sis,” p. 4018, Academic Press, Xew S’ork, 1955. (3) Cooper, G. R., hladel, E. E ., J .
Lab. Clin. Med. 44, 636 (19541. Bioc:hem. (4) Cremer, H. D., Tiselius, 8., 2. 320, 273 (1950). (5) Crook, E. M.,Harris, H., Ha ssan, F., Warren, F. L., Biochem. J ‘. 56, 434 (1954).
Crook, E. ll.,Harris, H K a rren, F. L., Ibid, 51, xxvi (19k2). Durrum, E. L., J . Am. Chem. SOC. 72,2943 (1950).
Franglen, G. T , Martin, N. E., Biochem. J . 57, 626 (1954).
Gornall. A. G.. Bardawill. C . J.. Grassmann,’k., Hannig, K., Klin. Wochschr. 32, 838 (1954).
(11) Griffiths, L. L., J . Clin. Pathol. 5, 296 (1952). (12) Jencks, W. P., Jetton, M. P., Durrum, E. L., Biochem. J . 60, 205 (1955). (13) Kunkel,’ H. G., Tiselius, A,, J . Gen. Phwiol. 35, 89 (1951). (14) Latner, A. L:, Molyneux, L., Rose, J. D., J . Lab. Clin. Med. 43, 15i (1954). (15) Mellor, D. P., Maley, L., A-ature 161, 436 (1948). (16) Rees, V. H., Laurence, D. J. R., Clinical Chem. 1, 329 (1955). (17) Sommerfelt, S. C., Scand. J. Clin. and Lab. Invest. 5, 299 (1953). (18) Von Frijtag Drabbe, C. A. J., Reinhold, J. G., ANAL.CHEX 27, 1090 (1955).
RECEIVED for review October 25, 1956. Accepted June 17, 1957. Presented in part at Fortieth Annual Meeting, Federation of American Societies for Experimental Biology, Atlantic City, N. J., March 1956. Investigation supported in part by funds from the Office of the Surgeon General, and carried out in one of the laboratories of the Southern Utilization Research Branch, Agricultural Research Service, U. s. Department of Agriculture. Trade names have been used only to identify equipment or materials actually used in the work, and such use does not imply endorsement or recommendation by the U. S. Department of Agriculture over other firms or similar products not mentioned.
Classification of Organic Compounds Based on Behavior of a Solvochromic and Thermochromic Indicator System SAUL SOLOWAY and PERRY ROSEN Deparfmenf o f Chemistry, City College, College o f the Cify of New York, New York, N.
b
Organic compounds are classified according to their effectiveness in promoting or inhibiting chelation between ferric chloride and n-propyl gallate. If this classification is used in conjunction with others based on solubility, elementary analysis, and acid-base indicators, 19 out of 28 types of compounds are identifiable as unique. Some examples are alcohols, phenols, carboxylic acids, amides, nitro compounds, and nitriles. Some aliphatic compounds may be distinguished from their aromatic counterparts on the basis of their stronger inhibitory properties. Explanations are offered for the apparently anomalous behavior of some functions which behave as promoters or inhibitors of chelation, depending on their concentration,
F
qualitative analytical purposes organic compounds are grouped according to their elementary composition, solubility in specified solvents (IO), and acid-base strength ( 2 ) . Such preliminary classifications are not only helpful in suggesting possible functional groups in a n unknown compound, but may also give indications of molecular weight, polyfunctionaIity, and bond type. Recent work on the solvochromic and thermochromic behavior of an indicator system ( l a ) suggested another preliminary classification to aid the analyst OR
1820
ANALYTICAL CHEMISTRY
further in inferring the presence of certain functional groups. The indicator system consists of ferric chloride, npropyl gallate, and o-chloroaniline. The solutions may be blue or yellow throughout the entire temperature range of the liquid state, or they may exhibit a reversible thermochromic transition from blue to yellow. The solvent and temperature control the extent of chelate formation between the indicator components. As the stoichiometry of the reaction is not precisely known, the chemistry is summarized by the following word equation. Ferric chloride (yellow)
Y.
