United States Patent (15) 3,668,255 Meuly et al. (45) June 6, 1972 54 PROCESS FOR ALKYLATION OF ALEPHATIC KETONES AND PRODUCT 3,114,772 12/1963 Lorette et al...... 260/586 72) Inventors: Walter C. Meuly, New Brunswick; Peter S. OTHER PUBLICATIONS Gradeff, Somerset, both of N.J. Babayan et al., “ Chemical Abstracts' Vol. 49, 10879d 73) (1954). Assignee: Rhodia Inc., New York, N.Y. Bosshard et al., " Helvetica Chimica Acta,' Vol. 42, Fasacu 22) Filed: Oct. 31, 1967 lus 7, pp. 2746-2750 (1959). (21) Appl. No.: 679,543 Primary Examiner-Daniel D. Horwitz Related U.S. Application Data Assistant Examiner-Norman Morgenstern Attorney-Janes & Chapman (63) Continuation-in-part of Ser. Nos. 241,036, Nov. 29, 1962, abandoned, and Ser. No. 502,585, Oct. 22, 1965, abandoned. (57) ABSTRACT A process is provided for the alkylation of aliphatic ketones (52) U.S. Cl...... 260/586R, 252/522, 260/593 R having an alpha hydrogen, substitution occurring on the car (51) Int. Cl...... C07c49/06, CO7 c 49/28, CO7 c 49/30 bon alpha to the carbonyl group, by use of solid alkali in the 58 Field of Search...... 2601586,593 presence of an organic amine and/or ammonia as a catalyst. 56) References Cited Alkenyl highly branched ketones having a pleasant odor also are provided, useful in the formulation of perfumes and per UNITED STATES PATENTS fume bases. 2,795,617 6/1957 . Kimel et al...... 260,593 7 Claims, No Drawings 3,668,255 2 PROCESS FORALKYLATION OF ALEPHATIC KETONES cessfully applied to ketones higher than acetone and when we AND PRODUCT repeated Nef's experiment by using methyl chloride instead of methyl iodide, or sodium hydroxide instead of potassium This application is a continuation-in-part of Ser. No. hydroxide, acetone did not undergo alkylation. 241,036, filed Nov. 29, 1962, and of Ser. No. 502,585, filed Oct. 22, 1965 both now abandoned, The second instance has been reported more recently in This invention relates to a process of general application for British Pat. No. 851,658 and German Pat. No. 1,112,731, for the alkylation of aliphatic ketones on an a-carbon atom hav the condensation of acetone with 1-chloro-3-methyl-2-butene ing a replaceable hydrogen, adjacent to the carbonyl group. in the presence of potassium hydroxide, which gave 6-methyl This invention also relates to highly branched aliphatic O 5-hepten-2-one. Kulesza et al. Zeszyty Nauk Politech Lodz., ketones made accessible for the first time by the process Chem. Spozywcza No. 10.21-6 (1966) Chem. Abs. 66 7985-6 described herein. (1967) reported that the yield of 2-methyl-2-hepten-6-one No simple satisfactory process is available for the direct al from acetone and 1-chloro-3-methyl-2-butene and sodium or kylation of aliphatic ketones and more generally, for the potassium, using this process of these patents, at 5' to 65°C. in synthesis of higher ketones from the lower members of the se 15 0.5 to 8 hours reaction time, was s 18 percent, and not ries. It is known, of course, that many aliphatic ketones may 40-50 percent as reported in the patents. We found that this be alkylated by the use of sodamide in liquid ammonia or such reaction also fails when applied to methyl ethyl ketone and reagents as metallic potassium and potassium tertiary butox cyclohexanone instead of acetone. Moreover, in the case of ide. For instance, methyl ethyl ketone has been prepared from acetone, the product obtained as described in British Pat. No. acetone by the use of sodamide in liquid ammonia, with the 20 851,658 is not pure, as indicated by the wide range in boiling very reactive methyl iodide, Fuson, Advanced Organic Chemis point and refractive indices of the several fractions obtained, try, New York, John Wiley & Sons (1950) p. 421. Similarly, as well as the discrepancy in refractive index with the refrac the reaction of cyclohexanone with allyl bromide, sodamide tive index of pure 6-methyl 5-hepten-2-one. This will be illus and liquid ammonia is described in Organic Syntheses, Collec trated further below. Another disadvantage is that, according tive Volume III, p. 44, to give 2-allyl-cyclohexanone. Certain 25 to the process of British Pat. No. 851,658, the more expensive cyclic ketones in the field of steroids have been successfully potassium hydroxide must be used, because sodium hydroxide reacted with potassium tertiary butoxide and methyl iodide, to is stated to give considerably inferior results. introduce angular methyl groups into the steroid nucleus, The foregoing summary demonstrates that, apart from the Fieser and Fieser, Advanced Organic Chemistry, Reinhold two instances of Nef and British Pat. No. 851,658, aliphatic (1961) p. 445. monoketones have not been successfully alkylated with alkyl The obvious disadvantage of the process described above halides, in the presence of an alkali hydroxide. with sodamide resides in the use of a reagent which is not con In the process of the instant invention, alkylation of venient for large scale operation, because it forms explosive aliphatic monoketones is conveniently conducted with sodium mixtures, on standing, and in the necessity of using large quan or potassium hydroxide in solid form in the presence of an or tities of liquid ammonia. Potassium tertiary butoxide obviates 35 ganic amine or ammonia, wherein the amino nitrogen or am the use of liquid ammonia but metallic potassium is a monia is not a part of nor attached to an aromatic system. hazardous reagent, which requires many special precautions Thus, organic amine bases, in their free state or in the form of and manifestly would constitute a problem on a large-scale derivatives such as their salts, organic hydroxy amines, or operation. amino acids; and amine-forming and ammonia-forming com Simple methods for the alkylation of ketones on the carbon 40 pounds which in the presence of alkali form amines or am atom adjacent to the carbonyl group, without the use of soda monia, can be used. Aromatic amines, such as aniline, mide or the condensing agents based on or derived from dimethylaniline, or heterocyclic nitrogen compounds having metallic sodium and potassium as mentioned above, are an aromatic character, such as pyridine and collidine, are not available only when the ketone contains a second activating 45 effective in this process. group. Two instances have been reported with ketones con The alkylation proceeds in accordance with the following taining an aromatic group. Crossley in U.S. Pat. No. reaction: 2,644,843, successfully alkylated benzyl methyl ketone with R R3 an alkyl halide and potassium hydroxide. Essentially under the d Solid NaOH or KOF same conditions, Schultz J. Am. Chem. Soc. 75 1072 (1953) 50 RX -- CH-CO-C-R --> | Amine base or ammonia alkylated desoxybenzoin. The success of these two experi R2 R5 ments is obviously due to the presence of at least one aromatic R1 R3 group, which is known to activate the hydrogen on the ad (KCl) jacent methylene group. R-G-co- -R4 -- (NaCl) -- H2O The alkylation of acetylacetone and ethylaceto acetate with 55 aqueous potassium hydroxide, in the presence of a quaternary R2. R5 ammonium compound as a catalyst, reported by Babayan et where R is hydrogen, alkyl having from one to about 12 car al. Zhur Obshschei Khim 24 1887 (1954); C.A. 49 10879 bon atoms, or alkenyl having from two to about 12 carbon (1955) is another instance of alkylation of a ketone in which atoms, allyl, propargyl, or cyclohexyl or a benzyl alkyl or alke the hydrogen on the methylene group is activated by two ad 60 nyl having from one to about 18 carbon atoms, preferably one jacent carbonyl groups. In fact, the o-hydrogen is so labile that to about eight carbon atoms; and R1 and Ror R and R can be a catalyst is not needed in this reaction; Brandstrom, Acta taken together to form a ring including the CO group to yield Chim. Scand. 13 607 (1959) reported better yields than the corresponding cyclopentanone or cyclohexanone deriva Babayan et al. were able to obtain with ethylacetoacetate, tlves, using alcoholic solution of sodium hydroxide, and no catalyst. 65 When the starting ketone contains at least one active In the case of aliphatic monoketones, however, alkylation hydrogen on each o-carbon atom, a mixture of two isomeric has not been successfully conducted, except with the con alkylated ketones is usually obtained, as exemplified thus for densing agents mentioned above, sodium and potassium metal methyl ethyl ketone: alcoholates, and sodamide, under strictly anhydrous condi tions. There are only two exceptions, to our knowledge. One 70 RX-CH-CO-CEI-CII - R CH-CO-CII-CH instance was reported by Nef in Annalen 310,318 (1900) who CH-CO-CfI(R) CII alkylated acetone with potassium hydroxide and methyl iodide, at 100- 140 C., and obtained a mixture of mono-, di in mixture , tri-, tetra-, and pentasubstituted products. The reaction, however, has no general application since it has not been suc- 75 productWhenever is a normal,the ketone straight-chain is a methyl product, ketone, if the the condensa reaction 3,668,255 3 4. tion takes place at the methyl group. If it takes place at an Among the ketones that may be alkylated according to the alkyl group containing two or more carbon atoms, the reac process of the present invention there may be mentioned alkyl tion product is an iso or branched-chain product as shown by ketones, for instance, acetone, methyl ethyl ketone, diethyl Example 33 below. ketone, methyl propyl ketone, methyl isopropyl ketone, If the ketone has the formula methyl isobutyl ketone, ethyl butyl ketone, methyl tertiary butyl ketone, propyl isopropyl ketone, methyl amyl ketone, methyl isoamylketone, methylhexyl ketone, olefinic ketones, exemplified by mesityl oxide, allyl acetone, methylheptenone, R IR alpha- and beta-ionone, alicyclic ketones, for instance, in which R, R2, Ra and R, have the same meaning as above O cyclopentanone and alkyl derivatives thereof, cyclohexanone and alkyl derivatives thereof, methyl cyclohexanone, and cycloheptanone, camphor. R Surprisingly, it has been discovered that the alkylation of –éH ketones proceeds in the presence of catalytic quantities of the k 15 nitrogen compound in accordance with the present