March 20, 1958
CLEAVAGE OF SIMPLE AROMATIC BORONIC ACIDS
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ORGANIC AND BIOLOGICAL CHEMISTRY [CONTRIBUTION FROM THE
DEPARTMENT OF CHEMISTRY, IOWA STATE COLLEGE]
Cleavage Studies of Simple Aromatic Boronic Acids BY HENRYGILMAN,D. R. SWAYAMPATI AND R. 0. RANCK RECEIVED AUGUST19, 1957 Benzeneboronic acid and o-hydroxybenzeneboronic acid anhydride were cleaved with n-butyllithium and the products characterized by carbonation. Benzeneboronic acid gave either 1-butaneboronic acid, benzoic acid or benzene, or a combination, the products depending upon the temperature at which the cleavage was run. o-Hydroxybenzeneboronic acid anhydride gave salicylic acid a s one of the products. The cleavage of o-hydroxybenzeneboronic acid anhydride with hydrogen peroxide and bromine behaved normally.
A number of cleavage reactions of alkyl- and arylboronic acids are known. Many of these have been summarized by Lappert' in his recent review on organoboron chemistry. For example, benzeneboronic acid can be cleaved with water a t elevated temperatures (140-150' under pressure for 40 hours) to give benzene and boric acid,2 or with concen trated sodium hydroxide or hydrochloric acid a t a lower temperature (reflux) and a t atmospheric pressure to give similar products.2 Both p bromobenzeneboronic acid and p-tolueneboronic acid were also cleaved with water a t elevated temperatures under pressure to give bromobenzene and toluene, respectively, and boric acid.3 These cleavages were accomplished in 6 hours, the first From a t 140-150° and the second a t 130-140'. this it appears t h a t some substituted boronic acids may be somewhat less stable to these cleavage conditions than the unsubstituted benzeneboronic acid. Both cy- and P-naphthaleneboronic acid4 and some substituted naphthaleneboronic acids (4dimethylamino-1-naphthaleneboronicacid and 4methoxy-1-naphthaleneboronicacid)6 also seem to be less stable to this type of cleavage than benzeneboronic acid. These boronic acid derivatives of naphthalene decomposed on recrystallization from water. Cleavage with hydrogen peroxide introduces an -OH group in the position previously occupied by the boronic acid group while cleavage with halogen (chlorine water, bromine water or iodine in potassium iodide) gives a halogen in place of the boronic acid group. Additional halogenation may also occur. Thus, phenol was obtained by treating benzeneboronic acid with hydrogen peroxide,2 bromobenzene by treating benzeneboronic acid with aqueous bromine water2 and 2-iodothiophene by treating 2-thiopheneboronic acid with an aqueous solution of iodine in potassium iodide.6 Cleavage also has been accomplished by salts of B subgroup elements (e.g., Cu, Ag, Zn, Cd, Hg) to give various products depending partially on the salt used. For example, benzeneboronic acid was converted t o chlorobenzene when treated with aqueous cupric chloride,2 but benzene and biphenyl (1) M. F. Lappert, Chcm. Reos., 66, 959 (1956). (2) A. D. Ainley and F. Challenger, J . Chrm. SOC.,2171 (1930). (3) F. Challenger and 0. V. Richards, i b i d . , 405 (1934). JounNAL, (4) D.L. Yabroff, G. E.K.Branch and B. Bettman, THIS 66, 1850 (1934). (5) H. R . Snyder and F. W. Wyman. i b i d . , 7 0 , 234 (1948). (6) J. R. Johnson, M. G. Van Campen and 0. Grummitt, ibid., 60, 111 (1938).
