This invention is of a composition comprised of a smectite clay modified with an organic chemical composition and a polymer. The composition consists of an organic chemical/smectite clay intercalate that has been ion-exchanged and reacted and intercalated with one or more quarternary ammonium compounds and an anionic material and further blended into a polymer resin to make a nanocomposite composition. This material can be blended into a wide variety of polymers. This kind of system gives improved dispersion over conventional organoclays, intercalates or hybrid clays described in the literature, especially in non-polar resins. The defined organoclay has been found to be highly dispersible in a variety of polymers, whether polar or non-polar.

1. Field of the Invention
The present invention is directed to improved polymer compositions that are made from a polymer blended with a smectite clay that has been reacted with a specified mixture of organic materials. The inventive compositions have the property that when the specified organically modified clay is added to the polymer, an exceptionally well dispersed composite results which is useful as a polymer nanocomposite. Polymer nanocomposites have enhanced structural and other properties that make them desirable materials for an ever growing number of uses.
2. Background of the Invention
Organically modified clays, also called organoclays, have been used for many years as rheological additives for solvent based systems. They are usually produced by making a water dispersion of a phyllosilicate clay, usually a smectite clay, and adding to it a quaternary ammonium salt of a long chain fatty acid to produce an organically modified clay by cation exchange reaction and adsorption. The reaction may cause the organoclay to coagulate from the water dispersion which allows for its isolation by filtration and washing. Similarly, organoclays can be made without water by extrusion mixing, with heat and shear, smectite clay and the quaternary ammonium compound or compounds with no water or other solvent being present.
Polymers, resins and plastics containing clay additives have recently become widely used as replacements for heavier steel and other metal products, especially in the field of automotive manufacturing. They have also found use in a growing number of other areas, including as bridge components and as replacements for heavier steel parts in ship construction. Using extrusion and injection molding, a nylon matrix, for example, has been successfully reinforced with smectite-type clays (and organoclays based on the smectite clays, bentonite and hectorite) dispersed therein to form molecular composites of nylon and finely dispersed silicate clay platelet layers. Such products, often called nanocomposites, have enhanced structural, tensile, impact and flexural strength.
The behavior of the resultant plastic/clay product (or nanocomposite) is qualitatively different from that exhibited by the plastic, polymer or resin alone and has been attributed by some workers in the field to the confinement of the matrix chains between the clays millions of microscopic layers. It has long been known that bentonite and hectorite are clays which are composed of flat silicate platelets of a thickness no more than about one nanometer.
The nanocomposite products created to date have important commercial applications not only in the applications discussed above but also in diverse areas such as where ultrathin polymer films confined between adsorbed surfaces are involved. These uses include polymer composites for polymer adhesives and films including polyethylene.
The clays used are typically smectite clays which are layered phyllosilicates. Smectite clays possess some structural characteristics similar to the more well-known minerals talc and mica. Their crystal structures consist of two-dimensional layers formed by fusing two silica tetrahedral sheets to an edge-shared dioctahedral or trioctahedral sheet of either alumina (for example bentonite) or magnesia (for example hectorite)xe2x80x94each of the different smectite clays having somewhat different structures. Stacking of these layers in nature in depths of hundreds or more caused by ionic and weak Van der Waals forces leads to voids or chambers between the separate layers. These chambers are occupied by cations which balance the charge deficiency that is generated by isomorphous substitution (often called disharmonies) within the platelet lattices.
Nanocomposites are most often prepared today using organically modified, silicates or organoclays produced by a cation exchange reaction between the silicate and an alkylammonium salt (usually quaternary ammonium compounds). The alkyl cations exchanged onto the natural clay platelets render the hydrophilic clay organophilic and this transformation makes the clay more easily dispersible into the polymer or plastic. Although excellent sorbents for some organics, natural bentonite and hectorite are themselves very hydrophilic.
3. Description of the Prior Art
The earliest scientific work using organoclays in the preparation of nanocomposites is reflected in U.S. Pat. No. 2,531,396, issued to a predecessor of Rheox, Inc., the assignee of this invention. This patent, filed in 1947, teaches the use of organically modified bentonites to provide structural reinforcement to elastomers, such as rubber, polychloroprene and polyvinyl compounds. Over a generation later, additional patents begin to appear. A number of patents obtained by Toyota starting in 1984: U.S. Pat. Nos. 4,472,538; 4,739,007; 4,810,734; 4,889,885; and 5,091,462 use organoclay additives for plastics and describe plastic structures commercially used, for example, to replace aluminum components in automobiles.
Manufacture to date of nanocomposite materials has often involved mixing an organoclay with a polymer powder, pressing the mixture into a pellet, and heating at the appropriate temperature. For example, polystyrene has been intercalated by mixing polystyrene with an alkylammonium montmorillonite and heating in vacuum. Temperature of heating is chosen to be above the bulk glass transition temperature of polystyrene, ensuring polymer melt.
