AU2002300378B2 - Ammonium Sulfide Solution - Google Patents

Description

P/00/011 Regulation 3.2

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION FOR A DIVISIONAL PATENT

ORIGINAL

TO BE COMPLETED BY APPLICANT Name of Applicant: Actual Inventors: Address for Service: Invention Title: E.I. DU PONT DE NEMOURS AND COMPANY and COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION ANDERSON, Albert GRIDNEV, Alexei CALLINAN LAWRIE, 711 High Street, Kew, Victoria 3101, Australia AMMONIUM SULFIDE SOLUTION The following statement is a full description of this invention, including the best method of performing it known to us:- 01/08/02,gcl2782.spe.2 -2- BACKGROUND OF THE INVENTION This invention concerns a colourless aqueous ammonium sulfide solution which has been found useful in the preparation of a nitroxide. The nitroxide that can be prepared using the sulfide solution of the invention can in turn be used with an alkoxyamine to yield polymers with low polydispersity and/or controlled molecular weight. Further details of these polymers can be found in Australian Patent Application No. 750626 (formerly 60229/98) from which the present application is divided. The subject matter of 750626 (formerly 60229/98) is incorporated therein by way of reference.

SUMMARY OF THE INVENTION This invention is to be colourless aqueous ammonium sulfide solution containing sodium thiocyanate and substantially no ammonium polysulfide.

DETAILS OF THE INVENTION Preferably the sulfide solution of the invention is prepared by titrating an aqueous ammonium sulfide solution containing ammonium polysulfide with sodium cyanide under nitrogen.

The sulfide solution of the invention can be employed in the preparation of nitroxides, particularly nitroxides of the Formula Formula (1) wherein R, R 2

R

3 are each independently selected from the group consisting of

C

1 to C 18 alkyl, substituted C 1 to Ci 8 alkyl, C 6 to C 1 8 alkyl C 6 to C 1 8 aryl, C 6 to Cg 1 substituted aryl; R groups in a geminal position with respect to each other can together form a 4-8 membered ring; and R groups in a cis position with respect to each other can together form a 4-8 membered ring; and 01 /0/02.g cl2782.spc.2 -3- X is selected from the group consisting of C 1 to C 1 8 alkyl, substituted C 1 to C 1 8 alkyl, C 6 to C 18 aryl, C 6 to C 1 8 substituted aryl; acyl; X and R can form a 5-8 membered ring; and X and R 3 can form a 5-8 membered ring.

Preferred nitroxides selected from the group above are the following: -0-4 Formula (4) where X is selected from the group consisting of alkyl, optionally substituted alkyl, benzyl; and i Formula where X is alkyl of Ci to C 1 8 The nitroxides of Formula can be made by preparing a colorless aqueous ammonium sulfide solution containing sodium thiocyanate by titrating an aqueous ammonium sulfide solution containing ammonium polysulfide with sodium cyanide under nitrogen; (ii) sequentially adding an aminonitrile and a ketone to the aqueous ammonium sulfide solution under nitrogen; (iii) adding base and then neutralizing; and (iv) oxidizing the reaction product of step (iii) to form the nitroxide.

01/08/02,gcl 2 7 82.1pc.3 -4- The most commonly used nitroxides in nitroxide-mediated living free-radical polymerizations have been 2 2 6 ,6-tetramethylpiperidin-N-oxyl (TEMPO) and derivatives of this compound and di-t-butyl nitroxide (diBuNO).

.1 .1I o 0 TEMPO diBuNO These and other nitroxides/alkoxyamines that are conventionally used in nitroxide-mediated living free-radical polymerizations are inherently of high cost. Substantial cost improvements for the overall process can therefore be achieved by the use of nitroxide a material obtainable from inexpensive precursor by a simple experimental route.

