3118
J.Org. Chem., Vol. 42, No. 19,1977
Rondestvedt
T.-L. Ho and C. M. Wong, Synth. Commun., 5,299 (1975); see further ref Vaalburg and Mrs. H. D. Beerling-Van der Molen for technical 3a. assistance in the radioactivity measurements, to Mr. A. F. 10) The low reactivity of &-tetralone may be due to enolization. 11) D. Hoppe, Angew. Chem., lnt. Ed. Engl., 13, 789 (1974) (review). Hamminga for support in the CO determination, and to 12) T. Saegusa and Y. Ito in "Isonitrile Chemistry", I. Ugi. Ed., Academic Press, Gist-Brocades N.V., Delft, for a generous gift of two steNew York, N.Y., 1971, Chapter 4. roids. 13) Cf. J. C. Jagt and A. M. van Leusen, J. Org. Chem., 39, 564 (1974). 14) G. R. Krow. Angew. Chem., lnt. Ed. Engl., 10, 435 (1971). Registry No.-%a, 35:356-00-9; endo-%b, 3211-87-8; exo-%b, 15) For example, in the reaction of benzophenoneand TosMlC (see Experi3211-90-3;endo- 2c, 62796-09-2;exo- 2c, 62796-08-1;2d, 32730-85-1; mental Section), 21% of 4-tosyloxazole was isolated in addition to 21 (69%). The former compound is the expected product of formylation of 2e, 766-05-2;2f, 56536-96-0;2g, 62796-10-5;2h, 57764-88-2;17a-2i, TosMICEb(cf. ref 20). Here, formylation may occur by 9, 11. or 15. 62796-11-6;17@-2i,62796-12-7;3a-2j, 1251-67-8;3@-2j,1251-66-7; 16) This view may derive some support from E. Gordon, S. J. W. Price, and A. 3a-2k, 62796-13-8;3B-2k, 62796-14-9;21,86-29-3;2m, 1823-91-2;2n, F. Trotman-Dickenson, J. Chem. Soc., 2813 (1957); H. N. Barham and L. 42186-06-1; 20, 13310-75-3; 2p, 62391-96-2; 2q, 21101-85-9; 13e, W. Clark, J. Am. Chem. Soc., 73, 4638 (1951). 52568-58-8; 14e, 39031-25-9; 2,2-dimethyl-1,2,3,4-tetrahydrona- (17) A number of reactions discussed here for ketones are observed for aldehydes as we11.8.1E,20However, in the case of aldehydes, the tosyloxaphthalene-1-carboxamide,62796-15-0; 4-tosyloxazole, 57764-94-0; zolines 13 (R' = H) can undergo another type of reaction, Le., the elimiTos14CH2N=C, 62796-16-I; 14CH20,3046-49-9;Tos~~CH~NHCHO, nation of TosH to oxazoles.20~8 For that reason we have left aldehydes out 62796-17-2;TosMIC,36635-61-7. of the discussion in the present paper.