invention. On the other hand, in the presence of one-hundredth mole of is different from catalyst or less, the condensation proceeds rapidly and results R in a high yield of the desired alkylated ketone. -bit 20 The organic amine catalysts that have given good results in R accordance with the present invention are primary, secondary and tertiary amines having from one to about 60 carbon a mixture of atoms, and are exemplified by the following: straight chain monosubstitution products is obtained. Thus, the process of and branched chain saturated and unsaturated aliphatic the present invention usually provides mixtures of two 25 amines and their salts, such as monomethylamine (anhydrous isomers, which, if desired, may be separated by fractional or in water solution); monomethylamine hydrochloride, glu distillation. Thus, the process of the present invention makes cosamine, mono-ethyl-, propyl-, -butyl-, -amyl-, -hexyl-, -hexe available many ketones which were otherwise inaccessible, or nyl-, -heptyl-, -octyl-, -nonyl-, -decyl-, -dodecyl-, -oleyl- and - accessible only by indirect routes, involving several steps. stearyl-amines; di-methyl-, -ethyl-, -propyl-, -allyl-, -isopropyl It is also possible to substitute more than one active a 30 , -butyl-, -isobutyl-, -tert-butyl-, -benzyl-, -pentenyl-, -hexyl-, - hydrogen per molecule, and reaction may occur at both posi heptyl-, -octyl-, -nonyl-, -dodecyl-, -stearyl-, -oleyl-, -behenyl-, tions adjacent to the carbonyl group. The polyalkylated and -myristyl-amines; tri-methyl-, -ethyl-, -propyl-, isopropyl-, products may be separated by fractional distillation, if desired. -butyl-, -isobutyl-, sec-butyl-, -tert-butyl-, -amyl-, -isoamyl-, - The ketones provided by this process that have not previ tert-amyl-, -hexyl-, -isohexyl, -isooctyl-, -dodecyl-, -stearyl ously been known are defined by the formula: 35 and-oleyl-amines; mixed di and trialkyl and alkenyl amines, the alkyl and alkenyl groups being selected from any of the above, such as dimethyl ethylamine, diethylbutyl amine, hex R. i. enyl dihexyl amine, diisopropyl butyl amine, diethyl propyl H- g- (-CH-CH= G-CH-R amine, methyl diisopropyl amine, dimethyl dodecylamine, R2 O R. CH3 40 benzyl dimethylamine; polyamines such as methylene diamine In this formula, dihydrochloride, ethylene diamine, propylene diamine, and 1. R is selected from the group consisting of hydrogen, alkyl hexamethylene tetramine; ion-exchange resins, such as Am and alkenyl groups (both straight and branched chain) having berlite IR-4B, Ionac A-260, and Ionac A-300, which contain from two to about five carbon atoms. 45 aliphatic polyamine groups; saturated and unsaturated hetero 2. R, R, R and R are selected from the group consisting cyclic amines, exemplified by piperidine, pyrrole, piperazine, of hydrogen and alkyl groups (both straight and branched dimethyl glyoxime, methyl nitro imidazole, and morpholine; chain) having from one to about five carbon atoms, and al saturated and unsaturated cycloaliphatic amines, exemplified kylene groups having from two to three carbon atoms wherein by cyclohexyl amine, cyclohexenyl amine, cyclopropyl amine, two of R and R or R and R are taken together to form a ring 50 cyclopropenyl amine, and cycloheptyl amine; alkylolamines, including the exemplified by monoethanolamine, diethanolamine, and triethanolamine; hydrazine NH-NH; and amino acids, exem C plified by glycine, taurine, and ethylene diamine tetraacetic s acid. Also useful are amine derivatives that hydrolyze in the 55 presence of sodium or potassium hydroxide to form an organic group, the total number of carbon atoms in R, R2, Ra and R. amine having from one to about 18 carbon atoms, such as or being from two to about six, and if R, R and Ra are hydrogen, ganic amides, for example dimethyl formamide, dimethyl R has at least three carbon atoms. acetamide, sulfanilamide, diamyl acetamide; and substituted These ketones have a pleasant odor, unlike their lower ureas such as dimethyl urea. homologues, and are useful in perfumes and in perfume manu 60 Also effective are ammonia and inorganic ammonium salts facture. that are hydrolyzed to form ammonia in the presence of sodi Among the organic halides useful in carrying out the alkyla um or potassium hydroxide, such as ammonium chloride, am tion according to the present invention there may be men monium bromide, ammonium nitrate, ammonium carbonate, tioned alkyl halides, such as methyl chloride, methyl bromide, ammonium sulfate, ammonium phosphate, and ammonium ethyl chloride, ethyl bromide, propyl chloride, isopropyl bro 65 ferric oxalate, ammonium cobalt sulfate and hydroxyl amine mide, hexyl bromide, alkenyl halides, such as 1-chloro-3-bu hydrochloride. tene, citronellyl chloride, allylic halides, exemplified by allyl The amine can be a solid, liquid, or gas; gaseous amines are chloride, allyl bromide, methallyl chloride, crotyl chloride, 1 effective, because they are soluble in the reaction mixture. chloro-3-methyl-2-butene, 1-bromo-3-methyl-2-butene, 1 When monoalkylation of the ketones is desired, optimum chloro-2,3-dimethyl-2-butene, 1,3-dichloro-2-butene, 1 70 results are obtained by using the ketone and the alkylating chloro-5,5,7,7-tetramethyl-2-octene, geranyl chloride, gera agent in the molar ratio of between about 1:1 and about 20:1. nyl bromide, benzyl bromide and chloride may be used. The alkali hydroxide in this case is in the proportion between Acetylenic halides, execimplified by propargyl chloride, pro 1 and 2 moles. The optimum proportion is about 1.1 to about pargyl bromide, cyclic halides, exemplified by cyclohexyl 1.5 moles with respect to the halide. The amount of the chloride, also may be used. 75 nitrogen compound used as catalyst, may be as low as about 3,668,255 5 6 0.003 mole and as high as about 1 mole per mole of alkylating agent. The preferred amount of the catalyst is between about (H, isogli, 0.001 and about 0.1 mole. CH-C=CII-CH-CH-C-CII In the case of poly-alkylation, the proportion of organic ha lide is increased, up to about 5 molar equivalents per mole of 5 (H, if p ketone, and the alkali metal hydroxide is increased cor CHa-C=CH-CH-CH-C-CH-CH respondingly, in proportion to the organic halide. Absolute purity of the starting materials is not essential. A GH, -Hi ketone recovered from a prior alkylation may be used. The re CH3-C=CH-CH-CH-C-CH agents need not be dry, since water is a by-product in the reac- 10 tion. (H, g In carrying out the process of the present invention, many CH3 -C=CH-CH-CH-C-CH variations are possible. The order of addition of the reactants (I, isoft, o (I, is not critical, but no reaction takes place until the catalyst is CHa-C=CH-CH-Cli-C-Clas-C-C, added. For instance, the reactants may be mixed simultane- 15 ously, or the organic halide and solid alkali metal hydroxide Chis (ii o can be added to the ketone and the catalyst, over a period of CE- e-et-et-...-e-c s time, if a gradual reaction is desired. Mixtures of sodium and potassium hydroxide may be used, but sodium hydroxide, - éti, which is less expensive, give very satisfactory results. CH3 CFI. O The particle size of the solid sodium or potassium hydroxide CH3- (=CH-CH- H- 6– CH-CH-CH-CH is not important, because in the presence of the catalyst reac tion takes place even with coarse solid alkali hydroxide. How CH3 CH3 O ever, the sodium or potassium hydroxide must be in solid C.H.-C=CHCH-CH-(-CH, form; aqueous or alcoholic sodium or potassium hydroxide 25 solution is ineffective in the process. CH3 O Auxiliary solvents or diluents are not necessary. Inert sol C6H11- C=CHCH-CH-C-C-H. vents, such as petroleum ether, benzene, and ethyl ether, have CH3 pH, no effect on the reaction; hydroxylated solvents, such as al cohols and glycols are harmful, inasmuch as they cause CH-C-CHCH-C-E-C-H hydrolysis of the organic halide to the corresponding alcohol, and thus decrease the condensation of the organic halide with the ketone. CE CH, O The operation is conveniently conducted at ordinary at 35 mospheric pressure, except in those cases where the organic CH3 CH, O CH halide has a boiling point below room temperature. In such cases, the reaction, for instance with methyl chloride, is car CH-C-CHCH-C-C-CH ried out in a pressure vessel. &H, CH, The reaction is usually mildly exothermic, and the tempera- 40 ture of reaction is not critical. Thus the operation may be con CH3 CH O CH ducted over a wide temperature range, between about -20°C. CH-C=CHCH- (-(-CH&H and about 150° C. Many alkylations which proceed satisfac CH, ÖH, torily at room temperature, are faster at 50 to 80° C. The reaction time may be as short as 1 hour, but if the reaction is 45 CH C2H5O CH kept at room temperature, 1 day or longer may be required. CH-C=CHCH-C-C-CH, bII In the process in accordance with this invention, it is &H, preferable but not essential to have anhydrous conditions. Up to about 0.5 mole of water per mole of halide can be present; CH3 CH5 O CE such water dissolves in the ketone. 50 CH-)-CHCH- --CHCH-off The progress of the reaction may be conveniently followed by the decrease in the content of organic halide. One method CH3 of working up the reaction mixture consists of filtering off the CH3 CH3 O CH3 solid halide salt and the excess of alkali metal hydroxide. The CH3-C-CHCH-C-C-CH2CH2CH/ resulting filter cake usually retains almost all the water of 55 d EI Yo H reaction, so that the excess ketone in the organic filtrate can be re-used as is, without purification. Another suitable method CH3 CH3 of working up the reaction mixture consists of adding enough water to the reaction mass to dissolve the inorganic salts, and separating the organic products in the organic layer. The 60 desired product may then be isolated either by steam distilla CH CH tion or by fractional distillation in purely conventional CH-)-CHCH- -C-CH3 ale. The following are exemplary ketones falling within the in bH, & vention: 65 CH-C-OHCH-CH-C-C-CH,CH3 CH3 O CH CH-C=CH-CH-CH-C-CH-CH-CH c?, YoH, 70 CH3 CH3 CH3. g CH CH-b=CHCH-CH-C-CHic?, CH-C=CH-CH-CH-C-CH-CH YoH, CH3 CH O CH 75 CH-C-CHCH-CH-C-CH, CIL-C=CH-CH-CH-C-CH-C-CH &H, is 3,668,255

