[CONTRIBUTION FROM
THE
CHEMICAL RESEARCH LABORATORY O F SCHERIKG C O R P O R A T I O S ]
REDUCTIONS WITH NICKEL-ALCMINUM ALLOY XND AQUEOUS rlLIL4LI. PART 11. THE DISPLACEMENT OF GROUPS BY HYDROGEN E R W I S SCIIWESK, DOMESICK PAPA, BRADLEY WHITMAN, HELEN GINSBERG
AND
Received June 8, 1943
In continuation of previous work in this laboratory on the reduction of carbonyl compounds by a nickel-aluminum alloy in alkaline solution (l),the displacement by hydrogen of methoxyl, halogen, and sulfonic acid groups from several benzenoid compounds was observed. This paper presents the results of our studies on this displacement reaction. The hydrogenolysis of sulfonic acid groups in the naphthalene series (2) and of halogens in many aliphatic and aromatic compounds has been observed during reductions with zinc and acid (3, 4). Several isolated instances of the displace(6) ment of other groups, such as the methoxyl groups ( 5 ) and the -C=OR have been reported in the course of the Clemmensen reduction. Catalytic reduction, particularly at high pressures, often brings about hydrogenolysis ( 7 ) . When treated with nickel-aluminum alloy and aqueous alkali,’ halogen and sulfonic acid groups (Tables I and 11),are displaced by hydrogen, the displacement of these groups being apparently independent of their number, their position, or the presence of other groups. A11 halogen-containing compounds which we have studied (Table I), be they aliphatic, aromatic, alicyclic, or heterocyclic, quantitatively exchanged their halogen for hydrogen.? Up to the present time the reductive displacement of sulfonic acid groups has been limited, in general, t o the alpha-naphthalenesulfonic acids, only a few instances of a similar displacement being observed for the beta compounds (2). Tl7ith our reduction method, sulfonic acid groups are displaced from alpha- and beta-naphthalenesulfonic acids, as well as from the benzenesulfonic acids. The low yields in some cases are quite likely due to a poisoning of the nickel catalyst by the sulfite or sulfide formed during the reaction. Two organometallic compounds were investigated, arsanilic acid and phenylmercuric acetate, the former yielding aniline and the latter diphenyl. 1 The reduction of the compounds given in the tables of this paper was carried out according t o the procedure previouslydescribed (1). The yields of the reduction products are calculated t o the starting material arid represent products purified by recrystallization or distillation. Ten grams of substance were used in those reductions in which only one product was obtained, whereas, twenty-five grams were used in those reductions where two or more products were formed. 2 In Table I are given only those halogen compounds whose reduction product has been identified. Halogen compounds belonging t o the aliphatic, alicyclic and heterocyclic classes are given in another publication which describes the application of this reduction procedure t o the quantitative detecmination of halogens in organic compounds. See Znd. Eng. Chem. Anal. Ed., 16, 576 (1943). I
2
SCHWENK, PAPA, WHITMAN, AND GINSBERG
Of the compounds studied, only halogen and sulfonic acid groups are displaced by hydrogen from monosubstituted benzene derivatives. In disubstituted benzene compounds, not only were halogen and sulfonic acid groups displaced, but alkoxyl groups as well. Whether or not an alkoxyl group will be displaced by hydrogen depends upon the nature and’ position of the other substituent. When subjected to this reduction procedure, p-anisidine (I) and 0- (11), m- (111), and p-cresyl methyl ether (IV) were recovered unchanged. When the ortho-para-directing methyl or amino group in compounds I to IV is replaced by the meta-directing carboxyl group, quantitative displacement of the methoxyl TABLE I HALOGEN COMPOUNDS COMPOUND
REDUCTION PRODUCT
7 0 YIELD
1. Bromobenzenea.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. m-Chlorobenzoic acid. . . . . . . . . . . . . . . . . . . . . . . . . 3. p-Chloronitrobenzene~... . . . . . . . . . . . . . . . . . . . . . 4. p-Chlorobenzaldehyde.. . . . . . . . . . . . . . . . . . . . . . . 5 . 5-Chloro-2-hydroxybenzaldehyde.. . . . . . . . . . . . . 6. p-Bromoacetophenone”. . . . . . . . . . . . . . . . . . . . . . . 7 . fl-(p-Chlorobenzoy1)propionicacid. . . . . . . . . . . .
