DE2260314C3 - 2-Carboxy-4'-morphollno-azobenzene, process for its preparation and its use as a means for determining pH - Google Patents

Description

a) couples with phenylmorpholine in acidic solution, or

b) couples with aniline and the 2-carboxy-4'-amino-azobenzene formed

<x) with a compound of the general formula I.

X-CH ₈ -CH ₂ -O-CHj-CH ₂ -X (I)

in aer X means a reactive acid residue, condensed, or

ß) with 2 mol of a compound of the general formula II

X-CH ₂ -CH ₂ -OH (II)

in which X has the above meaning,

condensed, the resulting 2-carboxy-4 '- [di-y? -hydioxyäihyl-amioo] -azobenzene with dehydrating agents to 2-carboxy ^ '- morpholino-azobenzene is cyclized or

_r , c) with N, N-Di - /? - hydroxyethyl-aniline couples and filter paper, asbestos,

^f then dehydrated. Plastic or fiberglass tile etc. in question, whereby

Filter paper is the preferred carrier
_r _ Das _ 2-Carboxy4 -morphoUno-azobenzene. According to the invention, prefabricated test following can be used in analogy to methyl red as Morphoün- s strips or rods directly with the impregnation red, is a wine-red solid, solution soak, dry and use as such. which is in an acidic solution with a red color and preferably a larger web of the neutral to alkaline solution with a yellow color absorbent carrier is soaked with the impregnation solution. The transition point is at a pH value dried and then into manageable pieces of about 5.0. 10 cuts. It is of course possible.

Since the envelope is in the pH range from 4 to 6, stick on a handle with impregnated pieces

the strong color contrast from red to yellow relative or to seal on or between two plastic films

is easy to read, is morpholine red as an indicator for or a plastic film and a fine mesh

this pH range is useful. Seal other color indicator networks. In the last two cases

goals in this area, such as B, methyl orange and 15 are obtained against contamination and contamination.

leine isomers as well as Meiiylrot and its isomers, walking secured test agents,

however, they are just as useful. Of note- Although the test papers described are preferred

Valuable advantage of morpholine red compared to the * anis diagnostic aid for determining the pH value

whose known indicators are intended to serve for the same area in urine, they can of course

SD lies in its significantly improved usability 20 for determining the pH value in other liquid

m indicator mixtures. In particular, dye chains are used,

The following examples are intended to explain the invention in more detail

from yellow, yellow-green or colorless to blue or explained.

Violet change, can be mixed with Morphoün example 1

red can be used advantageously. Examples of such as ^v

Indicators are preferably the known sulfo-2-carboxy-4'-morpholino-azobenzene

phthaleine, bromxylenoi blue, and bromothymol blue. .

The \ ananteA are preferred as reactive acid residues:

Halides, especially the chlorides and bromides, in a solution of 32.6 g (0.2 mol) phenylmor-

as well as sulfonic acid residues such as tolylsulfonyl or 30 pholine in 250 ml of 20% acetic acid with 16.7 ml of concentrated

Methykulfonyl residue in question. The hydrochloric acid trated during the reaction is added in portions

Acid released can be added by adding your base, stirring at 2O ⁰ C 47 g (0.2 mol) of o-carboxyphenyl-

z. B. a tertiary amine or an alkali metal carbonate, diazonium tetrafluoroborate. Then 1 hour at

be bound. Stirred at 20 ° C, by adding a drop of saturated sodium

The dehydration can be adjusted to pH 4 by boiling with trium acetate and a further 2 hours

concentrated mineral acids or stirred at 20 ⁰ C by reacting. After being cooled with ice

with a water-binding Lewis acid, e.g. B. suctioned off with the wine-red crystals formed, with

Phosphorus pentoxide, aluminum trichloride, zinc chloride 2 η-acetic acid and converted from glacial acetic acid

etc., in a suitable solvent, e.g. B. ether, crystallized. 10.21 g = 16.4% dark red,

Benzene, etc., can be carried out. 40 chromatographically uniform 2-carboxy-4'-mor-

Test papers made with a mixture of morpholino-azobenzene (morpholine red), melting point 196 to

red and dea above indicators impregnated 198 ⁰ C.

allow a good pH determination in the range of variant B;
from 4 to 9 pH units, those in water and

Colorations obtained in urine at the same pH-value are 45 In a 1-liter three-hat flask with stirrer, practical dropper do not distinguish. funnel, thermometer and dry ice bath