(H, Gil 3 Cl CH-C=CHCH-CH- -CEI5 CH-C-Cicil- II––c{ C3H, O (i. O CH (H, 5 U cII-C-CHCH-CH-i-CH. CII, CII (II O CII--Circii-,(i. (all 1-c-off C chi-c-clicil-gir-C-Cit, (i.i. s (: 3 CsIt O gil, (ii, (I, CH CH, Cis-(-CHCH--C-off CH-C-CHCH-CH-C-Citic?, 15 < s Cl (H & Yoit, (i. sil p Its c?, CH cis-e-cell--c-cis-cil, (H, CH, Cl ('ll CH3-CecCHCH-CH-C-CH 20 dCI. 3 CH3| O|| CH3 CI-C=CHCII-C-C-C, CH ... 3 CH In order to illustrate more fullyy the scopep of the presentp in CI-C=CHCH-g-g-cit, vention, the following Examples are set forth, it being un CH, O 25 derstood, however, that this description is presented by way of CH13 CH CH 3. clarification only, and not as limiting the scope of the inven tion. CH-C=CHCH-i-g-g H EXAMPLE I CH, O CH - - ...... ii.3 V V is 30 A pressure bottle was charged with 58 grams acetone ( 1.0 gil, (H, CH mole), 180 grams methyl iodide (1.28 moles), two grams H-C=CHCI-C-C-CII2C triethanolamine (TEA) and 183 grams potassium hydroxide CH3 2 | | 2 N flakes (92 percent KOH) (3.0 moles). After sealing the bottle, CH3 O CH it was kept at 100° C. for 7 hours. After cooling, the reaction CH3 CH 35 mixture was washed with acetone. Titrimetric analysisy of the l, / solid indicated that 0.92 mole of KOH had reacted to form CH3-C=CHCII-CII-C-CH| N KCl. Quantitative V.P.C. (vapor(vapor pphase chromatography)atography anal CH O CH3 ysis of the liquid filtrate indicated the formation of 0.46 mole cí, C3 methylated acetone, composed of over 90 percent methyl 40 ethyl ketone, mixed with some 3 percent methyl isopropyl ?i?, CIH. ketone and 2 percent diethyl ketone. The yield was 46 percent cis-e-clicit-?-s-clic Ery from the acetone and 35 percent based on methyl CEI () CII OCCle. EXAMPLE 2 ('El 45 Example 1 was repeated in every respect except for the (--(' clieil-it- --(I, omission of the 2 grams triethanolamine. These are essentially ( ' () the conditions described by J. U. Nef, loc. cit. The consump cí. Ye: tion of KOH was reduced to 0.22 mole and the yield of methyl

