The Principle of Vinylogy Subrahmanya Krishnamurthy Tuskegee Institute, AL 36088 The principle of vinylogy recognizes the possibility that the inductive effect of a functional group is transmitted through a douhle bond or a conjugated system of double bonds. This principle was reviewed by Fuson ( 1 ) in 1935. It can provide new insights and serve to direct attention to possible reactions which might superficially appear unlikely and thereby initiate fruitful lines of future enquiry. The purpose of this review is to hrine the subiect matter UD to date and to invite attention to the principle that has been found t o be delightfully refrrshinuand thus u) re\,italize it. Such revitalination is drrmed necessary because of the paucity of references to the principle in recent literature. The literature has been covered up to 1967. During the period 1967-79, there are no references on the subject. Fuson ( 1 ) has stated the principle thus: ~
phenoxide ion to give the corresponding ether, even though the chlorine atom is situated on an unsaturated carbon atom. CH,-C=CH-COOEt
I
+ -0Ph
-
CH,-C=CH
I
OPh (2)
~
When in a compound such as A-EI=E2 or A-EFEZ (whereEl and EPrepresent non-metallic elements), a structural unit of the type (-C=C-). is interposed between A and El, the function of Ez remains qualitatively unchanged, but that of El may be usurped by the carbon atom attached to A. This principle is of broad scope and some applications of it will he presented. Vinylogs of Compounds Having an Active Alpha Hydrogen Esters, Nitriles and Nitro Compounds Ethyl crotonate, CHrCH=CH-COOEt, a vinylog of ethyl acetate, undergoes the Claisen ester condensation at the gamma methyl group. Ethyl sorhate, CH3-(CH=CH)zCOOEt, similarly undergoes the Claisen ester condensation with ethyl oxalate thus COOEt CH,-(CH=CH),-COOEt + ( COOEt
-
CH,(CH==CH),COOEt (1)
I
COCOOEt Further, homophthalic ester
behaves like malonic ester and can he hydrolyzed and easily decarboxylated to give phenylacetic acid. Activation of a halogen atom is seen in the case of ethyl@-chloro-crotonate which undergoes displacement by the
.COOEt
In crotonitrile and sorhonitriles, the methyl groups undergo condensation with ethyl oxalate. In the case of ortho and para-tolunitriles (not the meta, since it is not a vinylog of acetonitrile), the activity of the methyl hydrogen is greater than that of the corresponding atom in toluene as evidenced by the following reaction:
Similarly both ortho and para-nitrotoluenes (vinylogs of nitromethane) condense with ethyl oxalate a t the methyl groups. Aldehydes and Ketones 2-Pyrryl carboxaldehyde (I) and the 3-aldehyde (11) exhibit peculiar properties (2).
They do not give positive Fehling's, Tollen's or Schiffs tests, and they fail to undergo Cannizzaro, benzoin or Perkin condensation. This perplexing behavior is easily rationalized if these com~oundsare recoenized as vinvloes of amides. The infrared spectrum of II revSialsthecarh;~lyl absorption to be in the rraion of the amides (1672 cm-'I. 'l'he u\, max. 260 and 289 nm &as unchanged by acid or base. The failure of this compound to give the usual aldehyde reactions is due to its existence in the zwitter-ionic form. The principle of vinylogy is also applicable to unsaturated ketones (3).A methyl group separated from a carbonyl by one vinylene group exhihits properties that are similar to those which i t would show when directly attached to the carhonyl. This effect is seen even if the vinylene group is part of a 6membered ring. Tetrahydrohenzophenone (111) was prepared
Volume 59 Number 7 July 1982
543
by the action of henzyl chloride on cyclohexenein the presence df aluminum chloride.
In I11 the carhonyl is outside the ring while the methylene group is part of the ring. 111 condenses with ethyl oxalate as shown in the following reaction.
Carvone (IV) was reported (4) to condense readily with henzaldehyde in the presence of alkali to give two different forms of heuzylidene carvones.