Benzene Benzoic acid Aniline Toluene o - Cr e so 1 Ethylbenzene 7-Phenylbutyric acid
100b 100
(I
65
60 75 67 70
25 cc. of alcohol used as solvent.
a The yield of benzene is based on the quantitative recovery of bromine as silver bromide.
TABLE I1 SULFONICACIDS COMPOUND
I
1. Benzenesulfonic acid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. o-Sulfobenzoic acid.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. m-Sulfobenzoic acid.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Naphthalene-@-sulfonic acid, . . . . . . . . . . . . . . . . . . . . . 5 . 2-Naphthol-6-sulfonic acid. . . . . . . . . . . . . . . . . . . . . . . . 6. 2-Naphthol-3,6-disulfonicacid. . . . . . . . . . . . . . . . . . . .
REDUCTION PRODUCT
Benzene Benzoic acid Benzoic acid Naphthalene @-Naphthol 8-Naphthol
1
% YIELD
10” 40
50 40
30 30
4 The poor recovery of benzene is very probably due t o the entrainment of the vapors by the hydrogen liberated from the alloy.
group takes place in 0- and p-methoxybenzoic acid. However, the m-methoxybenzoic acid is recovered unchanged. In none of our experiments has the displacement of a meta- substituted methoxyl group been observed. A similar displacement of the methoxyl group took place in compounds with other meta-directing groups, such as --r\;O2, -CHO, and --COCHS. In addition t o the displacement reaction, the meta-orienting groups in these compounds are themselves capable of reduction (1) to the ortho-para-orienting amino or alkyl groups. In a compound containing such a reducible substituent, elimination of the methoxyl group can occur only before the reduction has converted the meta-directing into an ortho-para-directing group. For example, in the reduc-
3
REDUCTIOKS WITH NICKEL-ALUMINUM ALLOY
tion of p-nitroanisole, a 20% yield of aniline and a 70% yield of p-anisidine w a ~ obt.ained. The aniline must result from an initial displacement of the methoxyl 2"
I
OCHs
I
OCHs
group followed by the reduction of the nitrobenzene thus formed, whereas the p-anisidine arises from the initial reduction of the nitro group. The two possible reduction products were also obtained in varying amounts from p-methoxybenzyl alcohol and from 0- and p-methoxybenzaldehyde. While only ethylbenzene was isolated from the reduction of p-methoxyacetophenone, it is quite possible that p-methoxyethylbenzene was also formed in small amounts. A third reaction product, benzoic acid, was isolated from the reduction of p-methoxybenzyl alcohol and p-methoxybenzaldehyde. A reinvestigation of the reduction products of benzyl alcohol and benzaldehyde also revealed the presence of benzoic acid in both cases. In the alkaline environment, part of the benzaldehyde and its substituted derivatives may undergo a Cannizzaro conversion to the corresponding alcohols and acids. The formation of benzoic acid from the benzyl alcohols can be explained by assuming an initial dehydrogenation of the alcohols to the aldehydes, followed by a displacement or Cannizzaro reaction, It is in agreement with this explanation that with p-methoxybenzyl alcohol, displacement of the methoxyl group was observed, notwithstanding the fact that the CHzOH group is essentially an ortho-para-directing group. It is probable that the displacement of the methoxyl group does not occur in the original compound but in the p-methoxybenzaldehyde and the p-methoxybenzoic acid with their meta-directing groups in para position to the methoxyl group. There are, then, several reactions possible in the reduction of the benzyl alcohols and benzaldehydes. The scheme shown on top of page 4 illustrates the probable course of the reaction, the asterisks indicating the compounds actually isolated in the case of p-methoxybenzyl alcohol. The displacement reaction is not restricted to the methoxyl group, a similar loss of the alkoxy1 group occurring in p-ethoxybenzaldehyde, and in p-ethoxy-, p-propoxy-, p-isopropoxy-, and p-butoxybenzoic acids. The yields of benzoic acid varied from 10% with p-ethoxybenzoic acid to 60% with p-propoxybenzoic acid, despite the fact that twice the usual amount of alloy and alkali mas used in these reductions. Benzyloxyl compounds are split in the same manner as observed with other reduction methods, o-benzyloxybenzoic acid yielding toluene and salicylic acid. o-Methylthiolbenzoic acid, however, behaves as the oxygen analog, giving only benzoic acid. The introduction of a hydroxyl or methoxyl group &s the third group in the
4
SCHWENK, PAPA, WHITMAN, AND GINSBERO
0 CHZ
OCHI
I.