( 3 3 13 CIIvill3 50 ethyl ketone was 12 percent of theory based on methyl iodide. ci-e-clicit-Gil (-oil-clict EXAMPLES3 to 10 CII5 O CII Shown below in Table I are Examples illustrating the alkyla CH - tion of lower ketones, that is, acetone and MEK, methyl ethyl 3 55 ketone, with lower alkyl halides, that is, chlorides, bromides, CH-C-CICH-II––cli; iodides using flake KOH and flake NaOH as condensing CH, O agents, conducted both in the presence and in the absence of &II the amine catalyst of the invention. The results of Examples 1 / N and 2 are included in the Table. Molar propproportions of halide, CHs CII ------60 ketone, alkali hydroxide, and catalyst are given. The yield is CH CH CH3 stated in percent based on the halide used. The data in Table I l, l / demonstrate that the yields of alkylated products were negligi CII-C=CIICH-C-C-C2CHCHN ble when the amine was omitted, and that goodygood yields were ob CII, O CII tained in the presence of the amine. TABLE I Alkali metal hydroxide Example No. Haide Ketone (fiake) Catalyst Conditions Yield percent of theory i------1. 8 SE;3 - 0.77- - - - astone.0------83; SE06----- triethanolamine.------100.- - - - 0- - 7- - hours------: Ey. ethyl ketone. 8.------1.0 CH3Cl 7.0 MEK 4.4/KOH 0.05 TEA------30°C., 20 hours----- 63 2 methyl isopropyl Estone:diethyl ketone, 4------1.0 CHI 0.77 MEK----- 3.0/KOH None------100° C., 7 hours----- T methyl isopropyl etOne. 5------1.0 CHCl 2.0 acetone. 2.0NaOH 0.01 TEA------25° C., 3 days - 45%. MEK.