Displacement Reactions of Alkyl Halides and Their Vinylogs
Ethyl chloride reacts more readily than methyl chloride, with KI. A similar trend was found in the reactions of their vinylogs, allyl hromide and crotyl bromide with KI, the crotyl bromide reacting much faster (k = 519) than allyl bromide (k = 126). Esterification of Aromatic Acids and Their Open Chain Vinylogs
The extension of the nrinciole of vinvloev - -.to ortho substituted henzoic acids requires some explanation. For henzoic acid, the ooen chain analoz is acrvlic acid. The rate constants for the estkrification withmethanol of henzoic, o-toluic, and o-ethyl and o-propyl benzoic acids as well as the rate constants for the hydrolysis of henzyl chloride and o-tolyl methyl chloride (from reference (6)) are resented in Tahle I1 and Table 111. When the rate constants for the esterification of o-suhstituted benzoic acids (Table 2) are compared with those for substituted acrylic acids (Tahle 1) and those for the pair henzyl chloride and o-tolylmethyl chloride (Tahle 3) with the pair allyl hromide and crotyl bromide, it is seen in each case that the pffect the saturated suhstituent on the reactivitv ~of ~ of the functional group is transmitted qualitatively unchanged throueh internenine vinvlene erouos. The orincinle of vinvloav can leid to satisfa&ry ;atioializations &d also to inter&& predictions. ~~~~~~
Wallach ( 5 ) ,however, reported the formation of amorphous material in the same reaction. The principle of vinylogy suggests the possibility of the formation of dihenzylidene carvone (V).
I t was found that V was indeed formed. althoueh i t could not he crystallized. This issimilar to thecondensatiuu of a mnlecule of menthenone (.V I .I with two molecule^ of benzaldehvde thus:
~
~~
~
~~~
~
Vinylogy in Organic "Name" Reactions Reformatsky Reaction
Vinylogs of haloacetic esters like undergo the Reformatsky reaction with henzaldehyde in the presence of Zn (7) as shown below
lmines
An example of activation in imines is the activity of the methyl groups in 2-methylquinoline, 4-methylpyridine, 2rnethylquinoxaline and l-methylisoquinoline. In all these cases, henzaldehyde condenses with the methyl group. In heterocyclic compounds, side chain activation is seen in 2-methyl-4-phenylthiazole (VII) hut not 2-phenyl-4methylthiazole (VIII).
Table 1. Rate Cbnstants lor Esherttkatbn wtth Methanol at 15% Acid
k
Acid
k
Formic Acetic Pmpionic
1224 104 91
Acrylic Crotonic EICH=CH.COOH PhC-HCOOH
3.09 1.26 1.5 0.937
Table 2.
Rate Constants lor Esterillcation at 15°C Acid
k
Rale Studles Esterification of Some Aliphatic Acids and their Vlnylogs
The trend seen in the values of the rate constants for the esterification with methanol of formic, acetir, und propanoic acids is also seen in the values of the rate constants for the esterification of their vinylogs: acrylic, erotonic, and 2-pentenoic acids (6). The rate constants from reference (6) are presented in Table 1. 544
Journal of Chemical Education
Table 3. Rate Constants lor the Hydrolysis ot Chlorides at 30°C The Chloride
k
Benzyi chloride o-tolylrnethylchloride
1 4.95
Thus, by using compound IX, i t is possible to extend a side chain by one isoprene unit.
upon as vinylogous urea. Compounds of the type of XVIII are easily prepared (16).
