Article No : a10_001

Ethanolamines and Propanolamines

MATTHIAS FRAUENKRON, BASF Aktiengesellschaft, Ludwigshafen, Germany

JOHANN-PETER MELDER, BASF Aktiengesellschaft, Ludwigshafen, Germany

GU¨ NTHER RUIDER, BASF Aktiengesellschaft, Ludwigshafen, Germany

ROLAND ROSSBACHER, BASF Aktiengesellschaft, Ludwigshafen, Germany

HARTMUT HO¨ KE, Weinheim, Germany

1. Introduction...... 405 4.3. Quality Specifications...... 417 2. Ethanolamines ...... 405 4.4. Uses ...... 417 2.1. Properties ...... 406 5. N-Alkylated Propanolamines and 2.1.1. Physical Properties ...... 406 3-Alkoxypropylamines ...... 418 2.1.2. Chemical Properties...... 406 5.1. Properties ...... 418 2.2. Production ...... 407 5.1.1. Physical Properties ...... 418 2.3. Quality Specifications...... 408 5.1.2. Chemical Properties...... 418 2.4. Uses ...... 408 5.2. Production ...... 418 2.5. Economic Aspects ...... 410 5.3. Quality Specifications...... 420 3. N-Alkylated Ethanolamines ...... 410 5.4. Uses and Economic Aspects ...... 420 3.1. Properties ...... 411 6. Storage and Transportation...... 421 3.1.1. Physical Properties ...... 411 7. Environmental Protection ...... 421 3.1.2. Chemical Properties...... 411 8. Toxicology and Occupational Health ..... 421 3.2. Production ...... 411 8.1. General Aspects...... 421 3.3. Quality Specifications...... 413 8.2. Ethanolamines ...... 424 3.4. Uses and Economic Aspects ...... 413 8.3. N-Alkyl- und N-Arylethanolamines ...... 425 4. Isopropanolamines...... 414 8.4. Propanolamines ...... 427 4.1. Properties ...... 414 References ...... 428 4.1.1. Physical Properties ...... 414 4.1.2. Chemical Properties...... 415 4.2. Production ...... 416

0 1. Introduction (DEA; 2,2 -iminodiethanol), and triethanola- mine [102-71-6](3) (TEA; 2,20,200-nitrilotrietha- Amino alcohols have been prepared industrially nol) can be regarded as derivatives of ammonia in since the 1930s. However, large-scale production which one, two, or three hydrogen atoms have started only after 1945, when alkoxylation with been replaced by a CH2CH2OH group. ethylene oxide and propylene oxide replaced the older chlorohydrin route. In industry, amino alcohols are usually designated as alkanola- mines. Ethanolamines (aminoethanols) and pro- panolamines (aminopropanols) are by far the most important compounds of this group. Both are used widely in the manufacture of surfactants and in gas purification [1–6].

2. Ethanolamines Ethanolamines were prepared in 1860 by WURTZ from ethylene chlorohydrin and aqueous Monoethanolamine [141-43-5](1) (MEA; 2- ammonia [7]. It was only toward the end of the aminoethanol), diethanolamine [111-42-2](2) 19th century that an ethanolamine mixture was

2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/14356007.a10_001 406 Ethanolamines and Propanolamines Vol. 13 separated into its mono-, di-, and triethanolamine 2.1.2. Chemical Properties components; this was achieved by fractional distillation. Because of their basic amino group and the hydro- Ethanolamines were not available commer- xyl group, ethanolamines have chemical properties cially before the early 1930s; they assumed resembling those of both amines and alcohols. They steadily growing commercial importance as in- form salts with acids, and the hydroxyl group termediates only after 1945, because of the large- permits ester formation. When mono- and dietha- scale production of ethylene oxide. Since the nolamine react with organic acids, salt formation mid-1970s, production of very pure, colorless always takes place in preference to ester formation. triethanolamine in industrial quantities has been With weak inorganic acids, e.g., H2SandCO2, possible [117–119]. All ethanolamines can now thermally unstable salts are formed in aqueous be obtained economically in very pure form. solution. This reaction of ethanolamines is the basis The most important uses of ethanolamines are for their application in the purification of acidic in the production of emulsifiers, detergent raw natural gas, refinery gas, and synthesis gas [1], [8]. materials, and textile chemicals; in gas purifica- In the absence of water, monoethanolamine and tion processes; in cement production, as milling diethanolamine react with CO2 to form carbamates: additives; and as building blocks for agrochemi- þ ! cals [120]. Monoethanolamine is an important 2 HOCH2CH2NHR CO2 HOCH2CH2CH2NRCOOH feedstock for the production of ethylenediamine RHNCH2CH2OH and ethylenimine. R ¼ HorCH2CH2OH Triethanolamine does not form a carbamate. 2.1. Properties By metal-catalyzed amination, the hydroxyl group of monoethanolamine can be replaced by 2.1.1. Physical Properties an amino group to form ethyleneamines such as ethylenediamine [107-15-3], diethylenetriamine Monoethanolamine and triethanolamine are vis- [111-40-0], piperazine [110-85-0], and ami- cous, colorless, clear, hygroscopic liquids at noethylethanolamine [111-41-1] [9], [10]: room temperature; diethanolamine is a crystal- line solid. All ethanolamines absorb water and carbon dioxide from the air and are infinitely miscible with water and alcohols. The freezing points of all ethanolamines can be lowered considerably by the addition of water. Some physical properties of ethanolamines are listed in Table 1.

Table 1. Physical properties of ethanolamines

a Compound Mr mp, Cbp Density r Heat of vaporization Specific heat cp Cubic expansion (101.3 kPa), C (20 C), g/cm3 (101.3 kPa), kJ/kg kJ kg1 K1 coefficient, K1

Monoethanolamine 61.08 10.53 170.3 1.0160 848.1 2.72 7.78104 Diethanolamine 105.14 28.0 268.5 1.0912 (30 C) 638.4 2.73 5.86104 Triethanolamine 149.19 21.6 336.1 1.1248 517.8 2.33 4.82104

Compound Viscosity 20 Surface tension Flash point,b Ignition temperature,c, Temperature class d nD (20 C), mPa s (20 C), N/m C C

Monoethanolamine 23.2 1.4544 0.049 94.5 410 T2 Diethanolamine 389 (30 C) 1.4747 0.0477 176 365 T2 Triethanolamine 930 1.4852 0.0484 192 325 T2 a According to DIN 53 217. b According to DIN 51 758. c According to DIN 51 794. d According to VDE 0165. Ethanolamines do not belong to any hazard class according to VbF (regulation governing flammable liquids). Vol. 13 Ethanolamines and Propanolamines 407

Considerable quantities of monoethanola- Reaction of triethanolamine with ethylene ox- mine are converted into ethylenimine (aziridine ide gives unstable alkaline quaternary compounds [151-56-4]) by adding sulfuric acid and cyclizing and the corresponding stable ethers [122]. For the hydrogensulfate with sodium hydroxide or by example, undistilled triethanolamine prepared using heterogeneous catalysts [121] (! Aziri- from mono- or diethanolamine always contains dines) [11], [12]: some triethanolamine monoglycol ether [16]. Mono- or diethanolamine can also be used as the amine component in aminoalkylation, the so- called Mannich reaction, which is very important in the biosynthesis of many alkaloids [17].

As primary and secondary amines, monoetha- nolamine and diethanolamine also react with acids or acid chlorides to form amides. The amine first reacts with the acid, e.g., stearic acid, to form a salt, which can be dehydrated to the amide by heating:

NH2CH2CH2OHþC17H35COOH !NH2CH2CH2OH C17H35COOH ! þ HOCH2CH2 NH CO C17H35COOH H2O Catalytic dehydrogenation of diethanolamine leads to iminodiacetic acid, an important build- When the ethanolamides of fatty acids are ing block for agrochemicals [120]. heated at fairly high temperature with removal -Nitrosamines can be formed by treating of water, oxazolines are formed: N diethanolamine or, under suitable conditions, triethanolamine with nitrous acid, nitrites, or oxides of nitrogen. Animal experiments have shown that N-nitrosamines are carcinogenic [18]. Formaldehyde reacts with monoethanolamine and diethanolamine to form hydroxymethyl compounds, which can be reduced to the N- methyl derivatives [14] (see Section 3.2). Monoethanolamine reacts with carbon disul- fide to form 2-mercaptothiazoline [ ] [15]: 96-53-7 Monoethanolamine and triethanolamine can form complexes with transition metal ions (e.g., chromium, copper, nickel, cobalt, and iron); some of these complexes are water-soluble [123–125]. The hydroxyl groups of ethanolamines can be replaced with chlorine by reaction with thionyl 2.2. Production chloride or phosphorus pentachloride. The chlor- oethylamines formed are hazardous because of their Ethanolamines are produced on an industrial skin toxicity. For example, tris(2-chloroethyl)amine scale exclusively by reaction of ethylene oxide has been used as a gas in warfare (N-lost). Bis(2- with excess ammonia, this excess being consid- chloroethyl)amine is obtained in good yield by erable in some cases [19]. reaction of diethanolamine with thionyl chloride: The reaction of ethylene oxide with ammonia takes place slowly and is accelerated by water. Anhydrous procedures employ a fixed-bed cata- lyst consisting of an organic ion-exchange resin or thermally more stable acidic inorganic clays or zeolites [20–23]. 408 Ethanolamines and Propanolamines Vol. 13