References a n d Notes (1) Chemistry of Sulfonylmethyl Isocyanides. 13. For parts 12 and 14, see ref 2a and 2b, respectively. (2) (a) A. M. van Leusen, J. Wildeman, and 0. H. Oldenziel, J. Org. Chem., 42, 1153 (1977); (b) A. M. van Leusen and J. Wildeman. Synthesis, 501 (1977). (3) Part of this work was presented in preliminary form: (a) 0. H. Oldenziel and A. M. van Leusen, Tetrahedron Lett., 1357 (1973); (b) Synth. Commun., 281 (1972). (4) D. T. Mowry, Chem. Rev., 42, 231 (1948). (5) For recent multistep processes via additionof HCN to hydrazonederivatives, see F. E. Ziegler and P. A. Wender, J. Am. Chem. Soc., 93,4318 (1971); S. Cacchi, L. Caglioti, ,and G. Paolucci, Chem. Ind. (London), 213 (1972). (6) After publication of our preliminary communications3other research groups too have applied this synthetic principle with success. Of their contributions the following published results have come to our attention: (a) E. J. Rauckman, G. M. Rosen, and M. B. Abou-Donia, J. Org. Chem., 41,564 (1976); (b) J. R. Bull and A. Tuinman, Tetrahedron, 31,2151 (1975); (c) S. Kishimoto and S. Noguchi, Japan Kokai 75 59,359 [ Chem. Abstr., 63, 131366k (1975)]; (d) B. !;, E. Carnmalm, T. DePaulis, S. B. Ross, S. I. Ramsby, N. E. Stjernstrom, and S. 0. Ogren, German Offen 2 360 027 [Chem.Abstr., 81, 169367h (1974)]; (e) R. W. Freerksen and D. S. Watt, Synth. Commun., 6, 447 (1976); (f) T. Sasaki. S. Eguchi, and M. Mizutani, Tetrahedron Lett., 2685 (1975); (9) M. L. Raggio and D. S. Watt, J. Org. Chem., 41, 1873 (1976); (h) G. BUchi, D. Berthet, R. Decorzant, A. Grieder, and A. Hauser, ibid., 41, :3208 (1976). (7) For a recent modification of the reaction of nitriles to amides, see J. H. Hall and M. Gisler, J. Org. Chem., 41, 3769 (1976); The conversion >CHC=N >F(OH)C=N was described recently: E. Vedejs and J. E. Telschow, ibid., 41, 740 (1976), and ref 6e. For the reversal of reaction 1 (i.e., >CHC=N >C=O) see S. J. Selikson and D. S. Watt, ibid., 40, 267 (1975). (8) (a) U. Schollkopf, R . Schroder, and E. Blume. Justus Liebigs Ann. Chem., 766, 130 (1972); (b) U. Schollkopf and R. Schroder, Angew. Chem., lnt. Ed. Engl., 12, 407 (1973) (9) Recent leading references: E. Vowinkel and J. Bartel, Chem. Ber., 107, 1221 (1974); J. B. Hendrickson, K. W. Bair, and P. M. Keehn, Tetrahedron Lett., 603 (1976); A. Antonowa and S. Hauptmann, Z.Chem., 16, 17 (1976);
-
-
(18) 0. H. Oldenziel and A. M. van Leusen, TetrahedronLett., 163 (1974). The reaction 13 -,18 is not a direct substitution of Tos, but a double addition-elimination involvingtwo molecules of EtoH via 2+thoxy3.oxazolines: 0. H. Oldenzlel, Thesis, Groningen 1975, Chapter 5. (19) 0.H. Oldenziel and A. M. van Leusen, Tetrahedron Lett., 167 (1974). (20) A. M. van Leusen, B. E. Hoogenboom, and H. Siderlus, Tetrahedron Lett., 2369 (1972). (21) We prefer the use of DME over THF (mostly used by Schollkopt's group8), but this does not affect the argument. (22) TuinmanEbhas previously recommended for the same reason the use of 10 equiv of t-BuOK for reactions in DME-t-BuOH. (23) This procedure has been submitted in a more elaborate form for publication in Organic Syntheses. (24) H. Stetter and V. Tilmanns, Chem. Ber., 105,735 (1972). (25) K. Alder, K. Heimbach, and R. Reubke, Chem. &r,, 91, 1516 (1958). (26) A mp of 163 OC is reported for a Z-cyanocamphane of unspecified stereochemistry: J. Houben and H. Doescher, Chem. Ber., 43,3435 (1910). (27) M. Mousseron, R. Jacquier, and H. Christol, Bull. Soc. Chim. Fr., 346 (1957). (28) K. Tori and T. Komeno, Tetrahedron, 21,309 (1965). (29) R. F. Zurcher, Helv. Chim. Acta, 44, 1380 (1961); 46, 2058 (1963). (30) R. Stolle and F. Schmidt, Chem. Ber., 45, 31 13 (1912). (31) See H. P. Sherr, Y. Sasaki, A. Newman, J. G. Banwell, H. N. Wagner, and T. R. Hendrix, N. Engl. J. M.,285, 656 (1971). (32) B. E. Hoogenboom, not published previously, Internal Report, Groningen 1970-1971; cf. U. Schollkopf and R. Schroder, Angew. Chem., lnt. Ed. Engl., 11, 311 (1972). (33) E. Muller and H. Huber, Chem. Ber.. 96, 670 (1963). (34) J. F. Bunnett and J. A. Skorcz, J. Org. Chem., 27, 3836 (1962). (35) R . W. Horobin, N. R . Kahn, and J. McKenna, Tetrahedron Lett., 5087 (1966). (36) D. N. Jones, R. Grayshan, and K. J. Wyse, J. Chem. SOC.C, 2027 (1970). (37) Beilstein, 9, E Ill, 2421. (38) R. F. Brown and N. M. van Gulick. J. Am. Chem. SOC.,77, 1083 (1955); F. C . B. Marshall, J. Chem. SOC., 2754 (1930). (39) C. G. Overberger and M. B. Berenbaum, J. Am. Chem. Soc., 74, 3293 (1952). (40) M. S. Newman. A. Arkell, and T. Tukunaga, J. Am. Chem. SOC., 62,2498 (1960).
Aminations with Ammonia and Formamide. Synthesis of Terephthalamic Acid and of p -Nitroaniline Christian S . Rondestvedt, Jr. Research and Development Division Publication No. 548, Jackson Laboratory, Organic Chemicals Department, E. I. d u Pont de Nemours and Company, Wilmington, Delaware, 19898 Received March 23,1977 Ammonolysis of potassium m e t h y l terephthalate (2k) t o potassium terephthalamate (3k) is markedly accelerated by formamide solvent. N o corresponding acceleration i s seen w i t h other amides, such as mono- or dimethylformamide or acetamide. Negligible hydrolysis t o a m m o n i u m terephthalate (4a) occurs. An efficient procedure for the H o f m a n n conversion o f potassium terephthalamate (3k) t o p-aminobenzoic acid is reported. Ammonolysis o f p nitrochlorobenzene occurs rapidly in formamide solvent a t 200-220 O C t o furnish high yields o f p-nitroaniline. p Chlorobenzotrifluoride a n d 1,2,4-trichlorobenzene are n o t aminated under these conditions.
We sought to develop an economical synthesis of P-aminobenzoic acid from commercial dimethyl terephthalate (DMT, 1).1 Attempts to half-ammonolyze DMT to methyl
terephthalamate (38) were unsuccessful, since all conditions tried formed excessive amounts of terephthaldiamide. However, half-hydrolysis of DMT by potassium hydroxide in
J . Org. Chem., Vol. 42, No. 19, 1977 3119
Synthesis of Terephthalamic Acid Scheme I
COOCH3
Q
COOCH, 1 (DMT)
COOCH,
-Q
COOM
+ +
COOM COOM 2,M=H 4,M=H 4a, M = NH, 2k, M = K 2a, M = NH, 4k, M = K
CONH,
I
Q
6OOM 3,M=H 3a, M = NH, 3e, M = CH, 3k, M = K methanol proved to be quite selective, and potassium methyl terephthalate (2k) was isolated in about 90% yield (Scheme The ammonolysis of 2k to potassium terephthalamate (3k) in various media was investigated in detail, and the results form the subject of this paper. Ammonolysis in 28% aqueous ammonia was examined first. At room temperature, ammonium methyl terephthalate (2a) required 20-24 h for complete reaction to ammonium terephthalamate (3a); &-lo% of diammonium terephthalate (4a) was also formed. However, heating the mixture at 50-100 "C accelerated hydrolysis of the ester group much more than ammonolysis, so that up to one-third of the product became 4a. Addition of anhydrous ammonia to raise the concentration to 40430% ammonia in water retarded both the hydrolysis and ammonolysis, but did not increase the selectivity appreciably. With the more basic potassium salt 2k, hydrolysis became still more prominent. Many ammonolyses of esters reported in the literature use an organic cosolvent for either aqueous or anhydrous ammonia. Methanol usually gives the fastest rates and highest yields of amide^.