SAMUEL R. ASPINALL
852
4.6 g. of the methoxy compound was heated at reflux for one-half hour with 10 g. of anhydrous aluminum chloride in 60 cc. of chlorobenzene. The mixture was then acidified with hydrochloric acid and the chlorobenzene removed by steam distillation; the excess water was distilled off and the residue allowed to cool, whereupon the anthocyanidin separated from solution. It was recrystallized from dilute alcoholic hydrochloric acid.
Summary 1. The familiar reactions involved in the
[CONTRIBUTION FROM
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Vol. 63
preparation of 2-phenyl benzopyrylium salts can be extended to include compounds having condensed benzene nuclei. 2. A series of 2-phenylnaphthopyrylium chlorides is described. As might be anticipated the members are very similar to those of the analogous 2-phenylbenzopyrylium series but their colors are much darker. CHAPELHILL, N. C.
RECEIVED NOVEMBER 18, 1940
CHEMICAL LABORATORY OF SWARTHMORE COLLEGE]
Ethylenediamine. IV.'
Monoalkyl Derivatives
BY SAMUEL R. ASPINALL Examples of every type of alkyl ethylenedi- work since only 2 g. of the sulfonamide could be amine (viz., RNHCH2CH2NH2, RNHCH2CH2- alkylated a t one time. (2) Winans and Adkins4 NHR, R ~ N C H ~ C H Z N H R ~ ,~ N C H Z C H ~ N H Rdescribe , the catalytic hydrogenation of CHR~NCHZCH~NR are ~ )to be found in the litera- NCHzCN to monomethylethylenediamine, but ture, but in some cases the syntheses are laborious the boiling point reported by them is not the and give poor yields or ill-defined products. It same as that found by others. (3) Von Braun5 was thought the amines represented by RNHCH2- and co-workers produced monomethylethyleneCH2NH2, which are secondary amines having the diamine by the nitrous acid dephenylation of the @-aminoethyl group in common, might be inter- acetyl derivative of C6H5(CH3)NCH2CHzNHz esting in themselves or as starting materials for (obtained from CsH6(CH3)NCK2CHzBrand liquid synthetic work. Several representatives of this ammonia), but the yield is only a few per cent. of type are known and have been characterized as the theoretical. (4) Schotte6 and co-workers derivatives, but the data on the free amines are describe the preparation of monoalkyl ethylenein many cases lacking or contradictory, pre- diamines in unspecified yields by the hydrochloric sumably because the syntheses yielded very small acid fission of @-guanidoethanols. NHzC(NH)amounts of impure products. N(R)CHzCHzOH HC! RNHCH2CHzNH2. (5) Since direct alkylation of ethylenediamine is Bleier' reports that monobenzylethylenediamine reported2 to yield only the bis-diquaternary is a by-product from the hydrochloric acid fission ammonium salt, several indirect methods of con- of sym-dibenzenesulfonyldibenzylethylenediamine trolled monoalkylation have been tried. (1) together with the expected dibenzylethyleneJohnson and Baileya discuss several reactions diamine. (6) Van Alphens states that monowhich might be expected t o yield monoalkylated benzylethylenediamine is produced in small ethylenediamines, but which in fact fail t o do so. amounts when the mixture resulting from the They obtained monomethylethylenediamine by interaction of benzaldehyde and excess ethylenethe following series of reactions diamine is reduced with sodium and alcohol. The present investigation has resulted in a synthesis for molecules of the type RNHCH~CHZNHZ CHsI O-CBH~(CO)ZNCH~CHZNHSOZCH~CIH~ in pure condition and reasonable yields using CHsONa well known reactions with cheap reagents. HCI ___f
o-C~H~(CO)ZNCHZCHZN( CH3)SOzCHzCeH6+ CHsNHCHzCHzNH2
The method is worthless for general synthetic (1) For the third paper of this series see THIS JOURNAL, 62, 1202 (1940). (2) Schneider, Bn.,88, 3073 (1895). (3) Johnson and Bailey, THIS JOURNAL, 88, 2135 (1916).
NHzCHzCHpNHa
CHaCOOCiHs ____f
(4) Winans and Adkins, ibid., 56, 4167 (1933). (5) Voo Braun, Ber., 70, 979 (1937). (6) Schotte, 2. physiol. Chem., 174, 119 (1928); German Patent 446,547. (7) Bleier, Bn.,88, 1829 (1899). (8) Van Alphen, Res. Ltao. chim., 54, 594 (1936).