6------1.0 CH3Cl ... -----do.------. 20/NaOH. None.....------do------Nil, Some residue formed.

8328 10O39 03 ?)4 3,668,255 9 O TABLE I - Continued Tr" ------Alkali metal Example No. Halide Ketona (flake)Egilde Catalyst Conditions Yield percent of theory 7------1.0 CEBr 3.) MEK 1.5/NaOil ().0(dimethyl forulanide 25' ('., 3 days, die 12%, it stylic, litty by(till hydrolysis). lethylun in liberated (. 1 hours. k(toil. 8.------1.0 CHSBr 3.0 MEK------1.5/NaOH Norty----...... ity, 1% unethyl soc. butyl 9------10n-Chi Br 3.0MEK...... 1.5/NaOH 0.025 dimethylamine-HCl 68 C.,., 4 1hours. day.------20%ketone. methyl-2-pentyl (dimethylamine is ketone and somer. 10------1.0n-CHBr 3.0MEK----- 1.5/NaOH None.------liberated as free base). do------N.

EXAMPLE 11 EXAMPLE 1.4 into a pressure bottle were charged 98 grams (1.0 mole) 15 A pressure bottle was charged with 19.6 grams cyclohex cyclohexanone, 51 grams (1.0 mole) methyl chloride, 58 anone (0.20 mole), 31 grams methyl chloride (0.60 mole), grams (1.4 moles) caustic soda flakes 96 percent pure, and 1.8 31.5 grams caustic soda flakes (0.75 mole), 0.9 gram grams triethanolamine (0.012 mole). The bottle was sealed, triethanolamine (0.006 mole) and 3 grams sodium iodide was kept at 25-30 C. for 2 days with occasional shaking, (0.02 mole). The sealed bottle was tumbled at 25°-30°C. for 2 after which time the caustic soda flakes had largely disin 2O days, after which time 11 grams (0.22 mole) unreacted methyl tegrated and were replaced by sandy sodium chloride. The in chloride was blown off. The inorganic solids were dissolved in organic solids were removed by dissolving in water and the 110 grams water; the dried organic layer, 24 grams, gave, on dried colorless organic layer weighing 104 grams was analyzed distillation, 22 grams of product and a residue of only 1 - 1.5 by V.P.C. It contained 50 mole percent of 2-methyl cyclohex grams. The molar composition of the colorless distillate by anone identified by comparison with the V.P.C. of a genuine 25 V.P.C. was sample. The yield of 2-methyl cyclohexanone from CHCl was about 50 percent. Cyclohexanone 6% 2-methyl cyclohexanone 30% EXAMPLE 12 Dimethyl cyclohexanone 43% 3O 2,2,6-trimethyl cyclohexanone 18% An experiment run under identical conditions, without 2,2,6,6-tetramethyl cyclohexanone 2% triethanolamine, yielded only a trace of 2-methyl cyclohex anoe. The yield of the valuable mono-, di and trimethyl cyclohex anones amounted to 86 percent theory based on cyclohex EXAMPLE 13 35 anone used, and 78 percent of methyl chloride used. A pressure bottle was charged with 49 grams (0.50 mole) The condensation of allyl-, benzyl- and propargyl halides cyclohexanone, 92 grams (1.8 moles) methyl chloride, 84 with ketones is described in Examples 15 to 35, which for grams (2.0 moles) caustic soda flakes (97 percent), and 3.0 brevity are listed partly in tabular form. The reaction condi grams (0.02 mole) triethanolamine. After shaking, the sealed tions throughout are generally similar to those of Example 15. bottle for 2 days at 25-30 C, 25 percent of the methyl 40 chloride was recovered. The organic layer, after dissolving the inorganic solids with water, was distilled to free it from any EXAMPLE 1.5 high boiling residue, V.P.C. of the distillate and comparison into a reaction flask provided with a stirrer were charged with authentic samples inclicated the following molar com 174 grams (3.0 moles) acetone, 76 grams (1.0 mole) allyl phiti in: 45 chloride, 2 grams (0.025 mole) dimethylamine hydrochloride and 63 grams (l.5 moles) caustic 96 percent soda flakes. Cyclohexanone 6% 2-methyl cyclohexanone % After stirring at 25-35 C. for 24 hours, the inorganic Dimethyl cyclohexanone 26% precipitate was filtered off, and the cake washed with acetone. 2,2,6-trimethyl cyclohexanone 33% The organic layer was distilled to separate it into acetone, 2,2,6,6-tetramethyl cyclohexanone 9% 50 crude allyl acetone and high boiling residue. V.P.C. analysis and comparison with an authentic sample of allyl acetone in The yield of the valuable mono-, di- and trimethyl cyclohex dicated a yield of 29 percent pure allyl acetone. anones was 60 percent based on cyclohexanone consumed, Similar results were obtained when the reaction was carried and 42 percent based on methylchloride consumed. out at reflux temperature (54°C.) for 6 hours. TABLE II Alkali metal hydroxide Yield of theory Example No. Haide Ketone (flake) Catalyst Conditions based on halide 16------1.0 allyl chloride.-- 3.0 acetone.---- i.5 NaOH 0.025 dimethylamine-HC--- 25-30 C., 1 day--- 29% alyl acetone. 16------do------do------15 NaOH None.------do------6%allyl acetone. 17------1.0 allyl bromide. 4.0 MEK------1.5 NaOH.-- 0.04 dimethylamine-HCl---- 25°C., 1 day------22% 1-methyl-l-allyl acetone, 18------1.01,3-dichloro-2- 3.0 MEK------1.5 NaOH 0.03 dimethylamine-HCl------do------22%and 3-methyl-6-chloro some 1-heptene-5-one. butene. 5-heptene-2-one. 19. ------1.01-chloro-5,5,7, 3.0 acetone.-- 1.5 NaOH... 0.04 dimethylamine-HCl-...-- 30° C., 6 hours.---- 50% 88,10,10-tetramethyl 7-tetramethyl-2- 5-undecene-2-one b.1 Octene. . E. 115° C.; Nd20: 20------1.0 geranyl 6.0 MEK------1.5 NaOH--- 0.05 dimethylamine-HCl---. 25°C., 2 days----- 34%.1. 3,6,10-trimethyl bromide. 5,9-undecendiene-2-one b.l 3 mm.; 110° C.; ND20:

3.0 acetone-...-- 15 NaOH 0.015 dimethylamine-HCl--- 35° C., 5 hours.--- 30%1.4684. benzyl acetone. ------w ando...------do------1.5 NaOHKOH 0.015None.------do------dimethylamine-HCl -- 30°C., 5 hours--- 0.5%22% benzyl benzyl acetone. acetone. 1.5 KOH None------do------4% benzyl acetone. 25------do------4.0 MEK------1.5 NaOH 0.06 dimethylamine-HCl ---- 25 C., 1 day------42% 3-methyl-4-phenyl butane-2-one; b. 112 Imm.; 26------1.0 propargyl .." 6.0 acetone 1.5 NaOH 0.03 dimethylamine-HCl ---- 30° C., 1 day------24%112° propargyl C.; ND30:1.5094. acetone. bromide.

3,668,255 TTH-m-m-m-m-m-m-m-m-lullTABLE III Mole Yield,of theoryE. Example NaOH. meshlegs. No. (flake) Mole ketone Mole catalyst Conditions ylheptenone

Ammonia and derivatives 1.5 6.0 acetone.------0.10hydrolysis). ammonium chloride (formed NH3 by 25° C., 1 day...... 46