^ In our hands, 2a reacted sluggishly with anhydrous ammonia in methanol. At 130 "C about 80% conversion was obtained in 6 h, and about 5% of 4a was also formed despite the anhydrous conditions. In dry dimethylformamide, conversion was nearly complete in 6 h a t 130 "C, but 25% of the product was 4a; the reaction was negligibly slow at 40 "C.The reaction was slightly faster in dimethyl sulfoxide at 130 "C and less 4a was formed. At this point it appeared that a protic solvent of high dielectric constant was required for rapid ammonolysis. Water fits this description, though hydrolysis is excessive at temperatures where the rate is practical. Formamide5 was tried, and the search ended. When potassium (or ammonium) methyl terephthalate (2k or 2a) was heated with excess anhydrous ammonia in formamide (500 mL/mol), almost complete conversion to 3k (3a) was achieved in 2 h a t 130 "C,or 1 h a t 140 "C. Vigorous agitation is required. About 80% yield of almost pure 3k was isolated merely by filtering the reaction mixture a t room temperature. When the filtrate was used as solvent in a second reaction, the solubility losses disappeared and the yield reached 95%. Curiously, although the 2k, formamide, and ammonia were rigorously dry, the ammonolysis reaction invariably produced about 5% of terephthalic acid salt (4). This is not a simple hydrolysis by adventitious water, since addition of up to 5 mol I).233
of water/mol of 2k did not increase the proportion of 4. Indeed, the rate of ammonolysis was increased slightly, in keeping with literature statements.6 In contrast to the acceleration caused by water, methanol caused a slight but definite retardation. In parallel experiments, 2k with only ammonia and formamide gave 98% conversion, while a run to which 3 mol of methanol had been added (per mole of 2k) gave only 85% conversion. Since methanol is a product of the ammonolysis, it is therefore desirable to strip out the methanol by heating under vacuum before reusing the filtrate. Still faster rates would be desirable for a continuous commercial process, hence catalysts were sought. Imidazole is a powerful catalyst for many transformations of carboxylic acid derivatives.? In the formamide system, imidazole increased the rate considerably. Thus, in parallel runs at 130 "C for 30 min, conversion of 2k to 3k was 33% without catalyst and 82% with 7.3 mol % of imidazole. But when this additive was tested in the aqueous ammonia system first studied, no change in rate of either hydrolysis or ammonolysis was apparent either at 25 or 60 "C. Polyhydric alcohols are known to promote ammonolysis of esters in aqueous dioxane;*,8 ethylene glycol, glycerol, and sorbitol are increasingly effective. Day found it essential to have water present because of the low solubility of polyols in many anhydrous organic solvents. We found that both ethylene glycol and sorbitol are quite soluble in dry formamide. In parallel runs at 130 "C for 30 min, ethylene glycol gave 75% conversion and sorbitol 95%, compared to the 33% obtained without additive. Both polyols were used in the proportion of two hydroxyl groups per ester function. Unexpectedly, the "hydrolysis" to 4 observed in the formamide-ammonia system was almost completely suppressed by either polyol. Glycol has been used as solvent for the ammonolysis of polyesters such as poly(ethy1ene t e r e ~ h t h a l a t e ) . ~ The remarkable ability of formamide to promote ammonolysis of esters seems to be restricted to this solvent alone. Acetamide ( D = 651°) gave 20% conversion of 2k to 3k under conditions where formamide ( D = 109) gave 95%; addition of 1 mol of water to the acetamide system increased the hydrolysis to 4 substantially, but did not improve the 20% conversion to 3k. N-Methylamides have enormous dielectric