THE SULFOMETHYLATION REACTION

compound with an aqueous solution of formaldehyde sodium bisulfite (sodium ... reaction of glyoxal sodium bisulfite with malonic acid (10) and the ...
1 downloads 0 Views 698KB Size
Download PDF
[CONTRIBUTION FROM

THE

CHEMICAL LABORATORY OF NORTHWESTERN UNIVERSITY ]

T H E SULFOMETHYLATION REACTION C. M. SUTER,' R . K. BAIR,'

AND

F. G. BORDWELL

Received J u n e 16, 1946

Introduction. The sulfomethylation reaction consists of the replacement of a hydrogen atom by an alkali sulfomethyl group, -CH2S03M. This condensation is formally analogous to the chloromethylation (1) and the Mannich (2) reactions, which are of considerable value in synthetic organic chemistry. The sulfomethylation reaction is accomplished by condensation of the appropriate compound with an aqueous solution of formaldehyde sodium bisulfite (sodium hydroxymethanesulfonate) with or without small quantities of alkali, or with an aqueous solution of formaldehyde and sodium sulfite. Formaldehyde alkali bisulfite has been reported to react with ethyl acetoacetate (3) and a few phenols (4,5, 6) with the establishment of a new carbon-carbon linkage. It also reacts with a variety of organic and inorganic nitrogen compounds (7,8,9), with establishment of a new carbon-nitrogen bond; benzaldehyde sodium bisulfite reacts similarly (9). Analogous to the condensations of formaldehyde bisulfite are the reaction of glyoxal sodium bisulfite with malonic acid (10) and the condensations of the bisulfite addition compounds of conjugated unsaturated aldehydes with malonic acid and alkali hydrogen malonate (11). It mas the purpose of this investigation to study the scope of the sulfomethylation reaction, considering the condensations of foimaldehyde bisulfite with various compounds containing relatively active hydrogen atoms, and secondarily, the condensations of other aldehyde and ketone bisulfite addition products with appropriate substances. In these studies it has been found that the sulfomethylation condensation can be carried out with some ketones and compounds with active methylene groups in addition to the phenols already mentioned. On the other hand, substances which were not sulfomethylated under the reaction conditions employed were alkyl aryl ethers, 2-nitropropane, a-picoline, and benzamide. In most experiments the sulfomethylating mixture consisted of an aqueous solution of formaldehyde and sodium sulfite, the latter material in excess. Reactions with phenols. Phenolic substances, which previously had been sulfomethylated were: 2-naphthol, 1-naphthol, 6-bromo-2-naphtho1, p-cresol, 2,4-dimethylphenol, and phenol. The sulfomethylation of 2-naphthol, 1naphthol, and phenol was reported as early as 1895 (4); reaction products were isolated, but data concerning them were incomplete. A more recent report (6) supplied information about the condensations involving the other three phenols, the products being isolated as sodium salts. In the present investigation the procedure given in the literature for the sulfomethylation of 2-naphthol was modified and then found to give a 75% yield of sodium 2-hydroxy-1-naphthylmethanesulfonate.Use of an equivalent amount of alkali in addition to the other reactants (2-naphthol, formaldehyde, 1