: s S3 ------89. SEE Eii ------...... 25 C., 2 days - 4. 1.5v . . 4.0 MEK------0.10 hydroxylamineurea (formed NH3 HCl by --...------.hydrolysis) 30°25° C.,C., 35 Sy:days. : Primary amines --- 1.5 6.0 acetone.------0.10 monoethanolamine.------. 30 c. 1 day 1.5 6.0 acetone.------0.10 butyl amine------30° 5. E: ... 1.5 4.0 MEK------0.10 propylenediamine-1,2------30 C., 2 days----- 37 Secondary amines and amides 13 3.0 acetone.------0.006 dimethylamine, 25% water solution.----- 30°C., 7 hours 1.25 4.0 acetone.----- 0.003 dimethylamine hyáchioide - - - - 30° 5. 1 day------: 1.5 5.05.0 acetone, benzene. 0.03 dimethylamine hydrochloride. ------... 30 C, 1 day------42 , is 6.) (to: ().03 timethyltinlne hydrochloride, (),50 water 30 C., 1 day.... . 47 .. . 5.0. aceton-...... 0.0250.10 diethylamine-...------dimethylainine, 1.0 Nal-...... 30.35 C., 43 hours---hours. . . . 4858 2. () 4.0 MEK -- 0.10 diethanolamine. -- 30 C., 3 days----- 44 1.5 4.0 MEK 0.10 piperazine.------25 C., 2 days----- 50 1, 5 4.0 MEK 0.08 dimethylacetamide ------30 C, 6 days----- 50 1.5 6.0 acetone.------1.0 dimethylformamide ------35 C., 3 hours---- 53 1.5 ----- do---- ... 0.06 dimethylformamide, 0.50 HO- -- 30 C., 6 hours---- 52 1.5 ----- do.-- .-- 0.06 dimethylformamide1------30 C, 1 day------45 1.5 4.0 acetone------Amberlite IR-4B------25 C., 3 days----- 40

Tertiary amines 1.5 5.0 acetone.------0.10 triethylamine------...------30 C., 3 hours----- 46 i. 5 4.0 MEK------0.10 triethanolamine.------30 C., 3 days----- 54 1.5 4.0 MEK------0.10 benzyldimethylamine.------30°C., 2 days. ---. 54 Amino acids 1. 4.0 ic ston(-- 0.08 glycine.------25 C., 3 days----- 34

!. Formed dimethylamine,. . by. . . tohydrolysis. ---- ().05 taurino---...------do------40

EXAMPLES 60 to 68 marketed in the perfume industry. The novel substance Examples 60 to 68 illustrate the alkylation of several prepared according to this instant invention, 3,6,10-trimethyl ketones other than acetone, with 1-chloro-3-methyl-2-butene, 40 5,9-undecenediene-2-one has a much richer floral-type odor in accordance with the process of this invention. The process than geranyl acetone and ethyl geranyl acetone, so that it has used for their preparation was as set forth in Example 27, sub greater ability to impart a fresh note in many florals, such as stituting the ketone in Table IV in the same molar proportion. rose, lily of the valley, lavender and gardenia. It is better suited The ketones listed in Table IV are new compounds. than geranyl acetone and ethylgeranyl acetone for reinforcing The new ketones are of value in the perfume industry, both 45 odor and for blending with a variety of floral compositions. in the pure form, as well as the isomeric mixtures which are One of its main advantages is that it does not have the sharp obtained when the starting ketone has more than one active and pungent characteristics of geranyl acetone and thus may hydrogen and is unsymmetrical. Careful fractionation permits be used in larger amounts in perfuming compositions to im isolation of the isomers in pure form. part roundness, lasting power and stability. Another ad The novel ketones of Table IV are also useful in the manu 50 vantage is that the compound of this application has a more facture of many novel perfume materials of the terpenoid stable odor than geranyl acetone, that is, the odor lasts longer type, that is, in the preparation of compounds of the linalool, and is not affected by aging. geraniol, citral and ionone types, as described in our copend ing application Ser. No. 300,907, now U.S. Pat. No. Determination of Odor Lasting Power of 3,6,10-trimethyl-5,9- 3,296,080. 55 undecenediene-2-one For instance, 4,7-dimethyl-6-octen-3-one prepared in Ex ample 60 may be reacted with vinyl magnesium bromide to The test for odor stability was conducted as follows: give a tertiary carbinol of the linalool type, which has valuable Two strips of blotting paper of 4 inch width were immersed odor properties. Further, the tertiary carbinols may be ox for equal length of time into (A) geranyl acetone and (B) idized to the aldehyde, the latter condenxed with acetone to 3,6,10-trimethyl-5,9-undecenediene-2-one. The strips were give a pseudoionone, which is then cyclized to the correspond allowed to stand at room temperature and the odor was evalu ing ionone, as described in our copending application Ser. No. ated and compared every day for a period of 7 days. The strip 300,907, now U.S. Pat. No. 3,296,080. The ionones obtained (A) exhibited a change in odor within 24 hours to a less from the novel ketones of the instant invention are of out pleasant and weaker odor. After 4 days, the odor has disap standing value in perfumery, 65 peared. The test strip (B) showed practically no odor change. In Examples 64 and 65, R and Ra in the general formula. The odor of (B) after 7 days was slightly weaker, but was still given in Table IV are linked, form a cyclic structure with the pleasant and essentially unchanged. Thus, 3,6,10-trimethyl carbonyl group in the ring, that is, the cyclopentanone and 5,9-undecenediene-2-one exhibits vastly superior stability and cyclohexanone ring. ------... -- lasting power than geranyl acetone. 3,6,10-Trimethyl-5.9-undecenediene-2-one, prepared--- in 70 Example 69 below illustrates the application of 3,6,10 Example 20, is a new compound. The substance exhibits out trimethyl-5,9-undecenediene-2-one in the perfume industry. standing value, as compared with geranyl acetone and ethyl geranyl acetone, the former being the trade name for 6, 10 EXAMPLE 69 dimethyl-5.9-hendecadien-2-one, and the latter being 6,10- 75 (Rose Bouquet) dimethyl-5,9-dodecadien-2-one. The latter two substances are The following ingredients were blended together:

