Oct., 1941
DERIVATIVES OF 3-NITRO-4-CHLOROPHENYLPHOSPHONIC ACID
[CONTRIBUTION FROM
THE
AVERYLABORATORY OF CHEMISTRY OF
THE
2637
UNIVERSITY O F NEBRASKA]
Organophosphorus Compounds. I. Derivatives of 3-Nitro-4-chlorophenylphosphonic Acid BY GEORGE B. ARNOLD'AND CLIFFS. HAMILTON Since phosphorus lies just above arsenic in the free base3-amino-4-a-carboxymethylaminophenylperiodic table, it was thought that the study of phosphonic acid but water was eliminated bederivatives of phenylphosphonic acids, corre- tween the amine group and the carboxy group sponding in structure to known arsonic acids2might and 1,2,3,4-tetrahydro-3-oxo-6-quinoxalinephosbe of interest from both a chemical and physio- phonic acid was obtained which was confirmed logical point of view. This investigation, there- by the phosphorus analysis and the negative fore, deals with certain derivatives of 3-nitro-4- primary amine test. A similar ring closure has chlorophenylphosphonic acid. been noted with the corresponding arylarsonic 9-Chlorophenylphosphinic acid was prepared acid.2 by the action of phosphorus trichloride on chloroPhenol reacted with 3-nitro-4-chlorophenylbenzene in the presence of aluminum chloride and phosphonic acid by heating the reactants in the hydrolysis of the resulting p-chlorophosphenyl- presence of potassium carbonate and a trace of dichloride. A simultaneous oxidation and nitra- copper powder. o-Chlorophenol and e-chlorotion of p-chlorophenylphosphinic acid with fuming phenol condensed in isoamyl alcohol to yield nitric acid at 100' gave 3-nitro-4-chlorophenyl- derivatives of 3-nitro-4-phenoxyphenylphosphonic phosphonic acid. This compound was identical acid. Catalytic reduction of the nitro compound with that obtained by Michaelis3 by nitration of gave the corresponding 3-amino-4-phenoxyphenylp-chlorophenylphosphonic acid. phosphonic acid derivative. The monosodium salt of 3-nitro-4-chlorophenylBy refluxing 3-nitro-4-chlorophenylphosphonic phosphonic acid condensed readily in aqueous acid with 4 N sodium hydroxide, 3-nitro-4-hysolution with n-propyl, n-butyl, i-butyl, n-amyl, droxyphenylphosphonic acid was obtained. Catai-amyl, monoethanolamine and morpholine to lytic reduction gave 3-amino-4-hydroxyphenylgive 3-nitro-4-N-alkylaminophenylphosphonicphosphonic acid, which turns brown quickly in acids (Table I). An excess of the amine prevented alkaline solution and darkens on exposure to air. the possible condensation of two moles of the acid Experimental with one mole of the amine to give 2,2'-dinitrop-Chlorophenylphosphinic Acid.-p-Chlorophenylphos4,4'-diphosphonodiphenyl-N-alkylamines. phinic acid was prepared by a modification of the method By reduction of the nitro compound with of M i ~ h a e l i s . ~The p-chlorophosphenyl dichloride was hydrogen a t forty pounds pressure and Raney extracted from the reaction mixture with petroleum ether nickel4 catalyst, the corresponding 3-amino-4- and, after removing the solvent by distillation, hydrolyzed alkylaminophenylphosphonic acid was obtained. to p-chlorophenylphosphinic acid. Two recrystallizations water gave a white crystalline compound; yield IO%, In all cases the aminophenylphosphonic acid from m. p. 131'. Michaelisa reported 130-131 '. melted much higher than the corresponding nitro 3-Nitro-4-chlorophenylphosphonic Acid.-p-Chlorocompound, a fact previously noted by Michaelis3 phenylphosphinic acid was added slowly with stirring to an with similar compounds. Most of the nitrophenyl- excess of fuming nitric acid (sp. gr. 1.52) heated over a phosphonic acids decomposed on melting and the water-bath. Dense brown fumes were given off and the aminophenylphosphonic acids behaved as amine solution was evaporated almost t o dryness. Sufficient fuming nitric acid to dissolve the solid was added and the salts. solution again heated over a water-bath until the solution Glycine condensed with 3-nitro-4-chlorophenyl- evaporated almost to dryness. On cooling the phosphonic phosphonic acid under anhydrous conditions to acid separated and was dried in a vacuum oven; yield 90%; yield 3-nitro-4-a-carboxymethylaminophenylphos-m. p. 166". 3-Nitro-4-N-alkylaminophenylphosphonicAcids.--& phonic acid. Catalytic reduction did not give the Nitro-4-chlorophenylphosphonic acid (4.75g.), 2 N sodium Avery Research Fellow: present address, The Texas ComBeacon, New York. Maclay and Hamilton, THISJOURNAL, 54, 3310 (1932). Michaelis, Ann., 298, 193 (1896). (4) Covert and Adkins, THIS J O U R N A L , 54,4116 (1932)
(1) pany, (2) (3)
hydroxide (12 ml.), and the amine ( 5 ml.) were heated in a flask fitted with a condenser and stirrer for six t o eight hours a t 120". The reaction mixture was evaporated to about 15 ml. and was made acid t o congo red paper. The
2638
GEORGE
B.