Present address, Winthrop Chemical Company, Inc., Rensselaer, N.Y. 470

THE SULFOMETHYL-4TION REACTION

47 1

and sodium sulfite) in this preparation resulted in a decrease in yield of the sulfonate to 45% with the formation of 30% of 2-hydroxy-l-naphthyhethanol. A number of derivatives of this methanesulfonate were made including the acetate, propionate, caproate, and the methyl and octyl ethers. The n-octyl ether s h o w the properties of a surface active agent. Higher molecular weight ethers and esters might prove to be of interest as wetting agents or detergents. S-Benxylthiuronium salts were made from sodium 2-hydroxy-l-naphthylmethanesulfonate and several of its derivatives and proved useful in their identification. The condensation of p-cresol with formaldehyde and sodium sulfite was studied under various conditions. Decrease of the amount of sodium sulfite or increase of the alkali concentration compared with optimum conditions decreased the yield of sodium 2-hydroxy-5-methylphenylmethanesulfonate. Substitution of sodium bisulfite for sodium sulfite gave about the same yields of the methanesulfonate, but the reaction was slower. The best yield of this methanesulfonate (60-65a/0) was obtained when an aqueous solution of p-cresol, formaldehyde, and sodium sulfite in molecular ratios of one to one to two mas heated on a steambath for several hours. A 32% yield was obtained previously (6). In the reaction of phenol with formaldehyde and sodium sulfite under conditions similar to those used in the 2-naphthol and p-cresol condensations, the mono- and di-sulfomethylated products were obtained. Isolation, purification, and identification of these substances presented difficulties. Raschig reported in 1924 without details (12) that phenol reacts smoothly with formaldehyde bisulfite to produce a sulfonic acid which probably had the formula, HOCeH4CH2S020H.It v a s found in our studies that the reaction is incomplete and results in considerable cleavage of the formaldehyde bisulfite. &e of formaldehyde and sodium sulfite gave better results in the sulfomethylation of phenol. The reaction of formaldehyde and sodium sulfite with p-t-butylphenol gave good yields of a sulfonate that was difficult to purify, and with l-naphthol yielded only about 5% of a crude product that appeared to be a sulfomethylated derivative of the phenol. No methanesulfonates were isolated from the attempted sulfomethylation of 2,4-dibromophenol and 4-hydroxybiphenyl under conditions similar to those used for 2-naphthol and p-cresol. Attempts t o condense 2-naphthol with sodium sulfite and acetaldehyde, acetone, or benzaldehyde resulted in the recovery of nearly all of the starting phenol. Reactions with ketones. Ketones which were successfully sulfomethylated include acetophenone, m-nitroacetophenone, propiophenone, cyclohexanone, and methone (1,l-dimethylcyclohexa-3 ,5-dione). All yielded dimethanesulfonates except propiophenone which produced the monosulfomethylated derivative. The sulfomethylation of methyl n-propyl ketone resulted in the isolation of a poor yield of crude material that was difficult to purify, whereas, 1,8-dibensoyloctane did not react with the sulfomethylating mixture. The best yields of sodium 2-benzoylpropane-l , 3-disulfonate were obtained when an aqueous mixture of acetophenone with excess formaldehyde and sodium

472

SUTER, BAIR, AND BORDWELL

sulfite was stirred for a period of twelve hours a t room temperature. Attempts t o prepare the mono- and tri-sulfomethylated derivatives resulted only in the formation of the disulfomethylated product. The yield of the corresponding nitro derivative (from m-nitroacetophenone) was poor, probably because of some reactions involving the nitro group. To obtain an appreciable yield of sodium 2-benzoylpropane-l-sulfonate,the aqueous mixture of propiophenone with formaldehyde and sodium sulfite required stirring for 12-24 hours on a steambath. The sulfomethylation of cyclohexanone and methone yielded only relatively small amounts of the corresponding dimethanesulfonates under the conditions used. No attempts were made to find the optimum conditions necessary for the formation of these two products. These two ketones are also capable of forming bisulfite addition compounds, thus complicating the study of their sulfomethylations. I n the sulfomethylation of methone, an additional product was isolated, which gave satisfactory analyses for a compound with the structure,

HO S 0 3 N a

I/ \ / \ C C(CH2S03Na)2 / / \ CH2-C CHa I\ CH3

CH2-C

HO SOSNa

Reactions with active methylene compounds. Compounds containing active methylene groups, which were included in these studies, were ethyl acetoacetate, ethyl n-butylacetoacetate, ethyl malonate, and phenylacetonitrile. The condensation of ethyl acetoacetate with an equivalent quantity of potassium hydroxymethanesulfonate (formaldehyde potassium bisulfite) in the presence of one-tenth as much alkali had been carried out as early as 1926 (3); good yields of the monosulfomethylated ester were reported. This condensation was carried out during the present investigation using formaldehyde with both sodium bisulfite and,potassium bisulfite; however, in both experiments, isolation and purification of the products were tedious. Attempts to prepare the disulfomethylated compound using excess formaldehyde and sodium bisulfite were unsuccessful, only the monomethanesulfonate being isolated; however, it is believed that disulfomethylation resulted when the sulfomethylating mixture of formaldehyde and sodium sulfite was used. The disulfomethylated ester was not isolated, but a substance giving satisfactory analyses for sodium 2-acetylpropane-1 ,3-disulfonate was obtained. This disulfonate could be formed from the decarboxylation of the saponified dimethanesulfonate of ethyl acetoacetate. This would be comparable to the Mannich reaction, in which the introduction of two diallrylamino groups into the acetoacetic acid molecule is accompanied by the elimination of carbon dioxide (2). Attempts to sulfomethylate ethyl n-butylacetoacetate were unsuccessful even