It has been found, that in various polymerizations, the use of certain 2 2 ,5,5-tetraalkylimidazlin-4-one- -oxyl derivatives in nitroxidemediated polymerization offer lower polydispersities for polymers than is obtained with other nitroxides used for this purpose TEMPO and derivatives, or diBuNO).

Low polydispersity polymers are those with polydispersities that are significantly less than those produced by conventional free radical polymerization. In conventional free radical polymerization, polydispersities (the polydispersity is defined as the ratio of the weight average and number average molecular weights M w/l n) of the polymers formed are typically in the range 1.6-2.0 for low conversions and can be substantially greater than this for higher conversions. Polydispersities are usually less than 1.5, often less than 1.3 and, with appropriate choice of the nitroxides alkoxyamines and the reaction conditions, can be less than 1.1. The low polydispersity can be maintained at high conversions.

Polydispersities in nitroxide-mediated polymerization are believed to depend on a number of factors. These include the rate of exchange between active and dormant species which is largely determined by the rate of bond homolysis between N-O and the adjacent moiety for the alkoxyamines involved either as initiator species or formed during the polymerization (for a discussion on this subject see Moad and Rizzardo, Macromolecules 1995, 28, 8722-8); and (ii) the significance of various side reactions.

For polymerizations involving nitroxides the rate of bond homolysis between N-O and the adjacent moiety and polydispersities obtained depend on the particular nitroxide or alkoxyamine used and in particular on the substituents R, R and X. A preferred group of nitroxides in this context are the N-alkyl-2,2,5,5-tetraalkylimidazolin-4-one-l-oxyl compounds (1) X=alkyl, for example, 2 ,5-bis(spirocyclohexyl)-3-methylimidazolidin-4-one- oxyl (NO-88-Me)) which are seen to offer the lowest polydispersities in styrene polymerizations or copolymerizations. Also preferred within each class (X=alkyl and X=H) are those with more bulky R-R 3 The following are structures of nitroxides described herein: H 0 H 0

.I

N N 0 °0 NO-67 NO-88

CH

3 c J

.I

o *0 NO-88-Me NO-67-Me -6- PhCH 2 CH 3

CH

2

CH

2

H

2 N N .I .1 o 0 NO-67-Bn NO-67-nBu It is believed that an important side reaction in nitroxide-mediated polymerization is disproportionation between the nitroxide and the propagating species. It has been found that in methyl methacrylate (MMA) polymerization the use of 2,2,5,5-tetraalkylimidazolin-4-one- I-oxyl derivatives offer low polydispersities and good living character for polymerizations.

While not wishing to be bound by a particular mechanism, these advantages are believed to be in part a consequence of the 5-membered ring imidazoline nitroxides providing a higher combination: disproportionation ratio for the reaction with propagating radicals than 6-membered ring TEMPO) or open chain nitroxides diBuNO). These pathways are illustrated in Scheme 1 for MMA polymerization. Note that the products of the disproportionation reaction, vinyl terminated macromonomer and hydroxylamine can also react further under polymerization reaction conditions leading to further complications. Clearly, minimization of this side reaction is important to obtaining polymerization with living characteristics.

Scheme 1

H-Q

Y-CH2- CH2-C\ CO2Mej

CO

2 Me n disproportionation fQ" MMA 3/ MMA Y. Y- CH2-C- CH2-C.

C0 2 M C0 2 Me fprQ" combination iQ*

CH

3

CH

3 I I CH2-C- CH 2

-C-Q

CO

2 Me CO 2 Me -n In Scheme 1, Q is a nitroxide.

Similar side reactions have also been shown to occur during nitroxide-mediated styrene polymerization. In styrene polymerization at 90°C, the rate constants for hydrogen transfer from the propagating species to NO-67 and TEMPO relative to the rate constant of propagation have been measured as 0.18 and 0.43 respectively.

In the synthesis of nitroxides of Formula the product nitroxide can be isolated by conventional means, preferably from the reaction mixture by filtration or by extraction with an organic solvent that is substantially insoluble in water.