In all conventional processes, reaction takes place in the liquid phase, and the reactor pressure is usually sufficiently large to prevent vaporization of ammonia and ethylene oxide at the reaction temperature. In current procedures, ammonia con- centrations in water between 50 and 100%, pres- suresupto16MPa,reactiontemperaturesupto 150 C, and an excess up to 40 mol of ammonia per mole of ethylene oxide are used. The reaction is highly exothermic; the enthalpy of reaction is about 125 kJ per mole of ethylene oxide [24]. The following competing reactions occur: Figure 1. Product distribution of monoethanolamine (a), diethanolamine (b), triethanolamine (c), and glycol ethers of triethanolamine as a function of the molar ratio of ammonia to ethylene oxide (EO) in aqueous solution at 100 – 200 C

obtained by recycling monoethanolamine or diethanolamine to the reactor or by treating them with ethylene oxide in a separate unit [127], [128]. For safety reasons, ethylene oxide must be metered into the ammonia stream; in the reverse procedure, ammonia or amines may cause ethyl- ene oxide to undergo an explosive polymeriza- tion reaction. In all industrial processes, complete conversion to the three ethanolamines, without significant formation of byproducts, is achieved. Therefore, feedstock costs are independent of the type of Side reactions forming tetrakis(hydroxyethyl) production process. On the other hand, manufactur- ammonium hydroxide or any ethers are of no ing costs and, in particular, energy costs depend to a importance in the synthesis [126]. The kinetics of large extent on the product composition desired, these reactions have been studied [25]. plant design, and degree of thermal integration. All the reaction steps have about the same activation energy and show a roughly quadratic dependence of the reaction rate on the water 2.3. Quality Specifications content of the ammonia – water mixture used. Therefore, product composition depends solely Today, all ethanolamines are prepared with on the molar excess of ammonia and not on water > 99 % purity. Water, the two other ethanola- content, reaction temperature, or pressure [26]. mines, and a small amount of triethanolamine The product distribution as a function of the molar glycol ether are minor components; all other ratio of the reactants is shown in Figure 1 [27]. impurities are in the ppm range. Table 2 gives Unconsumed ammonia and water are separated specifications for commercial ethanolamines. from the products in a distillation line downstream Purity is determined by gas chromatography, of the reactor and are recycled. In large-scale and the residual water content by the Karl Fischer continuous single-line plants, the requirement for method. After pretreatment, the N-nitrosamine low energy use (i.e., operation with minimum content can also be determined by gas chroma- steam consumption) determines both the transport tography with a thermal analyzer. of heat from the reactor and the design of the thermally integrated distillation line (Fig. 2). Product distribution of the three ethanolamines 2.4. Uses can be controlled by appropriate choice of the ammonia : ethylene oxide ratio. A higher dietha- Surfactants. Ethanolamines are used wide- nolamine or triethanolamine content can also be ly as intermediates in the production of surfac- Vol. 13 Ethanolamines and Propanolamines 409

Figure 2. Flow sheet for the production of ethanolamines a) Aqueous ammonia tank; b) Tubular reactor; c) Ammonia and ammonia solution columns; d) Dehydration column; e) Vacuum fractionation columns tants, which have become commercially impor- amine soaps prepared from oleic acid, stearic tant as detergents, textile and leather chemicals, acid, lauric acid, or caprylic acid are constituents and emulsifiers [2–6]. Their uses range from of many toiletries and medicinal soaps. drilling and cutting oils to medicinal soaps and Ethanolamine soaps produced from fatty acids high-quality toiletries [28] (Fig. 3). are among the most industrially important emulsi- Properties of ethanolamine derivatives can be fiers. They are used in cosmetics [33], polishes, varied within wide limits by appropriate choice shoe creams, car care products, drilling and cutting of the ethanolamine, the acid component, and oils, and pharmaceutical ointments. Ethanolamine their ratio. Synergistic effects in complex emul- soaps combined with wax and resins are used as sifier systems can be obtained by simultaneous impregnating materials, protective coatings, and use of different combinations of amines and products for the care of textile and leather goods. acids. Ethanolamines, particularly triethanola- Ethanolamine soaps obtained from alkylaryl- mine, which had presented problems with regard sulfonic acids, preferably alkylbenzenesulfonic to color, are now produced in sufficient purity acids, or from alcohol sulfates are growing that no color problems arise when they are treated with acids or heated [29–32]. Ethanolamine-based surfactants can be formu- lated as weakly basic or neutral products and are therefore particularly well tolerated by the skin; this is especially true for triethanolamine soaps. Moreover, they are noncorrosive and can be used on virtually all textiles without damage. Ethanol-

Table 2. Specifications of commercial ethanolamines

Compound Purity, r (DIN 51 757), Color wt % g/cm3 (DIN-ISO 6271), APHA

Monoethanolamine > 99 1.016 (20 C) 10 Diethanolamine > 99 1.0912 (30 C) 20 Triethanolamine > 99 1.1248 (20 C) 30 Figure 3. Percentage consumption of ethanolamines accord- ing to use (1996) 410 Ethanolamines and Propanolamines Vol. 13 steadily in importance and dominate the market Cement Additives. Since the 1960s, aque- for household cleansers [34]. The use of linear ous solutions of triethanolamine and triethano- alkyl groups instead of branched chains in these lamine acetate have been used as milling addi- products has resulted in greater biodegradability. tives in cement production [41]. During grinding Fatty acid ethanolamides and products ob- of the clinker in ball mills, the small amount of tained by further ethoxylation have foam-stabi- triethanolamine added prevents agglomeration lizing ability and are therefore important addi- and cushioning of the grinding medium by satu- tives for detergents [35], [36]. Diethanolamides rating the surfaces of the freshly broken particles. obtained from coconut fatty acids and from oleic Like other milling additives (e.g., various gly- acid are used industrially. These amides were first cols), they reduce the power required for milling described in 1937 [37]. Liquid detergents are the clinker. The milling of virtually all high- based predominantly on triethanolamine [38–40]. quality portland cement involves milling addi- In the manufacture of leather, ethanolamine- tives. In addition to assisting the milling process, based chemicals are used for dressing, dyeing, triethanolamine also improves the flow proper- and finishing. For paints and coatings, ethanola- ties and setting behavior of the cement [42]. mines are employed both in production and in softeners and paint removers. 2.5. Economic Aspects Corrosion Inhibitors. Diethanolamine and triethanolamine are important components of Large-scale, economical production of ethano- corrosion inhibitors, particularly in coolants for lamines from ethylene oxide and ammonia in automobile engines, as well as in drilling and large, single-line plants has greatly promoted cutting oils. They are also employed as additives their use in many industrial sectors. In 1999, world ethanolamine capacity was about in lubricants. 6 When the corrosion inhibitor sodium nitrite 1.09 10 t/a (Table 3). About 50 % of world production is monoethanolamine; 30 – 35%, and diethanolamine are used together, N-nitro- samines may form. These nitrosamines are car- diethanolamine; and 15 – 20%, triethanolamine. cinogenic; therefore, sodium nitrite and dietha- nolamine or triethanolamine should not be used 3. N-Alkylated Ethanolamines simultaneously. N-Alkylated ethanolamines are amino alcohols Gas Purification. Large amounts of etha- that contain a secondary or tertiary nitrogen atom nolamines, principally diethanolamine, are used and one or two hydroxyl groups. in absorptive gas purification to remove weakly acidic components. For example, hydrogen sul- fide and carbon dioxide are removed from natural gas, refinery gas, and synthesis gas [1].

Intermediates. A substantial portion of the monoethanolamine is used as a starting material in the preparation of ethylenimine and ethylene- diamine. Ethylenimine is converted to polyethy- lenimine, an important chemical in paper tech- Numerous compounds with different proper- nology. Diethanolamine is used as a building ties and uses can be synthesized by varying the block for agrochemicals (e.g., Glyphosphate). alkyl group.

Table 3. Approximate ethanolamine capacity and production in 1998

Capacity, 103 t/a Estimated production,103 t/a

United States 569 456 Mexico 20 19 Western Europe 275 242 Southeast Asia 123 68 South America 30 16.8 Total 1017 759 Vol. 13 Ethanolamines and Propanolamines 411

3.1. Properties tinuous reaction of primary, secondary, or terti- ary amines with ethylene oxide [46–48]. For 3.1.1. Physical Properties safety reasons, ethylene oxide must be added to the amine, never vice versa (see Section 2.2). N-Alkylated ethanolamines are generally liquid Depending on the product involved, reaction and have a faint amine-like odor. They tend to temperature varies from 50 to 170 C and pres- discolor on prolonged storage, especially if ex- sure from 0.2 to 4 MPa. Water accelerates the posed to air, light, and temperatures above 40 C. reaction. This tendency to discoloration can be reduced Figure 4 shows a flow sheet for the batchwise substantially by the use of additives when puri- production of alkanolamines. The procedure is fying the products by distillation, or by pretreat- also suitable for the manufacture of isopropano- ing the crude products before distillation lamines (see Chap. 5); in this case, propylene [43–45]. N-Alkylated ethanolamines are partial- oxide is used instead of ethylene oxide. ly to readily soluble in alcohol, water, acetone, The oxygen-free reaction kettle (a) is filled glycols, glycerol, and glycol ethers. They are with the amine raw material from the stock only sparingly soluble or even insoluble in non- tank (b); water is added in an amount of 10 – polar solvents, e.g., aliphatic hydrocarbons. 60 %, based on the amine; and the kettle is 2-Dimethylaminoethanol [108-01-0](N,N-di- heated to a minimum temperature around methylethanolamine) and 2-diethylaminoetha- 50 C. Metering of ethylene oxide is then nol [100-37-8](N,N-diethylethanolamine) form begun, the feed rate depending on the removal azeotropes with water; N-methyldiethanolamine of heat and the operating pressure of the [105-59-9] does not form an azeotrope. All N- reaction kettle. alkylethanolamines are hygroscopic and also The optimum amount of ethylene oxide in absorb CO2 from air. Physical properties of relation to starting amine is determined by cost- typical compounds are listed in Table 4. effectiveness (byproducts, work-up costs). When addition of ethylene oxide is complete, the minimum reaction temperature is main- 3.1.2. Chemical Properties tained for some time to ensure that the product discharged from the reactor is free of ethylene The chemical properties of N-alkylated ethano- oxide. The reaction mixture is separated by lamines are very similar to those of unsubstituted fractional distillation. Unconverted amine and ethanolamines (see Section 2.1.2). They form water are removed as the first fraction and unstable salts with inorganic acids such as CO2 recycled to the subsequent batch. Pure alkano- and H2S [129–131]. Salts with organic acids give lamines are obtained by distillation under re- a neutral to weakly basic reaction. N-Alkylated duced pressure. ethanolamines also react with acids or acid deri- When primary amines are used, a mixture of vatives to give the corresponding esters. Impor- N-alkylethanolamines and N-alkyldiethanola- tant products are dimethylethanolamine acrylate mines is always formed: [2439-35-2] and diethylethanolamine acrylate [2426-54-2], which are used as intermediates in the synthesis of flocculating agents. Secondary N-alkylethanolamines also react with acids to form acid amides. The reaction of N-alkylethanolamines with ethylene oxide to give longer chain alkoxy derivatives gives low yields. The larger the excess of amine, the lower is the proportion of N-alkyldiethanolamines. If N-al- 3.2. Production kylethanolamines are desired, a continuous pro- cess is usually preferred for economic reasons. Industrially, N-alkylated ethanolamines are pro- Excess amine is distilled from the reaction prod- duced almost exclusively by batchwise or con- uct and recycled. 1 taoaie n Propanolamines and Ethanolamines 412 Table 4. Physical properties of N-alkylethanolamines

