GENERAL METHOD FOR PREPARATION OF GLYOXALS, ETC. 2453

CCSX1X.-A General Method f o r the Preparation of Glyoxals txnd their Acetals.

By HENRY DRYSDALE DAKIN and HAROLD WARD DUDLEY. ONLY a few representatives of the group of a-ketonic aldehydes or glyoxals have been hitherto prepared, and no method of wide applicability for their synthesis has been described. Glyoxal itself has been obtained by Harries (Ber., 1907, 40, 165) as a yellowish- green substance on distilling with phosphoric oxide the crude poly- merised product derived from the oxidation of acetaldehyde or similar substances. The acetal of methylglyoxal was prepared by Wohl and Lange (Ber., 1908, 41, 3612) by treating the piperidide of ethyl diethoxyacetate with magnesium methyl iodide. This sub- stance on hydrolysis with dilute sulphuric acid was shown by Meisenheimer (Ber., 191 2, 45, 2635) to yield methylglyoxal, which was eventually isolated as an intensely yellow, volatile liquid readily undergoing polymerisation. isoPropylglyoxa1 was obtained by Conrad and Ruppert (Ber., 1897, 30, 862) by heating the acid COH*CO:CM%*CO,H with water. Phenylglyoxal was prepared by von Pechmann (Ber., 1887, 20, 2904) by hydrolysing with dilute sulphuric acid the product of the action of sodium hydrogen sulphite on oximincacetophenone, whilst by the same method p-tolylglyoxal was obtained by Miiller and von Pechmann (Ber., 1889, 22, 2560). It is a curious fact that the synthesis of phenyl- glyoxal is frequently unsuccessful owing t o the production of large quantities of a compound believed by Pinner (Ber., 1902, 35, 4134) to be 2-benzoyl-5-phenylglyoxaline-1-sulphonic acid. The conditions necessary for siiccess do not appear to be completely known. These various ;nethods which have heen employed for the preparation of glyoxals do not appear to be generally applicable for the prepara- tion of other homologous gIyoxaIs. The authors have recently adduced evidence tending to show that glyoxals may play a r61e in the intermediary metabolism of plant and animal cells, and it became desirable t o devise a method for the convenient synthesis of these compounds. It has been shown that a-amino- and a-hydroxy-acids on digestion in dilute aqueous solution with pnitro- phenylhydrazine give the bis-p-nitrophenylhydrazones of the corre sponding glyoxals ( J . Bid. Chem., 1913, 15, 127), but this reaction is totally unsuited for the preparation of the glyoxals themselves.*

* We have assumed in this reaction that the hydroxy-(or amino-)acids dissociate directly into glyoxals and water (or ammonia) :

R*CH(OH)*CO,H R*CO*CHO + H 2 0 R-CH(NH,)*CO,H R*CO*CHO + NH,,

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2454 DAKIN AND DUDLEY : A GENERAL METHOD FOR THE

A convenient method for the synthesis of most glyoxals and their acehals is based on the preparation of ethyl y-diethoxyacetoacetate. This ketonic ester is readily obtained in excellent yield by the con- densation of ethyl diethoxyacetate and ethyl acetate by means of sodium.

On hydrolysing ethyl y-diethoxyacetoacetate with dilute aqueous potassium hydroxide the acetal of methylglyoxal is readily obtained, which in turn gives methylglyoxal on boiling with dilute sulphuric acid : CH(OEt),*CO,Et + CH,*CO,Et + CH(OEt),*CO*CH2*CO2Et +

CH(OEt),*CO*CH, + COH*CO*CH,. Ethyl y-dietlioxyacetoacetate is readily substituted by one or two

alkyl groups by successive treatment with sodium and alkyl haloids, and froill the resulting substituted esters w0 have prepared a variety of glyoxals and their acetals in satisfactory yields.