MONOALKYL DERIVATIVES OF ETHYLENEDIAMINE
March, 1941
853
stays in solution in the cool mother liquor. The pure N-benzenesulfonyl-N1-acetylethylenediamine melts a t 103 ’ RX (cor.)ll and weighs 500 g. (about 70% theoretical). C+H6SOzNHCHzCHpNHCOCHs_ _ f The following description of the preparation of monoNaOH methylethylenediamine applies also for the preparation of HCI CsHsSOzN (R)CH2CHzNHCOCHs --f monoethylethylenedianiine and, with modifications, for RNHCHiCHzNHz the preparation of monobenzylethylenediamine. hundred twentyThe previously describede monoacetylation of oneMonomethylethy1enediamine.-One grams (0.5 mole) N-benzenesulfonyl-N1-acetylethylethylenediamine was modified by carrying out enediamine is dissolved in one equivalent of boiling althe reaction a t room temperature. This procedure coholic potassium hydroxide (35 g. of 85% potassium gives slightly lower yields than heretofore reported hydroxide dissolved in 200 cc. absolute ethanol) and 142 g. but enables one t o prepare large quantities of (1 mole) of methyl iodide added dropwise during fifteen minutes, The mixture is refluxed for two hours and the material a t once. The benzenesulfonation was precipitated potassium iodide (about 60 g.) filtered from conducted in the usual Schotten-Baumann man- the cool reaction mixture. The filtrate is steam distilled ner and the alkylation was according t o Hinsberg, until excess methyl iodide and ethanol are completely rebut fission of the mixed acetyl-sulfonyl amide was moved and the remaining alkylated sulfonamide12 reaccomplished by refluxing with 25% hydrochloric fluxed for twelve hours with 500 cc. of concentrated hydrochloric acid to which is added additional amounts of acid according to Schreiber and Shriner.’O This concentrated acid from time to time. The hydrolyzate modification of the original Hinsberg fission is distilled nearly to dryness under diminished pressure permits hydrolysis of large amounts of material and after addition of excess solid sodium hydroxide a without resort to pressure apparatus. The free concentrated water solution of the amine is distilled over. base is liberated from its hydrochloride by one of Solid sodium hydroxide is added to the distillate until the amine appears as a separate phase which is then drawn the standard methods, and after drying succes- off and successively dried over fresh sodium hydroxide sively over solid sodium hydroxide and metallic and finally by refluxing over metallic sodium. The sodium sodium the water-white amine is fractionated. hydroxide is filtered and the amine is obtained as a waterThe high degree of purity of the products is white liquid by fractionation through a Vigreux column indicated by the narrow boiling ranges and the from a fresh piece of sodium metal. The yield is 28 g. theoretical). fact that they may be quantitatively converted to (80% Monobenzylethy1enediamine.-The isolation of monosolid derivatives. benzylethylenediamine is accomplished by freeing the amine from the crude hydrochloride with excess sodium Experimental hydroxide, extracting with chloroform, drying over anMonoacetylethy1enediamine.-Five hundred twenty- hydrous magnesium sulfate and distilling a t reduced preseight grams (6 moles) of ethyl acetate and 1550 g. (18 sure. The monobenzylethylenediamine is finally remoles) of commercial 70% aqueous ethylenediamine are fluxed over metallic sodium and fractionated through a allowed to stand together several days after the mixture Vigreux column. The yield is 15 g. (20% theoretical). has become homogeneous. The fraction boiling about The low yield of the benzyl derivative is in part a reflection of two observed facts. (1) A significant amount of benzyl 115-130’ (5 mm.) is collected and redistilled a t 125-130’ (5 mm.). The monoacetylethylenediamine weighs 365 g. chloride is liberated during the hydrochloric acid fission (60% theoretical) and contains only traces of ethylenedi- of the benzylated amid+ and (2) a considerable residue containing nitrogen and sulfur remains after distillation amine, lysidine and diacetylethylenediamine. of the pr0duct.1~ N Benzenesulfonyl N’ acetylethy1enediamine.Complete identification of the amines was accomplished Five hundred thirty grams ( 3 moles) of benzenesulfonyl chloride and 1200 g. (3 moles) of 10% aqueous sodium by converting them to dipicrates, dibenzamides and disulhydroxide are slowly and simultaneously added with stir- fonamides. The picrates were prepared in the usual way ring to 306 g. (3 moles) of monoacetylethylenediamine dis(11) Amundsen and Longley report l 0 j 0 (cor.), ibid., 62, 2811 solved in an equal weight of water. After standing for (1940). several hours the solution is faintly acidulated with mineral (12) The alkylated sulfonamide may be triturated with 10% alkali acid and the amide filtered. The N-benzenesulfonyl-N1- to remove traces of unalkylated amide, but in some cases this is not necessary. No purpose is served by isolating the alkyl amides and acetylethylenediamine is recrystallized from dilute eth- they are rather difficult to crystallize, but the benzyl derivative anol, enough of the organic solvent being used t o prevent may be obtained in good crystalline form from dilute ethanol: oiling out of the amide. Dibenzenesulfonylethylenedi- m. p. 92’ (cor.) N calcd. 8.43: found 8.37. (13) This “de-benzylation” is consistent with Bleier’s observation amine, arising from the traces of ethylenediamine present in the monoacetylethylenediamine, is not soluble in the that srm.-dibenzenesulfonyldibenzylethylenediamine yields some monobenzylethylenediamine during hydrochloric acid fission. dilute ethanol and is filtered from the hot solution, while Ber., 82, 1829 (1899). the diacetylethylenediamine also present as an impurity (14) This residue represented some by-products rather than unre-
-
-
-
(9) A. J. Hill and Aspinall, THISJOURNAL, 61, 822 (1939). (10) Schreiber and Shriner, W d . , 56, 1618 (1934).
acted material, because repeated treatment with boiling hydrochloric acid for twenty-four hours failed to yield more of the monobenzyl amine.