The indicator according to the invention is dissolved in amounts of 20 g of o-aminobenzoic acid in 600 ml of water and from 0.05 to 0.1%, preferably 0.015 to 0.30%, 60 ml of concentrated hydrochloric acid and added with 10 g of the impregnation solution. This amount of sodium nitrite at 0 to 5 ⁰ C under stirring .n about depend on the desired hue. 50 diazotized for 30 minutes. The diazonium salt solution is The recipe can also be mixed with the usual additives such as additive for a further 30 minutes. Special wetting agents are added to a 2-1 three-necked thickener, color stabilizer and, in particular, a flask with stirrer, cooler and dropping funnel. Suitable wetting agents are 24.8 g Phenylmorphoisa in 200 nu water and 20 ml, in addition to the non-ionic, in particular the concentrated hydrochloric acid dissolved and the diazonium anionic wetting agents. Particularly proven 55 salt solution added dropwise in about 10 minutes. The darker is dioctyl sodium sulfosuccinate, which, in addition to the red solution, is added with 200 gk of crystallized sodium to its wetting effect, as acetal; whereby a yellow precipitate is slightly insignificant in the transition area of the sulfophthaleins. It is alkaline with stirring on a water bath to move, which in the reading P "rich heated at about 30 ⁰ C, in turn, occurs 8 further improved to 9 under pH Rotvon. 60 dye solution a. After four hours of stirring at

The materials to be impregnated as usual 40 ⁰ C is cooled and excluded with chloroform

Dissolved in volatile solvents and shakes on the. The chloroform solution is used several times

impregnated with absorbent carrier. A 2 η sodium hydroxide solution has proven to be effective, whereby the color

Additives of highly polar solvents, such as dimethyl substance as the sodium salt, are produced from the chloroform solution.

sulfoxide or dimethylformamide, which in particular is removed. By adding acetic acid, the

in the presence of wetting agents eras a more uniform aqueous solution adjusted to pH Λ and then

Distribution of the indicators on the saugiähigcn turn TSII chloroform exirahiert Concentration

Effect carriers. the dried chloroform solution is the return

stood recrystallized from glacial acetic acid. This gives 4.63 g Morpholinrot (10.2% of theory), Schrap, 196-197 ⁰ C.

Variant C:

10.0 g of 2-carboxy-4 '»[üi- / Maydroxyäthyl-amino] -azobenzene are dissolved in 100 ml of concentrated sulfuric acid in the cold and heated to 10O ⁰ C for 5 hours. It is then poured onto one liter of ice and adjusted to ρ i4 with sodium hydroxide solution and extracted three times with 100 ml of chloroform each time. After evaporation of the solvent, the residue is recrystallized from glacial acetic acid. This gives 6.3 g Morpholinrot (66% of theory), mp. 194 to 197 ⁰ C.

The 2-carboxyxs used as the starting product 4 '- [di - /? - hydroxyethyl-amino] -azobenzene is obtained as follows:

In a 1-1 three-necked flask equipped with a stirrer, thermometer and dropping funnel, 36 g of N, N-di (2-hydroxyethyl) are added to a mixture of 250 ml of 20% acetic acid and 16.7 ml of concentrated hydrochloric acid while cooling with ice ) -aniline and with stirring 46 g of o-carboxyphenyldiazonium tetrafluoroborate are then stirred for 2 hours at room temperature and the acidic solution (pH 2) is adjusted to pH 4 by adding 99 ml of saturated sodium acetate solution After filtering off with suction, washing with dilute acetic acid and drying over diphosphorus pentoxide, 55.61 g of 84.4% red-violet crystals of 2-carboxy-4 '- [di- /? -hydroxyethyl-amino] -azobenzene are obtained obtained of mp. 154-157 ⁰ C.

Example 2

Vird filter paper with a solution of 20 mg and 80 mg Morpholinrot bromoxylenol blue in 100 ml of methanol impregnated and dried at 40 ⁰ C. The colors with urine or water of different pH values are shown in Table 1. set.

Table 1

PH value colour 4th Orange red 5 orange yellow 6th olive 7th dark green 8th greenery ic- blue

Example 3

Filter paper with a solution of 30 mg Morpholinrot impregnated Bromthymoibiau 100 mg and 2.0 g Hydroxypropylceilulose in 100 ml methanol and dried at 4O ⁰ C. The colors with urine or water at different pH values are shown in Table 2,

Table 2

PH value ; - arbe 4th Orange red 5 orange yellow 6th yellow 7th light green 8th green 9 blue

Example 4

Filter paper is impregnated with a solution of the following composition and dried at 8O ⁰ C.

