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Aspects of tautomerism. Part 15. Investigations on oxo-participation in δ-oxocarboxylic acid chlorides during their formation and alcoholysis |
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Journal of the Chemical Society, Perkin Transactions 2,
Volume 1,
Issue 3,
1986,
Page 355-358
M. Srikantaiah Shashidhar,
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摘要:
J. CHEM. soc. PERKIN TRANS. 11 1986 355 Aspects of Tautomerism. Part 15.' Investigations on Oxo-participation in 6-Oxocarboxylic Acid Chlorides during their Formation and Alcoholysis M.Srikantaiah Shashidhar and M.Vivekananda Bhatt Department of Organic Chemistry, Indian Institute of Science Bangalore 560 0 72,India Oxalyl chloride converts ring-substituted 4-benzoylbutyric acids into a mixture of normal and pseudo- acid chlorides by two independent and competing pathways. Pseudoacid chlorides are formed by a concerted 2, + 2, + 2, pathway. It is suggested that the reaction of acid chlorides with a poor nucleophile involves a transition state wherein the attacking nucleophile and the departing group make an angle of ca. 45" to the plane of the carbonyl group.There is evidence against involvement of any common transition state or an equilibration process during the formation of normal and pseudoacid chlorides. Alcoholysis of normal acid chlorides derived from the above mentioned acids does not involve oxo- participation. y-Oxoacids as a rule form exclusively pseudoacid chlorides. Table 1. Yields of the normal acid chloride and enol lactones formed There are only two y-oxoacids which are exceptions to this from substituted benzoylbutyric acids (1a-e) rule.* 6-Oxoacids, on the other hand, give a mixture of pseudo and normal isomers. The reagent used apparently does not have Yield by 'Hn.m.r. analysis" A 3a bearing on the nature of the product. It is not clear from the r Isolated yield literature whether there is an equilibrium between the two forms Compound % Lactone % Acid chloride % lactone in the case of 6-oxoacid chlorides.(Ib) b b 8.7 We report an investigation into the factors which govern (W 19.8 80.2 13.1 pseudoacid versus normal acid chloride formation. We believe (14) 21.0' 79.0' 15.5 that this question is linked to the more fundamental problem of (Id) 36.8 63.2 32.1 45.0 32.0the stereochemistry of substitution at the carbonyl carbon and (le) 55.0 the nature of the transition state involved therein. "Olefinic proton signal was observed near 6 5.8. Percentage of lactones In the present work we have converted variously ring- and normal acid chlorides were computed using peak areas. * No signal substituted 6-benzoylbutyric acids into their acid chlorides due to olefinic proton was observed as the amount of lactone was very using oxalyl chloride and determined the proportion of the two low in the mixture.'Unaffected after treatment with lithium chloride. isomers formed. Also we have studied the alcoholysis of the normal acid chlorides to find out whether there is 0x0 participation during solvolysis. (COCL 1*1Results and Discussion 4-Benzoy lbutyric acid and its four ring-su bstituted derivatives R I(la-) (R = p-OMe, p-Me, p-Br, and rn-NO,) were treated with oxalyl chloride and the resulting products were analysed by 'H n.m.r. spectroscopy. It was found that during their formation pseudoacid chlorides underwent dehydrochlorin- ation to yield the corresponding enol lactones3 (4a--e).Accordingly, the proportions of enol lactones and normal acid chlorides were estimated. Also, the mixture of products was treated with aqueous ammonia and the resulting products consisting of enol lactone and the amide were separated and their proportions computed. These results are summarized in Table 1. 