were produced when an aqueous solution of cupric sulfate was used.2 Recently a cleavage of an aromatic boronic acid with n-butyllithium' has been reported.* I n an attempt to achieve a halogen-metal interconversion on 2-hydroxy-5-bromobenzeneboronicacid, these workers obtained, after carbonation using a Dry Ice-ether slurry and hydrolysis of the reaction mass, a mixture of products. When the reaction was carried out for 1.5 hours in refluxing ether using five equivalents of n-butyllithium, 1-butaneboronic acid, 5-bromosalicylic acid and p-hydroxybenzoic acid were obtained. When an 18-minute reflux time was used with the same quantities of material, 1-butaneboronic acid and 5-bromosalicylic acid were obtained. No mechanism was postulated. I n the work reported here, some cleavage reactions were carried out on benzeneboronic acidQand o-hydroxybenzeneboronic acid anhydridelo with nbutyllithium in an effort to gain additional information concerning the possible nature of the cleavage. With benzeneboronic acid, reactions were carried out a t ether reflux, a t 20' (room temperature) and a t -50 to -60'. The reactions were terminated by pouring jet-wise into an agitated Dry Iceether slurry and any acidic products isolated by extraction with base. When five equivalents of nbutyllithium was used a t reflux for 1.5 hours, no acidic products could be isolated nor any product containing the benzene nucleus. This perhaps indicates complete decomposition. When the reaction was carried out a t either reflux or room temperature for 20 minutes with three equivalents of n-butyllithium, 1-butaneboronic acid and a small amount of benzene, characterized as the mdinitro compound, were obtained. There was no evidence of benzoic acid in either case. At - 50 to -60' for a period of 25 minutes using three equivalents of n-butyllithium, benzoic acid was the only product isolated t h a t was identified. Another high melting product, possibly a salt, was also obtained. When o-hydroxybenzeneboronic acid anhydride was treated with three equivalents of n-butyllithium a t room temperature for 20 minutes, followed by carbonation and hydrolysis in the usual manner, salicylic acid and an unidentified unstable product were isolated. (7) H.Gilman, J. A. Beel, C. G. Brannen, M. W. Bullock, G. E. Dunn and L. S . Miller, ibid.. 71, 1499 (1949). ( 8 ) L. S n t u c c i and H . Gilman, ibid., 80, 193 (1958). (9) Kindly furnished by the American Potash and Chemlcal Cow. (10) H.Gilman. L. Santucd, D.R. Swayampati and R. 0. Ranck, TEISJOUIZNAL., 79, 3077 (1967).
lTol.so
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I n all of these cleavage reactions, other products of other o-substituted acids containing au aiiiino or resulting directly from the n-butyllithium and of no hydroxy group. Both 0- and p-aminobenzoic acid immediate interest were also isolated. These in- gave 2,4,6-tribromoaniline upon treatment with clude valeric acid, di-n-butyl ketone and possibly bromine water 1 3 ; sulfanilic acid and arsanilic acid n-octane. likewise gave 2,4,(i-tribromoaniline,l 3 and -3,.1--tliThese cleavages can, in some aspects, be pic- carboxyphenol gave 2,4,(i-tribroiiiophenol.I-] tured as occurring by processes similar to metalaAcetylation of o-hydroxybenzeneboronic acid m i tion" or halogen-metal interconversion" in which hydride was attempted also in pyridine with a i i t l a n attack by the anion of n-butyllithiuni on either without a sulfuric acid catalyst, but 11011e ( i f the t l c the hydrogen or halogen occurs, a positive hydro- sired product was isolated. Only starting material gen or halogen being displaced. I n the cleavage or the cleavage products, phenol and boric acid, of boronic acids, the process may occur by the could be recovered. The sulfuric acid catalyst was nucleophilic attack of the butyl anion on the boron found t o be necessary for the acetylation of salicylic to give, after displacement, 1-butaneboronic acid acid to destroy the chelation between ad jaccrit (thus explaining the formation of this compound in groups. The attempted acetylztion of ?,3,-disome of the cleavage reactions) and an aryllithium carboxyphenol using sulfuric acid ;LS a catalyst 11:~s compound. Carbonation of the aryllithium com- also been reported.14 pound followed b y hydrolysis would explain the Experimental formation of such products as 5-brornosalicylic Cleavage of Benzeneboronic Acid with Three Equivalents acid,* benzoic acid and salicylic acid from the reof n-Butyllithium. ( a ) At Room Temperature for 20 Minspective cleavages of 2-hydroxy-5-broniobenzene- utes.