I
.1 COOH
0 -0 COOH
Displacement
,
OCH,
CHtOH
disubstituted benzene derivatives alters considerably the course of the displacement reaction. The most striking change in the displacement reaction is that in many cases displacement of meta-orienting groups was observed, a reaction for which no parallel could be found in the literature. It compares, however, with observations made by others, who have shown that carbonyl groups are displaceable by hydrogen, halogen, and nitro groups (8, 9, 10, compare also 11). In the trisubstituted compounds (VI to XI) displacement of the aldehyde group by hydrogen occurred, notwithstanding the diversified position relationships of the hydroxyl and methoxyl groups to the aldehyde group. Although the only product isolated in the reduction of these aldehydes was guaiacol or dimethoxybenzene, it is evident from an inspection of the formulas (VI to XI)
CH,
R
CHO
V VI VI1 RxCH~OH, CHO, C o c a
CHO
VI11
CHO
CHO
CHO
IX
X
XI
5
REDUCTIOSS WIT13 SICKRIr.4LUMINUM .4LLOY
that other reduction products may be formed. For example, in isovsnillin (TITI) small amounts of meta-cresol and 3-hydroxy-4-methosytoluene(V) may have been formed, but, in the presence of large amounts of guaiacol, detection of these compounds is difficult and was not considered within the scope of this investigation. TABLE I11 DISURSTITUTED BESZESE DERIVATIVES
--__
COMPOUND
REDUCTION PXODUCT
1. o-Methoxybenzaldehyde.. . . . . . . . . . . . . . . . 1. o-Cresyl methyl ether 2. Toluene 3. Benzoic acid 2. o-3lethoxybenzoic acid. . . . . . . . . . . . . . . . . . Benzoic acid 3. o-Methylthiolbenzoic acid, . . . . . . . . . . . . . . Benzoic acid 4. o-Benzyloxybenzoic acid. . . . . . . . . . . . . . . . . Salicylic acid Recovered unchanged 5. Diphenyl e t h e r . .. . . . . . . . . . . . . . . . . . . . . . . . G . p-Methosybenzyl alcohola . . . . . . . . . . . . . . . 1. p-Cresyl methyl ether 2. Toluene 3. Benzoic acid 7 p-1Irthoxybenzaldehydea 1. p-Cresyl methyl etherc 2. Toluene 8 p-Sitroanisoleo 1. p-Anisidine 2. Aniline Benzoic acid 9 p-Anisic acid . . . . . . . . . . . . . . . . . . . . . 10. p-Etliosybenzaldehgde". . . . . . . . . . . 1. Benzoic acid 2. p-E t hoxytoluene 3. Toluene 11, p-Ethoxybenzoic acidb.. . . . . . . . . . . . . . . . . . Benzoic acid 12. p-Methoxyacetophenone". . . . . . . . . . . . . . . . Ethyl benzene 13. &(p-Methoxybenzoy1)propionic acid. . . . . 7-Phenylbutyric acid 14, p-Isopropoxyhenzoic acidb.. . . . . . . . . . . . . . Benzoic acid 15, p-Propoxybenzoic acidh.. . . . . . . . . . . . . . . . . Benzoic acid 16. p-Butoxybenzoic acidb... . . . . . . . . . . . . . . . . Benzoic acid 17. p-llethosyphenylacetic acid. . . . . . . . . . . . . Recovered unchanged 18. p-Methoxycinnamic acid. . . . . . . . . . . . . . . . . p-Methosyhydrocinnamic acid I O . ni-1lethosyberizaldehyde".. . . . . . . . . . . . . . . m-Cresyl methyl etherc 20. nt-!tfethosybenzoic acid. . . . . . . . . . . . . . . . . . Recovered unchanged 21. p-Dimethylaminobenzaldehydea... . . . . . . . p-Dimethyltoluidinec
% YIELD
45 15 20 100 75 75 50 15 20 30 45 70 20 100 40 15 25 10 50 65 30 60 40 95
55 70
b Recovered from the reduction mixture, p-ethoxyI 25 cc. of alcohol used as solvent. bcrizoic acid 90%, p-isopropoxybenzoic SO%, p-proposybenzoic acid 25%, p-butoxybenzoic acid 6070. Thew aldehydcs were reduced before we were aware of the presence of benzoic arid in the aqueous phase.