854
ARMANDONOVELLIAND J. C. SOMACLINO
Vol. 63
TABLE I MONOALKYL ETHYLENEDIAMINES AND SOLIDDERIVATIVES B. P . , OC.
Base
Mm.
Yield,a
PDipicrateM. P.,
%
'C.,
cor.
7 -
Calcd?' 'i(je1d.b
Dibenzamide-
5.C.,P.. cor.
CalcdN' %jeld.b
--Disulfonamide-
y .C.P.. cor.
C a l 2 %Kjeld.b
CHa-CzH7Nz 115-116' 757 33 220d 21.05 20.98 112 9.93 9.92 94e 7.91 7.82 759 20 195' 20.51 20.36 120 C ~ H S - C Z H ~ N ~ 129-131' 126' 5.32 5.32 9.46 9.47 100; 4 10 222' 18.42 CsHsCH2-CzH7Nz 18.36 18Sk 7.82 7.86 4.76 4.75 198' Over-all yield from ethylenediamine. Reported analytical results are the averages of two or more determinations none of which differs from the theoretical by more than 0.15%. e 115-117', Ber., 70, 979 (1937). 220-222' decomp., THISJOURNAL, 38, 2135 (1916); 225' decomp., 2.physiol. Chem., 174, 119 (1928). Dibenzenesulfonamide. "About 130"," German Patent 446,547. @ Precipitates as a solvate. After drying a t 100" over phosphorus pentoxide for several Di-p-bromobenzenesulfonhours, the picrate is distinctly lighter in color, melts higher and gives the correct analysis. amide. Recrystallized from absolute ethanol. 162-165" a t 20 mm., Ber., 32, 1829 (1899); 165' a t 18 mm., Rec. trav. chim., 54, 594 (1935). 222' decomp., Ber., 32, 1829 (1899). 187', Rec. trao. china., 54, 594 (1935). Di-pbromobenzenesulfonamide. Recrystallized from glacial acetic acid.
'
'
'
in dilute ethanol and recrystallized from the same solvent. The amides were made from the appropriate acid chlorides by the shotten-Baumann technique and were recrystallized from dilute ethanol except when otherwise stated.
The author is indebted to Mr. Samuel M. Raymond for some of the analytical data in this publication. The production of N-alkylated ethylenediamines by the reductive alkylation of
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monoacetylethylenediamine will be described in a forthcoming paper.
Summary 1. A practical synthesis for pure monoalkyl ethylenediamines has been developed. 2. * The amines produced have been thoroughly characterized as solid derivatives. SWARTHMORE, PA.
RECEIVEDNOVEMBER 26,1940
OXGANIC CHEMICAL LABORATORY, MEDICALSCHOOL OF BUENOSAIRES]
Sulfonamide. 11.' Diphenyl Derivatives BY ARMANDO NOVELLIAND J. C. SOMAGLINO~ The appearance of a report by Van Meter and co-workers3prompts us to advance the publication of our results in the same field. By a method similar to that described by the above authors, we have prepared some derivatives, part of which we report here; we are not publishing details because they coincide along general lines. As we have prepared these compounds by another procedure as well, which also corroborates their structure, this experimental part is reported in detail. The reactions are summarized in the chart; we start from p-(p-nitropheny1)-benzenesulfonylchloride (1)and p-(p-nitrophenyl) -benzenesulfonamide (11) prepared according to Gabriel and D a m b e r g i ~ . ~
I
(1) First paper, Ciencie, 1, 260 (1940). (2) With a grant from the Asociacion Argentina para el Adelanto de las Ciencias. (3) Van Meter, Bianculli and Lowy, THISJOURNAL, 62, 3146 (1940). (4) Gabriel and Dambergis, Ber., 13, 1408 (1880).
I1 and IV H~NQ-~\-SO~NHR
R = H or C @ H ~
I11 or V
The aim of this work has been to determine whether, when amino and sulfonamide groups, fundamental in the action of sulfonamide as demonstrated by Fourneau and co-worker~,~ are found in different nuclei, they are still capable of maintaining their bactericidal effect. This is also interesting from a chemical point of view, because Le FPvre and Turnefl accept that in the molecule of diphenyl both of the nuclei are independent. Besides the compounds described in this work, the derivatives 2-aminopyridine and 3-methyl-2aminothiazole are being prepared (patent). (5) Fourneau, Trbfouel, Trefouel, Nitti and Bovet, Comgf rend biol., 122, 652 (1936). ( 6 ) Le FBvre and Turner,J . Chem. Soc., 246 (1928).
SOC.