dants, organic as well as inorganic, caused irreversible destruction of the indicator. This was recognized by the formation of a permanent red-brown color. EXPERIMENTAL
Indicator Solutions. Indicator A was made b y dissolving 2 grams of anhydrous ferric chloride a n d 4 grams of n-propyl gallate in 100 ml. of warm glacial acetic acid. Then 1.5 ml. of acetyl chloride were added, a n d the solution was quickly filtered through a large piece of fluted paper, t o mini-
+ propyl gallate + chloroaniline e chelat,e- + chloroanilinium ion (colorless) (colorless) (blue) (colorless)
The designation of the products as ions is a matter of conjecture. It is thus written to emphasize the function of the amine as a proton acceptor. The effectiveness of a given compound toward promoting or inhibiting chelate formation in the indicator system was studied in two solvent media as a function of temperature: one in which the compound itself was substantially the total solvent, and the other in which it was a further diluent to a bromobenzene solution of the indicator. Although most substances were either promoters or inhibitors of chelation in both media, most alcohols and amides were promoters as bulk solvent but inhibitors in dilute hromobenzene solution. Some oxi-
+
mize contact with moisture in t h e air. T h e final solution was a light brown. It darkens rapidly on exposure t o a moist atmosphere, because water is a strong promoter of chelate formation. This indicator has been used t o detect water in alcohols and t o determine their relative basicities ( I S ) . Indicator B was prepared b y adding 2 ml. of indicator A, 1 ml. of benzene sulfonyl chloride, and 1 ml. of ochloroaniline t o 90 ml. of bromobenzene. The final solution or possibly colloidal dispersion was blue. As some solid matter separates with time, the mixture is well shaken before use. T h e change of color with temperature was somewhat sharper after t h e solution had been aged several days. T h e relation of this phenomenon t o sulfon-
amide formation or another reaction was not investigated. Test A was performed b y adding 1 drop (0.05 ml. per drop) of indicator A and 1 drop of o-chloroaniline t o 1 ml. of a liquid. If a yellow solution resulted, i t was cooled t o observe a n y color change at 20', lo', and - 10' C. T h e d a t a at 10" C. were taken for judging t h e rate of thermochromic change rather t h a n for class designations. If a blue solution resulted at room temperature, i t was heated t o determine m-hether a thermochromic change occurred a t a n elevated temperature. Changes a t 40"and 100" C. were recorded. T h e critical thermochromic temperature ( C T T ) of a solution is defined as t h a t temperature at which the yellow solution, on cooling, just turns pure blue after passing through a brief green phase. Observation is made with t h e naked eye against a white background. These tests were repeated on t h e same solutions in order t o determine reversibility. I n a number of instances, permanent reactions set in quickly at high temperatures. Test B was performed b y heating 1 ml. of indicator B until i t became yellow. T o t h e hot solution 3 drops of a liquid or 50 t o 100 mg. of a solid compound n-ere added. T h e same temperature observations were recorded on t h e down side as in Test A, b u t 125' C. as t h e upper boundary in this test.
It was too grcat a task to purify or verify the purity of all the substances tested. Most compounds were obtained as samples from the manufacturer or purchased from reputable supply houses. I n the case of old samples of ethers 2nd olefins, permanent color changes to red or red-brown were observed in both tests. Purification to remove the presence of oxidants (hydroperoxides, etc.) caused these compounds to hehave normally. RESULTS
Indicator B had a critical thermochromic temperature of 34" & 2" C. If an added compound elevated the critical thermochromic temperature above 40" C. in Test B, it mas designated as a promoter of chelation, P. A depression of the critical thermochromic temperature below 20" C. categorized a compound as a n inhibitor, I. Any substance which gave a value between 20" and 40" C. was termed a neutral, K, Because of concentration dependence a few cases of overlap at these artificial boundaries were observed. These same designations a t the identical boundaries mere used in Test A. Subscripts m and d applied t o the three main groups refer to Tests A (compound as the solvent medium) and B (compound as the diluted medium).
Superscripts are used to subdivide the promoter and inhibitor classes further. Superscript w (weak) attached t o I refers t o the fact that the chromic transition !vas observed between - 10" and 20' C. in both tests. Superscript T I attached to P refers to a chromic transition in the region of 40' to 100' C. in Test A and 40" to 125" C. in Test B. Superscript s (ftrong) means t h a t a chromic transition may occur below -10" C. for an inhibitororabove 100OC. for a promotor in Test A or above 12;" C.in T w t I3. This information is siimni~irizcdin thc following kcy.
indicator classifications (2, I O ) are also given. I n the interest of brevity the individual compounds are not listed. The variations for a given type of compound were chain length, chain isomerization, unsaturation, presence of halogen atoms, arylation, and multiplicity of function. Whenever any of these factors or others so affected a given type, another group was made in this or a subsequent table. Table I1 lists the exceptions t o the generalizations in Table I as specific compounds or groups. Table 111 cites the behavior of some miscellaneous com-
I n Table I the behavior of many common types of organic compounds is classified in accordance with their decreasing ability to promote chelation or increasing ability t o inhibit chelation in Test A. If the designation in regard t o Test A is the same, the position in the table is determined by the same considerations in Test B. For the purpose of further discussion the solubility and Davidson
pounds. Table IV lists compounds and mixtures resulting from the autoxidation of known compounds which irreversibly oxidized the indicator to yield permanent red or red-brown colors. DISCUSSION
An examination of Table I shows that 19 of the 28 types of compounds listed
Table I.