It has been found that the ammonium polysulfide reacts with. either aminonitrile or cyanide ion, thereby reducing the amount of cyanide below stoichiometric proportions thus lowering the overall yield. This can be prevented by prior addition of cyanide ion to the point of decolorization of the polysulfide and formation of harmless thiocyanate.

The procedure disclosed herein for synthesis of nitroxides X=H) is as follows:

R

I

CN

RX NH 2 SCHEME 2 0 R) R 3

(NH

4 2

S

S

R

R

R

3 NaOH

SH

2 0 2 R IN

R

2

N%%R

[Ox.]

I

O.

(1) alkoxyamnines can be made by a variety of methods such as alkylating the derived hydroxylamines of nitroxides of Formula and alkoxylating the compound of Formula as will be obvious to one skilled in the art.

EXAMPLES

General Experimental Conditions Monomers were purified (to remove inhibitors) and flash distilled immediately prior to use. Degassing was accomplished by repeated freezeevacuate-thaw cycles. Once degassing was complete ampoules were flame sealed under vacuum and completely submerged in an oil bath at the specified temperature for the specified times. The percentage conversions were calculated gravimetrically.

The structures of polymers and block copolymers have been verified by application of appropriate chromatographic and spectroscopic methods. Gel permeation chromatography (GPC) has been used to establish the molecular weight and molecular weight distribution (polydispersity) of the polymers. A Waters Associates liquid chromatograph equipped with differential -9refractometer and 106, 10', 10', 10'. 500 and 100 A Ultrasryragel columns was used. Tetrahydrofuran (flow rate of 1.0 ml/min) was used as eluent. The molecular weights are provided as polystyrene equivalents. The terms M, and M,,JM, are used to indicate the number and weight average molecular weights and the polydispersity respectively. NMR spectroscopy was used to elucidate the structures of polymers and provide evidence for the polymers' end-groups. NMR spectra were obtained on a Bruker (200 MHz) spectrometer and CDCI 3 was used as solvent.

xcramples 1 and 2 Syntheses of Nitroxides of Formula (1) The following Examples 1 and 2 illustrate a process for synthesis of nitroxides where X=H).

Example 1 Preparation of 2,5-diethyl-2,5-dimethylimidazolidin-4-one-l-oxyl (NO-67) Preparation of 2.5-diethvl-2,5-dimethvlimidazolidin-4-thione A I liter 4-necked round-bottomed flask equipped with a mechanical stirrer, thermocouple thermometer, nitrogen bubbler, bleach-filled scrubber, and reflux condenser was charged with 17.4 g ammonium chloride (0.32 mol), 35.9 g AN-67 (0.3 mol, 87% 2-amino-2-methylpropionitrile in water, 'H NMR (ppm) of freshly distilled AN-67 in D 2 0: 1.03 3H), 2.45 3H), 1.75 (q, 2H), 23.1 g 2-butanone (0.32 mol), and 132.9 g of 20% ammonium sulfide solution (0.39 mol). As the solution was heated to 50 0 C, a slight exotherm occurred that increased the temperature to 65 0 C and some ammonium hydrosulfide sublimed into the condenser. After 20 minutes, the temperature declined to 55 0 C and was held there for 18 hours. An oily liquid layer forms on top of the aqueous solution during the first 5 minutes. The yellow polysulfide color is discharged in the first minute; this is caused by reaction of cyanide ion with sulfur to give colorless thiocyanate ion and a decrease in yield. The next day, the solution was cooled to -15 0 C, 25 g of NaCI added to salt out the thione, and filtered cold to give 39 g of product. The mother liquor was treated with 10 g of K.CO 3 to precipitate an additional 5 g of product. K 2

CO

3 is more effective at salting out thiones, amides, and nitroxides than NaCI. The solids were combined -11to give 44 g (80% yield) of thione after 2 days of air drying, mp. 58-64°C. IR (nujol) 1540 cm-1; 'H NMR ppm (D20) 0.96 (overlapping t, 12H, CH 3 on 4 ethyls), 1.39,1.40,1.42,1.43 (4 singlets, total of 12H, CH, for four isomers, 2 cis-trans pairs), 1.75 8H, 4 CH, groups).

combustion analysis: calcd. for C,HiN 2 S-0.1(H 2 0) obs.