Representative U.S. Pat. No. 4,810,734 to Toyota describes a different process for producing a composite material which comprises a step of contacting a layered smectite clay mineral having a cation exchange capacity of up to 200 milliequivalents per 100 g with a swelling agent in the presence of a dispersion medium, thereby forming a complex which has the property of being swollen by a molten monomer of a polymer, and a polymerization step of polymerizing said monomer in said mixture. The xe2x80x9cswelling agentxe2x80x9d used is one which has both an onium ion and a functional group capable of reacting with a polymer. Toyota U.S. Pat. No. 4,889,885 describes a composite material, which comprises (a) at least one resin selected from the group; consisting of a vinyl-based polymeric compound, a thermosetting resin and a rubber, and (b) a layered bentonite uniformly dispersed in the resin, the layered silicate having a layer thickness of about 7 to 12 xc3x85 and an interlayer distance of at least about 30 xc3x85, where at least one resin is connected to a layered silicate through an intermediate.
There are a number of ECC America patents issued starting around 1987 where gaseous NH3 is used to provide modification of the smectite clay surfaces prior to making a nanocompositexe2x80x94See U.S. Pat. Nos. 4,690,868 and 4,798,766.
Two other major companies appear to be working in the field; Amcol International Corporation and AlliedSignal. Both have issued recent patents in the area of this invention. See for example AlliedSignal""s U.S. Pat. Nos. 5,514,734 and 5,385,776xe2x80x94these patents are in general directed toward a nylon 6 matrix and clays using non-standard organic modifications. See also in this regard Vaia et al., the article entitled Synthesis and Properties of Two-Dimensional Nano Structures By Direct Intercalation of Polymer Melts in Layered Silicates, Chemical Materials 1993, 5, pages 1694-1696. An additional patent, WO 93/04118 from Allied, discusses nanocomposite materials of polymer matricles with platelets having an average thickness of less than 50 xc3x85 having chemicial species bonded to them. This patent gives several examples of nanocomposites comprising nylon, PET and polypropylene (PP). While the nylon samples used up to 6% dispersed clay, the PET example used only 0.38% clay and the PP example only 0.14% clay. Property improvements in tensile modulus for the PP example were only about 10%, which is within the normal measurement error. The use of such low levels of clay to gain such a modest property benefit suggests that the clay dispersion was inadequate using more efficacious amounts such as used in the nylon examples.
Amcol International Corporation (Amcol) has been issued as least three recent patents, U.S. Pat. Nos. 5,552,469, 5,578,672 and 5,698,627 which teach the exclusion from their clay-based nanocomposites of xe2x80x9conium ionxe2x80x9d products (which would include most known commercial organoclays made with traditional quaternary ammonium compounds). See also Amcol U.S. Pat. No. 5,721,306.
European patent application (WO 99/03914) discloses a dispersant that is an intercalant of a clay that uses, in its broadest definition, a water-dispersible polymer that has at least an inherent viscosity of 0.1 dL/g, which defines low or higher molecular weight polymers. The clay-intercalant, discussed on page 5, line 3 of the European patent application, discusses the xe2x80x9cdispersible polymers . . . strongly influenced by the presence of anionic sulfo-salt modificationxe2x80x9d. The clay minerals used can include, xe2x80x9cuntreated or metal intercalated, organically modified through cation ion exchange; intercalated with other high molecular weight pretreatment compounds.xe2x80x9d The exemplary claim of the patent application discloses a dissipatible disperse clay material into a polyester polymer.
Several patents of the Cornell Research Foundation have issuedxe2x80x94U.S. Pat. Nos. 5,032,546, 5,032,547 and 5,554,670. One or more of these patents describe the use of organoclays in thermoplastics to form nanocomposites.
General Electric Company U.S. Pat. No. 5,530,052 describes silicate materials, including montmorillonite clays, modified with at least one heteroaromatic cation and used as additives to specified polymers to make nanocomposites.
Other prior art shows making polymer-clay intercalates directly by reaction of the monomers in the presence of clays. See Interfacial Effects On The Reinforcement Properties Of Polymer Organoclay Nanocomposites, H Shi, T Lan, T H Pinnavaia, Chemistry of Materials, 1996, pages 88 et seq.
While not related to nanocomposites, Rheox, Inc. has issued patents describing organoclay compositions useful as rheological additives which comprise the reaction product of smectite clay, quaternary ammonium compounds and organic anions wherein a quaternary-organic anion complex is intercalated with the smectite clay. These patents comprise U.S. Pat. Nos. 4,412,018, 4,434,075 and 4,517,112 (descriptions herein incorporated by reference) and are described to include a large variety of organic compounds, including carboxylic and sulfonic acids, capable of reacting with the quaternary used. These patents do not describe the use of these organoclays in thermoplastic polymers.