Friedel-CraFts Reaction Vinylogous acid halides undergo Friedel-Crafts reactions with aromatic compounds. Thus 5-chloromethylene rhodanine as a vinylogous acid chloride reacts with aromatic compounds (8) to give 5-arylidene rhodanine as shown below XVI
XVII
The product of the preceding reaction was converted by desulfurization into 8-arylpropionamide. XVIII
Inverse Michael Reaction Toluene was found to add to maleic anhydride in the manner shown as follows
The anhydride-like 5-membered cyclic lactone becomes involved as a part of a vinylogous urethane and this is seen in the IR spectra: a down-field shift to 5.7,5.74; the G=N double bond becomes a single peak a t 5.99 p. When acetylatioo a t both N and 0 is done using acetic anhydride, the product showed a peak a t 5.56 p1 (lactone), no longer involved electronically with an enamine and so is restored to its original position. Vinylogy in Amlnoalkylatlon
Compound X was the starting point for the synthesis of the interesting compound XI.
Mischler's hydrol (XIX), a colorless vinylogous carbinolamine was condensed with dimedone (17) to give cherry-red crystals of XX.
AH Amides and Related Compounds
XIX
Vinylogous amides (10-12) and amidines (13) are recognized as classes of suhstances quite different from other basic ketones and their derivatives. The spectral shift caused by a - p conjugate interaction between two parts of a rr electron elongated functional group applies to both open chain and cyclic compounds. The aminomethylene compounds XI1 and XI11 are typical vinylogous amides.
XX
The hydrol was also condensed with OHC:NH.CH(COOM~)~, antipyrine, indole, isatin, and benzene sulfonamide to give the corresponding aminoalkylated products. Compound XX on heating to a violet melt and distilling gave Ph.NMez. This thermal decomposition proceeds through a vinylogous m i n e elimination, and the reaction rates and pH dependence indicate that carhenium-imonium ions participate in the aminoalkylation reaction. Schlff's Bases
They are reduced by LiAIHl (14) to hydroxaminoketones X N and XV. The structures XI1 and XI11 are.clearly confirmed by their IR spectra which showed a strong bonded hydroxyl hand in the solid state at 3.05 and 3.00 p (15), vinylogous amide bands at 6.10 and 6.14 p, and intense peaks a t 6.54 and 6.41 p, which all are associated with suhstances of this type. Electronic shifts alone are responsible for the development of amide-like spectra in XI1 and XIII. In the IR of XIV and XV, the carbonyl band is seen at 5.93 and 5.80 p, now no longer involved electronically with nitrogen. Further, both the vinylogous amide bands found in XI1 and XI11 are missing in XIV and XV. I t has been shown that vinylogous tertiary amides derived from @-ketoaldehydes (hydroxymethylene ketones) are more susceptible to reductive attack at the aminomethyl end than a t the carhonyl. Compounds XI1 and XI11 with sodium horohydride gave neutral and basic components. Compounds XVI and XVII resemble compounds XI1 and XI11 and show exceptionally strong IR bands at 6.56 and 6.33 p. The intense vinylogous amide peak for compound XVI is in the usual location (6.11 p). Compound XVII can he looked
The principle of vinylogy has been combined with the principle of isostery (18). Based on the assumption that the groups -CH=CH-, -N=Nand, consequently, CH=Ncan be used as connecting links between two moieties known to be pharmacologically active, keeping them a t equal distance (isostery), a number of Schiffs bases containing active groups were prepared. The Schiffs bases were prepared by briefly refluxing the aldehyde and the amine in alcoholic solution. Thus for example, starting with sulfonamide, by a series of steps involving diazotization, coupling with Salicylaldehyde and condensation with p-phenylene diamine, compound XXI was obtained.