0From Table 1 it is clear that when .electron-withdrawing groups are present they favour the formation of a larger proportion of enol lactone and the parent acid chloride at the expense of the normal acid chloride. The opposite situation prevails when electron-donating groups are present. These results would clearly rule out the involvement of an equilibrium Scheme 1. process during the reaction of the above mentioned acids with oxalyl chloride.Further these results indicate that pseudoacid chloride formation is a competing pathway during the conversion of 6-benzoylbutyric acid into the normal acid chlorides and not because of any constraints on the formation of chloride (Scheme 2). Data presented in this paper together with normal acid chlorides. those in the literature permit the following conclusions. (ii) The y-0x0 function presents an ideal neighbouring group (i) Oxoacids give pseudoacid chlorides only when their for a concerted attack by the 0x0 oxygen on the carboxy formation is kinetically favoured over that of the normal acid carbon when it is being subjected to nucleophilic attack by 0 I* COCl (2) b;R= p-OMe c; R= p-Me d;R= p-Br R e; R=m-NOp (3) d (41 OH CO2H scheme 3.chloride. The geometrical requirements of this type of transition state are present optimally in y-oxoacids. (iii) In 6-oxoacids although this type of transition state is possible, bringing the oxygen end of the carbonyl group to the bonding distance of the carboxy group and keeping it aligned against the considerations of entropy seems to make such a transition state favoured to a smaller extent than in the case of y-oxoacids. A corollary of this analysis is that the structural features of y-ketoacids, which (a) make it dimcult to bring the 0x0 oxygen near the carbonyl carbon or (b) which prevent or hinder the attack by the chloride on the carbonyl carbon, should disfavour pseudoacid tlersus normal acid chloride formation.Fortunately the literature provides one example of each of these 9-Oxofluorenecarboxylic acid (5) is one of the y-oxoacids which does not give a pseudoacid chloride. A failure to form the pseudoacid chloride could be recognized as arising due to the difficulty in bringing the carbonyl group to the bonding distance of the carboxy carbon, at an angle appropriate for bimolecular nucleophilic displacement.* Support for this view comes from the fact that the corresponding alcohol, 9-hydroxyfluorene-1-carboxylic acid (6), does not form the J. CHEM. SOC. PERKIN TRANS. II 1986 1 0 0 b -Goc, @CI CI CI (9) scbeme 4. lactone (7)whereas in the case of analogous o-benzoylbenzoic acid, the hydroxy acid cannot be isolated except as its metallic salt and the reduction of the oxoacid yields the lactone as the only isolable produ~t.~ The failure of o-mesitoylbenzoic acid to form the pseudoacid chloride arises from the severely decreased accessibility of the carbonyl group for a lateral attack by the chloride.In mesitoyl derivatives steric hindrance at the carbonyl carbon is well documented. If the carbonyl group were to be in the plane of the aromatic ring and if its nucleophilic reaction were to take place from the direction of the IC cloud, there should be no steric hindrance. But it has been established that the carbonyl group orients out of the plane of the aromatic ring and consequently the approach of the nucleophile to the carbonyl group is hindered.Hence pseudoacid chloride formation is not observed in this case also. From the foregoing it is clear that the formation of the pseudoacid chloride is a concerted reaction involving a carboxylic acid derivative, a 0x0 group, and the halide. In modem terminology it is a 2, + 2, + 2, concerted reaction. Newmann and his co-~orkers~.~ who recognized this reaction as one involving a distinct type of transition state have designated it as a [3.2.l]bicyclic pathway. Thermal isomerization of pseudo (8)to normal (9)phthaloyl chloride 'is another concerted reaction of acid chlorides. It can be considered as the reverse of the reaction of the normal acid chloride with nucleophiles. Both these reactions may be expected to go through analogous transition states.Phthaloyl chloride isomerization is a thermal 2, + 2, concerted reaction that goes through a non-planar transition state (Scheme 4). The reaction of acid chlorides with nucleophiles is basic to organic chemistry and has attracted a great deal of investigation. In spite of this some of the main issues are not defined, e.g. (a) the stereochemistry of displacement i.e., geometry of the transition state and (b) the conditions and structures which favour addition-elimination, SN1, or &2 types of displacement. In previous papers 'wU we presented evidence in support of our view that carboxylic acid chlorides as a rule are hydrolysed by an SN2pathway without involving addition4imination. This conclusion was arrived at after studying the solvolysis of a number of normal and pseudoacid chlorides.Previously re- ported isotopic exchange studies are clearly consistent with this view, although a number of workers continue to advocate A referee has suggested that decreased carbonyl reactivity, because of the better conjugation of the carbonyl group with the aromatic ring, might contribute to the absence of pseudoacid chloride. J. CHEM. soc. PERKIN TRANS. 11 1986 Nu Nu Nu I CIc1 A 6 C 0 I1 Figure. Table 2. Pseudo-first-order rate constants for the methanolysis of ring-substituted benzoyibutyric acid chlorides (2a--e) in 50% (v/v) acetone-methanol at 30 "C Substrate pWH3 pCH3 H pBr m-NO, lo3 klmin-' 4.75 4.66 4.80 4.60 4.66 addition4imination and S, 1 mechanisms.A recent indepen- dent study also supports an SN2pathway." If the most common pattern of solvolysis is by an SN2 mechanism not involving addition-elimination or S,l path-ways, the question naturally arises as to the stereochemistry of the transition state. Very little information is available in the literature on this subject. Bender '' has suggested that the carbonyl carbon in carboxylic acid derivatives may undergo nucleophilic displacement involving an approximately perpen- dicular attack at the carbonyl carbon. Bellard and Bamford l2 have presented a case wherein the direction of approach of the nucleophile is similar to that found. in simple nucleophilic substitution at the tetrahedral carbon.One can therefore consider three types of transition states as in the Figure, based on the data available in the literature. From the Figure it is clear that both phthaloyl chloride isomerization and pseudoacid chloride formation are not possible through either A or C. This leaves B as the only plausible transition state which can explain both concerted reactions. One can only conceive of a transition state where the oxygen end of the carbonyl group attacks the carboxy carbon at an angle of ca. 45", after approaching the bonding distance. We suggest that phthaloyl chloride isomerization and pseudoacid chloride formation involve attack at the carbonyl carbon by chloride at an angle of ca. 45" to the plane of the carbonyl group in the transition state.This may be the general pattern for the reaction of the majority of acid chlorides with nucleophiles. A recent molecular orbital study on nucleophilic substitution in acyl chlorides also supports this view.' The product composition obtained, viz. the proportions of the normal acid chlorides and the enol lactones, remained unaffected when stirred with lithium chloride in acetonitrile. This observation also argues against the isomerization of normal and pseudoacid chlorides after they are formed. A study of methanolysis of ring-substituted normal 4-benzoyl- butyric acid chlorides (8a-e) under pseudo-unimolecular con- ditions was made. All compounds solvolysed at the same rate without displaying any substituent effect (see Table 2).The acid chlorides are solvolysed by direct attack by the solvent on the acid chloride function; this means that there is no oxo-participation during solvolysis. This is contrary to our earlier finding that oxo-participation is observed during the basic hydrolysis of e~ters.'~ It is well known that the carbonyl reactivity decreases in the order RCOCl > RCOR' > RC0,R'. The pathway involving oxo-participation takes place only when it becomes competitive, or it is faster than direct attack. If it is slower, such a pathway would not be availed of. This apparently happens in the case of normal acid chloride because direct attack is much faster than that through the keto carbonyl group. Experimental M.p.s are uncorrected.'H N.m.r. spectra were recorded on either Varian T60 or Varian HA 100 spectrometers. Chemical shifts are referred to internal tetramethylsilane. 