A recently filed patent application by the assignee hereof (U.S. patent application Ser. No. 09/064,216 filed Apr. 22, 1998) describes a hybrid organoclay system that gives improved dispersion in a polyester resin over conventional organoclays or simple intercalates to form a nanocomposite.
One of the more vexing problems in the nanocomposites field is the manufacture of useful composites with non-polar resins. Such resins as polyethylene, polypropylene and fluoropolymers can benefit from the reinforcing and other enhancements of nanocomposites but, up until now, it has been too difficult to incorporate organoclays into them directly. Indeed, Professor Giannelis of Cornell University (Adv. Materials 1996, 8, No. 1, p29) has stated, xe2x80x9cIdeally, polymers should be polar or contain groups capable of interacting with the silicate surface. If the enthalpy cannot compensate for the entropy penalty no intercalation will take place leading to undispersed or immiscible hybrids.xe2x80x9d Such undispersed hybrids will result in poor properties in the final resin composite. Workers in the field have devised a number of complex systems to avoid this problem. Hasegawa (N. Hasegawa, M. Kawasumi, M. Kato, A. Usuki, and A. Okada, Preparation And Mechanical Properties Of Polypropylene-Clay Hybrids Using A Maleic Anhydride Modified Polypropylene Oligomer, JAPS 67, 87, 1998) has used a maleic anhydride grafted system to improve the compatibility of the polymer with the clay. A similar idea using grafted polypropylene is proposed by Inoue and Hosokawa in European Patent No. 807659. Fukui in U.S. Pat. Nos. 5,091,462 and 5,206,284 uses a modified nylon graft polyethylene to create compatibility with the clay. Serrano, Beall and Cruz in European Patent No. 822163 propose a complex process involving intercalants and organic solvents at high temperatures to make a nanocomposite with non-polar resins. All these attempts require special resin modifications or create complex, costly schemes to improve organoclay dispersion in non-polar resins and are likely not commercially viable.
The present invention provides a practical way to disperse smectite clays into thermoplastic polymers without resorting to expensive processes or special resin materials to insure compatibility to produce well-dispersed nanocomposites.
It is an object of the invention to provide a modified clay/polymer composition using a thermoplastic polymer and a smectite clay modified with organic chemicals. The organoclay used is easily dispersed into both polar and non-polar thermoplastic polymers to form a composition useful as a nanocomposite.
It is a specific object of the invention that the organoclay can be made inexpensively and the polymer needs no special compatibilizer or grafting to allow dispersion and intercalation of the organoclay into it.
This invention is of a composition comprising a polymer system and a smectite clay modified with an organic chemical composition. The modified clay an organic chemical/clay intercalate prepared by the ion exchange and reaction of a smectite clay and one or more quaternary ammonium compounds and one or more anionic organic material. The organoclay is then blended into a polymer resin to give a nanocomposite composition.
It is a surprising result that this kind of system gives improved dispersion over conventional organoclays, intercalates or even hybrid clays described in the literature, especially in non-polar resins. The organoclay composite has been found to be highly dispersible in a variety of polymers, whether polar or non-polar.
In one aspect, the present invention provides a clay/organic chemical composition that comprises: (a) one or more smectite clays, modified with (1) one or more quaternary ammonium compounds, and (2) one or more defined anionic organic materials to form an organoclay composition and (b) one or more thermoplastic polymer resins; whereby the organoclay composition is mixed or blended into the polymer resin.
Further advantages and features of the invention, as well as the scope, nature and utilization of the invention, will become apparent to those of ordinary skill in the art from the description of the preferred embodiment of the invention set forth below.
The clay, organic chemical and polymer compositions of this invention may be made using a variety of materials and by a variety of methods disclosed hereafter, or which will appear obvious when the disclosure of this patent occurs. Applicants do not intend to limit the materials or methods of manufacture of such additives by the following descriptions.
One important aspect of the invention is a clay/organic chemical and polymer composite comprising:
A reaction product obtained by the intercalation and reaction of (a) one or more smectite clays; (b) one or more quaternary ammonium compounds and (c) one or more anionic organic materials which is then dispersed into;
(d) one or more polymers.
Clays useful for element a) are smectite clays. Such days are swellable layered clays which contain individual platelets. Useful swellable layered materials include phyllosilicates such as smectite clay minerals, e.g., montmorillonite, particularly sodium montmorillonite; bentonite; hectorite; saponite; stevensite; beidellite; and the like.
As used herein the term xe2x80x9cinterlayer spacingxe2x80x9d refers to the distance between the internal faces of adjacent dry smectite clay platelet layers as they are assembled in the layered clay before any delamination takes place. The interlayer spacing is measured when the clay is dry; i.e. contains less than 3-6% by weight of water based on the dry weight of the material.