THE SULFOMETHYLATION REACTION

473

under more strenuous reaction conditions than were used in the sulfomethylation of ethyl acetoacetate. No definite product was obtained in the attempted sulfomethylation of phenylacetonitrile; a sulfonate was obtained but this could not be satisfactorily purified. This substance was believed to be impure disodium 2-phenyl-2,2-disulfomethylaceticacid. Using the same reaction conditions necessary for the monosulfomethylation of ethyl acetoacetate, there was no reaction with ethyl malonate. However, when formaldehyde and sodium sulfite were used, a good yield of the disulfomethylated ester was obtained. The monosulfomethylated ester was not formed under the conditions used. Miscellaneous reactions. Under the same conditions used successfully in the sulfomethylation of phenols and ketones, the following substances were found not to undergo sulfomethylation : anisole, 2-ethoxynaphthalene, a-picoline, 2-nitropropane, and benzamide. In each experiment, all, or practically all of the starting reactant x a s recovered. It should be recalled that benzamide does react (8) with formaldehyde and sodium bisulfite if the reaction is carried out in a sealed tube a t 200"; it appears possible that some of these other substances could be sulfomethylated under other conditions. Mechanism of the sulfomethylation reaction. Since the scope of the sulfomethylation reaction is somewhat similar to that of the Mannich reaction, i t might appear that similar mechanisms are involved in both condensations. The mech anism of the Mannich reaction has not been established, but there is evidence to indicate that neither methanolamine nor the hydroxymethyl derivative of the phenol, ketone, etc., is a probable intermediate (2). In the sulfomethylation reaction it is not likely that the hydroxymethyl compound is ordinarily an intermediate, since it has been found that 2-hydroxy1-naphthylmethanol does not react with sodium sulfite under the conditions employed in the sulfomethylation reaction. Also ethyl acetoacetate has been reported to give only the dimethyl01 compound (13) even a t -15", while the monosulfomethylation product is readily obtained from this ester. It should be noted, however, that o-hydroxybenzyl alcohol (saligenin) and its nuclear homologs react with sodium bisulfite to form the corresponding methanesulfonates (6). As has been previously demonstrated ( 6 ) sodium 2-hydroxy-1-naphthylmethanesulfonate is formed in part by the cleavage of bis-(2-hydroxy-lnaphthy1)methane with sodium sulfite. This cleavage is not unexpected in view of the vinylogous relationship of this compound to dihydroxymethane, but intermediates of this type in the sulfomethylation of ketones and esters seem unlikely. The disubstituted methane derivatives have not been isolated in the sulfomethylation of other phenols, or ketones and esters. A mechanism, involving as the initial step the formation of HOCH2SO,-, a hich then reacts with some active form of the phenol, ketone, or ester in question, appears to be a plausible explanation of most sulfomethylation condensations.

474

SUTER, BAIR, A N D BORDWELL EXPERIMENTAL~B~

Sodium 2-hydroxy-1-naphthyZmethanesuljonute. To an aqueous solution containing 18.8 g. (0.25 mole) of 40y0aqueous formaldehyde, 63 g. (0.50 mole) of sodium sulfite and 250 ml. of water in a flask equipped with a stirrer and reflux condenser was added 36.0 g. (0.25 mole) of 2-naphthol, and the resulting mixture stirred over steam for four hours. The naphthol went into solution almost immediately and after five minutes the reaction mixture became filled with small needles [di-(2-hydroxynaphthyl-l)methane],which slowly dissolved t o form a clear, light brown solution within thirty-five minutes. The hot solution was allowed t o cool, was filtered from a negligible amount of flocculent residue, and was neutralized with dilute sulfuric acid, whereupon mass solidification resulted. The solid was filtered (filtration slow) with suction, washed with ether, and dried at 50". The dried residue was extracted with boiling 50% ethanol; on cooling t o room temperature the extract yielded 34.9 g. of beautiful platelets. Further cooling of the resulting filtrate t o 10" produced another 13.4 g., giving a total of 48.3 g. (75% yield) of sodium 2-hydroxy-1-naphthylmethanesulfonate, containing a small amount of sodium sulfate. One recrystallization of this crude product from 50% ethanol gave a sulfonate free from inorganic salts with a 91% TABLE I SODIUM, %b

DEXIVATlVE

Acetate. . . . . . . . . . . . . . . . . Propionate. . . . . . . . . . . . . . Caproate. . . . . . . . . . . . . . . . Octyl ether" . . . . . . . . . . . . . Methyl etherc . . . . . . . . . . .