Compound CAS registry , C Densityd) Cubic Heat of Specific Specific Viscosity 20 Surface Flash Ignition Temperature Mr mp bp nD number (101.3 r, (20 C) expansion vaporization heat, kJ electrical (20 C), tension point, temperature, class kPa), C g/cm3 coefficient, kJ/kg kg1 K1 conductivity, mPa s (20 C), C C K1 W1 cm1 mN/m

4 6 Methylethanolamine [109-83-1] 75.11 ca. 3 159 0.939 – 7.8 10 564.4 2.55 3.33 10 13.0 1.4389 34.4 ca. 74 350 T2 0.942 (25 C) (22 C) 4 7 Methyldiethanolamine [105-59-9] 119.17 ca. 21 247 1.038 – 7.5 10 418.7 1.72 8.1 10 101 1.4694 40.9 137 265 T3 1.041 (20.3 C) 3 7 Dimethylethanolamine [108-01-0] 89.14 70a 134 0.887 1.35 10 454.3 2.30 3.8 10 3.85 1.4296 27.1 ca. 38 235 T3 (24.5 C) 3 3 Diethylethanolamine [100-37-8] 117.19 70a 162 0.883 – 1.07 10 383.9 2.42 1.1 10 5 1.4417 29.2 ca. 46 260 T3b 0.889 4 7 n-Butylethanolamine [111-75-1] 117.19 2.1 199 0.8917 7.6 10 397.7 2.45 2.9 10 19.7 1.4435 29.9 85 265 T3 (22 C) 4 7 n-Butyldiethanolamine [102-79-4] 161.25 45a ca. 270 0.970 7.7 10 329.5 2.26 6.3 10 75.9 1.462 33.9 130 260 T3 (22 C) 4 7 Dibutylethanolamine [102-81-8] 173.30 75a 222 – 234 0.860 8.1 10 277.6 2.32 9.5 10 7.4 1.4444 26.3 96 240 T3c (22 C) 4 8 Cyclohexylethanolamine [2842-38-8] 143.23 37.5 235 0.9797 7.6 10 327.2 2.45 2.0 10 317 1.4860 39.5 122 270 T3 (25.1 C) 4 4 Cyclohexyldiethanolamine [4500-29-2] 187.29 297 1.0339 6.6 10 319.0 2.30 6.6 10 815 1.4930 40.1 172 255 T3 4 7 1-(2-Hydroxyethyl)piperazine [103-76-4] 130.19 24 112 1.0592 7.5 10 411.1 2.00 6.1 10 1040 1.110 38.3 135 280 T3 (1.33 kPa) (40 C) 4 5 4-(2-Hydoxyethyl)morpholine [622-40-2] 131.18 1.5 – 2 224 1.0714 8.1 10 342.7 1.91 4.7 10 26.6 1.4783 40.8 113 205 T3 3 Hydroxyethylaniline [122-98-5] 137.18 30a 282 – 287 1.0954 1.14 10 439.2 2.08 102 1.5796 ca. 148 410 T2 4 Ethylhydroxyethylaniline [92-50-2] 165.24 37 270 1.030 7.3 10 2.14 86 139 335 T2 (40 C) N-Ethylethanolamine [110-73-6] 89.14 5.8 167 0.914 15.1 78 330 T2 n-Propylethanolamine [16369-21-4] 103.17 0.5 180 – 181 84 290 T3 Hydroxyethylpiperidine [3040-44-6] 129.21 16.7 198 – 203 0.973 20.9 1.4804 83 240 T3 (25 C) Dihydroxyethylaniline [120-07-0] 181.24 52 346 1.0161 1.27 200 380 T2 (200 C) (200 C) tert-Butylethanolamine [4620-70-6] 117.19 40 – 43 176 – 177 0.8576 5.9 81 345 T2 (60 C) (60 C) tert-Butyldiethanolamine [2160-93-2] 161.25 44 – 47 136 – 139 0.9556 21.0 148 300 T3 (1.6 kPa) (60 C) (60 C) a Pour point. o.13 Vol. b Hazard class AII (VbF). c Hazard class AIII (VbF). Vol. 13 Ethanolamines and Propanolamines 413

Figure 4. Flow sheet for the batch production of alkanolamines a) Reaction kettle; b) Ammonia tank; c) Vessel; d, e, f) Storage tanks

With secondary amines, only one product is Pure components are obtained from the crude formed: products by distillation. The reaction of epichlorohydrin with amines to give N-alkylethanolamines is of only minor commercial importance.

3.3. Quality Specifications Trialkylammonium Chlorides yield the cor- responding 2-hydroxyethylammonium chlor- Table 5 lists specifications of commercial pro- ides. One of the commercially most important ducts. Purity is almost always measured by gas salts is choline chloride [67-48-1](! Choline): chromatography.

3.4. Uses and Economic Aspects

-Alkylethanolamines are used mainly as inter- Choline chloride can also be prepared from N mediates, especially in the production of phar- trimethylamine and ethylene chlorohydrin, but maceuticals such as the local anesthetics pro- this route has no commercial significance. caine (diethylethanolamine 4-aminobenzoate Another common method of preparing N-alky- [ ]) and tetracaine (dimethylethanolamine lethanolamines is by -alkylation of ethanola- 59-46-1 N 4-butylaminobenzoate [ ]), crop protec- mines [49]. Methyl derivatives can also be 136-47-0 tion agents, and flocculants (dimethylethanola- obtained by reacting monoethanolamine or dietha- mine acrylate) [50]. They are also important in nolamine, or their homologues, with formaldehyde the preparation of chemicals for the paper and and then reducing the hydroxymethyl compound: leather industries. Use of N-alkylethanolamines in the production of plastics has risen substan- tially in recent years. Direct uses of N-alkylethanolamines, espe- cially methyldiethanolamine [51], include gas- purification methods for removing acidic gases 414 Ethanolamines and Propanolamines Vol. 13

Table 5. Specifications for commercial N-alkylethanolamines

Compound Boiling range 5 – 95 mLa, C Purityc (min.), % Water contentd, % Colore, APHA

Dimethylethanolamine 133.5 – 135.5 99.8 < 0.05 15 Diethylethanolamine 161.5 – 163 99.5 < 0.05 15 Methylethanolamine 158.5 – 160.0 99.0 < 0.1 10 Methyldiethanolamine 115.5 – 118 99.0 < 0.2 50 4-(2-Hydroxyethyl)morpholine 223 – 225 99.0 0.2 40 1-(2-Hydroxyethyl)piperazine 121 – 123 b 99.0 0.2 40 1-(2-Hydroxyethyl)piperidine 92 – 96 b 99.5 0.1 40 Hydroxyethylaniline 282 – 287 99.0 0.3 100 – 150 Ethylethanolamine 167 99.5 0.2 15 Dibutylethanolamine 226 – 228 99.0 0.2 40 Butylethanolamine 196 – 198 99.5 0.1 15 n-Propylethanolamine 180 – 181 99.5 < 0.1 10 Butyldiethanolamine 264 – 278 99.0 < 0.3 10 tert-Butylethanolamine 178 99.0 < 0.3 tert-Butyldiethanolamine 136 – 139 (1.6 kPa 99.0 < 0.3 a DIN 51 751. b DIN 53 406. c Determined by gas chromatography. d Determined by Karl Fischer method. e According to DIN-ISO 6271.

(CO2,H2S). Choline chloride is very important in important members of this class of compounds are the animal feedstuff industry (! Choline) [52]. the isopropanolamines, which are used as mix- World production was ca. 160 000 t/a in 1999. tures of various isomers. World capacity for iso- Annual worldwide demand for N-alkyletha- propanolamines is estimated at 40 000 t/a. nolamines (excluding choline chloride) ranges from 2 to 15 000 t, depending on the product and application. Some products in the category of more than 1000 t/a are N,N-dimethylethanola- mine, N,N-diethylethanolamine, 1-(2-hydro- xyethyl)piperazine derivatives, N-methyldietha- nolamine, and N-methylethanolamine.

4. Isopropanolamines

The propanolamines described here are propanol derivatives containing one amino group. They have the following general formulas:

3-Amino-1-propanol, H2NCH2CH2CH2OH, which is obtained not from propylene oxide but from hydrogenation of ethylene cyanohydrin, is discussed in Chapter 5.