The reduction of the acids (XI1 to SYI)corresponding to the aldehydes (VI to XI) illustrates the complex nature of these reactions. While vanillic acid (XII) mas recovered unchanged, isovanillic acid (XIII) yielded m-hydroxybenzoic acid. However, it was necessary to use about five times the normal amount of alloy and alkali in order to bring about this conversion. That the methoxyl group was displaced in isovanillic acid suggests the possibility of a
0
SCHWENK, PAPA, WHITM.43, AND GINSBERG
COOH
COOH
O..., OH
XI1
()OH OCHs
XI11
COOH
(JZ: XIV
COOH
OOCHa OCHS
xv
COOH
QCHa OCHa
XVI
similar cleavage in isovanillin, but the rate of its displacement is apparently much slower than that of the aldehyde group. The acids (XIV to XVI), when TABLE IV TRISUBSTITUTED BENZENE DERIVATIVES COMPOUND
REDUCTION PRODUCT
"; YIELU -~
1. 2,3-Dimethoxybenzaldehydea.. . . . . . . . . . 2. 2,3-Dimethoxybenzoic acidb.. . . . . . . . . . . . 3. 3, 4-Dimethoxybenzaldehydea.. . . . . . . . . . 4. 3,4-Dimethoxybenzoic acidb.. . . . . . . . . . . . 5. @-(3,4-Dimethoxybenzoyl) propionic acid.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Veratrole Recovered unchanged Veratrole Recovered unchanged
70 76
70
y- (3,4-dimethoxyphenyl)bu-
tyrolactonec 6. 3,4,5-Trimethoxybenzoic acid.. . . . . . . . . . Recovered unchanged 7. 2,4-Dimethoxybenzaldehydea.. . . . . . . . . . Resorcinol dimethyl ether 8. 2,4-Dimethoxyacet~phenone~. . . . . . . . . . . Resorcinol dimethyl etherd 9. 2,4-Dimethoxybenzoic acide.. . . . . . . . . . . . Recovered unchanged 10. 3-hlethoxy-4-hydroxytoluene.. . . . . . . . . . . Recovered unchanged Guaiacol 11. Vanillyl alcohol. . . . . . . . . . . . . . . . . . . . . . . . Guaiacol 12. Vanillin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Guaiacol 13. Isovanillin.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14. 3-Ethoxy-4-hydroxybenzaldehyde.. . . . . . o-Et hoxyphenol 15. 3-Methoxy-2-hydroxybenqaldehyde.. . . . . Guaiacol 16. 3-hlethoxy-4-hydroxyacetophenone.. . . . . Guaiacol Recovered unchanged 17. Vanillic a c i d . . . . . . . . . . . . . . . . . . . . . . . . . . . m-Hydroxybensoic acid' 18. Isovanillic acid .........................