Nitrogen, %

m.p , "C.

Calc'd

Found

7.61 7.27 6.43 6.18

7.34 7.20 6.45 6.01 -

-

16&169

-- / 148-149 173-175

Calc'd

1

6.28

-

5.53 6.69

I

i

I

Found

6.47

-

5.69 6.97

Ether melted a t 213-216'. All sodium sulfonates in this paper were dried in vacuo at 100" before analysis. c Prepared previously (5).

0

b

recovery. An aqueous solution of sodium 2-hydroxy-1-naphthylmethanesulfonate plus a drop of ferric chloride solution produced a dark green color. The S-benzylthiuronium salt was prepared and found t o melt at 225-227". Anal. Calc'd for CloH&'20&3z: N , 6.93. Found: N, 7.26. The derivatives of sodium 2-hydroxy-1-naphthylmethanesulfonatelisted in Table I were prepared. Sodium 8-acetoxy-f -naphthyZmethanesuljonate. Five grams (0.019 mole) of sodium 2-hydroxy-1-naphthylmethanesulfonatewas refluxed for twenty-five minutes with 70 ml. of a 50-50 mixture of acetic acid and acetic anhydride, filtered, and allowed to cool. The finely divided solid, which separated, was filtered, washed with ether, dried, and found to weigh 3.6 g. (62%). The crude product was recrystallized twice from alcohol for analysis. An aqueous solution of this substance plus a drop of ferric chloride solution imparted no color. Analytical data are given in Table I. Sodium 2-octoxy-1 -naphthyEmethanesulfonate. T o a solution containing 13.0 g. (0.05 mole) of sodium 2-hydroxy-1-naphthylmethanesulfonateand 2.0 g. (0.05 mole) of sodium hydroxide in 60 ml. of water in a flask equipped with a stirrer and a reflux condenser was added 9.65 g. (0.05 mole) of octyl bromide, 50 ml. of 95% ethanol, and 0.25 g. of copper 2

The melting points in this section are all uncorrected. All nitrogen and sulfur analyses were made by Dr. T. S.Ma, University of Chicago.