The clays which may be used in the present invention are preferably smectite-type clays having a cationic exchange capacity of at least 50 milliequivalents per 100 grams of clay, 100% active clay basis, as determined by the well-known ammonium acetate or methylene blue methods. Preferred smectite materials are bentonite and hectorite clays particularly of the 2:1 type having a negative charge on the layers ranging from about 0.15 to about 0.9 charges per formula unit and a commensurate number of exchangeable metal cations in the interlayer spaces.
Smectite-type clays are well known in the art and are commercially available from a variety of sources. Prior to use in the invention, the clays may preferably be converted to the sodium form if they are not already in this form. This may be conveniently carried out by preparing an aqueous clay slurry and passing the slurry through a bed of cation exchange resin in the sodium form. Alternatively, the clay can be mixed with water and a soluble sodium compound, such as sodium carbonate, sodium hydroxide, etc., and the mixture sheared, such as with a pugmill or extruder.
Representative smectite clays useful in accordance with the present invention are the following:
Montmorillonite
[(Al4xe2x88x92xMgx)Si8O20(OH)4xe2x88x92fFf]xR+
where 0.55 less than x less than 1.10, f less than 4 and R is selected from the group consisting of Na, Li, NH4, and mixtures thereof;
Bentonite
[(Al4xe2x88x92xMgx)(Si8xe2x88x92yAly)O20(OH)4xe2x88x92fFf](x+y)R+
where 0 less than x less than 1.10, 0 less than y less than 1.10, 0.55 less than (x+y) less than 1.10, f less than 4 and R is selected from the group consisting of Na, Li, NH4, and mixtures thereof;
Hectorite
[(Mg6xe2x88x92xLix)Si8O20(OH)4xe2x88x92fFf]xR+
where 0.57 less than x less than 1.15, f less than 4 and R is selected from the group consisting of Na, Li, NH4, and mixtures thereof;
Saponite
[(Mg6xe2x88x92yAly)Si8xe2x88x92xxe2x88x92yAlx+yO20(OH)4xe2x88x92fFf]xR+
where 0.58 less than x less than 1.18, 0 less than y less than 0.66, f less than 4 and R is selected from the group consisting of Na, Li, NH4, and mixtures thereof; and
Stevensite
[Mg6xe2x88x92xSi8O20(OH)4xe2x88x92fFf]2xR+
where 0.28 less than x less than 0.57, f=4 and R is selected from the group consisting of Na, Li, NH4, mixtures thereof.
Beidellite
[(Al4+y)(Si8xe2x88x92xxe2x88x92yAlx+y)O20(OH4xe2x88x92fFf]xR+
where 0.55 less than x less than 1.10, 0 less than y less than 0.44, f less than 4 and R is selected from the group consisting of Na, Li, NH4, and mixtures thereof;
The preferred clays used in the present invention are bentonite and hectorite. Bentonite and its properties are described at length in the chapter entitled xe2x80x9cBentonite,xe2x80x9d in Carr, D., ed. 1994, Industrial Minerals and Rocks, 6th Edition (published by the Society For Mining, Metallurgy and Exploration, Colorado).
It will be understood that both sheared and non-sheared forms of the above-listed smectite clays may be employed. In addition, the smectite clay employed can be either crude (containing gangue or non-clay material) or beneficiated (gangue removed). The ability to use crude clay in the smectite-type clay of this invention represents a substantial cost savings, since the clay beneficiation process and conversion to the sodium form do not have to be carried out.
Compound(s) (b) of the invention can be any quaternary ammonium compound. Particularly useful are quaternary ammonium compound(s) which includes those having the formula:
wherein R1 comprises a group selected from (i) linear or branched aliphatic, aralkyl, or aromatic hydrocarbon groups having from 8 to 30 carbon atoms or (ii) alkyl or alkyl-ester groups having 8 to 30 carbon atoms; R2, R3 and R4 are independently selected from the group consisting of (a) linear or branched aliphatic, aralkyl and aromatic hydrocarbon, fluorocarbon or other halocarbon groups having from 1 to about 30 carbon atoms; (b) alkoxylated groups containing from 1 to about 80 moles of alkylene oxide; (c) amide groups, (d) oxazolidine groups, (e) allyl, vinyl, or other alkenyl or alkynyl groups possessing reactive unsaturation and (f) hydrogen; and Xxe2x80x2 comprises an anion selected from the group consisting of chloride, methyl sulfate, acetate, iodide and bromide, preferably chloride. For purposes of this invention, quaternary phosphonium and sulfonium based salts are defined as within the definition of quaternary ammonium compound.