4.1. Properties 2-Amino-1-propanols (8) and 1-amino-2-pro- panols (9) have been prepared industrially since 4.1.1. Physical Properties 1937 by reacting propylene oxide with the appro- priate amine. The products are mixtures which are Isopropanolamines are hygroscopic, virtually processed further; the isomer mixtures are not colorless substances with a slight amine-like usually separated on an industrial scale. The most odor. They are readily soluble in water, ethanol, Vol. 13 Ethanolamines and Propanolamines 415

Table 6. Physical properties of propanolamines

Compound CAS registry Mr fp, C bp r (20 C, Cubic Heat of Specific Viscosity, Refractive 3 number (101.3 g/cm expansion vaporization, heat, mPa s index nD kPa), C coefficient kJ/kg kJ kg-1 K-1 (40 – 100 C), K1

1-Amino-2-propanol (d,l) [78-96-6] 75.11 0.3 159.7 1.4466 (25 C) 2-Amino-1-propanol (d,l) [6168-72-5] 75.11 þ7.5 168.5 1.4481 (25 C) Monoisopropanolaminea 75.11 þ1.9 159 0.962 8.2104 604 2.73 30 1.4463 (20 C) (60 C) (45 C) Diisopropanolamineb [110-97-4] 133.19 þ38.9 244 0.9842 8.2104 375 2.49 58 1.4542 (60 C) (60 C) (60 C) Triisopropanolamineb [122-20-3] 191.27 ca. 55 291 0.9904 6.9104 309 2.47 141 1.4555 (60 C) (60 C) (60 C) a Commercial isomer mixture consisting of ca. 94 % 1-amino-2-propanol and 6 % 2-amino-1-propanol. b Commercial isomer mixture. glycol, and acetone but only slightly soluble in isopropanolamines differ only slightly from the hydrocarbons and diethyl ether. Monoisopropa- ethanolamines described in Section 2.1.2. nolamine is more soluble than monoethanola- Isopropanolamines react with acidic gases mine in organic solvents; it forms a miscibility (H2S, CO2) in aqueous solution to form salts, which gap with heptane and toluene. decompose to the starting materials when heated. Diisopropanolamine and triisopropanolamine This effect is utilized in the purification of natural undergo thermal decomposition above ca. 170 C gas and synthesis gas. The salts of strong acids, and can therefore be distilled only at reduced such as HCl or H2SO4, are crystalline compounds. pressure. The freezing points of diisopropanola- Diisopropanolamine sulfate eliminates water mine and triisopropanolamine can be greatly at elevated temperature to form 2,6-dimethyl- depressed by adding a small amount of water. morpholine sulfate [54]. All isopropanolamines have at least one The sodium salt of the sulfuric acid half-ester asymmetrically substituted carbon atom and thus of monoisopropanolamine undergoes cyclization can be optically active. The commercial products when heated, and propylenimine is formed [55]: are racemic mixtures. Important physical data are listed in Table 6 and safety data in Table 7.

4.1.2. Chemical Properties Fatty acids, such as stearic acid, react with isopropanolamine at room temperature to form The properties of amines and alcohols are com- neutral, waxlike isopropanolamine soaps. In reac- bined in isopropanolamines, and these com- tions above 140 C and with elimination of water, pounds exhibit typical reactions of both func- amides are formed preferentially, and minor tional groups; the amino group can be primary, amounts of fatty esters [56] are produced in a side secondary, or tertiary. In chemical behavior, reaction. Complete esterification can be effected

Table 7. Safety data for isopropranolamines [53]

Monoisopropanolamine Diisopropanolamine Triisopropanolamine

Flash point, C 71 135 160 Ignition temperature, C 335 290 275 Explosion limits, vol % 1.9–10.4 1.6 – 8.0 0.8 – 5.8 Vapor pressure, hPa 1.9 (20 C) 2.06 (100 C) 1 (100 C) 416 Ethanolamines and Propanolamines Vol. 13 by reaction with acyl chlorides in the presence of Compounds containing an active hydrogen pyridine [57]. The reaction of esters with isopro- atom undergo a Mannich reaction with formal- panolamines above 100 C gives amides [58]: dehyde and an isopropanolamine that has a pri- mary or secondary amino group.

ð Þ ¼ þ þ 1 2 CH3 2C O HCHO HNR R 1 2 !CH3Cð¼ OÞCH2CH2NR R þH2O

1 2 R ¼ H; C3H6OH; R ¼ C3H6OH

Diisopropanolamine reacts with nitrous acid or its salts to form N-nitrosamines. Isopropano- lamines react with optically active acids, such as When thionyl chloride is used as a reactant tartaric acid, to form diastereomeric pairs of and chloroform as the solvent, the hydroxyl salts; this enables the separation of isopropano- group can be exchanged for chlorine. Isopropa- lamines into their enantiomeric forms [63]. nolamine is converted to 2-chloropropylamine The use of triisopropanolamine as an esterifi- [59], which is obtained in good yield. cation catalyst has been suggested [64]. Isopropanolamine and diisopropanolamine react with epoxides to give mixed isopropanola- mines. The amino group is several times more 4.2. Production reactive than the hydroxyl group [60]. In the presence of suitable catalysts such as sodium Isopropanolamines are produced like ethanola- hydroxide or sodium alkoxides, the epoxide re- mines (see Section 3.2, Fig. 4), by treating pro- acts preferentially with the hydroxyl group to pylene oxide with NH3 in the liquid phase in a form polyethers [61]. Alkylating substances, continuous or batchwise procedure [65], [66]. e.g., alkyl halides or dimethyl sulfate, give N- The product is always a mixture of 1-amino-2- alkylated derivatives [62]. propanols and 2-amino-1-propanols, with the 1- Isopropanolamine can be converted to 1,2- amino isomers being the major component. diaminopropane by catalytic amination under pressure (! Amines, Aliphatic, Section 8.1.2.). Aldehydes and ketones react with the primary nitrogen atom of isopropanolamine to form a Schiff base.

CH3CHðOHÞCH2NH2þRCHO!CH3CHðOHÞCH2N

¼ CHRþH2O Industrially, the manner in which the propylene Formaldehyde reacts with isopropanolamines oxide ring is cleaved, and hence the isomer ratio of to form the corresponding hydroxymethyl com- isopropanolamines, cannot yet be controlled. pounds, which can be converted to the methyl Excess ammonia (about 2 – 20 mol per mole of derivatives by catalytic hydrogenation. propylene oxide) facilitates removal of the reaction heat (about 93 kJ/mol) and reduces the amount of polypropoxylated byproducts. This amount also depends on the relative reaction rates of propylene oxide with any amines present in the mixture. Reaction temperatures can vary from 50 to 150 C but are preferably around 100 C. The resulting pressure can be reduced by adding water (ca. 10 – 60 %). Water and hydroxyl-containing compounds such as alcohols, phenols, and alkano- lamines (autocatalysis) accelerate the reaction [67]. Vol. 13 Ethanolamines and Propanolamines 417

A continuous procedure is used for large- corresponding soaps which are used in lubricant scale production, e.g., of monoisopropanolamine additives, textile finishing, and coating paper and and diisopropanolamine [68], [69]. This proce- wood [70]. Salts of isopropanolamines with fatty dure is similar to that used to produce ethanola- acids are also used as ionic emulsifiers in emulsion mines (see Section 2.2). paints and as dispersants for pigments. Salts of The most important manufacturers of isopro- isopropanolamines with alkylarylsulfonic acids panolamines are Air Products, BASF, Bayer, are employed as degreasers and cleaning promo- Sasol, and ICI in Western Europe, and Dow ters [71]. The fatty acid amides of isopropanola- Chemical in the United States. mines and mixtures of these with esters are fre- quently used in the cosmetics industry as shampoo thickeners and foam regulators [72]. 4.3. Quality Specifications Isopropanolamines are effective corrosion in- hibitors in antifreezes [73] and cutting oils. Si- Because isopropanolamines are manufactured, multaneous use of nitrites should be avoided, sold, and used worldwide, the commercial pro- since carcinogenic nitrosamines may form under ducts differ only slightly in delivery specifica- certain circumstances. Isopropanolamines are tions. Typical specifications are listed in Table 8. important catalysts for urethane foams [74]. In Purity is usually determined by gas chroma- epoxy resin systems, they have proved useful tography. Depending on analytical conditions, additives to curing agents [75]. isomeric and enantiomeric forms of isopropano- Sulfur-containing isopropanolamine deriva- lamines exhibit different numbers of peaks, tives are used to extract metal ions, such as which can be identified by test analyses. Deri- mercury, gold, and platinum, from salt solutions vatives obtained by reaction with trifluoroacetic and wastewater [76]. anhydride can be analyzed more easily and anal- A very important use of aqueous diisopropa- ysis time can be reduced. nolamine solutions is as a gas wash in the Adip and Sulfinol processes. Here, CO2 and H2S, in particular, are washed out of natural gas, synthesis 4.4. Uses gas, or coke oven gas and, after desorption, can be obtained in some cases in their pure form [77]. Possible uses of isopropanolamines are similar to Monoisopropanolamine is employed exten- those of ethanolamines; as a rule, the isopropano- sively as an intermediate in the production of lamine derivatives exhibit better solubility in hy- 1,2-diaminopropane (! Amines, Aliphatic, Sec- drophobic media. For example, neutralization with tion 8.1.2.), while diisopropanolamine is used for fatty acids, such as stearic or lauric acid, gives the the synthesis of 2,6-dimethylmorpholine [54].

Table 8. Minimum quality requirements for commercial isopropanolamines (as of 2000)

Quality criterion Method Monoisopropano- Diisopropanolamine Diisopropanolamine Triisopropanolamine Triisopropanolamine

lamine containing 10 % H2O containing 15 % H2O Water content, DIN 51 max. 0.2 max. 0.2 10 1 max. 0.2 15 1 wt % 777 Purity, %* GC min. 99.0 min. 99.0 88 min. 99.0 84 Low boilers GC 0.3 0.3 0.3 0.3 0.3 (max.), %*

(excluding H2O) High boilers GC 0.5 0.5 0.5 0.5 0.5 (max.) %* Color (max.), DIN-ISO 20 50 50 100 100 APHA 6271 Acid consumption, mL of 1 N HCl 13.15 – 13.45 7.35 – 7.65 6.60 – 6.90 5.10 – 5.40 4.30 – 4.60 per gram Freezing point, C BS 523 : ca. 2 ca. 39 ca. 10 ca. 58 < -10 1964 * Determined as area under GC peak. 418 Ethanolamines and Propanolamines Vol. 13 5. N-Alkylated Propanolamines and mine does not form an azeotrope with water, but an 3-Alkoxypropylamines azeotrope is formed upon distillation of aqueous dimethylisopropanolamine and 3-methoxypropy- lamine. Physical properties of -alkylated isopro- N-Alkylated propanolamines can be divided into N panolamines are given in Table 9 and those of 3- N-alkylated 1-amino-2-propanols, 2-amino-1- propanols, and 3-amino-1-propanols. amino-1-propanols and 3-alkoxypropylamines in Table 10.