ARNOLD A N D
CLIFF
s. HAMILTON
Vol. 63
TABLE I COMPOUNDS AND -adnophenolphosphoric acid Compound Descriptionh
1 3-Nitro-4-~-propyl2 3-Nitro-4-n-butyl3 3-Nitro-4-i-butyl-
Yellow needles, oblique ext. Yellow rods, oblique ext. 4 3-Nitro-4-n-amylYellow rods, parallel ext. 5 3-Nitro-4-i-amylYellow needles, parallel ext. 6 3-Nitro-4-6-hydroxyethyl- Orange plates, parallel ext. i 3-Amino-4-n-propylWhite needles, 8 3-Amino-4-n-butylparallel ext. White powder 9 3-Amino-4-i-butyl10 3-Amino-$-%-amylWhite needles, 11 3-Amino-4-i-amylparallel ext. 12 3-Amino-4-P-hydroxyWhite needles, ethylparallel ext. 13 3-Nitro-4-morpholinoOrange prisms, phenylphosphonic acid anisotropic 14 3-Amino-4-morpholinoBrown powder phenylphosphonic acid 15 3-Nitro-4-a-carboxyYellow rods, parallel ext. methylaminophenylphosphonic acid 16 1,2,3,4-Tetrahydro-3-0~0- White needles, parallel ext. 6-quinoxaline-phosphonic acid
PROPERTIE3
Yield,
%
Anal. P. %a Calcd. Found
178-179 dec. 176-178 dec. 176-180 dec.
52 51 60
11.9 11.24 11.24
11.8 11.11 11.22
132-134
53
10.14
IO. 20
171-173 dec.
58
10.78
10.69
182 dec.
50
11.83
11.77
>200 >200 >200 >200
74 79 78 79 67 73
13.48 12.70 12.70 11.98 11.98 13.33
13.35 12.68 12.73 11.86 11.87 13.18
176
33
10.76
10.71
>200
50
12.01
11.87
>200
50
9.96
9.87
>200
76
13.59
13.51
>200
57
CizHioNOeP.3HzO
8.87
8.91
>200
22
CizHaNO.jPCl.Hn0
8.92
8.91
>200
36
CinHoNOe,PC1.2H20
8.48
8.37
>200
58
CizHizNO,P.2HnO
10.30
10.34
>200
80
CizHiiNO4PC1~2HzO 9.27
9.41
>200
57
CizHiiN04PC1.3HzO
8.44
M. p., OC.
>200 >200
CiiHirNnOsP
-phenylphosphonic acid
17 3-Nitro-4-phenoxy18 3-Nitro-4-(o-chlorophenOXY)19 3-Nitro-4-(p-chlorophenOXY
1-
20 3-Amino-4-phenoxy21 3-Amino-4-(o-chlorophenOXY)22 3-Amino-4-(p phenoxy)-
Tan needles, parallel ext. Tan isotropic, crystals Tan isotropic plates Gray needles, anisotropic White needles, parallel ext. Gray needles, parallel ext.
8.77
-phenylphosphonic acid
23 3-Nitro-4-hydroxy24 3-Amino-4-hydroxy-
214-216 78 13.09 12.98 Isotropic crystals 67 15.07 >200 14.07 Brown needles, parallel ext. Analysis for phosphorus was by the method of Neurnann described in H. Meyer, "Analyse und KonstitutionerinittelCrystals were studied under a polarizing microung organishen Verbindungen," Julius Springer, Berlin, 1909, p. 289. scope.
'
acid sepaphosphonic acid separated and was purified by two re- The 3-amino-4-N-alkylaminophenylphosphonic crystallizations from water accompanied by treatment rated, was filtered off, washed well with water and dried. 3-Nitro-4-a-carboxymethylaminophenylphosphonic Acid. with activated charcoal. -3-Nitro-4-chlorophenylphosphonic acid (9.5 g.), glycine 3--0-4-N-alkylaminophenylphosphonic Acids.-The monosodium salts of the 3-nitro-4-N-alkylaininophenyl-(5 g.), anhydrous potassium carbonate (9 g.), and isoamyl phosphonic acids were reduced in aqueous solution using alcohol (30 ml.) were heated for nine hours a t 145" in a flask fitted with a stirrer and a condenser. The iso-amyl hydrogen a t forty pounds pressure and Raney nickel' catalyst. After reduction was complete the catalyst was alcohol was removed by steam distillation and the residual filtered off and the solution made acid to congo red paper. solution acidified to congo red paper. The phosphonic
1,~-J>IMII:S~TYL- ~-PKOP&N-I-Ol.