Morpholine red 0.025 g

Bromxylenol blue 0.075 g

Dioctyl sodium sulfosuccinate 0.5 g

Dimethyl sulfoxide 30.0 ml

Methanol to 100.0 ml

The reaction colors with urine or water at different pH values are listed in Table 3.

Table 3

pH wide colour 45 4th
5
6th Orange red
orange yellow
helloüv 50 7th
8th
9 green
blue green
blue

Claims (9)

Claims *. 1. ^ -Carboxy - ^ - morpholino-azobenzene,
_{> itt} 2. Process for the preparation of 2-carboxy-4? | morpholmo- <tzobenzQl, characterized in that o-aminobenzoic acid is diazotized in a manner known per se and either a) couples with phenylmorpholine in acidic solution, or J: b) couples with aniline and the 2-carboxy-4'-amino-azobenzene formed α) with a compound of the general formula I. X-CHj-CH ₂ -O-CH ₂ -CHs-X (I) in which X is a reactive acid residue, condensed, or B) with 2 moles one: compound of general Formula II X-CH ₂ -CH ₂ -OH (II) in which X has the above meaning, condensed and the 2-carboxy-4 '- [di - /? - hydroxyethyl-amino] -azobenzo! subsequently dehydrated or c) couples with N.N-Di-ß-hydroxyethyl aniline and subsequently dehydrated. 3. Use of 2-carboxy-4'-morpholinoazobenzene as a pH indicator. compared to a reading accuracy of about O ^ pH units, but usually only encompass a pH range of 2 to 4 units. For medical diagnostics, especially for examining the urine, it is necessary to have a Determine pH range from pH 4 to 9. The former occurs in certain comatose states, the latter with certain kidney diseases. Most test papers known for this purpose allow ίο either a determination in the pH range from 4 to 8 or in the pH range from 5 to 9. An indicator paper placed on the market by the applicant, which is impregnated with a mixture of methyl red and bromothymol blue and special additives, allows a relatively precise determination of the entire pH range from 4 to 9, but has the Disadvantage that the necessary for the determination Additives can easily be washed out of the paper, which is another one with combined test strips λο can cause additional disruption of the neighboring test. Furthermore, colorless substances occurring in varying concentrations in the urine cause a certain falsification of the color.
The object of the invention was therefore to provide a to find a new indicator that is a simple and accurate determination of the whole physiological important pH range from 4 to 9, its color depends on the nature of the test medium is independent and does not have any bleeding aggregates 30 required. More surprisingly, it was found that the dem Methyl red ü-carboxy ^ dimethylamino-azobenzene) relative similar new compound of the following formula 35 The invention relates to 2-carboxy-4'-morpholino-azobeizole, Process for its manufacture and its use as an improved diagnostic Means for pH determination in liquids, especially urine, in a pH range between 4 and 9. The pH determination with dye indicators, which depend on the pH of the solution protons schott has been known for a long time to attach or split off and change their color in the process. Besides their use it was used at an early stage in medical diagnostics to control chemical reactions, since the pH value of various body fluids, especially urine, is an indication of pathological conditions Can give changes to the patient. For easier handling, these tests were carried out at an early stage with test papers that contain were impregnated with suitable indicators. A very well-known example of this is litmus paper. This, as well as other test papers that are impregnated with only one indicator, allow a quantitative Statement only in a range that is about one pH unit above and below the transition point of the relevant indicator. ^ t. To a bigger one To record the pH range, indicator mixtures were therefore also used relatively early on, whereby the individual indicators change at different pH values. Mixed indicators from three and more Components that make a statement in the entire, technically interesting range from 1 to 12 pH units deaf, are because of the relatively weak diffefenziemng the color changes are very imprecise and have an error of 1 to 2 pH units. Mischindi capacitors made up of only two components allow which has the chemical name 2-carboxy-4'-morpholinoazobenzene carries, has the desired advantages. The compound according to the invention can be carried out in analogy to known azo dyes (Organic Syntheses, Vol. 1, p. 374) are prepared by in a known manner o-aminobenzoic acid and either diazotized