5.1.2. Chemical Properties

Because N-alkylated propanolamines contain hy- droxyl groups and basic nitrogen, they possess the properties of both amines and alcohols. They form salts with organic and inorganic acids [79]. The sulfuric acid esters of propanolamines can be cy- clized with sodium hydroxide to give propyleni- mines (see Section 4.1.2) [80]. Propanolamines with secondary amino groups form alkanolamides with fatty acids. Reaction of the amides with ethylene oxide gives water-soluble or easily dis- persible nonionic surfactants [81]. 1-Amino-2-pro- panols are chiral and can be separated into enan- tiomers by means of appropriate reagents [63], [82]. N-Alkylpropanolamines with tertiary amino groups can be converted by means of benzoyl chloride, without the assistance of a base, into the amino 2-Amino-1-propanols and 1-amino-2-propa- alcohol ester hydrochlorides; with thionyl chloride, nols are referred to industrially as isopropanola- they give 2-chloropropylammonium chlorides. mines (Chap. 4). -Alkylated isopropanolamines N The condensation of 3-amino-1-propanol are prepared by reacting propylene oxide with the with carbonyl compounds yields tetrahydro- corresponding amines, which yields almost ex- 1,3-oxazines [83], Schiff bases, or mixtures of clusively 1-amino-2-propanols [78]. Alkylated 2- both compounds. 3-Amino-1-propanol and 2- amino-1-propanols have no industrial importance hydroxy-3,3-dimethylbutyrolactone react almost and are not discussed in this chapter. quantitatively to give panthenol [84]. Alkoxypropylamines react analogously to pri- mary aliphatic amines. They form salts with 5.1. Properties inorganic or organic acids, and can be converted to acid amides, sulfonamides, urethanes, and 5.1.1. Physical Properties Schiff bases. They can be alkylated with formal- dehyde or formic acid to give dimethylamino With a few exceptions, -alkylated isopropanola- N compounds. 3-Methoxypropylamine catalyzes mines, 3-amino-1-propanols, and 3-alkoxypropy- the addition of hydrogen cyanide to vinyl esters lamines are colorless liquids at room temperature. to give 1-cyanoethyl esters [85]. 3-Methoxypro- Some of them, such as cyclohexylisopropanola- pylsulfanilylurea obtained from the 3-methoxy- mine, are crystalline solids. The compounds tend to propylammonium salt of -di(acetylsulfani- discolor on prolonged storage, especially if ex- N,N lyl)urea is an oral antidiabetic agent [86]. posed to light, air, and heat (> 40 C). They have an amine-like odor, and absorb water and carbon dioxide. They are soluble in water, alcohol, ace- 5.2. Production tone, glycol, glycerol, and glycol ethers, but only sparingly soluble in aliphatic or aromatic hydro- Industrially, N-alkylated isopropanolamines are carbons and diethyl ether. Methyldiisopropanola- prepared primarily from amines and propylene o.13 Vol. Table 9. Physical properties of N-alkylated isopropanolamines

Compound CAS registry , C (101.3 r, (20 C) Cubic Heat of Specific Specific Viscosity 20 Surface Flash Ignition Temperature Mr mp bp nD number kPa), C g/cm3 expansion vapori- heat, kJ electrical (20 C), tension point, C temperature, class coefficient, zation kg1 K1 conductivity, mPa s (20 C), C K1 kJ/kg W1 cm1 mN/m

7 Monomethyliso-propanolamine [16667-45-1] 89.14 12.5 149 0.9062 455.6 4.8 10 1.4340 28.7 58.7 305 T2 (22 C) 7 Methyldiisopropanolamine [4402-30-6] 147.22 32 226 0.945 329.3 1.4 10 47.3 1.4472 31.0 110.5 300 T3 (25 C) (22 C) * 4 6 Dimethylisopropanolamine [108-16-7] 103.17 85 125.8 0.849 – 7.0 10 393.6 2.45 2 10 1.5 1.4189 24.5 26 225 T3 0.852 (25 C) (25 C) Diethylisopropanolamine 131.22 157.5 – 0.8570 1.4265 159 Dibutylisopropanolamine 187.33 80* 229.1 0.8419 7.8 104 246.6 3.5 1.4361 205 Cyclohexylisopropanolamine 157.26 45.1 238 0.9365 329.3 2.47 9.0 104 11.5 1.4732 111 270 T3 (40 C) (60 C) (60 C) Cyclohexyldiisopropanolamine 215.34 2.0 Cyclooctylisopropanolamine 185.31 12.85* 275 0.953 7.6 104 234.5 2.24 5.1 104 665 1.4902 37.0 141 245 T3 (20 C) (20.3 C) Cyclooctyldiisopropanolamine 243.39 29.6 318 0.977 7.4 104 233.95 1.98 5.7 1011 10870 1.4890 38.0 176 245 T3 (20 C) (20.3 C) * Aminoethylisopropanolamine [123-84-2] 119.19 38 0.9868 145 1.4750 123 345 T2 1-(2-Hydroxypropyl) 144.22 17* 1.0108 423 1.4910 115 290 T3 piperazine

1,4-Bis(2-hydroxypropyl) 202.30 97 – 98 157 250 T3 419 Propanolamines and Ethanolamines piperazine 4-(2-Hydroxypropyl) 145.21 47* 218 1.0163 314.3 1.92 11.0 1.4642 34.5 92 215 T3 morpholine (12) * 4 4 N,N,N0N0-Tetrakis 292.43 þ11 190 1.03 6.7 10 2.297 2.4 10 45 1.478 35.1 201 285 T3 (2-hydroxypropyl) (133 Pa) (25 C) (50 C) (100 C) (25 C) ethylenediamine * Pour point. 420 Ethanolamines and Propanolamines Vol. 13

oxide according to the following reactions [67], [87]: Temperature class C Ignition temperature, C 57 Flash point 33.7 245 T3 C) 27 270 T3 20 D n C) 1.4159 (25 C) 1.460 – 1.462 98 – 100 385 T2 s N-Alkylated 1-amino-2-propanols are formed 0.9 (25 Viscosity, mPa predominantly [66], [88], [89]. The isomeric 2-

1 amino-1-propanols are obtained only as bypro- K ducts (0.2 – 5 %, depending on the nature of the 1 amino component). The reactions are carried out

Specific heat, kJ kg at 80 – 160 C and pressures up to 5 MPa, batchwise or continuously. A detailed descrip- tion can be found in Section 4.2. As in ethanol- amine production, the oxide must be added to the Heat of vaporization, kJ/kg 641422.9 2.71 36 (20 amine, not vice versa (see Section 2.2). The

1 crude reaction products are purified by continu-

4 3 ous or batchwise distillation. 10 10 3-Amino-1-propanol is obtained by hydroge- nating ethylene cyanohydrin. -Methylated 3- Cubic expansion coefficient, K N amino-1-propanols are prepared from 3-amino- 1-propanol and formaldehyde, with subsequent C)

3 hydrogenation of the adducts [90]. 3-Alkoxypro-

, (20 pylamines are prepared from acrylonitrile by r g/cm addition to alcohols and subsequent hydrogena- C tion [91]. bp (101.3 kPa), C 70 118 0.8729 1.2 70 237 0.8466 258.85 2.27 104 220 T3 70 134.7 0.861 , 32.7 162 – 163 0.882 – 0.885 5.3. Quality Specifications mp < < < Table 11 gives the specifications for commercial r M N-alkylated propanolamines and 3-alkoxypropy- ] 103.17 ] 89.14 ] 187.33 ] 103.17

] 75.11 11.5 189 0.98 – 0.99 8.3 lamines. Purity is generally determined by gas chromatography. [ 3179-63-3 number [ 5397-31-9 5.4. Uses and Economic Aspects

N-Alkylated propanolamines and 3-alkoxypro- Physical properties of 3-amino-1-propanols and 3-alkoxypropylamines pylamines are used mainly as intermediates, especially in the preparation of crop-protection agents and pharmaceuticals. 3-Alkoxypropyla- 3-Methoxy-propylamine [ 5332-73-0 3-Dimethyl-amino-1- propanol 3-Amino-1-propanol [ 156-87-6 Table 10. Compound CAS registry 3-Ethoxy-propylamine [ 6291-85-6 3-(2-Ethylhexyloxy)- propylamine Vol. 13 Ethanolamines and Propanolamines 421

Table 11. Specifications for commercial N-alkylated propanolamines and 3-alkoxypropylamines

Compound Purity, % r (20 C, DIN Boiling range Color Water content 51 757), g/cm3 5 – 95 mL (DIN 51 (DIN-ISO (DIN 51 777), % 751, DIN 53 406), C 6271), APHA

Monomethylisopropanolamine 98 0.906 146 – 152 50 Methyldiisopropanolamine 98 0.954 226 – 230 50 Dimethylisopropanolamine > 99.5 0.849 – 0.852 125 – 127 50 < 0.2 Aminoethylisopropanolamine 98 0.9868 232.5 – 235.5 20 N,N,N,N0-Tetrakis(2-hydroxy- propyl)ethylenediamine 99 1.009 – 1.013 20 3-Dimethylamino-1-propanol 99 0.882 – 0.885 162 – 163 3-Methoxypropylamine 99 0.871 – 0.873 117 – 119 20 < 0.2 3-Ethoxypropylamine 99 0.855 – 0.861 130 – 135 5 < 0.2 3-(2-Ethylhexyloxy)propylamine > 99 0.847 – 0.848 233 – 238 40 < 0.2 mines have considerable commercial importance closures to prevent absorption of water and car- in the preparation of dyes. N-Alkylated propa- bon dioxide. Zinc and other nonferrous metals nolamines and their derivatives have been em- are attacked by alkanolamines. For transporta- ployed, in the form of soaps, as lubricating oil tion, particular national regulations, such as additives, mold release agents [92], [93], textile GGVS in Germany, should be observed [102]. finishes, and coatings for paper and wood [94]. Rubber gloves and safety goggles should be The propanolammonium salts of alkylarylsulfo- worn when handling alkanolamines. In some nic acids are used as cleansing boosters and cases, especially with 3-alkoxypropylamines, a degreasing agents [95]. 3-Alkoxypropylamines full face shield and rubber clothing are advisable. are utilized as catalysts in the production of For safety data of alkanolamines, see the polyurethane foams and epoxy resins. sections on physical properties. 3-Alkoxypropylamines and N-alkylpropano- lamines are used as corrosion inhibitors and in the preparation of aqueous polymer solutions 7. Environmental Protection [96–100]. Anion exchangers can be prepared by reacting cellulose with dimethylisopropanola- Ammonia- or amine-containing off-gases from mine and epichlorohydrin [101]. alkanolamine production are either burned or World demand for N-alkylpropanolamines purified by acid scrubbing. Very low amine and 3-alkoxypropylamines is estimated at concentrations (103 ppm) can be determined 5000 t/a. More than 100 t/a of 3-methoxypropy- by modern analytical methods [103]. lamine and dimethylisopropanolamine are used. Wastewater from plant cleaning and acid scrubbing is treated in a sewage plant. When properly fed into a biological treatment plant, 6. Storage and Transportation alkanolamines are readily degraded by appropri- ate bacteria. Alkanolamines should be stored in stainless steel Spilled product should be removed with an containers with exclusion of air (O2,CO2) and absorptive material such as urea resin foam moisture, preferably under dry nitrogen. Storage (Hygromull) or peat dust, which is then incinerated. temperature should not exceed 40 C (50 C for ethanolamines). Steel tanks may be used if ab- sorption of iron (up to 10 ppm) is not important. 8. Toxicology and Occupational Alkanolamines turn yellow on prolonged stor- Health age, especially in the presence of oxygen. Depending on quality requirements and sen- 8.1. General Aspects sitivity of the products, steel, stainless steel, or polyethylene containers can be used for trans- All alkanolamines considered here are compiled portation. The containers must possess airtight in Table 12 along with available data on acute Table 12. Acute toxicological data and occupational exposure limits of alkanolaminesa 2 taoaie n Propanolamines and Ethanolamines 422 Acute toxicity Local irritation OELd, mL/m3 (mg/m3)