XXI
Other starting materials used were Isonizide, Sulfamezathine and sulfathiazole. Volume 59
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July 1982
545
Alkylatlon of Tertiarybutyl Esters
*
The condensation of 1,4-dihromo-trans-2-butene with diethyl malonate led to the exclusive formation of ethyl 2-vinylcylcopropane-1,l-dicarboxylate (19) according to the equation
CH-CH
0
XXIV
Pyrones
Whether aromatic thioketones containing the When t-butyl acetate was condensed with 1,4-dibromo-2butene in the presence of lithium amide, di-t-butyl-trans4-octene, 1,8-dioate was ohtained and no cyclopropane compound was produced (20). Alpha-dialkylation of ester by means of LiNH2 was observed in the benzylation of t-hutyl crotonate according to the equation
Similarly n-butyl bromide with t-butyl crotonate gave the mono and di-alkylated products. The y-alkylated products were not obtained in the above cases. Thermochromlsm and Vinylogy
Some substances in solution exhibit striking color changes with temperature, observable with the naked eye. Such striking color changes (usually between O°C and higher temperatures) come under the purview of thermochromism. Bianthrol (21) (XXII) and dixanthylenes (22) (XVIII) are colorless a t low temperatures, but develop vivid colors with a rise of temperature.
group will underao the aldol tvoe condensation is a auestion that cannot be answered by a direct experiment owing to the fact that these comoounds are sensitive to alkali and show a pronounced tendency to polymerize. 2-Methylchromone (24)
and 2,3-dimethylchromone (25),are vinylogs of ethyl ketones condensed with benzaldehyde. 2-Methyl-4-thiochromone (XXV) and 2,3-dimethyl-1,4-dithiochromone(XXVI) were found to condense with aromatic aldehydes in the presence of piperidine (26).
dH8 &. xxv
XXVI
These thiochromones are vinylogs
In contrast to many thioketones, 2,6-diphenyl-4-thiopyrone (XXVII), like thiohenzophenone, reacts (27) on heating, according to the equation: 9
Chemical evidence suggested that thermochromism is due to a chanee of the molecules. the "colored molecules" - of ~lanaritv . having a greater degree of planarity and since thermochromic substances are thermostable; the phenomenon is not due to the production of radicals or biradicals. In overcrowded molecules in which planarity is hindered, the degree of nonplanarity changes with temperature. This is associated with change of color; one reason is that resonance is related t o planarity. If the molecule absorbs in the visible region, thermochromism is observed with the naked eye. Several such crowded comnounds were ~ .r e.n a r e dand found to be thermochromic. 1,2-Bis(9,9' anthrony1idene)ethane (XXIV) (a vinylog of the strongly thermochromic (XXII) was prepared and found to be thermochromic (23). Strong reversihle thermochromic effect was observed in powdered XXIV, in addition to the thermochromism displayed in solution. The substance was orange a t O°C and changed to deep violet at 240°C. 546
Journal of Chemical Education
Thiobenzophenone (28) decomposes at 170-180°C forming tetraphenylethylene and sulfur. Compound XXVII is a vinylog of thiobenzophenone, and this explains the similar behavior of the two compounds. The ease of hydrolysis of 5-methoxychromone is also accounted for by the principle of vinylogy. The facile demethylation of visnagin (XXVII) can be understood if it is considered as a vinylogous ester. However, the quite similar compound visnaginone (XXIX) did not get demethylated under similar conditions.
XXVII
XXlX
Tautomerism
The tautomeric behavior of several substituted pyruvic esters has been studied (29). Ethyl-p-nitrophenylpyruvate
(XXX), in the enolic form, is a vinylog of p-nitrophenol and can be methylated diazomethane. Both ethyl-l-phenyl-5tetrazolylpyruvate XXXI and ethyl-8-phenyl-l-methyl5-tetrazolylpyruvate (XXXII) were remarkably resistant to decarbonylation and both gave colored complexes with F e C 1 3 , showing a high en01 content. 2-Benzoxazolylpyruvatebehaved similarly.
where all the intermediate compounds were tasteless, but the final vinylog of Dulcin ~ t e c H = c H - - m ~
was sweet. Haloform Reaction:
Pulegone,
I
a vinylogous methyl ketone, gave the iodoform reaction.