The raw materials used to make the quaternary amonium compounds can be derived from natural oils such as tallow, soya, coconut and palm oil. Useful aliphatic groups in the above formula may be derived from other naturally occurring oils including various vegetable oils, such as corn oil, coconut oil, soybean oil, cottonseed oil, castor oil and the like, as well as various animal oils or fats. The aliphatic groups may likewise be petrochemically derived from, for example, alpha olefins. Representative examples of useful branched, saturated radicals included 12-methylstearyl and 12-ethylstearyl.
Examples of useful aromatic groups, that is benzyl and substituted benzyl moieties, include benzyl and benzylic-type materials derived from benzyl halides, benzhydryl halides, trityl halides, halo-phenylalkanes wherein the alkyl chain has from 1 to 30 carbon atoms, such as 1-halo-1-phenyloctadecane; substituted benzyl moieties, such as those derived from ortho-, meta- and para-chlorobenzyl halides, para-methoxybenzyl halides, ortho-, meta- and para-nitrilobenzyl halides, and ortho-, meta- and para-alkylbenzyl halides wherein the alkyl chain contains from 1 to 30 carbon atoms; and fused ring benzyl-type moieties, such as those derived from 2-halomethylnaphthalene, 9-halomethylanthracene and 9-halomethylphenanthrene, wherein the halo group comprises chloro, bromo, or any other such group which serves as a leaving group in the nucleophilic attack of the benzyl type moiety such that the nucleophile replaces the leaving group on the benzyl type moiety.
Examples of other aromatic groups include aromatic-type substituents such as phenyl and substituted phenyl; N-alkyl and N,N-dialkyl anilines, wherein the alkyl groups contain between 1 and 30 carbon atoms; ortho-, meta- and para-nitrophenyl, ortho-, meta- and para-alkyl phenyl, wherein the alkyl group contains between 1 and 30 carbon atoms; 2-,3-, and 4-halophenyl wherein the halo group is defined as chloro, bromo, or iodo; and 2-, 3-, and 4-carboxyphenyl and esters thereof, where the alcohol of the ester is derived from an alkyl alcohol, wherein the alkyl group contains between 1 and 30 carbon atoms, aryl such as phenol, or aralkyl such as benzyl alcohols; and fused ring aryl moieties such as naphthalene, anthracene, and phenanthrene.
Some examples of preferred quaternary ammonium compounds to make the compositions of this invention are:
Dimethyl dihydrogenated tallow ammonium chloride (2M2HT):
wherein HT=hydrogenated tallow.
Dimethyl dibehenyl ammonium chloride:
Methyl tris[hydrogenated tallow alkyl]chloride (M3HT):
Another preferred quaternary ammonium compound for purposes of the invention comprises a quaternary ammonium salt that contains at least one, preferably two or three, hydrocarbon chains having from about 8 to about 30 carbon atoms and either no hydrophilic carbon chains or having hydrophilic radicals having a total of about 9 moles of ethylene oxide or less.
Materials suitable for element (c) of this invention include materials listed as anionic components in U.S. Pat. Nos. 4,412,018, 4,434,075 and 4,577,112. These include materials that are capable of reacting with component (b) of this invention and for intercalation with component (a) as an alkyl quarternary ammonium-organic anion complex. The molecular weight (gram molecular weight) of the organic anion is preferably 3,000 or less, and most preferably 1,000 or less and contains at least one anionic moiety per molecule as disclosed herein. The organic anion is preferably derived from an organic acid having a pKA less than about 11.0. As indicated, the source acid must contain at least one ionizable hydrogen having the preferred pKA in order to allow the formation of the alkyl quarternary ammonium-organic anion complex.
Exemplary types of suitable acidic functional organic compounds useful in this invention include:
(1) Carboxylic acids including:
a benzene carboxylic acids such as benzoic acid; ortho-, meta- and para-phthalic acid; 1,2,3-benzenetricarboxylic acid; 1,2,4-benzenetricarboxylic acid; 1,3,5-benzenetricarboxylic acid; 1,2,4,5-benzenetetracarboxylic acid; 1,2,3,4,5,6benzenehexacarboxylic acid (mellitic acid);
b alkyl carboxylic acids having the formula CH3(CH2)nxe2x80x94COOH, wherein n is a number from 0 to 20; such compounds include acetic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, lauric acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoicanoic acid, heptadecanoic acid, octadecanoic acid (stearic acid), nonadecanoic acid, eicosonic acid.
c Alkyl dicarboxylic acids having the formula HOOCxe2x80x94(CH2)nxe2x80x94COOH wherein n is 0 to 8 such as oxalic acid; malonic acid; succinic acid; glutaric acid; adipic acid; pimelic acid; suberic acid; azelaic acid; sebacic acid;
d Hydroxyalkyl carboxylic acids such as citric acid; tartaric acids; malic acid; mandelic acid; and 12-hydroxystearic acid;
e unsaturated alkyl carboxylic acids such as maleic acid; fumaric acid; and cinnamic acid;
f Fused ring aromatic carboxylic acids such as naphthalenic acid and anthracenecarboxylic acid;
g Cycloaliphatic acids such as cyclohexanecarboxylic acid; cyclopentanecarboxylic acid; furancarboxylic acids.