constants, but N-methylformamide ( D = 200), N-methylacetamide ( D = 165), and N-methylpropionamide gave no detectable 3k under the standard conditions where formamide itself gave 95% of 3k. Pyrrolidinone (butyrolactam), with a very high dipole moment resulting from the enforced cis configuration, was likewise inactive. Apparently, two protons on nitrogen and a high dielectric constant are both necessary. Acids, esters, and other acid derivatives may sometimes be converted to amides by heating with formamide, acetamide, or their N-substitution products with or without acid or base catalysis.ll T o test this possible explanation for our formamide-ammonia ammonolysis, 2k was heated with formamide without ammonia at temperatures to 180 "C for times known to be sufficient for complete conversion in presence of ammonia. In none of these experiments was 3k detected. The active ammonolytic reagent is believed to be the ammonia adduct of formamide, diaminomethanol(5, Scheme 11). If one of the amino groups adds to the carbonyl of the ester to form the tetrahedral intermediate 6, departure of methanol should be strongly promoted by hydrogen bonding to the hydroxyl function. Alternatively, if the hydroxyl group of 5 adds to the ester carbonyl, the tetrahedral intermediate 7 would dissociate to methanol, carboxylic acid, and formamidine. Formation and collapse of 7 explain the "hydrolysis" of the ester in the absence of free water. Promotion by glycols may result from formation of 8, in which additional possibilities for three-dimensional hydrogen bonding exist. Failure
Rondestvedt
3120 J. Org. Chem., Vol. 42, No. 19,1977 Scheme I1 OH HCONH,
I
+ KHJ a HCNH,
I
ArCOOR N attack
0
I I
/ \o-
HC-
2"
t H2NCOAr
2"
-I
ArCOOR
I HCNH,
+ ROH
I
+
HC=NH2
0 attack
OCHLCH20H
II
+ HC
+ RO- + HOOCAr
2"
2"
7
I
2"
8
of N- or C-substituted formamides may be a result of a very unfavorable equilibrium in the first step, formation of 5. Since equal conversions (within experimental error) were obtained with either the ammonium or potassium salts (2a or 2k),the reaction does not appear to be strongly catalyzed by either acid or base. A detailed study to confirm the proposed mechanism of this unusual reaction lay outside the scope of the present research. Silylation of Terephthalamic Acid a n d O t h e r Amides. Analysis of Acid Mixtures. The various combinations of 1, 2, 3,and 4 encountered in this work were analyzed by GC. Unexpected chemistry was also encountered. A mixture of trimethylsilyl chloride and hexamethyldisilazane in pyridine (commercial Tri-Sil) forms the volatile trimethylsilyl esters from these acids quantitatively in 1 min a t room temperature.12 The amide function in 3 reacts erratically with Tri-Sil; depending on the time and temperature of silylation, four different peaks with quite variable areas were obtained from pure 3.An amide may be 0-monosilylated, N-monosilylated, or N,0-disilylated.13 Subsequently, one or more of these may decompose to a nitrile. The first peak from 3 has the same retention time as trimethylsilyl p -cyanobenzoate. The more powerful reagent 0,N-bis(trimethylsily1)acetamide (BSA) was ultimately used as the preferred silylating reagent for analysis of mixtures containing 3. Pure 3 gave mostly the nitrile (3.6 min), but also variable small amounts of the 15.2- and 17.6-min peaks (Scheme 111).The amount of 3 in amidation mixtures was computed from the total areas under the three peaks, corrected for the response factors determined with authentic mixtures. The precision of the method for mixtures of 2,3,and 4 is about 3% relative. DennisI4 reported that dehydration of amides to nitriles by silylating reagents required temperatures