C 57.46 57.90 H 9.75 9.24 N 14.89 14.94 S 17.05 16.68 The thione can be purified by column chromatography on silica gel using hexane to elute an odorous fraction before the thione. The effect of variation of temperature and concentration of the reactants on yield and reaction rate was examined in a sealed NMR tube using D,O as a solvent and sodium tosylate as an internal standard. What was observed was a smooth decrease in concentration of starting materials and smooth increase in concentration of product. The reaction time can be reduced from 16 hours at 50°C to 6 hours at The compound, 2 -methyl-2-aminobutyrothioamide, was not observed indicating that this alicyclic intermediate reacts with MEK in a fast step to yield the cyclic product.

Preparation of 2,5-diethyl-2,5-dimethvlimidazolidin-4-one A 5 liter 4-necked round-bottomed flask equipped with a mechanical stirrer and thermocouple thermometer was charged with 250 ml water and 43.3 g (0.232 mol) of 2 ,5-diethyl-2,5-dimethylimidazolidin-4-thione. In order to make the thione dissolve, 1.8 g NaOH was added. The solution was cooled to 0-2"C with a dry ice-acetone bath. The flask was fitted with two additional funnels. Simultaneously, a solution of 16.7 g NaOH in 100 ml water (total of 18.5 g or 0.464 mol of NaOH used) was added through one of the funnels and 105 ml (0.928 mol) of 30% H 2 0 2 was added through the other funnel. The reaction mixture was stirred rapidly and required extensive cooling during the addition.

The 5 liter flask was used to provide a large surface area for efficient cooling of the exothermic reaction. The heat of reaction was 269.2 Kcal/mol; 124. The addition was completed in 2 hours; the mixture was stirred an additional half hour.

-12- At the end of this time, TLC indicated that no thione remained. Then, 27.9 g of NaHSO, (0.172 mol) was added to quench excess peroxide; this reaction is also somewhat exothermic (temperature increases from 26 to 43 0 The reaction mixture was transferred to a 2 liter round-bottomed flask and the solvent removed with a rotary evaporator (aspirator pressure) to give a white residue. The residue was extracted with 850 ml of boiling ethanol. Then, 50 ml of toluene was added to the solution and 130 ml of water/ethanol/toluene azeotrope distilled to remove any remaining water. The solution was cooled and filtered to remove a small amount 1 g) ofNa 2 SO and then the ethanol was removed on the rotary evaporator to give a syrup that crystallized on cooling to room temperature. The yield was 37.5 g mp 58-64 0 C. IR (nujol) 1705, 1659 cm-1. 'H NMR (CDC13 DO) ppm (combination of equal amounts of 2 sets of cis-trans pairs) 0.95-0.98 12H, CH, on 4 ethyls), 1.27, 1.31, 1.34, 1.38 (4 s, total 12H, 4 1.50-1.70 8H, CH 2 on 4 ethyls). The singlets at 1.34 and 1.38 collapse to a singlet in D 2 0 but now integrate 6H.

combustion analysis: calcd. for CgH,,N 2 0 obs.