THE SULFOMETHYL.4TION REACTION

475

powder; the resulting mixture was refluxed gently for twenty-three hours (probably longer than necessary since all of the bromide was in solution after eight hours). The reaction solution was filtered, allowed t o cool, neutralized with dilute sulfuric acid and placed in a cold room at O", whereupon mass solidification resulted. The solid was filtered, allowed t o dry at room temperature and found t o weigh 16.2 g. Another 1.0 g. of product was obtained when the mother liquor was chilled again giving a total of 17.2 g. (92.5%) of crude ether. This crude product was washed with ether, dried and recrystallized from absolute ethanol; a n inorganic residue of 1.5 g. remained insoluble. The recrystallized salt melted at 213-216'. (See Table I ) . Condensation of phenol with formaldehyde and sodium sulfite. T o a mixture containing 37.6 g. (0.50 mole) of My0 formaldehyde and 96.0 g. (0.75 mole) of sodium sulfite in 200 ml. of water (all of sulfite not in solution) in a flask equipped with a stirrer and a reflux condenser was added 47.0 g . (0.50 mole) of phenol. The resulting mixture was heated over steam for three hours, allowed t o cool and the supernatant liquid was decanted from the undissolved sodium sulfite. This reaction solution was neutralized with dilute sulfuric acid and evaporated t o dryness over steam (at one-half volume, 30 g. of inorganic salts separated and was filtered). The residue was extracted with portions of boiling 95% ethanol (about two and one-half liters) ; an appreciable amount of product (probably the disulfomethylated phenol since most of the monosulfomethylated derivative was obtained from the first extract) was not dissolved by the hot alcohol. The extracts were placed in a cold room a t -15'. The first extract of about 900 ml. yielded 12.5 g. of product free from inorganic salts; an aqueous solution of this substance plus a drop of ferric chloride gave a dark blue color. Evaporation of the alcoholic filtrate to dryness yielded another 22.5 g. of crude product which contained a small amount of inorganic salts. Other alcohol (95%) extracts of 900 ml. and 700 ml. yielded, respectively, 3.2 g. and 1.2 g. of crude product only after evaporation to dryness. A sample of the above 12.5 g. was dried at 55" for analysis. Anal. Calc'd for C7H7Na04S:Ka, 10.96. Found: Na, 10.93. I n another run a small amount of fine needles was obtained by extracting the crude residue (mixture of sulfomethylated products and inorganic salts) with 70% ethanol. A sample was dried a t 85" for analysis. Anal. Calc'd for C8H8Xa20,S2:Na, 14.1. Found: 14.5. Sodium 2-benzoylpropane-1 ,S-disulfonate. To a solution of 15.0 g. (0.20 mole) of 40% formaldehyde and 25.2 g. (0.20 mole) of sodium sulfite in a flask fitted with a stirrer was added 12.0 g. (0.10 mole) of acetophenone; the resulting mixture was stirred at room temperature for twelve hours. The cloudy, light yellow mixture with a small amount of floating solid residue was filtered, neutralized with dilute sulfuric acid, extracted with ether (the ether extract discarded) and evaporated to a residue of 42.2 g. which was extracted with boiling portions of 95% ethanol. -4total of 17.8 g. (510/0)40f crude product,containing a trace of sulfate was obtained when the extracts were placed in a cold room a t -5". A sample was recrystallized three times from 95% ethanol (65-70% recovery on each recrystallization). Anal.6 Calc'd for CloHloNa20?Sz: Na, 13.07. Found: ?;a, 13.1. The S-benzylthiuronium salt was prepared, recrystallized three times from dilute alcohol, and found to melt at 202-203". Anal. Calc'd for C2BH&407S4: P;,8.75. Found: N, 8.82. Sodium .Z-(b-nitrobenzoyl)propane-l, 3-disulfonate. The procedure used was similar to the previous preparation, 3-nitroacetophenone being used instead of acetophenone. A yield of only 12% crude sulfonate was obtained, about 10% of the original ketone being recovered. It appears that some side reaction takes place, possibly involving the nitro group. The crude product was recrystallized three times from 90% ethanol. Anal. Calc'd for CI0HgNN&2O9S2: Na, 11.59; S,16.1. Found: Na, 11.3; S,16.14.

* A yield of 69% was obtained when the reaction was carried out a t room temperature for 21 hours with 3.3 moles of formaldehyde and sodium sulfite per mole of acetophenone. 6 A sample dried at 100' and atmospheric pressure gave analysis for the monohydrate.