45 15
60 70 70 75 75 70
_~
50
25 cc. of alcohol used as solvent. b The reduction of these acids with 5 times t h e normal amount of nickel-aluminum alloy did not yield any m-methoxybenzoic acid. 11.p. Residue 116-117"; Calc'd. for Cl2H1,O4:C, 64.87; H, 6.36. Found: C, 65.25; H, 6.40. from the distillation (60%) gave the dinitrophenylhydrazone of the original compound. e This acid was quantitatively recovered on treatment with alloy and alkali a t 125' for 5 hours. f Further treatment with alloy and alkali converted 90% of the isovanillic acid t o m-hydroxybenzoic acid. 0
treated in the same manner BS isovanillic acid, did not undergo any displacement of the methoxyl groups. As in the case of 3,4-dimethoxybenzoic acid (XV) j3-(3,4-dimethosybenzoyl)propionicacid (XVII) did not undergo any displacement of the p-methoxyl group, despite the fact that 0-(p-methoxybenzoy1)propionic acid (XVIII) gave a 65% yield of 7-phenylbutyric acid. From the reduction of XVII 7-(3,4-dimethoxyphenyl)butyrolactone (XIX) was obtained in
REDUCTIONS WITH XICKEL-ALUMINUM ALLOY
COOH
XVII
7
COOH
XVIII
XIX
70yc yield in addition to a small amount of intractable oil. The behavior of these acids (XIV to XVII) is somewhat surprising in view of the fact that all four have a methoxyl group in either the ortho and/or para position to a metadirerting group. No change occurred in 2,4-dimethoxybenzoic acid (XVI) even after heating under pressure with nickel-aluminum alloy and alkali at 125” for 5 hours. The reduction of 3,4,5-trimethoxybenzoic acid was also studied to determine whether the presence of three methoxyl groups might bring about the displacement of the carboxyl group. However, neither the carboxyl nor any one of the methoxyl groups was displaced. SUMMARY
1. Treatment of compounds containing halogen, sulfonic acid, alkoxyl, carbonyl, and metallic groups with nickel-aluminum alloy and aqueous alkali has resulted in the displacement of these groups by hydrogen. 2 . The displacement of halogen and sulfonic acid groups has been found to be independent of the structure of the compound. 3. Alkoxy1 groups are displaced from disubstituted benzene derivatives when they are ortho or para to a metu-directing group. 4. In trisubstituted benzene derivatives of the general formula RCBH~R’R’’, where R is a meta-directing group other than carboxyl, R‘ is either a hydroxyl or alkoxyl group, and R” is an alkoxyl group, displacement of the meta-directing groups by hydrogen was observed, this displacement being independent of the position relationship of the three groups. 13LOOMFIELD, N. J. REFERENCES ( 1 ) PAPA,SCHWENK, AND WHITMAN, J . Org. Chem., 7 , 587 (1942). (2) FRIEDL-DER AND LUCHT,Ber., 26, 3031 (1893); CLAUS,Ber., 10, 1304 (1877); FRIED-
et al., Ber., 28, 1535 (1895); Ber., 29, 1978 (1896). HAWORTH, AND WALTON, J . Chem. S O C . , 2368 (1929); JOHNSON AND HODGE, J . Am. Chem. SOC.,36, 1014 (1913); FINKEAND RISTIC,J . prakt. Chem., 146, 151 (1936). (4) FIESER AND SELIGYAN, J . Am. Chem. SOC., 60, 170 (1938). (51 FIESERAND HERSHBERO, J . A m . Chem. Soc., 68,2382 (1936). (6) ADAMS, CAIN,AND BAKER,J . Am. Chem. Soc., 62,2201 (1940) ; v. BRAUN,KIRSCHBAUM, AND SCHUHMANN, Ber., 63, 1155 (1920). LANDER
(3)
CLEBfO,
8
SCHWENK, PAPA, WHITMAN, AND GINSRERG
(7) ADKISS,“Reactions of Hydrogen with Organic Compounds over Copper-Chromium Oxide and Nickel Catalysts,” The Gniversity of Wisconsin Press, Madison Wis., 1937. (8) PAAL, Bel.., 28,2407 (1895); WERNER,Bull. S O C . chim., 46,277 (1886). (9) BENTLEY,Ani. Chem. J.,24, 171 (1900). For a review on “Displacement of Atoms and Groups in the Benzene Sucleus”, see DELASGE,Rec. trav. chim., 46, 19-60 (1926). (10) SALWAY, J. Chcnt. Soc., 96, 1163 (1909); PARYS,Rec. trav. chim., 49,17 (1930). Dissertation, University of Heidelberg, 1900. (11) KLAGES,
