the hypochlorous acidium ion H20Cl+ (or C1+ if hydrogen chloride is present) to give the carbonium ion shown below; the second stage is addition of the nucleophilic solvent (water). The only isolated by-products were ethylenic arising by elimination of a proton from the carbonium ion :
-
H20C1+ Me9C==CH2 -
+ Mel-CCH2C1 .1
H20
Me,C(OH)CH2C1
Me2C=CHCr(CHa=C(Me)CH2Cl (0.4%)
87.6% ~ 2 % ) (Figures even refer to % of isolated materbl.)
It is known (17) that none of the anti-Markovnikov addition product (2-chloro-2-methyl propan-1-01) is formed in the reaction. In Markovnikov's Rule, therefore, we have an excellent pedagogic example of the way in which an empirical generalization can be subsequently correlated
300
1 journal
of Chemical Education
>I g~wmlltheory, while nr the same tinu~ilh~strati~lg the uu~erinieutnldifficulticl;whivh inadt: wrrwr nmcrt~lizations remarkable in the early days of organic chemistry.
with
-
Literature Cited
V., Ann. der Chemie und Phannacie, 153, (1) MARKOVNIKOV, 228 (1870). H. M., J. CHEM.EDUC.,l8,53 (1941) (2) LEICESTER, J . . Chem. Soc. 483 (1865). (3) PFAUNDLER, L.. C m u t e ~ m n d u79. ~ . 1203 (81741. (41 HENRY. (5j M A R K ~ V N ~ K O ~V om , ~p~t .e,b & u , 2 6 6 11875). V., Cumptes rendus, 82,728 (1875). (6) MARKOVNIKOV, (7) MARKOVNIKOV, V., Comptes~endzwt,82,776 (1875). (8) HENRY, L., Comptes mendus, 82,1266 (1875). (9) HENRY,L., Cornptes rendus, 82,1396 (1875). (10) MICHAEL, A,, J m ~ n a 1fii)- P~akti~ehe Chemie [2], 50, 286, 409 (1899). (11) KRASSO~SKY, X., Journal de la Socidtd physico-chemipue R u m , 32,84 (1900). M.. Cmnutesrewh. 134.774 11902). (12) TIFFENEAU. L:, ~ u i l e t i mde 1;~cadbmied e ~ e l & e , Clam des Sciences, 397 (1903). (15) HENRY,L., Bulletins de 1'Aeaddmie de Belgipue, Classe des Sciences, 523 (1906). (16) DE LA MARE,P. B., AND SALAMA, A. J . Chem. Soc. 3337 (14j
HENRY;
(1956). (17) SMITH, L., AND SKYLE,S., Acla Chim. Scand.. 5.1415 (1951).