Since phenyl haloids do not react readily with the sodium deriv- atives of acetoacetic esters, i t appeared improbable that benzyl- glyoxal could be prepared by this method of synthesis. Accord- ingly we have synthesised this substance (J. Biol. Chem., 1914, 18, 42) by a modification of Wohl and Lange’s method by treating the piperidide of ethyl diethoxyacetate with magnesium benzyl iodide. Much dibenzyl is formed simultansously :

CH(OEt),*CO*NC,H,, + CH,Ph*MgI + With the exception of isopropylglyoxal and benzylglyoxal, which

are white, crystalline solids, all the glyoxals which we have prepared are yellowish-green liquids of characteristic odour. They may be distilled under diminished pressure without marked decomposition, and the vapours resemble chlorine in colour. All the glyoxals dissolve in organic solvents with the production of an intense yellowish-green solution. They reduce ammoniacal silver solutions in the cold and Fehling’s solution on warming. On treatment with sodium hydroxide they yield the corresponding hydroxy-acids, whilst the enzyme “glyoxalase,” which we have found in many animal tissues, brings about a similar reaction except that the resulting hydroxy-acids are optically active :

R*CO*CHO + H20 =R.C‘R(OH)*CO,H.

and that the glyoxal then unites with nitrophenylhydrazine, but it is perhaps equally plausible to assume that the first product of the reaction is an unsaturated acid obtained in very low concenlration by keto-enolic tautomeric change :

R’CH(OH)’CO,H R*C(OH):C(OH),.

CH(OEt),*CO*CH,Ph + COH*CO*C&Ph.

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PREPARATION OF GLYOXALS AND THEIR ACETALS. 2555

EXPERIMENTAL.

Ethyl y-Diethoxyacetotzcetate, CH(OEt),*CO*CH,-C0,Et.

Ethyl diethoxyacetate (86 grams: 1 mol.), sodium (34 grams: 3 mols.), and ethyl acetate (130 grams: 3 mols.) wme used for the condensation, which was carried out in an apparatus similar to that described by Wahl and Doll (Bzcll. SOC. chim., 1913, [iv], 13, 265). To the et.hyl diethoxyacet'ate heated t o 85-90°, portions of 2 grams of sodium wire and 9 C.C. of ethyl acetate were added a t half-hour intervals. The reaction was quite vigorous a t first, but subsided toward the end, when tho sodium and ethyl acetate could be added a lit'tle more rapidly. The seventeen additions of these substances should be made in about six hours. The liquid, which became dark brown and very viscous, was stirred continuously during the experiment. The reaction was allowed t o proceed for four hours after the last addition of sodium and ethyl acetate, when there was still a small amount of sodium undissolved. Alcohol (30 c.c.) was added to dissolve the sodium residue, and then the oil, cooled somewhat but not allowed t o become too viscous, was poured into a mixture of 130 C.C. of' concentrated hydrochloric acid and 130 grams of ice. The oily layer was immediately separated, and the aqueous layer extracted once with a small quantity of ether. The oil and ethereal extract were mixed, and shaken with sodium carbonate solution until the aqueous layer was distinctly alkaline. The supernatant oil was then removed, the aqueous layer extracted once with ether, and the combined oil and ethereal extract were dried. The dark red oil was then subjected t o fractional distilla- tion. As soon as ether, alcohol, etc., had ceased to distil over, the operation was conducted under diminished pressure, and a fraction boiling mainly a t 75-78O/7-8 mm. was obtained (bath a t looo). This fraction consisted mainly of unchanged ethyl diethoxyacetate and ethyl acetoacetate. The temperature of the bath was raised gradually to 135O, and a main fraction passed over, the thermo- meter rising rapidly to 1 1 2 O and then slowly to 115O. This fraction (82 grams) consisted of ethyl y-diethoxyacetoacetate.

I n order t o obtain a high yield of this ester it is essential that the reaction and distillation should be carried out in one day. On account of the short time which can be allowed for drying the esters before distillation, the et'hyl acetoacetate fraction contains a con- siderable amount of water, and a little is apt to pass over with the first portion of the main fraction, which should be collected sepa- rately. On refractionating the ethyl acetoacetate fraction with the bath heated to 75-80°, the distillate passed over a t 60--65O/

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2456 D A K I N A N D DUDLEY : A GENERAL METHOD FOE THE

6-8 mm., and about 5 C.C. of a liquid of higher boiling point remained in the distilling flask. The dry first portion of the main fraction was then added to this residue, and the bath heated to 105O. A few drops of liquid passed over a t 60-70°/4-6 mm., and were added t o the ethyl acetoacetate fraction. The bath was then heated to 130°, and the temperature of the distillate rose rapidly t o 112O/4-6 mm., and remained constant. This distillate was mixed with the main fraction. The final yields thus obtained were 32 grams of the ethyl acetoacetate fraction and 76 grams of ethyl y-diethoxyacetoacetate :

0.2116 gave 0.4263 CO, and 0.1556 H,O. C=54.94; H=8*17. CI,H,,O, requires C = 55.04 ; H = 8.25 per cent.