(2) Organic sulfuric acids including:
a sulfonic acids including:
1 benzenesulfonic acids such as benzenesulfonic acid; phenolsulfonic acid; dodecylbenzenesulfonic acid; benzenedisulfonic acid; benzenetrisulfonic acids; para-toluenesulfonic acid; and
2 alkyl sulfonic acids such as methanesulfonic acid; ethanesulfonic acid; butanesulfonic acid; butanedisulfonic acid; sulfosuccinate alkyl esters such as dioctyl succinylsulfonic acid; and alkyl polyethoxy-succinyl sulfonic acid; and
b alkyl sulfates such as the lauryl half ester of sulfuric acid and the octadecyl half ester of sulfuric acid.
3. Organophosphorus acids including phosphonic acids, phosphinic acids, thiophosphinic acids, phosphites and phosphates as described in U.S. Pat. No. 4,412,018
4. Phenols such as phenol; hydroquinone; t-butylcatechol; p-methoxyphenol; and naphthols.
5. Thioacids as described in U.S. Pat. No. 4,412,018.
6. Amino acids such as the naturally occurring amino acids and derivatives thereof such as 6-aminohexanoic acid; 12-aminododecanoic acid; N-phenylglycine; and 3-aminocrotonic acid.
7. Polymeric acids prepared from acidic monomers wherein the acidic function remains in the polymer chain such as low molecular weight acrylic acid polymers and copolymers; styrene/maleic anhydride copolymers.
8. Miscellaneous acids and acid salts such as ferrocyanide; sodium tetraphenylborate; phosphotungstic acid; phosphosilicic acid, or any other such anion which will form a tight ion pair with an organic cation.
In addition to the above additives, silane coupling agents can also be employed that covalently bind to the clay platelets of the type Si(R1)3R2 where R1 is the same or different at each occurrence and is alkyl, alkoxy or oxysilane such as trialkoxysilane compounds such as octadecyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropylphenyldimethoxysilane, glycidoxypropyltripropoxysilane, propionamidotriethoxysilane, N-trimethoxysilylpropyl-N(aminoethyl)amine, trimethoxysilylundecylamine, trimethoxysilyl-2-chlorophenylethane, trimethoxysilyl ethylphenylsulfonylazide, 3-mercaptopropyltrimethoxysilane, 3-isocyanatopropyltriethoxysilane and the like; and R2 is selected from the group consisting of organic radicals which are compatible with the polymer forming the composite.
Polymer resins suitable for element (d) of this invention include a very wide variety of resins and can be any plastic material whether polar or non-polar. Such resins can include polyolefins which can consist of polyethylenes, polypropylenes, polybutylenes, polymethylpentane, polyisoprenes and copolymers thereof; copolymers of olefins and other monomers such as ethylene-vinyl acetate, ethylene acid copolymers, ethylene-vinyl alcohol, ethylene-ethyl acrylate, and ethylene-methyl acrylate. lonomers are also useful and comprise metal salts of polyolefins copolymerized with acrylic acid. Other families of thermoplastic resins useful in this invention are acetals, acrylics, and cellulosics. Fluoropolymers and copolymers with other monomers are useful such as polytetrafluoroethylene (Teflon(copyright)), fluorinated ethylene-propylene, perfluoroalkoxy resins, polychlorotrifluoroethylene, ethylene-chlorofluoroethylene copolymer, polyvinylidene fluoride and polyvinylfluoride. Liquid crystal polymers, a family of polyester copolymers, can also be used.
Additional polymers are nitrile resins, polyamides (nylons), polyphenylene ether and polyamide-imide copolymers. Various polyesters are useful such as polyarylates, polybutylene terephthalate and polyethylene terephthalate. Engineering resins such as polycarbonate, polyetherimide, polyetheretherketone, polyphenylene sulfide and thermoplastic polyimides are good candidates. Polystyrene and copolymers such as ABS, SAN, ASA and styrene-butadiene are appropriate. Also included are the sulfone based resins such as polysulfone, polyethersulfone and polyarylsulfone. Elastomers comprising a wide variety of useful materials and include olefinic TPE""s, polyurethane TPE""s, and styrenic TPE""s. Chlorinated polymers such as PVC, and polyvinylidene dichloride can also be used. In addition, miscible or immiscible blends and alloys of any of the above resin combinations are useful for this invention. Thermoset polymers such as epoxies, polyester resins and curing rubbers can also be used.