b c Substance [CAS no.] LD50, g/kg Ref. AIH (rat) Ref. Skin Eye Ref.

Ethanolamines Monoethanolamine 1.5 (o, rt) [116], >8 h (520 ppm) [116], 1 – 5 min: c c [116] MAK: 2 (5.1) [141-43-5] 1.2 – 2.5 (o, rt) [142], [142] TLV: 3 (7.5) 1.0 – 2.5 (d, rbt) [104] Diethylanolamine ca. 1.6 (o,rt) [116] >8 h (0.37 ppm) [116] se i; 15 min: n i se i [116] OEL(NL): (15I) sk [111-42-2] 1.7 – 2.8 (o, rt) [142] [142] TLV: 0.46 (2) sk 8.1 – 12.2 (d, rbt) [142], [104] 1471 ppm [106] m/sl i i [142] (vapor/aerosol, 2 h) Triethanolamine ca. 7.2 (o, rt) [116] >8 h (0.0047 ppm) [116], 4 h: n i n i/sl i [116] OEL (S): (5) [102-71-6] 8.4 – 11.3 (o, rt) [142][142] 20 h: i TLV: (5) >20 (d, rbt) [142] 2-(2-Aminoethoxy)ethanol ca. 3.4 (o, rt) [116], >8 h [116] c se i [116] n.e. [929-06-6] ca. 2.5 (o, rt) [159], 3 min: n i se i [159] ca. 1.3 (d, rbt) [181], 1h:sei >3 (d, rbt) [159] 4 h: c Alkylalkanolamines Monomethylethanolamine 1.39 – 2.34 (o, rt) [114], [116], >8 h [114], 3 min: i 4 h: c [132], [133], n.e., sk [132] [116] [116] [109-83-1] >2 (d, rbt) [116] se i [114], [116] ca. 1.9 (d, rbt) [132] ca. 1.25 (d, rbt) [133] Ethylethanolamine 1.1 (o, rt) [116] >7 h [116] c se i [116] n.e. [110-73-6] 1.48 (o, rt) [114] >8 h [114] 3.67 (d, rt) [116] n-Propylethanolamine ca. 1 (o, rt) [116] >8 h 3 min: sl i c n.e. 1 1 [16369-21-4] >0.4 (d, rbt.) [116] >2.9 mg L (4 h) [116] 1 h: c [116] n-Butylethanolamine ca. 1 (o, rt) [116] >8 h [116] 5 min: sei/c c [116] n.e. [111-75-1] Hydroxyethylaniline 2.73 (o, rt) [116] >8 h [116] n i se i [116] n.e. [122-98-5] 2.23 (o, rt) [140] i i [140] 0.06 (d, rbt) [140] 1 Dimethylethanolamine 2 (o, rt) [116], [134] LC50 ca. 6 mg L [132], se i/c se i/c [116], [135], n.e. (4 h)1 [136] [132] [108-01-0] 1.24 – 1.6 (o, rt) [135] 1.2 (d, rbt) [132] 30 min [116] 1.7 – 2.4 (d, rbt) [135] Diethylethanolamine 1.33 (o, rt) [116], [113] >1 h [116] 1 h: c c [116] MAK: 10 (50) sk o.13 Vol. [100-37-8] ca. 0.89 (d, gp) [113] TLV: 2 (9.6) Dibutylethanolamine ca. 0.6 (o, rt) [116] >7 h [116] >5 min: i se i [116] OEL (NL): (14) sk [102-81-8] 1.68 (d, rbt) TLV: 0.5 (3.5) sk N-Hydroxyethylpiperazine ca. 4.2 (o, rt) [116] >8 h [116] se i se i [116] n.e. [103-76-4] >5 (d, rbt) [166] N-Hydroxyethylmorpholine ca. 6.8 (o, rt) [116] >8 h [116] n i sl i [116] n.e. [ ] >16 (d, rbt) [141] n i n i [141] 622-40-2 13 Vol. N-Hydroxyethylpiperidine ca. 1.1 (o, rt) [116] >8 h [116] c (>3 min) c [116] n.e. [3040-44-6] 1 – 2 (d, rbt) [116] Methyldiethanolamine ca. 4.7 (o, rt) [116], [114] >8 h [116], [114] n i i [116], [114] n.e. [105-59-9] 1.95 (o, rt) [132] >5 (d, rbt) [132], [114] mi [132] n-Butyldiethanolamine 0.6 – 1.0 g/kg (o, rt) [116] >8 h [116] 15 min: sl i c n.e. [102-79-4] 20 h: c [116] Propanolamines and Isopropanolamines Monoisopropanolamine 4.26 (o, rt) [104] >8 h [116] 15 min: c c [116] n.e. [78-96-6] 2.7 (o, rt) [116] 4 h (1-% sol.): [138] [6168-72-5]e 1.64 (d, rbt) [105] n i 2.7 (o, rt) [116] m i se i [104], [105] Diisopropanolamine 6.72 (o, rt) [104] >8 h [116] se i se i [104] n.e. [110-97-4] 6 (o, rt) [116] 15 min: n i m i [116] 20 h: m i [116] Triisopropanolamine 6.5 (o, rt) [104] >8 h [116] se i [104], [105] n.e. [122-20-3] >10 (d, rbt) [105] 2 h (vapors, [137] 170 C) 4 (o, rt) [116] 15 min: n i se i 20 h: sl i m i [116] 3-Amino-1-propanol 2.83 (o, rt) [104], [105] >8 h se i [104], [105] n.e. [156-87-6] 1.3 (o, rt) 5 min: se i c >2 (d, rt) [116] LC50 > [116] 15 min: c [116] 16.4 mg L1 h1 Alkylated Propanolamines/Isopropanolamines 3-Dimethylamino-1-propanol 1.86 (o, rt) [116] 8 h [116] 15 min: se i/c se i/c [116] n.e. [3179-63-3] 423 Propanolamines and Ethanolamines Monomethylisopropanolamine 1 (o, rt) [116] >7 h [116] 15 min: c c [116] n.e. [16667-45-1] Dimethylisopropanolamine 1.36 (o, rt) [116] 10 min [116] 5 min: c c [116] n.e. [108-16-7] 1.89 (o, rt) [104] Methyldiisopropanolamine 2.15 – 3.83 (o, rt) [116] n.e. [4402-30-6] 3-Alkoxypropylamines 3-Methoxypropylamine 6.26 (o, rt, aq, sol., pH 7) [116] 1 h [116] 5 min: c c [116] n.e. [5332-73-0] 0.63 (o, rt) [139] 3-Ethoxypropylamine 1.1 – 1.5 (o, rt) [116] 1 h [116] 1 min: c c [116] n.e. [6291-85-6] 3-(2-Ethylhexyloxy)propylamine 0.85 (o, rt) [116] 8 h [116] 5 min: c c [116] n.e. [5397-31-9] 0.32 (o, rt) 0.36 (d, rbt) [104] a Symbols: o ¼ oral; d ¼ dermal; rt ¼ rat; rbt ¼ rabbit; gp ¼ guinea pig; i ¼ irritating (n ¼ not, sl ¼ slightly, m ¼ moderately, se ¼ severely); c ¼ corrosive. b AIH ¼ acute inhalation hazard: rats inhale an atmosphere enriched with vapor at 20 C (when not otherwise indicated, vapor-saturated air); time ¼ duration of exposure required to cause the first death. c The skin irritation for the specific time of exposure to the substance is given. d OEL ¼ occupational exposure limit: MAK (Germany, 1999), TLV (USA, 1997); NL ¼ The Netherlands, S ¼ Sweden; I ¼ inhalable (total aerosol), sk ¼ skin; n.e. ¼ not established. e Monoisopropanolamine (d,l)[78-96-6] contains 2-amino-1-propanol (d,l)[6168-72-3]. 424 Ethanolamines and Propanolamines Vol. 13 toxicity, irritant/caustic properties, and occupa- to form lecithin. DEA interferes with the MEA tional exposure limits. and phospholipid metabolism by replacing cho- Most prominent among the toxic effects of line. The accumulation of atypical phospholipids alkanolamines is their caustic/irritant action on appears to be the determinant in the systemic exposed skin and mucous membranes. This toxicity of DEA. TEA does not exhibit these effect decreases from primary to tertiary alka- properties. nolamines and is distinctly less pronounced or There is no evidence that MEA and DEA absent in their salts due to compensation of have a sensitizing potential [142], while for alkalinity. An increase in the number of hy- TEA, occasional cases of allergic contact droxyl groups further alleviates the irritant dermatitis were reported [108], [109]; however, properties. no sensitizing effect was found in guinea The low vapor pressure of these compounds at pigs [110], [164], [142]. room temperature explains the generally low The majority of genotoxicity tests, including acute inhalation hazard. However, vapors formed bacterial and mammalian in vitro test systems, at elevated temperatures may irritate eyes and indicate the absence of mutagenic activity in respiratory tract. Aqueous solutions containing these ethanolamines [142]. 1 – 10 % of monoalkanolamines such as mono- ethanol- and monoisopropanolamine are still Monoethanolamine. Early inhalation stud- irritating to eyes and skin. In principal, this also ies with various animal species demonstrated that applies to the N-dialkanol derivatives, albeit to a the extreme irritancy of an MEA atmosphere to lesser degree. Available data suggest that alka- exposed skin and the respiratory tract resulted in nolamines can penetrate the skin. pronounced discomfort and behavioral depression In general, the acute toxicity of the tested already at concentrations of 5 – 15 ppm (ca. compounds is moderate to low and nonspecific; 12.5 – 38 mg/m3) [142]. Nonstop inhalation for it is probably dominated by local irritant effects about 3 – 6 weeks of 66 – 75 ppm MEA vapors owing to their alkalinity. In a few cases, acute or was lethal to guinea pigs and rats; 100 ppm was long-term systemic symptoms may involve lethal to dogs. The liver and the kidney were neuropharmacological effects that interact with identified as target organs at high doses [142]. acetylcholine synthesis and neurotransmitter Oral administration of 1.28 g kg1 d1 in the feed function or neurotoxicity as a consequence of to rats for 30 – 90 d was lethal, whereas a dose of disturbed neural membrane structure. 