Ethyl y-diethoxyacetoacetate is a colourless, highly refractive liquid, having an odour resembling that of ethyl amtoacetate, but somewhat sweeter. It gives a typical colour reaction with alcoholic ferric chloride solution.

Eydrolysis of Et hgl y-Die t hoxyacet oacetat e : M e t h ylgl yoxalacetal, C H, C 0- CH (0 E t ) 2.

Ethyl y-diet'hoxyacetoacetate (6.5 grams) was shaken with N-potassium hydroxide (34 c.c.), when the ester slowly dissolved, the solution turning slightly yellow. The liquid was boiled under reflux for fifteen minutes, when a colourless oil separated. This was ext,racted three times with ether, the ethereal solution dried, and distilled. After the ether had been removed the residual liquid was distilled under diminished pressure. The first fraction, boiling a t 58-65°'/24-30 mm. (bath , a t looo), consisted of methylglyoxal- acetal (3 grams). The second fraction distilling a t 90--103O/ 2-4 mm. (bath heated from looo t o 1 6 0 O ) was unchanged ester (1.5 grams).

The metihylglyoxalacetal thus obtained was identical in proper- ties with that described by Wohl and Lange, and on hydrolysis with N 10-sulphuric acid behaved- in typical fashion, giving a solution of methylglyoxal, which was identified by means of the bisnitro- phenylhydrazone, which melted and decomposed a t 300-30Z0, and gave the characteristic colour reaction with alcoholic sodium hydroxide solution (J. Biol. Chem., 1913, 15, 132).

Ethyl y-Diethoxy-a-met hylacetoacetn t e , CH(OEt),*CO*CHMe*CO2Et,.

A solution of sodium (4.4 grams: 1 mol.) in 50 C.C. of alcohol was added t o ethyl y-diethoxyacetoacetate (41.6 grams : 1 mol.), and 2 mixture of this and methyl iodide (30 grams) was heated

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PREPARATION OF GIXOXALS AND THEIR ACETALS. 2457

gently on the water-bath for half-an-hour, when i t was neutral t o litmus. Alcohol was then distilled off, water added to the residual liquid, the oil which separated was removed, and the aqueous layer extracted four times with small quantities of ether. The combined oil and ethereal extracts wexe dried and fractionated. After the ether had been removed, the oil boiled a t 110-112°/4-6 mm., the yield being 42 grams:

0.1985 gave 0.4146 CO, and 0.1536 H20. C=56.95; H=8*60.

The ester so obtained is a colourless liquid having, when freshly distilled, a faint, garlic-like odour. On adding a drop of ferric chloride solution t o an alcoholic solution of the ester only a very slight darkening takes place, the characteristic colour reaction of ethyl y-diethoxyacetoacetate having disappeared.

CllH2005 requires C= 56.90 ; H = 8-62 per cent.

Hydrolysis of E thy1 y-Diethoxy-a-methylace tometate : Ethyl- glyoxalacetal, C2H5*CO*CH(OEt),.

A solution of ethyl y-diethoxy-a-methylacetoacetate (15-5 grams : I mol.) in methyl alcohol (50 c.c.) was boiled with 2N-potassium hydroxide (50 C.C. : 14 mols.) under reflux for half-an-hour, when a colourless oil separated. The liquid was diluted with water, and extracted six times with small quantities of ether. After distilling off the ether and methyl alcohol from the dried ethereal solution 7 grams of ethylglyoxalncetal boiling a t 62--68O/ 10-12 mm. (bath a t 85O) were obtained. A few grams of unchanged ester remained in the distilling flask :

0.2197 gave 0.4834 CO, and 0.1981 H,O. C=60*0; H=10*0. C8H1603 requires C = 60.0 ; H = 10.0 per cent.

This acetal is a colourless liquid with a pleasant, fruity odour.

Hydrolysis of Ethylglyoxalacetal : Ethylglyoxal, C,H,-CO-CHO.

Ethylglyoxalacetal (4.5 grams) was boiled for one and a-half hours with sulphuric acid (50 C.C. of 2 per cent. by volume) under reflux. The acetal behaved like that of methylglyoxal, the liquid becoming milky on warming and then clearing again on boiling. All the oil passed into solution, and on distillation ethylglyoxal passed over readily with the steam, and separated from the first portion of the distillate as a yellow oil, which dissolved easily in water.