C k t . , 1941
“639
alkylaminophenylphosphonic acids to give 3-amino-4phenoxyphenylphosphonic acid derivatives. 3-Nitro-4-hydroxyphenylphosphonic Acid.-3-Nitro-41,2,3,4-Tetrahydro-3-oxo-6-quinoxaline-phosphonic chlorophenylphosphonic acid was refluxed for four hours in Acid.-When the monosodium salt of 3-nitro-4-a-car- 4 N sodium hydroxide solution. 3-Nitro-4-hydroxyphenylboxymethylarninophenylphosphonicacid was reduced with phosphonic acid separated slowly after the solution was hydrogen and Raney nickel‘ catalyst the free base, made acid to congo red paper and was purified by re3-amino-4-a-carboxymethylaminophenylphosphonicacid, crystallization from water. 3-Amino-4-hydroxyphenylphosphonic Acid.-Catalytic which was not isolated, lost water to form a quinoxaline derivative. 1,2,3,4-Tetrahydro-3-oxo-6-quinoxalinephos-reduction of 3-nitro-4-hydroxyphenylphosphonicacid in phonic acid which separated when the filtrate from the the same manner as the 3-nitro-4-N-alkylaminophenylreduction was acidified to congo red paper, was filtered off, phosphonic acids were reduced gave 3-amino-4-hydroxyphenylphosphonic acid which darkens quickly in air or in washed well with water and dried. solution. 3-Nitro-4-phenoxyphenylphosphonic Acid.-3-Nitro-4phenoxyphcnylphosphonic acid was obtained by heating a Summary mixture of 3-nitro-4-chlorophenylphosphonicacid (5 g.), anhydrous potassium carbonate (5 g.), phenol (10 g.), and 3-Nitro-4-chlorophenylphosphonic acid has been a trace of copper powder, for nine hours a t 125’ with agitaprepared and condensed with several aliphatic tion. The excess phenol was removed by steam distillation. The phosphonic acid was precipitated with dilute amines, namely, n-propyl, n-butyl, i-butyl, nhydrochloric acid and purified by two recrystallizations amyl, &amyl and ethanolamines, morpholine and from dilute acetic acid accompanied by treatment with glycine. The corresponding amine derivatives of activated charcoal. the condensation products were obtained by re3-Nitro-H o-chlorophenoxy)-phenylphosphonic Acid and duction except that of glycine which gave 1,2,3,43-Nitro4-(p-chlorophenoxy)-phenylphosphonic Acid.-3P\’itro-4-(chlorophenylphosphonicacid (5 g.), anhydrous tetrahydro-3-oxo-6-quinoxaline-phosphonicacid. potassium carbonate (5 g.), isoamyl alcohol (15 ml.), copper 3-Nitro-4-chlorophenylphosphonic acid has been powder (5 g.), and either a- or p-chlorophenol (2.5 g.) were condensed with phenol, o-chlorophenol and pheated a t 145Ofor seven to nine hours in a flask fitted with a chlorophenol to give phenyl ether derivatives. stirrer and a condenser. The isoamyl alcohol and excess The aminophenyl ether derivatives have been phenol were removed by steam distillation. The phosphonic acid was precipitated with dilute hydrochloric acid prepared from the corresponding nitro compounds. and purified by two recrystallizations from dilute acetic 3-Nitro-4-hydroxyphenylphosphonicacid has acid accompanied by treatment with activated charcoal. been prepared and reduced to 3-amino-4-hydroxy3-Amino-4-phenoxyphenylphosphonic Acid Derivatives. phenylphosphonic acid. -The 3-nitro-4-phenoxyphenylphosphonicacid derivatives were reduced in the same manner as the 3-nitro-4-N- LINCOLN, NEBRASKA RECEIVED APRIL 15, 1941
acid separated and was purified by two recrystallizations from water accompanied by treatment with activated charcoal.
[CONTRIBUTION FROM
THE
NOYESCHEMICAL LABORATORY, UNIVERSITY OF
ILLINOIS 1
Vinyl Alcohols. 11. 1,Z-Dimesityl-1-propen- 1-01 BY REYNOLD C. FUSON, D. J. BYERS~ AND NORMAN RABJOHN~
The vinyl alcohol 1,2-dimesityl- 1-propen-1-01 (I, Mes = mesityl), described in the preceding communication, is remarkable because it contains only hydrocarbon substituents. Most enolic comCHa OH MesLJMes
I
CBH~CO OH
I
t
(CeHJzCHC-CMes
Tishler and Potter4 is an example of this type. The stability of certain enols cannot be explained in this way, however. The enol form (111) of benzyl phenyl diketones has been shown by Kohler and Barnes6 to behave as an unchelated hydroxy ketone. The possibility of ascribing the staMesCO
I1
pounds have a carbonyl group and are probably chelated. The enol form (11) of benzohydrylbenzoylacetomesitylene described by Kohler, ( 1 ) Du Pout Post-doctorate Research Fellow, 1940-1941. (2) R6hm and Haas Research Assistant. (3) Fuson, Corse and McKeever, THIS JOURNAL, 62, 3250 (1940).
OH
I
0
/I
CsHsCH=C-CCsHs I11
I
CH, OH
I
I
MesC=CMes IV
(4) Kohler, Tishler and Potter, ibid., 57, 2517 (1935). (5) Moureu, Ann. chim., 1101 14, 303 (1930). (6) Kohler and Barnes, THIS JOURNAL, 66, 211 (1934).