CH,
XXX
XXXI
XXXlI
Literature Cited (1) (2) (3) 141
Miscellaneous Compounds Sulfonyl Compounds
isi
CI
is a vinylog of sulfonyl chloride and has a very reactive halogen, which reacts readily with alcohols, mercaptans, etc. (30). With NaOMe it gives R.S02--C=CHOMe
I
CI
where R is t-butyl. Further, it also reacts with amines giving enamines. Addition of a nucleophile HY to di-t-butylsulfonylacetylene takes place as follows R S O g C = C S O n R + HY R . S O r ( Y I C = C H . SOaR
-
Vinylogous Sweetening Agent:
A vinylog of Dulcin
has been prepared (31)starting from
FW0n.R.C.. Chem. Rev.. 16, I(1935). Herz, W. and Bresh,J., J Org Chem., 23,1513 (1958). Christ, R. E., and Fuson, R. C., J. Amen Chrm Soc., 59.893 (1937). Muller.Bar.54.1477 1l922t. ~~11~~h.o.,'~~~.,305:274i1899).
(6) B1att.A. H., J. Org. Chom., 1,154 (1936). (71 Fuson, R. C., and Southwiek, P. I., J. Amer Chem. Soc., 66.679 (19441. (8) Behringer,H.,Dillinger.E.,Suetcr,H.,sndKohl,K.,Chom. Bsr.91.2773 (1958). (91 Sylvestre, A. J.. Compt. Rend.. 241.882 (19551. (10) Glieckrnen,G.A.,sndCope,A. C., J A m e r Chem. Soe..67,1917 (19451. (11) Crornwdl, N.H., Miller,F.A.,Robiisoi, A . R . , F Chrm. Soc.,71.3337 (1949). (12) Albprtaon, N. F., J. Amer Chem. Soe..74,249(1952). (131 Walker. G. N.and Moore. M. A,, J. Org Chem., 26.432 (19611. (14) Ws1ker.G. N.. J. Org. Chem.,27,4227 (19621. (151 Nakankhi. M.and Webster.G.C., J. Org. Chem.,22.159(1957l. (16) Clarke. H. T., Johnson. J. 8 , and Rohinson,SiR. (Edilorr), "ChemistryolPenicillrn," Princeton Univer8ityPress. Princeton. N. J. 1949, pp. 367-386and 747-753. (17) Hellrnann, H.,endOptiz,G.,Ann.,604,214 (1957). (18) Runti,C.,Ed. Sci., 10,579 (1955l; C h m Ab~fr.,50,8638. (19) Birch, S. E.. Dean, R. A,, and Hunter. N. J., J. Olg. Chem.23.1390 (1958). (20) Sisidn,K.,Sei,K.,andNozaki. H., J. Or& Chom.,27.2681(1962). (211 Hirshbeq, Y..Lownthal, R.,Bergrnan,R. D..andPuUrnsn.B..Bvll. Soe Chim.. 18,
,."-.,.
PXllQ5ll uu
(22) S c h o n b ~A., ~ ,Mustaffa, A., andSobhy, E. D., J. Amar. Chem Sor., 75,2377 (1953). (23) Schonberg,A.. Muataffs. A,, and Asker, W., J. Amen Chem. Soe.. 76.4134 (1954). J Chem. Soc.925 (1932). (24) Cheerne,U.,Gulati,K.,andVenkatarsmsn,K.. (25) Hoilhron, I.,Barner. H.,andMorten,R., J. ChomSoe., 123,2559(1928). (26) Schonberg.A..Sidk~,M.M.,sndAziz,G.. J Amen Cham. Soe.,76.5115(1954). (27) Arndt. F..Schoh. &and Nachtwcy,F..Ber..57.1903 (1924). (23) Staudinger. H. and Freudonberger, H..Bc?,, 61.1580 (1928). (29)Stock. A.M., Dunahrne, W. H., and Amsutz, E. P.. J. Org. Chem., 23,1840 (195Sl. (30) Backer, H. J., Strating, J., and Hamnberg. J. F. A,, Rec. Tmu. Chim.. 72.813 (1953). (311 Noyce, W. H., Colernann, C. H., and Barr, J. J., J. Amer Chem. Soe., 73, 1295 (1951).
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