With an aqueous solution of semicarbazide hydrochloride, ethyl- glyoxal gives a monosemicarbazone, CkH9O2N3, which crystallises from water, and melts and decomposes a t 235-236O.

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2458 DAKIN AND DUDLEY: A GENERAL METHOD FOR THE

E t h y 1 y-17) ie t h ox y-a-dim e thy lace t oa c e tat e, CH(OEt)2-CO*CMe,*C0,Et.

A solution of sodium (2.3 grams: 1 mol.) in 35 C.C. of alcohol was added to ethyl y-diethoxyacetoacet'ate (1 mol.), and a mixture of this and methyl iodide (slight excess over 1 mol.) was gently boiled on the water-bath for half-an-hour, when it was neutral t o litmus. A second addition of 2.3 grams of sodium in 35 C.C. of alcohol and 18 grams of methyl iodide was then made, and after boiling for a further half-hour the reaction was complete. The alcohol was distilled off, and water was added to the residue, which was then extracted with five small quantities of ether. The ethereal solution was dried and evaporated, and then ethyl y-diethoxy-a-di- methylacetoacetate (19 grams) distilled a t 104-105°/4-6 mm. (bath a t 115-120O) :

0.2313 gave 0.4955 CO, and 0.1863 H20. C=58*42; H=8*95.

The ester is a colourless liquid, having, when freshly distilled, a It gives no colour reaction in alcoholic

C1,HB05 requires C = 58.54 ; H = 8.94 per cent.

faint, garlic-like odour. solution with ferric chloride.

Hydrolysis of E thy1 y-Diethoxy-a-dimethylace toacetate : isoPropylgl~oxa Znc e tal, CHMe,*CO*CH (OE t)2.

A solution of ethyl y-diethoxy-a-dimethylacetoacetate (12 grams : 1 mol.) in methyl alcohol (27 c.c.) was boiled with 2N-potassium hydroxide (27 C.C. : 1.1 mol.) under reflux for half-an-hour. Water was then added, and the liquid was extracted five times with small quantities of ether. After distilling off the ether and methyl alcohol from the dried ethereal solution, 7 grams of isolrropylglyoxaZacetaZ, boiling a t 75-77O/10-12 mm. (bath a t looo), were obtained, and about 1 gram of unchanged ester remained in the distilling flask. The acetal is a colourless liquid possessing a pleasapt, fruity

odour with a suggestion of peppermint.

Hydrolysis of i s~Pro~lgEyoxalace ta1: isoPropylglyoxa1, CHM%*CO*CHO.

Three grams of isopxopylglyoxalaceta1 were boiled for two hours under reflux with 40 C.C. of sulphuric acid (0.2 per cent. by volume). At the end of this time only a trace of oil was left. On distillation in a current of steam isopropylglyoxal (m. p. 95--96O), identical with the substance described by Conrad and Ruppert (Ber., 1897, 30, 862), was obtained. The bis - p - nitrophenylhydrazone, C1,HI8O4N6, crystallises from a mixture of nitrobenzene and toluene

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PREPARATION OF GLYOXALS AND THEIR ACETALS. 2459

in glistening, ,scarlet prisms, melting and decomposing a t 295O. The moihosemicadmzone, C,H,,0,N3, crystallises from water in masses of very pale' yellow prisms, meltdng a t 158-159O.

It was interesting t o note that the specimen of crystalline isopropylglyoxal, which had been dried over sulphuric acid and kept in a well-corked specimen tube, after a few days had become liquid, and developed an intense, pungent odour. The change is probably connected with some process of polymerisation.

Ethyl y-Die t hoxy-a-met hyl-a-e t hylace toace tat e, CH(OEt),-CO*CMeEt*CO,Et.

A mixture of ethyl y-diethoxy-a-methylacetoacetate (20 grams : 1 mol.) and a solution of sodium (2 grams: 1 mol.) in alcohol (30 c.c.) was boiled gently on the water-bath for two hours with ethyl iodide (1.2 mols.), when the reaction was complete. Ethyl alcohol was removed as far as possible on the water-bath, water added t o the residue, and the oil which separated was removed, the aqueous layer being extracted three times with ether. The mixed oil aEd ethereal extracts were dried and distilled. After removal of the ether, e t hyl y-diet hoxy-a-me thyl-a-ethylace toacetat e (19.5 grams) distiiled a t 117--118O/3*5 mm. (bath a t 130O) :

0.2166 gave 0.4756 CO, and 0.1778 H,O. C=59*87; H=9.13.