The materials (b) and (c) can be reacted and intercalated together, or in any order, with the smectite clay and the resultant product blended with the polymer to produce an inventive nanocomposite composition. As an alternative, the resultant product can be blended with a monomer or monomers for subsequent polymerization to make the polymer compositions of this invention.
At least two general methods can be used to make these anionic-cationic organoclays. One is to first disperse the smectite clay in water. The clay is preferably dispersed in water at a concentration of from about 1 to 80%, most preferably from about 2 to 8% by weight. Optionally, the slurry may be centrifuged to remove non-clay impurities that constitute about 10% to 50% of the starting clay composition. The anionic organic material is added to the clay/water dispersion and mixed. This mixture can then be heated and ion exchanged with a quaternary ammonium compound to form the final organoclay as coagulate, which is washed with water and isolated by filtration.
The second general method to prepare this invention uses dry clay that is intimately mixed with the anionic organic material in a heated device, such as an extruder. The mixture can also have some water present to facilitate intercalation. After the addition is complete, the quaternary ammonium compound is added and the final product is isolated. This composition can be washed with water and dried.
Both of the methods mentioned above can be modified by either: 1) reversing the order of addition, i.e., reacting the clay with the quaternary ammonium ion followed by the anionic organic material; or 2) adding the quaternary ammonium compound and anionic organic material to the clay simultaneously.
The reaction is followed by drying and grinding the organoclay product. Incorporation of the organoclay into the plastic resin can be accomplished by mixing or blending the organoclay by any means that can create sufficient shear. The shear can be provided by any appropriate method such as mechanical, thermal shock, pressure changes or ultrasonics as known in the art. Particularly useful are methods where a flowable polymer is mixed with the anionic-quaternary organoclay by mechanical means such as extruders, roll mills, stirrers, Banbury(copyright) type mixers, Brabender(copyright) type mixers and continuous mixers. Other methods for making this invention can be postulated by those knowledgeable in the art.
Nanocomposites that are made by these methods using the compositions of this invention will typically exhibit improved tensile modulus, tensile strength, gas barrier and heat distortion temperature values when sufficient energy is imparted to the blend to create substantially intercalated or exfoliated mixtures.
The preferred amounts and types of clays, anionic organic material, quaternary ammonium compound and polymers used to make the compositions of this invention will vary depending upon the type of matrix polymer that each composition is to be mixed into with the goal to achieve substantially complete exfoliation of the clay platelets in the matrix polymer. This amount is defined as the millequivalent ratio which is the number of milliequivalents (M.E.) of the organic anion in the organoclay per 100 grams of clay, 100% active clay basis. It is typical that the ratio of component (c) will have an anion milliequivalent ratio of 5 to 100 and more preferably 10 to 50. The ratio of component (b) to component (a) clay will be determined by the ability to make the final product sufficiently hydrophobic to allow for good incorporation in the polymer matrix. This will vary depending on the hydrophobicity of the carbon chains attached to the quaternary and the polarity of the polymer to be blended with. Typically, at least 75 M.E. of organic cation, more typically 95 to 120 M.E. of quaternary salt based on the M.E. of the clay are preferred.
A preferred clay/organic chemical composition for purposes of the instant invention is comprised of:
1. The ion-exchanged reaction product of:
(a) a smectite-type clay having a cation exchange capacity of at least 50 milliequivalents per 100 grams of clay; and
(b) one or more quaternary ammonium compounds in an amount of from about 20% to about 200% of the cation exchange capacity of the smectite-type clay and
(c) one or more anionic organic materials in an amount of 1% to 100% of the cation exchange capacity of the smectite-type clay; and
2. One or more thermoplastic resins or copolymers where the amount of organoclay from the reaction of (a), (b) and (c) above is from 0.1% to 40% of the weight of the polymer resin.
The smectite-type clay can be sheared in slurry form prior to reaction with the quaternary ammonium salt, or treated in solid form with a pugmill or similar apparatus.

Smectite clay/organic chemical/polymer compositions useful as nanocomposites


The present invention is directed to a device that provides thermal energy therapy, compression therapy and negative pressure therapy simultaneously and/or in conjunction with each therapy. The outcome of the present invention is that a patient's bodily fluids can be maintained, controlled, and/or adjusted with decreased medication dependence. Using these three therapies individually does not obtain these desired results of controlling, maintaining or adjusting the patient's bodily fluid. This combination of therapies is beneficial to the patient.