1.r. spectra were recorded on a Perkin-Elmer 78 1 spectrometer. Chromato- graphic separations were carried out using silica gel (60-120 mesh). Substituted Benzoylbutyric Acids.4-Benzoylbutyric acid, 4-(p- bromobenzoy1)bu t yric acid, 4-@-toluoyl) but yric acid, and 4-(p-methoxybenzoyl)butyricacid were prepared by the Friedel-Crafts reaction of glutaric anhydride with benzene, bromobenzene, toluene, and anisole respectively. 5-1 4-(m-Nitrobenzoy1)butyric acid was prepared by the nitration of 4-benzoylbutyric acid with a mixture of concentrated sulphuric acid and fuming nitric acid (d.1.42). Acid Chlorides.-Acid chlorides of the acids mentioned above were prepared by reaction, with oxalyl ~hloride,~' of the corresponding acids with catalytic amounts of dimethyl-formamide. Solid products (sometimes gummy solids) obtained were used without further purification. Acid chlorides were also obtained by the use of thionyl chloride, but this procedure usually gave dark coloured products. Oxalyl chloride was, therefore, used throughout the present work. Typical procedure. 4- Benzoylbutyric acid chloride. 4-Benzoyl- butyric acid (500 mg, 2.6 mmol) was stirred with oxalyl chloride (1 ml) and dry ether (2 ml) at room temperature for 6 h. Ether and excess of oxalyl chloride were removed in vacuo, without heating the reaction mixture (increase of temperature results in dark coloured products).The semi-solid obtained was analysed by * H n.m.r. spectroscopy. Preparation of Dihydropyrones.-Acid chlorides obtained as above were dissolved in the minimum volume of chloroform or acetonitrile and stirred with aqueous ammonia. The enol lactones were separated by column chromatography. Typicalprocedure.3,4-Dihydro-6-phenyl-Z-pyrone.Acid chlor- ide obtained from 4-benzoylbutyric acid (500 mg, 2.6 mmol) was dissolved in chloroform (5 ml) and aqueous ammonia was added dropwise with stirring, till a faint smell of ammonia persisted.* Stirring was continued for another 5-8 min. Ammonium chloride was removed by filtration and the product * Use of excess of ammonia and/or longer reaction times results in lower yield or total loss of material.was chromatographed over silica column (eluant benzene), yield 70 mg (15.5%); m.p. 51-52 "C (lit.,21 4748.5 "C), G(CDCI,)2.6 (m, 4 H),5.8 (t, 1 H), and 7.5 (m, 5 H). 3,4-Dihydro-6-tolyl-2-pyrone.Yield 13.1%, m.p. 58-59 "C, v,.(Nujol) 1 760 and 1 660 cm-',G(CDCI,), 2.4(s, 3 H),2.6 (m,4 H), 5.8 (t, 1 H), and 7.5 (q,4 H). 3,4-Dihydro-6-(p-methoxyphenyl)-2-pyrone.Yield 8.7%, m.p. 87-88 "C, v,,.(CHCl,) 1 740 and 1 640 cm-', G(CDC1,) 2.6 (m, 4 H), 3.8 (s, 3 H), 6.0(t, 1 H),and 7.2 (q,4 H). 3,4-Dihydro-6-(pbromophenyl)-2-pyrone.Yield 32.1%, m.p. 81-82 "C, v,,.(Nujol) 1 760 and 1 660 cm-', G(CDC1,) 2.5 (m, 4 H), 5.8 (t, 1 H), and 7.5 (m, 4 H). 3,4-Dihydro-6-(m-nitrophenyf)-2-pyrone.Yield 32%, m.p.103-104 "C, v,,.(Nujol) 1 750 and 1 650 cm-',G(CDC1,) 2.6 (m, 4 H), 5.9 (t, 1 H), and 8 (m, 4 H). All the lactones were treated with dilute sodium carbonate solution and, on neutralization, the original acids were obtained. Effect of Lithium Chloride on the Relative Amounts of Acid Chloride and Enol Lactone in the Mixture.-Acid chloride-lactone mixture from 4-benzoylbutyric acid (500 mg, 2.6 mmol) was dissolved in dry acetonitrile (5 ml) and stirred at room temperature with lithium chloride (100 mg, 2.3 mmol) for 12 h. The proportions of acid chloride and lactone was estimated by 'H n.m.r. spectroscopy before and after the experiment (see Table 1). 9-Hydroxyjuorene-1-carboxylic Acid.-9-Oxofluorene- 1-carboxylic acid (1 g, 4.5 mmol) was dissolved in THF (15 ml) and stirred with sodium borohydride (300 mg) for 24 h.More sodium borohydride was added at this stage (200 mg) and stirring continued for another 24 h. THF was removed by distillation, decomposed with dilute HCl, and the product extracted with ethyl acetate and the extract was dried (MgSOJ. A pale yellow solid was obtained (800 mg 79.379, m.p. 190-191 "C (lit.,22 194-195 "C). Pyrolysis.-9-Hydroxyfluorene-1-carboxylic acid was heated to 250 "C under vacuum for 5-10 min. A dark gummy solid was obtained (further heating resulted in charring of the compound). It was analysed by i.r. spectroscopy. No absorption for a five-membered lactone carbonyl could be detected. Estimation of Amount of Enol Lactone and Normal Acid Chloride in Mixtures by 'H N.m.r.