The eater is a colourless, highly refractive liquid with a pleasant, fruity odour. It gives no colour reaction in alcoholic solution with ferric chloride.

CI3Hz4O5 requires C =59.99; H = 9 * 2 3 per cent.

Hydrolysis of Ethyl y-Biet hoxy-a-me thyl-a-et htylace toace tat e : set.-Butylglyoxalaceial, CHMeEt*CO-@H(OEt)z.

A mixture of ethyl y-diethoxy-a-methyl-a-ethylacetoacetate (1 6 grams) dissolved in methyl alcohol (46 c.c.) and 2s-potassium hydr- oxide (46 c.c.: 1.5 mols.) was boiled fox forty-five minutes, then diluted with water, and extracted six times with et*her. The dried ethereal solution was distilled, when sec.-butylglyoxalacetal (8 grams), boiling a t 82--83O/1@ mm. (bath a t looo), was obtained, and 1 gram of unchanged ester remained in the distilling flask:

0.2316 gave 0.5426 CO, and 0.2237 H,O. C=63*90; H=10*72.

The acetal is a colourless liquid having a pleasant odour sugges- @loH,,03 requires C == 63.83 ; H = 10.64 per cent.

tive of acetone.

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2460 DAKIN AND DUDLEY : A GENERAL METHOD FOR THE

Hydrolysis of sec.-~utylglyoxalacetal: sec.-Butylglyoxal, CHMsEt- CO CEO.

The acetal (4.5 grams) was boiled under reflux with sulphuric acid (45 c.c, of 2 per cent. by volume) for five hours. On distilla- tion in a current of steam a yellowish-green oil, fairly readily soluble in water, passed. over, which posseeed the characteristic caramel odour of glyoxals.

The free glyoxal gives a rnonosemicarTbazone, C7HI3O2N3, a waxy solid, which is much more soluble in water than the corresponding compounds of other glyoxals. The bis-p~itrophenylhy~razone was prepared by boiling a solution of the glyoxal with pnitrophenyl- hydrazine sulphate. After recryst$allisation from a mixture of nitro- benzene and toluene it melted and decomposed a t 275-276O :

0.1089 gave 0.0238 N,. N=21.85. C,,H,,O,N, requires N =21*88 per cent.

The biscpnitrophenylhydrazone crystallises in scarlet prisms, and gives tlhe characteristic blue solution in alcoholic sodium hydroxide solution.

Ethyl y-Biethoxy-a-isopropylacetoacetate, CH(OEt),*CO*CHPr~*CO,Et.

Preliminary experiments in which it was attempted to introduce the isopropyl group by boiling an alcoholic solution of ethyl y-di- ethoxyamtoacetate with isopropyl iodide in the presence of sodium ethoxide under reflux were unsatisfactory. The reaction took place much better in a sealed tube.

A mixture of ethyl y-diethoxyacetoacetate (20 grams: 1 mol.), sodium (2.1 grams: 1 mol.) dissolved in alcohol (25 c.c.), and isopropyl iodide (22 grams :- 1.4 mols.) was heated in a sealed tube in a boiling water bath f o r eight hours. The product was then neutral to litmus. The alcohol was distilled off, the oil diluted with water, and extracted three times with ether. The dried ethereal soluticin was distilled, and after removing alcohol and ether, a fraction (15 grams) was obtained, which boiled a t 112-116°/ 4-5 mm. (bath a t 125-130°):

0.2190 gave 0.4786 CO, and 0.1799 H,O. C = 59.6 ; H = 9.13.

E thy1 y-diethoxy-a-isopropylacetoncetate is a colourless, pleasant CI3Hz4O5 requires C = 59.99 ; H = 9.23 per cent.

smelling liquid, resembling the other esters of this series.

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PREPARATION OF GLYOXALS A N D THEIR ACETALS. 2461

Hydrolysis of Et 11 y l 7 - I ! i e t hox:y-a-isopropyla ctc toace tat e : isoBir tylglyoanlnce f n7, CHMe,*C'H,*CO*CH(OEt),.