C 63.49 63.07 H 10.66 10.01 N 16.45 16.23 0 9.40 9.49 Preparation of 2 .5-diethvl-2.5-dimethvlimidazolidin-4-one- I-oxvl A one liter polymer jar equipped with a mechanical stirrer, bleach filled odor trap, heating mantel, reflux condenser, and thermocouple thermometer was charged with 153.3 g (0.45 mol) 20% ammonium sulfide solution. To this solution was added 1.47 g (0.03 mol) NaCN to react with the ammonium polysulfide impurity in the ammonium sulfide solution. Then, 35.9 g AN-67 (0.3 mol) and 21.7 g 2-butanone (0.3 mol) was added. The solution was stirred and heated under nitrogen at 55C for 18 hours; some ammonia was evolved. Two liquid layers form; the lower layer is thioamide. The volume of the reaction mixture is now 200 ml. The mixture was cooled to room temperature and a solution of 36 g NaOH (0.9 mol) in 100 ml water was added. The solution was 13cooled to 0°C and 306 g (2.7 mol) 30% H0, added dropwise with stirring and cooling at 4-10°C. The addition took 65 minutes. After stirring for one hour, the solution was brought to pH 7 by addition of a solution of 58 g concentrated HzSO 4 and 56 g of water at 13°C. Then, 68 g (0.6 mol) of 30% H 2 0 2 was added.

No exotherm was noted at this time. To this was added 5.0 g Na 2

WO

4 .2H 2 0. The total reaction volume is 763 ml. An initial greenish-yellow color (pertungstate ion) is replaced by a deeper yellow color (nitroxide). The temperature of the mixture climbs from 13 to 31 0 C over 3-1/2 hours The next day, the solution was filtered to give 27.5 g (40% yield) of nitroxide, mp 117-122 0 C. It was subsequently found that 1/3 of the AN-67 is destroyed by hydrolysis and irreversible reaction with sulfur to form thiocyanate ion. If this is taken into account, the yield is 82%; each step is about 93%. The solubility in NMP is at least 1:1. IR(nujol) 1720, 1675 cm-1; (toluene solution) 1713.3 cm-1. The nitroxide displays a triplet in the ESR. Aliquots of reaction mixture were withdrawn at selected times and diluted with a known amount of xylene. The integrated intensity of the ESR triplet was plotted as a function of time when the concentration of peroxide was doubled or the concentration of tungstate ion was increased to three. The data were fitted to parabolas. The initial slopes of the lines are obtained by differentiating the empirically fitted curves to determine the slope of the line and solving the equation so obtained at x 0; the rate law at 24 0 C was found to be K k[H 2

O

2 10-'[WO4"] 10 combustion analysis: calcd. for C 9

H

7

NO,

2 0.03(CH 2 Cl) obs.

C 57.75 57.71 H 9.16 8.82 N 14.92 15.21 0 17.04 17.28 Example 2 Preparation of 2 ,5-bis(spirocyclohexyl)imidazolidin-4-one-loxyl (NO-88) Preparation of 2 .5-bis(spirocyclohexvl)imidazolidin-4-thione.

A 2 liter 4-necked round-bottomed flask equipped with a mechanical stirrer, heating mantel, reflux condenser, thermocouple thermometer, -14nitrogen bubbler and exit tube connected to a bleach filled odor trap was charged with 132.9 g (0.39 mol) of 20% ammonium sulfide solution followed by 0.5 g NaCN to decolorize the polysulfide impurity in the ammonium sulfide solution.

Under a positive nitrogen flow, 16.1 g (0.3 mol) of ammonium chloride and 14.7 g (0.3 mol) of NaCN was added. The temperature of the solution dropped to 8gC.

Then, 58.9 g (0.6 mol) of cyclohexanone that had previously been deoxygenated by bubbling nitrogen through it for 10 minutes was added dropwise while stirring during 25 minutes. The temperature rose to 30°C. The temperature of the solution was increased to 47 0 C, at which point external heating was stopped and the reaction spontaneously allowed to exotherm to 63 0 C. The temperature was then maintained at 55°C. After 1 hour, 1.0 g NaCN was added and a mild exotherm to 63*C followed by a return to 55 0 C was noted. An additional 1.0 g NaCN was added 30 minutes later; this caused only a mild exotherm to 58 0

C.