--A solution of 0.225 mole of n-butyllithiurn' in 200 boronic acid, benzeneboronic acid and o-hydroxy- nil. of ether was added to a mixture of 10.38 g. (0.085 ~ n o l e ) benzeneboronic acid anhydride. It could also of benzeneboronic acid in 220 ml. of ether over a period of explain the formation of such products as p-hy- 10-15 minutes at room temperature. Stirring was cotia t room temperature for 20 minutes after which the droxybenzoic acid and benzene from the cleavages tinued mass was carbonated b y pouring into a Dry Ice-ether slurry. of 2-hydroxy-5bromobenzeneboronic acid and T h e mixture was acidified to a pH of 4-5 with loc; hydrobenzeneboronic acid if hydrolysis of the aryllith- chloric acid and the ether layer was extracted with 100 ml. ium compound had occurred prior to the carbona- (0.1 mole) of 8%, sodium bicarbonate in four portions and 100 ml. (0.131 mole) of 5y0 sodium hydroxide, also in four tion. However, it does not explain why, in the portions. Acidification of the sodium bicarbonate extract case of benzeneboronic acid, I-butaneboronic acid, with 10ychydrochloric acid produced no solid, but acidificabenzoic acid and benzene could not all be isolated tion of the sodium hydroxide extract gave, after recrystallifrom the same experiment; and why a different zation from toluene, 2.5 g. (29y0)of 1-butaneboronic acid identified b y melting point (90-92'), mixed melting point combination of products was isolated when the with an authentic sample prepared according t o the methutl reaction was carried out a t different temperatures, of Snyder, Kuck and Johnson,'G a n d the infrared spectruiii. the isolation step remaining unchanged. I t also Fractionation of the ether layer gave a quantity of inipure fails to explain why a different combination of prod- benzene which mas identified by conversion to the ni-dinitro n-Octane, di-n-butyl ketone and valeric acid ucts was isolated from 2-hydroxy-5-bromobenzene- derivative. were also present. boronic acid when the reaction time was varied. (b) At Reflux Temperature for 20 Minutes.-This experiThese experiments do show, however, that the ment was carried out as the one described above except 1hat a reflux temperature was used. Two and fifteen-hundredths cleavage of the boronic acid group is extremely fagrams (25%) of 1-butaneboronic acid, a small amount of cile when a strong base such as n-butyllithium is benzene and the other usual products, valeric acid, di-nused, the cleavage occurring a t very low tempera- butyl ketone and n-octane, were isolated. There TXIS 110 tures. There is also some indication that 2-hy- evidence of benzoic acid. (c) At -50" to -60' for 25 Minutes.-Twelve and twodroxy-5-bromobenzeneboronic acid is possibly tenths grams (0.1 mole) of benzeneboronic acid in 2,W 1111. somewhat more resistant to cleavage than benzene- of ether was treated with 0.3 mole of n-butyllithium' i n 218 boronic acid. This is based on the experiments ml. of ether added over a 20-minute period. The t e r n ] ~ r : ~ run for 1.5 hours a t reflux in which p-hydroxyben- ture mas kept a t -50 to -60" during the additioii a n d for zoic acid, 5-bromosalicylic acid and l-butanebo- 25 minutes following. At this time Color Test 1" wah i)osiand Color Test 11'8 was negative. The mixture \r:tS ronic acid were obtained from the former compound tive carbonated in the usual manner, acidified with 100 nil. ( O . L ' ! I while nothing has been isolated from the latter. mole) of 10%. hydrochloric acid and the ether IaJ-cr exWhen benzeneboronic acid was treated with n-bu- tracted four times with 25-ml. portions (0.1 molv'i i l f 8' tyllithium under milder conditions, reflux or room sodium bicarbonate and four times with 25-1111. portii)iis temperature for 18 minutes, products (l-butane?icidification of the sodium bicarbonate la>-ergave 0.75 g. boronic acid and benzene) somewhat comparable to (6.25;) of benzoic acid identified by melting point a n d i i i i i c > ( l those obtained from the 2-liJ'droxy-;S-bronioben- melting point a s well a s the infrared spectrum. -\cidifimtion of the sodium hydroxide extract caused the foriiixtio1i zeneboronic acid were produced. f white needles which did not melt uiitlcr :;T,no. So 1 Since o-hydrosybenzeneboronic acid anhydride is obutaneboronic acid \\-ah isolated. a relatively new compound, some of the more common cleavage reactions were also carried out on it. Treatment with hydrogen peroxide in acetic acid gave catechol and treatment with bromine water it1 acetic acid gal-c L',1.,(i-tr;bri)mophenol. This latter reaction corresponds closely to the cleavage ('
(111 H . Gilman and J . Th-. l l o r t o n , J r . , i n "Organic Reactions," X-oI, VIIT, J o h n Wiley and Sons, Inc.. N e w l'ork, S . V , 19.54, p. 2.58.
I121 R . G. Jones and H. Gilman, in "Organic Reactii,n.." Johu \Viley and Sons, Inc., N e w York, N.Y . , 1031, p.
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