0.64 g kg1 d1 led to changes in the liver and The mutagenic potential of alkanolamines is kidney weights; a dose of 0.32 g kg1 d1 was very low. However, in the presence of nitrite or tolerated without any toxic effects [105], [142]. under other appropriate conditions, primary and MEA produced no signs of developmental secondary alkanolamines form nitroso com- toxicity in standard developmental toxicity tests pounds which may be mutagenic or carcinogen- when applied orally to pregnant rats [142], [143] ic. Existing regulatory limitations on the use of and dermally to pregnant rabbits [144]. This compounds need to be considered as well as refutes the putative increases in the incidence of work-place regulations. fetal malformations, unrelated to dose, in a pre- The skin-sensitizing potential of alkanola- vious nonstandard study [142]. mines is very low. Diethanolamine. All toxicity data for re- peated exposure suggest that DEA can be incor- 8.2. Ethanolamines porated in cell membranes and affects their sta- bility [142]. The liver and kidneys are the major The chemistry, biochemistry, and toxicity of target organs, but demyelinization of nerve fibers monoethanolamine (MEA), diethanolamine and anemia, presumably due to altered composi- (DEA), and triethanolamine (TEA) have com- tion of the erythrocyte membranes, is also possi- prehensively been reviewed [142]. MEA is a ble. Toxic effects were observed after continuous natural building block of a group of important inhalation of 25 ppm for 9 d or 6 ppm for membrane components, the phospholipids, and 13 weeks (5 d/week), which was lethal to some the precursor in the de-novo synthesis of choline of the exposed rats, and after a seven-week Vol. 13 Ethanolamines and Propanolamines 425 administration to rats of neutralized diethanola- the chronic, age-related nephropathy usually mine at a concentration of 4 mg/mL in drinking observed in this rat strain [112], [142], while water [107], [142]. Oral administration of 0.02 g there were no morphological effects in mice kg1 d1 to rats for 90 d was tolerated without under comparable conditions [150], [142]. No any signs of toxicity, whereas a dose of 0.09 g conclusions about apparently positive oncogenic kg1 caused an increase in liver and kidney findings can be drawn from another nonverifiable weights. A dose of 170 mg kg1 d1 was lethal lifelong feeding study in mice [111], [142]. [105], [142]. A subchronic no observed adverse A dermal carcinogenicity study in mice sug- effect level was established at a dose of 20 – gested a significant increase in the spontaneous 25 mg kg1 d1 for oral exposure in rats [145]. tumor rate of hepatocellular adenomas in the high- In two-year dermal carcinogenicity studies, dose male and female groups (2 and 1 g kg1 d1, increased incidence of liver tumors was observed respectively). However, because of an infection of in mice, but not in rats [146]. Follow-up studies in the animals with Helicobacter hepaticus, the study two transgenic mouse lines, which were expected could not be evaluated and was abandoned as being to exhibit enhanced sensitivity to carcinogenic inadequate [165]. There was no significant carci- substances, clearly failed to elicit any carcino- nogenicity in rats epicutaneously administered genic potential of DEA [147]. Furthermore, the TEA at doses from 30 to 250 mg kg1 d1 development of DEA-related neoplasia in mouse [165]. However, because of a marginally positive liver could reasonably be explained by a non- trend in the incidence of renal tubular adenomas in genotoxic mechanism expressed by disruption of males, the Peer Review concluded on ‘‘equivocal choline metabolism [148]. evidence’’ in male rats [165]. DEA was maternally toxic and fetotoxic (i.e., retarded ossification) at oral doses of 0.2 g kg1 2-(2-Aminoethoxy)ethanol (diglycolamine) d1 [142], [149], and at dermal doses of 1.5 and applied as 10 % ethanolic solution showed no 0.35 g kg1 d1 in rats and rabbits, respectively, skin-sensitizing activity in the Buehler test but failed to produce structural malformations in [159], [167]. The Ames test [143], [159] and a any test [142]. DNA repair assay in rat hepatocytes failed to indicate a genotoxic potential [159]. A cell trans- Triethanolamine has a low systemic toxic- formation study using mouse BALB/3T3 cells ity, mainly restricted to the kidney as target was also negative [159]. organ [112], [142]. In contrast to DEA it is readily eliminated via the urine without under- going appreciable metabolism. Extensive muta- 8.3. N-Alkyl- und N-Arylethanolamines genicity testing did not reveal a genotoxic effect [154], [154]. In subacute inhalation studies with Methylethanolamine was not mutagenic in rats and mice exposed to TEA aerosols over a the Ames test [169]. Continuous inhalation ex- 16-d period (0.125 – 2 g/m3, 6 h/d, 5 d per posure to 1.8 and 9.7 ppm (ca. 0.006 and 0.03 g week), only minimal to slight acute inflammation m3, respectively) for 90 d resulted in local of the submucosa of the larynx but no effects on irritation (inflammatory effects on the nasal epi- nasal or lung tissue were noted; this indicates a thelium), but no treatment-related systemically lack of severe irritation from TEA exposure toxic findings in rats and guinea pigs. In male [153], [153]. Oral administration of 0.08 g kg1 dogs, dose-related atrophic degenerations in the d1 to rats in the feed for 90 d was tolerated testes were noted under comparable test condi- without toxic effects. A dose of 0.17 g kg1 d1 tions [151]. After 32-d administration of 0.004, caused changes in the liver and kidney weights, 0.04, and 0.4 g kg1 d1 in the diet to rats, while 0.73 g kg1 d1 led to histopathological relative liver weights were increased in all dose changes in both organs and deaths [181], [105]. groups with slight hepatic vacuolization at the High doses of ca. 1.4 g kg1 d1 administered in two upper levels, and slight testicular edema and the drinking water for 14 d produced no signifi- atrophy in the high-dose male group [151]. There cant signs of intoxication in rats and mice [142]. was no evidence of embryotoxic and teratogenic Two-year exposure to doses above 0.5 g kg1 effects on fetuses after inhalation exposure to d1 in the drinking water led to an acceleration of 150 ppm (ca 0.47 g/m3) in pregnant rats [152]. 426 Ethanolamines and Propanolamines Vol. 13