83.31 1030 anry 3,668,255

Eijis' C SSat N if cCYf ; ; ; 10 parts 3,6,10-trimethyl-5,9. ii. 5 3. a SS ; ; ; undecenediene-one 1 part phenylacetaldehyde to S 5 parts citronellyl acetate s ; : : 19 parts geraniol 5 25 parts citronellol 40 parts phenylethyl alcohol ; i & :::: : 100 is a , i Se s EESea : 10 The resulting composition had a very pleasant rose bouquet kissE3 E:is a: Ote.Also 3-isopropyl-6-methyl-5-hepten-2-one of Example 63 asst ES5 is b EESE5 p roved of far greaterg value than the known 6-methyl-5-hepy p of tt to Zee ten-2-one. The latter substance has a sharp, citrus-type note, & st 3 & S. S. 15 which limits its use to low-cost products and even then, only in ses small amounts. - 2. The novel substance 3-isopropyl-6-methyl-5-hepten-2-one S. g. 3; 33.33 & exhibits an entirely different character from 6-methyl-5-hep z is 5555 ten-2-one. It exhibits a lasting, soft, sweet, and floral character - - - - 20 which makes it a far superior blender for incorporation into a ; : ; , ; ; ; variety offloralf floral compositions.p In direct contrastrp with 6-methyl us.' ... ." : 2'2' : heptenone, the 3-isopropyl compound has a fresh outdoor, "- £ 3 2 sei: ; cooling' note. When allowed to evaporate on a test blotting 5 f f : a É paper, 3-isopropyl 6-methyl-5-hepten-2-one is free of the pun EE 25 gent, sharp, metallic and undesirable note which is detected in ES Ss. S. gegs & the case of 6-methylheptenone, under the same conditions. is A. A. A. A. AAAA. A A A AA AAAA a ; : : ; : : 3O Deterimination of Odor Lasting Power of 3-isopropyl-6- ; ; : methyl-5-hepten-2-one ; : : 2.- ; :; ; ;: The 3-isopropyl compound exhibits greatly improved last : ; ; ; : : : ing power over 6-methyl heptenone. The test was conducted ; : : 5 ; : : : by dipping test paper strips, for the same length of time, into : ; ; ; ; ; ; d 35 both products and comparing the time required for evapora ; ;:t ; g 52s : as tion at room temperature.p The 3-isopropylpropy 6-methviy hepp : ; ; ; ; ; tenone required a period of 4 hours for evaporation, while, in ; ; ; ; ; ; ; ; the case of 6-methylheptenone, the evaporation time was 30 s ; : : Ed 5555S. A minutes : a ia sas C. G.s 40 The isopropyl substitution- . . . product of this invention is su : ... Sg8 8. perior to and more suited than methyl heptenone for incor 2 3. e s poration into a variety of high quality soaps and other g as do atN. 3 cosmetics. It is valuable for muguet, verbena, lavender, is E 5 a chypre-fougere notes. g g Si 2 45. In view of the better odor characteristics, the isopropyl a E E : SEE compound may be used in perfume compositions in larger 5. É 2 5. amounts than methylheptenone, and may be used particularly 2. - bei () -- - - - in finer perfume compositions, where the pungent note of ; : fi; ; : is : methylheptenone cannot be tolerated. 2-5-3 :S s ; : iš 50 Example 70 below illustrates the application of 3-isopropyl I 5 I illf 6-methyl-5-heptene-2-one in the perfume industry. E. 3 is g-g-gir i EiEEi EXAMPLE 70 l s :g c c : 5555CN en 5.era 15 - 55 (Verbena Bouquet) , i.... Eigg,SS is S O-O fig5 5ESSSS II II iii. 60 5 parts 3-propyl-6-methyl-5-hepten-2- l, t rts y3, atis gigi.us?" 3 parts 6-methyl-5-hepten-2-one gig? E: 1012 parts citrallinalool : : ; ; ; ; ; 15 parts dipentene : ; ; a; ; ; ; 5; 9R- 65 .E.p Stoeneoalpha terpeneo is E 5.ii is ig8 5SS 8 388g5 5.8 The ingredients were blended together in any sequence. EE E SEE f s: The resulting composition exhibited an outstanding Verbena 4 CS CO o 55SC A SE 70 Bouquet odor. ; : : : ; ; ; ; ; The other novel compounds of this invention also exhibit ; : : : valuable properties in the perfume industry. a ; Example 71 below demonstrates the utility of 4,7-dimethyl res ; ; ; ; ; Aez,SS 6-octen-3-onep (Example 60) and 8-methyl-7-nonen-4-oney y 8 : : ; ; ; ; a U. 75 (Example 61), in the perfume industry. ?a I 3o y c CN& 2 arecoco eerto to COso

tim v. Y. - Yo 3,668,255 17 8 EXAMPLE 71 was filtered off, and the cake washed with acetone. The or ganic layer was distilled to separate it into acetone, crude allyl (Lavender Synthetic) acetone and high boiling residue. V.P.C. analysis and com parison with an authentic sample of allyl acetone indicated a The following ingredients were blended together: 5 yield of 29 percent pure allyl acetone. 100 parts linally acetate Similar results were obtained when the reaction was carried 75 partsp linaloolinally a out at reflux temperature (54°C.) for 6 hours. 35 parts coumarin 150 parts 4,7-dimethyl-6-octen-3-one EXAMPLES 8.5 to 96 140 parts 8-methyl-7-nonen-4-one 10 Table VI below lists Examples 85 to 96 in which flake The composition had a very fresh true lavender character, NaOH was used as the condensing agent and the catalyst was Example 72 below illustrates the application of the mixture either an organic amine, or a nitrogen compound liberating an of 2,7-dimethyl-6-octen-3-one and 3,3,6-trimethyl-5-hepten-2 amine in situ, or an inorganic ammonium compound liberating -one (Example 62) in perfumery. 15 ammonia in situ. The alkylating agent was 1-chloro-3-methyl 2-butene. EXAMPLE 72 The foregoing Examples illustrate the utility of this instant - invention in providing a simple and inexpensive process for (Rosewood Oil Artificial) the alkylation of aliphatic monoketones and in providing 20 novel compounds which have great value in the perfume in dustry. Although many examples have been given, those E. SEE skilled in this art will readily visualize that many variations and 5 parts E. terpineol modifications of this instant invention are possible, without 10 parts Cedarwood Oil departing from the spirit of the invention, which is to be 75 parts linaool 25 limited only by the scope of the appended claims. Having regard to the foregoing disclosure, the following is claimed as the inventive and patentable embodiments thereof: The above ingredients were blended together. The resulting 1. A method for the alkylation in the position alpha to the composition had a very pleasant rosewood oil character. carbonyl group of a ketone having the formula: The condensation of allyl-, benzyl- and propargyl halides 30 with ketones and various amines is described in Examples 73 R R to 84, which for brevity are listed partly in tabular form. The Ci-CO-C-R reaction conditions throughout are generally similar to those R? Yr 5 of Example 73. TABLEW Alkali metal Example hydroxide No. Halide Ketone (fake) Amount and catalyst Conditions Ketone product 73------1.0 allyl chloride------3.0 acetone.--- 1.5 NaOH 0.025 tributylainine------25-30 C, 1 day.---- Allyl acetone. 7------do------do------15 NaOH 0.025 cyclohexylamine - 25-30 C, day----- Do. 75------1.0 allyl bromide.------4.0 MEK------1.5 NaOH 0.1 pyrrole------25°C., 1 day------1-methyl-l-ally acetone, and some 1-heptene-5-one. 76------1.0,3-dichloro-2-butene... 3.0 MEK------1.5 NaOH 0.05 coconut oil alkyl 25 C., 1 day------3-methyl-6-chloro-5-heptene dimethylamine. 2-one. 77------1.0 1-chloro-5,5,7,7-tetra- 3.0 acetone.---- 1.5 NaOH 0.06 monooleylamine------30° C. 6 hours------8,8,10,10-tetramethyl-5- methyl-3-octene. tundecene-2-one. 78------1.0 geranyl bromide------60 MEK 1.5 NaOH 0.1 isopropyl amine-HCl-...-- 25 C., 2 days.------3,6,10-trimethyl-5,9- undecendiene-2-one, 79------1.0 benzyl chloride. ------3.0 acetone... 15 NaOH 0.1 methyl amine-HCl ------35 C., 5 hours.---- Benzyl acetone. 80 ---do------do------1.5 NaOH 0.3 ethylene diamine.----.... 35 C., 5 hours-- Do, 8. -do------do------1.5 KOH 0.01 benzylamine------Do. 82. -do------do------1.5 KOH 0.1 dinnethylglyoxiIne- D0. 83.------do------4.0 MEK.-- 1.5 NaOH 0.06 trisooctyl amine.------25 C, 1 day...... ethyl-4-phenyl butane role. 84------1.0..propargyl bronide----- 6.0 acetone - 5 NaOH 0.1 Amberlite LA-2 Sec- 30 C., day.------Propargyl acetone. ondary amine.