4%

SUTER, RAIR, . W D BORDWELL

The S-benzylthiuronium salt was prepared, recrystallized twice from dilute alcohol, and found t o melt a t 190-192'. A n d . Calc'd for CzeHaN6O9S4:K,10.2. Found: N, 9.93. Sodium b-benzoylpropane-Z-sulfor,ate. T o a solution containing 15.0 g. (0.20 mole) of 40% formaldehyde and 50.4 g. (0.40 mole) of sodium sulfite in 180 ml. of water contained in a flask fitted with a stirrer and a reflux condrnser was added 26.8 g. (0.20 mole) of propiophenone; the resulting mixture was stirred over steam for twenty-five hours (time of heating cut in half does not decrease yield of product appreciably). The reaction niixtore, containing a floating layer of 14.0 g. of the unreacted ketone and a dark brown aqueous layer, was allowed to cool, whereupon 11.2 g. of crystals separated. After separation of the ketone layer, the aqueous solution was placed in a cold room, yielding another 0.8 g. of crystals. N o additional product was obtained when the aqueous filtrate was evaporated t o dryness and extracted with boiling 95% ethanol. The 12.0 g. (50%, based on reacted ketone) of crude product, containing a small amount of sodium sulfate, v a s recrystallized from 95% ethanol, 7.7 g . of beautiful platelets free from inorganic salts being obtained. Before analysis a second recrystallization from alcohol was carried out. Anal. Calc'd for C10HllNa04: Na, 9.20; S, 12.8. Found: Na, 9.22; S, 13.3. The S-benzylthiuronium salt was prepared, recrystallized three times from dilute alcohol and found to melt a t 146-148". A n d . Calc'd for C,~HzzNz04Sz: N, 7.11. Found: N, 7.40. Sulfomethylation of cyclohezunone. T o a solution of 7.5 g. (0.10 mole) of 40% formaldehyde and 25.2 g . (0.20 mole) of sodium sulfite in 100ml. of water in a flask fitted with a stirrer and a reflux condenser was added 9.8 g. (0.10 mole) of cyclohexanone (b.p. 151-151.5'); the resulting mixture was stirred over steam for five hours. After being allowed to cool, the aqueous layer was separated from 1.3 ml. of floating layer, neutralized with dilute sulfuric acid, extracted with ether and evaporated to a residue of 38.2 g., which was extracted with boiling portions of: (a) 200 ml. of 95% ethanol, (b) same, (c) 180 ml. of 95% ethanol, (d) 180 ml. of 95% ethanol plus 20 ml. of water, and (e) 200 ml. of 50% ethanol. An insoluble inorganic residue of 18.0 g. remained. All extracts were placed overnight in a cold room at - 12", and the first three yielded negligible precipitates, while the latter two yielded, respectively, 1.8 g. and 0.7 g. of solid. More product, containing an appreciable amount of inorganic salts, mas obtained by evaporation t o dryness of the first three extracts and the filtrates from the latter two. The 1.8-g. portion contained only a trace of inorganic salts and was recrystallized once from 70% ethanol. The crystals thus obtained were free from sulfate or sulfite and gave satisfactory analyses for the disulfomethylated derivative. Anal. Calc'd for CsHlzNazO&: S a , 13.94; S, 19.4. Found: Na, 13.8; S, 19.84. The yield of the dimethanesulfonate could undoubtedly be increased by using a two-toone molar ratio of formaldehyde to ketone. The estracting solvent used should be 70-75% ethanol. Sulfomethylation of methone. To a solution of 7.5 g. (0.10 mole) of 40% formaldehyde and 25.2 g. (0.20 mole) of sodium sulfite in 100 ml. of nyater in a flask fitted with a reflux condenser w'as added 14.0 g. (0.10 mole) of methone; the resulting mixture was heated over steam for three hours. The clear solution was allowed to cool, neutralized with dilute sulfuric acid, and placed in a cold room (O"), but nothing separated. Evaporation over steam was started, but was stopped when coloration resulted. An appreciable amount of ethanol was added, and the mixture was digested over steam and filtered, leaving an inorganic residue of 8.2 g. The alcoholic filtrate solidified when placed in a cold room. The solid mass was partially filtered and the mushy mass which started t o darken when warmed slightly was extractedwith 200 ml. of 9574 ethanol. The extract became filled with crystals (8.7 g.) which were extremely soluble in water (an aqueous solution gave a purple color with ferric chloride solution), and which contained a trace of sulfate. Another 4.8 g. separated when the resulting filtrate was placed in a cold room at 0". This solid proved t o be a mixture; when extracted with 95% ethanol, long, adhesive needles, which gave satisfactory analyses for the disulfomethylated product, were obtained.

THE SULFOMETHYLSTION REACTION

477

Anal. Calc’d for CloH14SaOsSp: Na, 12.37. Found: Na, 12.4. When extracted with 86-S9% ethanol, the above mixture yielded granular needles, which were recrystallized from 89$& ethanol, and which gave analysis for the di(bisu1fite addition compound) of the disulfomethylated product. Anal. Calc’d for Cl~HleNaO14S4: Ka, 15.86. Found: Na, 15.8. As in the previous condensation with cyclohexanone, the yield of dimethanesulfonate could probably be increased by using two-to-one molar ratio of formaldehyde t o ketone. Sulfomethylation of ethyl malonale. Condensation with malonic ester was first attempted using equal amounts of formaldehyde and sodium bisulfite with one-tenth and one-half the molar ratio of alkali, and with even an equivalent amount of sodium sulfite, but no reaction took place in any run even after stirring long periods a t room temperature. To a solution of 7.5g. (0.10 mole) of 40% formaldehyde and 25.2g. (0.20mole) of sodium sulfite in 100 ml. of water in a flask equipped with a stirrer was added 16.0g. (0.10mole) of malonic ester; the resulting mixture was stirred a t room temperature for thirty-two hours. A floating layer of 5.5 ml. of unreacted ester was separated from the aqueous layer, which was neutralized with dilute sulfuric acid and evaporated t o a residue of 37.4g. This residue was triturated with 50 mi. of 95y0ethanol a t room temperature, the mixture was filtered and the remaining residue was extracted with 100-nil. and 200-ml. portions of boiling 95% ethanol. The extracts yielded a total of 4.9g. of platelets, which were recrystallized twice from 9570 ethanol for analysis. Anal. Calc’d for CsH14NazOl&: Ka, 11.73;S, 16.3. Found: Na, 11.7;S, 16.01. In subsequent runs i t was found that an increase in the yield of the dimethanesulfonate could be obtained if twice the amount of formaldehyde were used, and if the reactants were mixed and stirred in an ice-bath for ten minutes before stirring a t room temperature for periods of about twenty-five hours. Also, relatively pure portions of product were obtained by evaporation of the alcoholic filtrate (from extracts) to dryness. Attempted reaction of sodium sulfite with i-hydroxymethyl-2-naphthol. A mixture of 1.1 g. (6.3 millimoles) of l-hydroxymethyl-2-hydroxynaphthaleneeand 1.59 g. (12.6millimoles) of sodium sulfite with 10 ml. of water y a s heated on a steam-bath with stirring for one hour. An additional 10 ml. of water plus 5 ml. of 95’3& ethanol was added and heating was continued for another three hours. Keutralisation of the cooled reaction mixture resulted in the recovery of all of the starting naphthol. SUMVlRY