near 200 "C; our nitriles may have been formed in the hot injection port. Some other aromatic amides were tested qualitatively. Benzamide with BSA yielded only a little benzonitrile; the main product was a single monosilyl peak. m-Toluamide also yielded but little nitrile; the main peak was a poorly resolved doublet, presumably a mixture of 0-and N-monosilyl derivatives. By contrast, p -nitrobenzamide yielded only p -nitrobenzonitrile. p -Carbomethoxybenzamide (3e) yielded mostly nitrile plus a little monosilylamide as a chromatographic doublet. Evidently, an electron-attracting group markedly increases the rate a t which aromatic amides are dehydrated by BSA, either because that group increases the acidity of the amide and thus the rate of disilylation, or because it accelerates the breakdown of the disilylamide. Several other silylating reagents15 (used in excess) were
tested with 3 in various solvents. Only trimethylsilyldiethylamine [(CH3)3SiN(CzH5)2]yielded any significant amount of cyanobenzoic ester. The others gave varying proportions of the 12.5-, 15.2-, and 17.6-min peaks. This result suggests that nitrile formation indeed occurs during the silylation step, not in the injection port. Interestingly, the 12.5-min peak was never seen in the same chromatogram as the 15.2-min peak. The column used in this work was 20% SE-30 silicone gum rubber on Chromosorb W AW-DMCS, 60-80 mesh. The carrier gas was helium; the temperature was 215 "C isothermal. The instrument was an Aerograph Model 202-B with a thermal conductivity detector. Hofmann Degradation of 3 t o p-Aminobenzoic Acid. The Hofmann degradation was first applied to terephthalamic acid by Toland and Heaton.16 Since they began with a crude 3 of uncertain purity (prepared by oxidation of p-xylene with ammonium sulfate, hydrogen sulfide, and water), their yield of p-aminobenzoic acid based on 3 is uncertain; it averaged 75% based on chlorine. We studied the Hofmann reaction with 3k,pure or containing known amounts of 4k.p-Aminobenzoic acid was obtained consistently in 8 0 4 5 % yield by careful attention to the factors discussed below. The Hofmann reaction involves the following steps: ArCONHz
+ NaOCl
ArN=C=O
--
ArCONHCl ArCON(C1)Na
+ 2NaOH
Overall: ArCONHz
+ C12 + 4NaOH
-
-
ArNHz
ArNHz
-
ArN=C=O
+ Na2C03
+ Na2C03
+ 2NaCl t H20 (Ar = p-KOOCCsH,)
Since our terephthalamic acid was already the salt 3k,we conducted the N-chlorination in basic medium, rather than in acid as preferred by Zengel and BergfeldagN-Chlorination of 3k was complete in about 10 rnin at 15-25 "C. Longer contact times permit hydrolysis of the N-chloroamide to salts of 4.Blank experiments showed that 3k suffered very little hydrolysis in this period. The rearrangement itself set in a t about 50 "C, and the heat of reaction raised the temperature to 90 "C in a few minutes. Reaction was complete in 5-15 min under these conditions. Accordingly, the preferred conditions detailed in the Experimental Section provide 10 min for Nchlorination and 10 min a t 90 "C for the rearrangement. The quantity of sodium hydroxide is critical. The overall reaction requires 4 mol, two to neutralize the chlorine and two to neutralize the carbon dioxide. However, with only 4 mol of base, the yields were consistently about 10% lower than when
J.Org. Chem., Vol. 42, No. 19,1977 3121
Synthesis of Terephthalamic Acid Scheme 111' COOCH,
COOT 4
4
hooT 10.5 rnin
COQT 6.5 rnin CONH
I
3
-
9
COOT 125 min
I
boro T
I
COOT 17.6 rnin
I
COOT 3.6 min
15.2 rnin CONHT
8.7 min
COOCH~ 10.6 min
COOCH3 10.9 min
B
COOCH, 2.4 rnin a Abbreviations: reagent A = Tri-Sil; reagent B = BSA; T = (CH,),Si.
5 mol were used, and the product was much darker. With