Ethylethanolamine is reported to be nega- tem [136]. At 24 ppm (ca. 0.08 g/m3) over 13 tive in the Ames test [155]. After ingestion in weeks, no systemic toxicity was noted, and tran- drinking water for 30 d, mainly dose-related sient corneal opacity was observed as a local histopathological changes in the kidneys devel- adverse effect [136]. oped in rats, with diffuse edema in the tubular Following the administration of 0.2 – 0.3 g epithelia at about 0.023 g kg1 d1 and progres- kg1 d1 in drinking water for more than 100 sive degenerative lesions at higher doses; fur- weeks, no increase in tumor incidence was ob- thermore, counts of white and red blood cells served in mice in a special test model using two were enhanced [156]. After 90-d administration, mice strains infected with mammary-tumor pro- the above-mentioned effects appeared to be less virus [162]. pronounced at corresponding dosage [156]. There was no evidence of developmental ef- In a specially designed test, ethylethanola- fects on fetuses after inhalation exposure to ma- mine applied at an oral dose of about 0.18 g kg1 ternally toxic concentrations (up to 100 ppm or d1 during the implantation period (day 1 0.48 g/m3) during pregnancy of rats [135], [161]. through 6 of gestation), produced implantation losses of some 50 % in pregnant rats [157]. Diethylethanolamine is also a metabolite of the local anesthetic procaine and has some n-Propylethanolamine was nonmutagenic pharmacological activity (vasodilatation, de- in the Salmonella typh./E. coli reverse mutation pression of nerve conductivity). No skin sensiti- test [158]. zation was induced in guinea pigs [168], and no mutagenicity in Ames tests [143], [169]. Inhala- n-Butylethanolamine was nonmutagenic tion toxicity is associated with strong local irri- in the Salmonella typh./E. coli reverse mutation tation of the nasal region and extreme discomfort test [158]. of the exposed animals; no pathological changes of inner organs occurred in rats exposed to con- Hydroxyethylaniline was nonsensitizing in centrations of up to 76 ppm (0.37 g/m3) for 14 the guinea pig maximization test [143] and was weeks [170], [171]. Likewise, there were no mutagenic in a bacterial assay using only Salmo- significant treatment-related findings in rats that nella typh. TA 98 [143]. Methemoglobinemia received ca. 0.013 and 0.033 g kg1 d1 and developed in cats after oral and dermal exposure successively increased doses of up to 0.67 g (54.5 and 545 mg kg1, respectively), a known kg1 d1 in the diet for two years [172]. Marked effect of aromatic amines [116]. neurological action was observed in dogs at repeated dietary doses of ca. 0.04 g kg1 d1 Dimethylethanolamine occurs as interme- and above, expressed as tremor and head shaking diate in endogenous choline synthesis and followed by ataxia and convulsions at elevated therefore interferes with phospholipid and ace- doses [172]. There was no evidence of develop- tylcholine metabolism. It is said to have some mental effects on fetuses after inhalative expo- stimulatory effect on the CNS by influencing sure to maternally toxic concentrations (up to neurotransmitter activity [163]. No skin sensiti- 100 ppm or 0.48 g/m3) during pregnancy of rats zation was induced in guinea pigs [160]. A broad [173]. spectrum of various genotoxicity assays, includ- ing bacteria [135], [169], mammalian cells [135], Dibutylethanolamine. Five-week adminis- [161] and an in-vivo micronucleus test in mice tration of neutralized dibutylethanolamine in [135], [161] gave no evidence of mutagenic drinking water in doses of 0.43, 0.20, and 0.13 g potential. kg1 d1 (male rats) and 0.33, 0.24, and 0.14 g Inhalation toxicity is associated with strong kg1 d1 (female rats) produced no substance- local irritation in the nasal region and the eyes; no related, histopathological effects; the lowest dose pathological changes of inner organs occurred in was devoid of any macroscopic findings [115]. rats exposed to concentrations of 98 ppm (ca. Irritation of the eyes and nose was observed after 0.36 g/m3) for two weeks. Thymus atrophy was inhalative exposure of rats (70 ppm or ca. 0.5 g seen at 288 ppm (ca. 1 g/m3), but no histological kg1 d1, 5 d per week, 6 h/d). This exposure lesions of the central or peripheral nervous sys- was lethal to one of five animals and led to an Vol. 13 Ethanolamines and Propanolamines 427 increase in the relative liver and kidney weights effects were reported, but weight changes of the and to liver damage. A concentration of 22 ppm liver and kidney occurred at high dosage [181]. (ca. 0.16 g kg1 d1) for 6 h/d over a period of No increase in tumor incidences occurred in rats six months was tolerated by rats without any that received 1 % in the feed (ca. 0.67 g kg1 signs of toxicity [115]. d1) for 94 weeks. However, in combination with 0.3 % sodium nitrite in drinking water, endoge- Hydroxyethylpiperazine and Hydroxy- nously produced nitroso compounds induced ethylmorpholine. Hydroxyethylpiperazine tumors [182]. [175] and hydroxyethylmorpholine [176] were nonmutagenic in an Ames test. But the latter Diisopropanolamine applied as 2 % aque- substance is reported to exhibit some genotoxic ous solution induced no skin-allergic and photo- activity by inducing DNA damage and repair in allergic reactions in a repeated insult patch test rat liver cells and cell transformation in cultured with 25 volunteers [179]. One case report of mouse embryo fibroblasts [176]. contact allergy has been published [183]. Der- matological testing programs using 1 % diiso- N-Hydroxyethylpiperidine (2-piperidino- propanolamine in facial sunscreen resulted in ethanol) was not mutagenic in an Ames test with two positively responding subjects out of two Salmonella typh. TA100, TA98, and E. coli WP2 random collectives of 424 volunteers in total [177] and in a cytogenetic assay using Chinese [179]. Based on a nonverifiable test report, a hamster cells [178]. weakly allergic potential was concluded in guin- ea pigs [184]. The substance was nonmutagenic Methyldiethanolamine is reported to be in the Ames test and induced no chromosomal nonsensitizing in a guinea pig maximization test aberrations in rat lymphocytes [185], [186]. [174] and proved to be nonmutagenic in various When it was administered to rats at doses of genotoxicity assays, including bacterial [161], 0.1–3gkg1 d1 in the drinking water for [169] and mammalian cells and an in vivo micro- 2 weeks, no symptoms were observed up to 0.6 g nucleus test [161]. After prolonged dermal ad- kg1 d1. The dose of 3 g kg1 d1 was lethal to ministration to rats, no systemic effects were two out of five male animals; the prominent found up to the top dose of 0.75 g kg1 d1; but effects for this dose group included a significant local changes at the treated site, characterized as loss in body and organ weight, acute inflamma- acanthosis and hyperkeratosis, were induced at tion and degeneration of kidneys and urinary doses of 0.25 g kg1 d1 and higher. No patho- bladder, and general liver atrophy [138]. After logical changes were noted at 0.1 g kg1 d1 four weeks of dermal exposure to up to 0.75 g [174]. kg1 d1, no pathological changes were noted in rats, except for skin irritation at the treated site at n-Butyldiethanolamine was nonmutagenic 0.5 g kg1 d1 and higher [186]. No clinical and in the Salmonella typh./E. coli reverse mutation organotoxic findings, as well as no increase in test [158]. tumor incidences, were reported in rats that re- ceived 1 % in the feed (ca. 0.5 g kg1 d1) for 94 weeks. However, in combination with sodium 8.4. Propanolamines nitrite in drinking water, endogenously produced nitroso compounds induced tumors [187]. Monoisopropanolamine induced no skin- allergic and photoallergic reactions in 150 hu- Triisopropanolamine is reported to be non- mans tested in a repeated insult patch test [179]. sensitizing in humans when patch-tested as a Negative mutagenic results were obtained in 1.1 % additive in a cosmetic lotion [179] and as Ames tests using Salmonella and E. coli tester such in a guinea pig maximization test [184]. It strains [180], [169]. The ninefold inhalation of up was nonmutagenic in the Ames test [169] and to 0.24 g/m3 (5 d/week, 6 h/d) failed to produce failed to induce chromosomal aberrations in a clinical signs of intoxication or macroscopic mouse micronucleus assay [143]. When it was changes in rats and mice [179]. Likewise, after administered to rats at doses of 0.1 to 0.2 g kg1 90-d feeding of 0.14 to 2.2 g kg1 d1 to rats, no d1 in drinking water for two weeks, no effects 428 Ethanolamines and Propanolamines Vol. 13 were observed at 0.1 and 0.33 g kg1 d1, with 10 L. P. Somogyi: ‘‘CEH Product Review Ethylenea- minor, but noncharacteristic findings at the high- mines’’, Chemical Economics Handbook, SRI Interna- er doses [138]. No evidence of a fetotoxic and tional, Menlo Park 1996. teratogenic potential was found in the progeny 11 H. Kindler et al., Chem.-Ing.-Tech. 37 (1965) 400 – 402. 12 H. Wenker: ‘‘Preparation of Ethyleneimine from Etha- from pregnant rats exposed to oral doses reaching nolamine,’’ (1935) 2328. maternal toxicity [137], [143]. J. Am. Chem. Soc. 57 13 W. Seeliger, H. Hellmann et al., Angew. Chem. 78 (1966) 913 – 927; Angew. Chem. Int. Ed. Engl. 5 Propanolamine (3-amino-1-propanol) (1966) 875. showed no skin-sensitizing potential in an early 14 BASF, DE-OS 2 618 580, 1977 (H. Hoffmann, K. Mer- epicutaneous nonstandard test with guinea pigs kel, H. Toussaint, D. Voges). [188] and no mutagenic activity in the Ames test 15 L. Knorr, P. Rossler:€ ‘‘Zur Kenntnis des Ethanolamins,’’ [143], as well as in an SCE assay with CHO cells Ber. Dtsch. Chem. Ges. 36 (1903) 1281. 16 BASF, FR 2 307 902. 1976 (H. Bosche, H. Ludemann).€ [189]. In a screening test, oral treatment of rats and 1 1 17 H. A. Bruson, J. Am. Chem. Soc. 58 (1936) 1741–45. cats with about 0.78 g kg d in 4 and 5 % 18 H. Druckrey, R. Preussmann, S. Ivankovic, D. Schm€ahl, aqueous solutions for two weeks (10 applications) Z. Krebsforsch. 69 (1967) 103 – 201. caused no significant macroscopic and histologi- 19 BASF, DE-OS 1 768 335, 1972 (R. Dahlinger, W. cal abnormalities [188]. Goetze, G. Schulz, U. Sonksen).€ 20 Mo och Domsjo€ AB, US 3 697 598, 1972 (B. J. G. 3-Methoxypropylamine caused skin sensi- Weibull, L. U. F. Folke, S. O. Lindstrom). tization in the Buehler test (5 %in ethanol) [139]. 21 Nippon Shokubai, EP 0 652 207, 1994 (A. Moriya et al.). There was no evidence of mutagenic activity in 22 Texaco, US 4 438 281, 1984 (F. L. Johnson, Jr., the Ames test [139], [143], two unspecified as- 23 Texaco, EP 0 375 267, 1990 (N. J. Grice et al.). says, a UDS assay, and a micronucleus test [139]. 24 BASF, unpublished measurements. 25 Yukagaku 15 (1966) no. 5, 215 – 220. 3-(2-Ethylhexyloxy)propylamine was re- 26 G. Schulz, W. Goetze, P. Wolf: ‘‘Kinetische Untersu- ported to be nonmutagenic in the Ames test [19]. chungen zur Oxethylierung von NH3 in konz. w€assrigen Losungen,’’€ Chem.-Ing.-Tech. 40 (1968) no. 9/10, 446 – 448. 27 Oxirane Limited, GB 0 760 215, 1956 (A. J. Lowe References et al.). 28 W. Wirth: ‘‘Nichtionische Tenside: Bedeutung, Herstel- General References lungsverfahren, Eigenschaften und Einsatzmoglichkei-€ 1 A. L. Kohl, R. Nielsen: Gas Purification, 5th ed., Gulf ten,’’ Tenside Deterg. 5 (1975) 245 – 247. Publishing Co., Houston 1997. 29 BASF, DE-OS 2 810 135, (H. Bosche, H. Hammer, G. 2 K. Lindner: Tenside-Textilhilfsmittel-Waschrohstoffe, Jeschek). 2nd ed., vol. 1, Wissenschaftliche Verlagsgesellschaft, 30 Texaco, US 4 673 762, 1987 (J. H. Paslean et al.). 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