1. Sulfomethylation of 2-naphthol with formaldehyde and sodium sulfite gave a 75% yield of sodium 2-hydroxy-1-naphthylmethanesulfonate.The acetate, propionate, caproate, methyl ether, and octyl ether of this compound were made. 2. X o condensation took place d x a acetaldehyde, benzaldehyde, or acetone was substituted for formaldehyde in the reaction with 2-naphthol. 3. Similar condensation products were obtained from p-cresol and phenol, while a crude material, difficult to purify, was procured from p-t-butylphenol. Little or no sulfomethylated products were obtained from 1-naphthol, 2,4dihomophenol or 4-hydrosybiphenyl. 4. The dimethanesulfonate of ethyl malonate was formed in the condensation of the ester with formaldehyde and sodium sulfite. In the corresponding condensation with ethyl acetoacetate, it is believed that the dimethanesulfonate 6 The identity of this compound was established, since i t decomposed a t 188-190°, and an alcoholic solution with a drop of ferric chloride solution produced a green color that soon changed t o yellow-brown. See Reilstein, Vol. V I , p. 988.

478

SUTER, BAIR, AND BORDWELL

was formed. No sulfonate was isolated in the attempted sulfomethylation of ethyl n-butylacetoacetate, most of the starting ester being recovered. 5. Acetophenone, m-nitroacetophenone, propiophenone, cyclohexanone, and methone all formed disulfomethylated products. except propiophenone which was monosulfomethylated. Methyl n-propyl ketone gave a poor yield of crude material difficult to purify, while 1,8-dibenzoyIoctane did not react with the sulfomethylating mixture. 6. Other substances, which were found not to undergo sulfomethylation under the conditions employed, were anisole, 2-ethoxynaphthalene, a-picoline, benzamide, 2-nitropropane, and phthalimide. EVANSTON, ILL. REFERENCES (1) ADAMS,“Organic Reactions”, John Wiley and SONE,Inc., New York (1942), Volume I, p. 63.

(2) ADAMS,ibid., p. 303. AND PRAHL, Ann., 448, 265 (1926). (3) RASCHIG German Patent 87,355. (4) BAEYERAND COMPANY, (5) CLUTTERBUCK AND COHEN,J . Chem. SOC.,2507 (1923). (6) SHEARING AND SMILES,J. Chem. SOC., 1348 (1937). (7) KNOEVENAQEL, German Patent 153,193;J.Chem.SOC.,86,867 (1904). (8) KNOEVENAGEL AND LEBACK, Ber., 37, 4094 (1904). AND SCHWALBE, Ber., 39, 2796 (1906). (9) BUCHERER (IO) BEHREND AND KOOLMAN, Ann., 394, 228 (1913). (11) NOTTBOHM, Ann., 412, 49 (1916). (12) RASCHIG,“Schwelfel und Stickstoff-Studien”, Metzer and Wittig, Leiprig (1924), p. 243. (13) GAULTAND BURKHARD, BUZZ.SOC.chim., (5), 6 , 385 (1938).