Classification of Types of Organic Compounds in Order of Increasing Ability as Inhibitors of Chelation Therrnochromic Davidson Type of Indicator Indicator Solubility Compound A B Claw Claw Aliphatic amine Epoxide Aromatic and heterocyclic amines Phenol A, Aliphatic amide* s Alcohol N Carboxylic acid0 Ai Diary1 ether N Hydrocarbon N s,I Mereaptand z A,, A I Aromatic nitro compound N &I Aryl alkyl ether N ?IT Aromatic nitrile N h4 Aliphatic nitro compound A, Alkyl aryl sulfonate ester E Aliphatic monoether x Aliphatic nitrile N Aryl alkyl ketone N Ester x Aldehyde s Aliphatic acid anhydride Aliphatic ketone 4 ' Aliphatic polyether Carboxylic acid chloride Phosphonic acid Saturated heterocyclic ether Sulfonic acid Trialkyl phosphate a For variations of classifications ( 2 , 1 0 ) should be consulted. Solubility class S was largelj ignored. Sumbrr of amides tested xas relatively small because of low solubility in bromobenzene. Drsignation in Test B results from behavior of acetyl piperidine, N,N-dimethyl acetamide. n',S-dimethyl formamide, and N-methyl acetamide. Polycarboxylic acids exhibited poor solubility in Test B. d Precipitates formed in Test A with n-propyl and sec-butyl mercaptans.
VOL. 2 9 ,
NO. 1 2 , DECEMBER 1957
1821
form unique classes on the basis of their elements, solubilities, and reaction to Davidson and thermochromic indicators, The remaining nine types fall into three groups. The first, consisting of diaryl ethers and hydrocarbons, is not differentiatable by a class test, if the given hydrocarbon is aromatic. Othermise, formaldehyde-sulfuric acid or a n y other test for aromaticity is applied. The second group consists of aldehydes, aliphatic ketones, aliphatic polyethers, and heterocyclic ethers. Aldehydes and ketones are readily distinguished from one another as well as from ethers by application of the 2,4-dinitrophenylhydrazine and Tollens reagents. No reliable test of wide applicability is available for confirmation of the ether function. The third group of aryl alkyl ketones, esters, and aliphatic ethers can be differentiated by the use of the 2,4-dinitrophenylhydrazine and hydroxamic acid tests. Thus, three functional group tests are sufficient to differentiate 24 of the 28 types in Table I after preliminary classification. These thermochromic indicators are also useful for the detection of organic oxidants, as shown in Table IV. Exposure of 1-dodecene to the atmosphere
Table II. Exceptions to General Classification Given in Table I
Kame of Thermochromic Compound Indicator A B or Type o-Bromoaniline o-Chloroaniline Dimethylhexynol Glycolsa Methanol Oleyl alcohol Stearyl alcohol* Trichloroethanol Dicetyl ether o-Nitrochlorobenzene Laurone .. 12 Benzyl methyl ether 1; Nd Di-a-methvl benzyl ether :I S d p,p’-Dichl&oisop acetanilide > water > dioxane s acetonitrile > di-n-butyl ether, acetone, ethylene diacetate. The authors’ findings with respect to decreasing basicity toward ferric chloride in broniobenzene solution are: acetamide, acetone, dioxane (all I;) >, acetanilide, acetonitrile, di-nbutyl ether (a11 I;). I n both series diowne is stronger than di-n-butyl ether and acetamide is stronger than acetanilide. A coniparison of dissimilar functions, however, shows that although acetamide is a stronger base than acetonitrile toward both acids, acetone and acetonitrile show specificity in their preference. One n-ould expect that a substance which promoted or inhibited chelation in dilute broniobenzene solution.jvould go further in that direction as the total solvent for the indicator system. This \\as true of most types of compounds. I n many amines, n-hich boiled a t over 100” C., the solution remained blue lvith practically no change in intensity a t the boiling point, Solutions in acetone, methyl acetate, and diethyl ether remained yellow a t -90” C. (?). On the other hand, the change in behavior of alcohols and amides with dilution demonstrates a radical difference between the liquid polymer and the solvated monomer. Although the structural features of liquids are neliulous, the existence of hydrogen bonding in alcohols, acids, and amides is ne11 established ( 3 ) . This perhaps accounts for the promoter action of alcohols as 3olvents of the indicator system. Even if ferric chloride is assumed t o be the strongest acid present, a proton can be more readily bound into the tight netlyork. The positively charged polymer can be resonancestabilized, a i s1i011-n in the following structurci R
I