A mixture of ethyl y-diethoxy-a-isopropylacetoacetate (15 grams : 1 mol.), dissolved in methyl alcohol (37 c.c.), and 2N-potassium hydroxide (38 c.c.: 1.3 mols.) was boiled under reflux for one hour. The liquid was then diluted with water and extracted five times with ether. The dried sthereal solution was distilled, when isobutylglyoxalacetal (6.5 granis) boiling a t 77-80°/ 10-12 mm. (bath a t looo) was obtsined :

0.2060 gave 0.4813 CO, and 0.1912 H,O. C = 63.73 ; H = 10.31.

On hydrolysis the acetal yielded isobutylglyoxal ( J . Biol, Ch e m . ,

C,,,H,,,O, requires C = 63.83 ; H = 10.64 per cent

1914, 18, 38).

Zflt k y l y-Diet Ii ozy-a-Aenzylnc Ptonc Pfcctr, CH( OE t),-CO C H (C,H,) C0,Et.

A mixture of ethyl y-dietlioxyacetoacetate (7.4 grams : 1 mol.), sodium (0.8 gram: 1 mol.) in 15 C.C. of alcohol, and benzyl chloride ( G grams: 1.3 mols.) was boiled under reflux for four and a-half hours. The alcohol was distilled off, and water was added to dissolve the sodium chloride formed. An oil heavier than water separated, which was ex- tracted l-hree, times with ether, and the dried ethereal solution 'distilled under 4-5 mm. pressure (bath a t looo). There remained in the flask 11 grams of a pale yellow oil, which was mainly ethyl y-diethoxy-a-benzylacetoacetate. It was not' distilled because pre- vious attempts had resulted in decomposition.

The ester gives a port-wine coloration in alcoholic solution with ferric chloride.

The liquid was then neutral t 'o litmus.

Hydrolysis of Ethyl y -Die t hoxy-a-b e I I zylace toace tat e : Yhe iaylet hylglyoxnlnce tn7, CH,Ph*CH,-CO*CH( OEt),.

A mixture of the ester (11 grams: 1 mol.), dissolved in methyl alcohol (21 c.c.), and 2N-potassium hydroxide (21 C.C. : 1.3 mols.) was boiled under reflux for two hours. The liquid was then diluted with water and extracted five times with ether. The dried ethereal solution was distilled, when phenylethy7nlyoxalac~tnl (5.5 grams) passed over a t 135-137°/3--5 mm. (bath a t 160-170°).

flydrolysis of I'h et~?/lr:thyl!/l!/oxrrlncetrrl: P A ~nyletJiylg7yoxnl, CH,Ph*CIX2*CO*CH0.

The acetal (5.5 grams) was boiled under reflux with sulphuric acid (60 C.C. of 2 per cent. by volume), and the product was

VOL. cv. 7 x

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2462 SENIER AND FORSTER: STUDIES IN

extracted f m r times with ether, the dried ethereal solution being distilled, when phenylethylglyoxal, boiling a t 99-10a0/ 3-5 mm. (bath a t 130-140°), was obtained. The vapours were yellow, and condensed to a viscid, oily, intensely yellow liquid, having a sweet odour. It is only sparingly soluble in water, and not very readily volatile in steam. On keeping, the colour becomes less intense, and the liquid very much more viscous, due possibly to polymerisation.

The bis-p-nitrophen ylhydrazone, C22H200,N,, is best prepared by dissolving ~-1iitrop1ieiiylhydraziiie in alcohol, adding the glyoxal, anti warming tlie sol ii tion. On keeping, tlie bis-p-nitrophenyl- liydrazone is slowly deposited in a pure condition from the solution. It crystallises in scaxlet needles from a mixture of nitrobenzene and toluene, and melts and decomposes a t 269O.

The constitution of phenylethylglyoxal was confirmed by convert- ing it into a-hydroxy-y-phenylbutyric acid by the action of dilute alkali. About 1 gram of phenyletlhylglyoxal was boiled with 30 C.C.

of IV-sodium hydroxide solution for fifteen minutes. The product was filtered to remove the oily scum, acidified, and extracted with ether. Crystalline a-hydroxy-y-phenylbutyric acid was obtained, which, on recrystallisation from a mixture of ether and light petroleum, melted a t 104-105°.

THE HERTER LABORATORY, NEW yon^ CITY.

NU rR1TION RESEARCH LABORATORY, THR UNIVEhSITP, LEEDS.

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