EXAMPLE 73 wherein each of R,1, R,R2, RRa, R and RsR is selected from the 55 group consisting of hydrogen, alkyl and alkenyl having from Into a reaction flask provided with a stirrer were charged one to about 18 carbon atoms, and alkylene having from two 174 grams (3.0 moles) acetone, 76 grams (1.0 mole) allyl to three carbon atoms wherein two of R and R or R and R. chloride, the amount of organic amine as noted on Table V, are taken together to form a ring including the CO group, and 63 grams (1.5 mole) caustic 96 percent soda flakes. After which comprises reacting said ketone at a temperature within stirring at 25°-35° C. for 24 hours, the inorganic precipitate 60 the range from about -20 to about 150 C. with an alkylating TABLE WI

Mole NaOH Example No. (flake) Mole ketone Mole catalyst Conditions

i.5 6.0 acetone...... 0.1 ammonium nitrate ------25 C., 1 day. 1.5 30 acetone -- 0.1 ammonium sulfate------25 C., 2 days. i.5 4.0 MEK -- 0.1 annonium ferric oxalate--- 30 C, 2 days. 1.5 A, OMEK. -- 0.10 ammonium cobalt sulfate.-- 25 C., 5 days. 1.5 6.0 acetone.------0 10 methyl nitro imidazole.---- 30 C, 1 day. 1.5 -----do------0.0 hexamethylene tetramine. 30 C., 1 day. 1.5 4.0 MEK ... 0-0 glucosamine. ------30 C, 2 days. 1.3 3.0 acetone. 30 C., 7 hours. 1.25 4.0 acetone. - 30 C, 1 day. 15 { 8 E. 0.05 Amberlite XLA-3 primary amine------30 C, 1 day. 1.5 6.0 acetone. 0.1. Ionac A-260 aliphatic polyamineion exchange resin- - 30 C, 1 day. 1.5 8.0 acetone.------0.1 sulfanilamide------30 C., 3 days.

xt A. rea 3,668,255 19 20 agent selected from the group consisting of alkyl and alkenyl straight and branched chain alkyl and alkenyl groups hav chlorides and bromides having from one to about 12 carbon ing from two to about five carbon atoms, and atoms, and allyl, propargyl, cyclohexyl, and benzyl chlorides 2. R, R2, Ra and R are selected from the group consisting and bromides, in the presence of a solid alkali metal hydroxide of hydrogen, straight and branched chain alkyl groups and selected from the group consisting of potassium hydrox having from one to about five carbon atoms, and alkylene ide, sodium hydroxide and mixtures thereof, and as a catalyst groups having from two to three carbon atoms wherein a nitrogen compound which is selected from the group con two of R and Ra or R, and R are taken together to form a sisting of ammonia and aliphatic, cycloaliphatic and hetero ring including the cyclic hydrocarbon amines having from one to about 60 car bon atoms, such hydrocarbon amines containing hydroxy sub 10 C stituents, such hydrocarbon amines containing carboxylic acid substituents, and such hydrocarbon amines containing nitro O substituents, the amounts of the ketone and alkylating agent being in the molar ratio of from 1:5 to about 20:1, the alkali group, the total number of carbon atoms in R, R2, R and R. hydroxide being in the proportion of from 1 to 2 moles per 5 being from two to about six, and R, R and Ra are hydrogen, mole of alkylating agent, and the amount of nitrogen con R has at least three carbon atoms. pound being within the range from about 0.003 mole to about S. A process in accordance with claim 1, wherein said 1 mole per mole of alkylating agent. ketone is unsymmetrical and contains one active hydrogen on 2. A process in accordance with claim 1, in which the each of the two carbon atoms adjacent to the carbonyl group catalyst is ammonia. and a mixture of monosubstitution products is obtained. 3. A process in accordance with claim 1, in which the 6. A process in accordance with claim 1, wherein the molar catalyst is an organic amine. ratio of said ketone to said alkylating agent is between 1:1 and 4. A process in accordance with claim 1, in which the 20:1, the ratio of alkali metal hydroxide to said alkylating ketone has the formula: agent is between 1:1 and 1:2, and the ratio of said nitrogen compound to said alkylating agent is between 0.0,003:1 and 25 1:1, and a monoalkylated product is obtained. 7. A process in accordance with claim 1, wherein said R Rs ketone contains more than one active hydrogen in the two CH-C-G-CH-CH=C-CH-1 positions alpha to its carbonyl group, and the molar ratio of R O R. CH3 said ketone to said alkylating agent is between 1:2 and 1:5, the 30 molar proportion of said alkali metal hydroxide corresponds to the molar proportion of said alkylating agent, and a polyal wherein: kylated product is obtained. 1. R is selected from the group consisting of hydrogen and k six k k e 35

40

45

50

55

60

65

70

75 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,668,255 Dated June 6, 1972 Inventor(s) Walter C. Meuly et al. It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 15, Table IV: "CH,Coi-C 3 H 7 ' should read w CHCO i SOe ? - C3H7r ed ... Collinn 19,9 1ine 11,s insert "and" after -- substituents --; and after "acid" insert COOH --. eigned and eealed this ninth Day of March 1976 Attest:

RUTH C. MASON C. MARSHALL DANN At testing Officer Commissioner of Patents and Trademarks

For M. po- 1050 (O-69) scomMadC 6037 6-89 U.S. WERNMENT PRENNs office: 869 - 930