The temperature was held at 55°C overnight. A sample of the resulting slurry was then withdrawn and divided into two parts. One part was dissolved in acetone, and checked by TLC (9:1 CHCl 2 :acetone); two species were present. The other part was filtered to give white crystals, mp 225-230 0 C. The precipitate was filtered in place with a filter stick to avoid handling the odorous mixture. The insoluble precipitate was thione; the other impurity was cyclohexanone, which remained in the filtrate. The thione was washed by adding 300 ml of water to the flask, stirring, and then removing the water through the filter stick. IR (nujol) 1520 cm-1.

Preparation of 2 .5-bis(sDirocyclohexvl)imidazolidin-4-one To the wet crystalline residue obtained above was added in the same flask 24 g (0.6 mol) of NaOH dissolved in 300 ml of water. The crystals failed to dissolve; the crystals were finally dissolved by addition of 485 ml of methanol. The solution does not show the characteristic exotherm upon addition of 30% hydrogen peroxide at 0-5°C. The temperature of the solution was increased to 40°C; at this temperature addition of peroxide is exothermic. After adding 147 g (4x0.32 mol) of 30%o peroxide, the solution temperature was held at for 30 minutes and then stirred at room temperature overnight; by TLC, the mixture consisted of amide and thione. The mixture was filtered and the precipitate washed with 3x100 ml of water. To the filtrate was added 57 g of peroxide [total peroxide used 204 g (1.8 mol)] and the solution was warmed to 0 C. A slight exotherm to 46 0 C occurred. To aid the oxidation, 1 g of Na,W0 4 .2H,O was added. After 15 minutes, a white precipitate began to deposit.

The mixture was allowed to stir at room temperature for 18 hours and then filtered. By IR both precipitates were identical and were combined and air dried, mp 216-220°C, 58.5 g (88% yield based on cyclohexanone). IR (nujol) 1690 cm-1.

Preparation of 2.5-bis(spirocvclohexyl)imidazolidin-4-one- -oxvl An acetone solution of 260 ml of 0.08M dimethyldioxirane (0.0208 mol), prepared as above, was treated with 2.3 g of 2,5-bis(spirocyclohexyl)imidazolidin-4-one dissolved in 75 ml of chloroform (previously freed of ethanol preservative by washing with 2x20 ml water and drying over magnesium sulfate) and allowed to react at room temperature overnight. The preparation was repeated using 1.7 g of amide and 270 ml of 0.0721 M dimethyldioxirane solution. Removal of the ethanol preservative is necessary to prevent the ethanol from being oxidized to acetaldehyde by the dimethyldioxirane/nitroxide system. The solvent was removed on the rotary evaporator, the residue (4.2 g) dissolved in 400 ml hot benzene, filtered to remove a trace of insoluble material, the filtrate reduced to 100 ml, rewarmed to bring all the crystals into solution, and allowed to crystallize overnight at room temperature. The yellow crystals were collected by filtration and dried in an oven at 75°C for 10 hours to give 2.4 g of nitroxide, mp 178-183°C. IR (nujol) 1707 cm-1.

combustion analysis: calcd. for C, 3

H

2 ,iNO, obs.

C 65.79 65.67 H 8.92 8.84 N 11.80 11.71 0 13.48 13.31 -16- Where the terms "comprise", "comprises", "comprised" or "comprising" are used in this specification, they are to be interpreted as specifying the presence of the stated features, integers, steps or components referred to, but not to preclude the presence or addition of one or more other feature, integer, step, component or group thereof.

01/08/02,gcl 2782.spel 6

Claims (2)

1. A colorless aqueous ammonium sulfide solution containing sodium thiocyanate and substantially no ammonium polysulfide.

2. The solution according to claim 1, substantially as hereindescribed with reference to either of the Examples. Dated this 1~ day of August, 2002. E.I. DU PONT DE NEMOURS AND COMPANY By their Patent Attorneys: CALLINAN LAWRIE 01/08/02.gcl 2782.spe,l 7