-A signal due to an olefinic proton was observed near 6 5.8 and that due to methylene protons (lactone and acid chloride) was observed near 6 2.5.A typical calculation is shown for the p-bromo derivative.Number of olefinic protons = 1 Number of methylene protons = 10 (6 due to acid chloride and 4 due to lactone) Percentage of olefinic protons (ratio) = 1/11 x 100 = 9.09% Area below the signal due to olefinic proton = 0.7units Area below the signal due to methylene protons = 10 units Ratio of olefinic proton to methylene protons = 1 :14 = 1/15 x 100 = 6.7% If the percentage ratio is 9.09 then the mixture has 50% lactone and 50% acid chloride. If the percentage ratio were 6.7% the mixture would have 6.7 x 50/9.09 = 36.8% of the lactone. J.CHEM. SOC. PERKIN TRANS. II 1986 Kinetic Procedure.-The reaction of acid chlorides with alcohols and water is described by equations (1) and (2). It is RCOCl + R'OH -RC0,R' + HCI (1) RCOCl + H20-RC0,H + HCI (2) evident that one mole of acid chloride upon hydrolysis requires two equivalents of alkali whereas alcoholysis requires one equivalent of alkali. Thus theoretically, if Y ml of alkali is consumed by an aliquot portion at the beginning of the reaction (zero time), Y/2 ml will be consumed at the end (infinite time). The decrease from Y to Y/2ml with time forms the basis for the measurement of the rates of alcoholysis of the acid chlorides. Methyl alcohol was dried using magnesium methoxide.Acetone used was of GR grade. Barium hydroxide solution used for titration was stored out of contact with air. The temperature of the reaction mixture was maintained at 30 & 0.1 "C throughout. Acid chloride (5 mmol) was dissolved in acetone and made up to 50 ml in a standard flask. This solution (10 ml) was diluted with acetone (10 ml) and thermostatted for 1 h. Methanol (20 ml) thermostatted at the same temperature was added to the acid chloride. The solution was mixed well and 5 ml of the mixture was withdrawn without delay and quenched with aqueous acetone and titrated with standard barium hydroxide solution. This titre value gave Y. Then aliquot portions were withdrawn at known intervals, quenched, and titrated as above.If Y, is the volume of alkali consumed by a portion at time t, (Y, -Y/2) gives (a -x). A plot of (a -x) uersus t gives a straight line with slope -k/2.303. References I Part 14, M. V. Bhatt, V. Somayaji, and M. S. Shashidhar, Indian J. Chem., 1984, 23B. 1219. 2 M. V. Bhatt, V. Somayaji, and S. H. El Ashry, lndian J. Chem., 1980, 19B,473. 3 J. Cason and J. R. Elmer, J. Org. Chem., 1958, 23, 1492. 4 M. S. Newman and Courduvelis, J. Am. Chem. SOC., 1964,86,2942. 5 M. S. Newman, J. Org. Chem., 1961, 26, 2630. 6 M. S. Newman, N. Gill, and B. Darre, J. Org. Chem., 1966,31, 271 3. 7 M. V. Bhatt, S. H. El Ashry, and V. Somayaji, Proc. Indian Acad. Sci., Sect. A, 1980, 89, 7. 8 M. V. Bhatt, S. H. El Ashry, and M. Balakrishnan, Proc. Indian Acad. Sci., Sect. A, 1977, 88, 421. 9 S. Patai 'The Chemistry of Acyl Halides,' Interscience, New York, 1972, p. 197. 10 T. W. Bentley, G. E. Carter, and C. H. Harris, J. Chem. SOC., Chem. Commun., 1984, 387. 1 1 M. L. Bender, Chem. Rev., 1960,60, 53. 12 D. G. H. Ballard and C. H. Bamford, J. Chem. SOC., 1958, 355. 13 S. Yamabe and T. Minato, J. Org. Chem., 1983, 48, 2972; D. I. Asubiojo and J. I. Brauman, J. Am. Chem. SOC., 1979, 101, 3715. 14 M. V. Bhatt, M. Ravindranathan, V. Somayaji, and G. Venkoba Rao J. Org. Chem., 1984, 49, 3170. 15 L. F. Somerville and C. F. H. Allen, Org. Synth., 1950,Coll.Vol. II,8 1. 16 V. Somayaji, Ph.D. Thesis, Indian Institute of Science, 1980. 17 S. C. Sengupta and P. Krishna Sen, Sci. Culture, 1962, 28, 343. 18 D. Chakravarti and N. K. Roy, J. Indian. Chem. SOC., 1965,42,607. 19 N. L. Allinger and E. S. Jones, J. Org. Chem., 1962, 27, 70. 20 H. Staudinger, Ber. Dtsch. Chem. &, 1908,41, 3558. 21 M. S. Newman and Zia Ud Din, J. Org. Chem., 1971,36,2740. 22 L. Christiaens and M. Renson, Bull. SOC. Chim. Belg., 1969, 78,359. Received 5th September 1984; Paper 411533
ISSN:1472-779X
DOI:10.1039/P29860000355
出版商:RSC
年代:1986
数据来源: RSC
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