DVT Apparatuses
Gaymar Industries, Inc. is the assignee of this application and expired U.S. Pat. No. 4,597,384. The '384 patent is incorporated herein by reference as disclosing a well-made deep vein thrombosis cuff. In the '384 patent, Gaymar wrote, "[T]herapeutic and prophylactic devices for the alleviation of deep venous thrombosis by mechanical as opposed to chemical means. Deep venous thrombosis (DVT) is a condition in which clotting of venous blood occurs generally in the lower extremities due to lack of sufficient muscular activity in the lower extremities. Thus it is important that the velocity of blood flow in the patient's extremities be maintained at the requisite level in order to prevent pooling of blood in such extremities so that stasis of blood will not develop. This is particularly important since it is well known that stasis of blood is a significant cause leading to the formation of thrombi in the patient's extremities which could ultimately cause the death of the patient.
Devices are presently in use for the purpose of increasing blood velocity to prevent problems set forth above. Many of these devices comprise compression sleeves which fit over and around the limb requiring care. Fluid pressure producing means are provided for sequentially inflating the compression sleeve and allowing for a simultaneous deflation of all sleeve components.
Applicant's U.S. Pat. No. 4,453,538 which is entitled "Medical Apparatus" and issued on Jun. 12, 1984, is hereby and herewith incorporated for all of its disclosure into this application. Among other features this patent describes a flexible pad formed for external enwrappment about a patient's limb. The pad includes a plurality of relatively large individual fluid receiving cells adapted to receive and retain sufficient fluid to exert pressure upon the enwrapped limb for a specified period of time. More particularly, the cells are sequentially pressurized starting at the limb extremity and proceeding in the direction of the patient's heart. It is desirable that the sleeve compression pressure proceed smoothly and [progressively] along the patient's limb from the extremity heartward. Most pressure sleeves currently in use cannot do this. In fact most of them leave continuous pressure gaps between respective sleeve portions. Such results are undesirable.
In view of the foregoing it is an object of [the '384 patent] to provide a compression sleeve for a patient's limb which will provide a smooth pressure flow with no pressure gaps extending completely around the patient's limb.
It is yet another object of [the '384 patent] to provide a device for use in applying successive compressive pressures against a patient's limb to produce a smooth pumping action from the patient's limb extremity heartward.
It is a still further object of [the '384 patent] to provide a sleeve for use in applying compressive pressures against a patient's limb wherein the sleeve comprises a plurality of laterally extending separate fluid pressure members arranged longitudinally along the sleeve from a lower portion of the encased limb to the upper portion thereof with the adjacent lateral edge portions of adjacent pressure members being curved upwardly and then downwardly in unison whereby the respective contiguous edges thereof follow each other so that when pressure is sequentially applied from the lowermost pressure members upward there will never be a continuous circumferential pressure gap on any lateral circular portion of the encased limb.
Another object of [the '389 patent] is to provide a device of the type described in the proceeding object and further wherein the successive pressurization of each pressure member from the lowermost heartward produces a plurality of circumferential spaced radially inward maximum and minimum forces interdigitated with successive pressure members having similar maximum and minimum forces to produce a smooth gap free pressurization from start to finish."
Gaymar's apparatus is just one of many types of deep vein thrombosis (DVT) apparatuses. There are numerous designs for such DVT apparatuses. Representative samples of such DVT apparatus designs are found, and hereby incorporated by reference, in the following U.S. Pat. No.: 2,531,074 to Miller, Nov. 21, 1950; U.S. Pat. No. 4,091,804 to Hasty, May 30, 1978; U.S. Pat. No. 4,269,175 to Dillon, May 26, 1981; U.S. Pat. No. 4,343,302 to Dillon, Aug. 10, 1982; U.S. Pat. No. 4,396,010 to Arkans, Aug. 2, 1983; U.S. Pat. No. 4,989,589 to Pekanmaki et al., Feb. 5, 1991; U.S. Pat. No. 4,311,135 to Brueckner et al., Jan. 19, 1982; U.S. Pat. No. 5,080,089 to Mason et al., Jan. 14, 1992; U.S. Pat. No. 5,186,163 to Dye, Feb. 16, 1993; U.S. Pat. No. 5,383,894 to Dye, Jan. 24, 1995; U.S. Pat. No. 5,554,103 to Zheng et al., Sep. 10, 1996; U.S. Pat. No. 5,591,200 to Cone et al., Jan. 7, 1997; U.S. Pat. No. 5,626,556 to Tobler et al., May 6, 1997; U.S. Pat. No. 5,795,312 to Dye, Aug. 18, 1998; U.S. Pat. No. 5,830,164 to Cone et al., Nov. 3, 1998; U.S. Pat. No. 5,876,359 to Bock et al., Mar. 2, 1999; U.S. Pat. No. 5,997,540 to Zheng et al., Dec. 7, 1999; and U.S. Pat. No. 6,176,869 to Mason et al., Jan. 23, 2001.
Some of the above-identified references disclose DVT apparatuses having a therapy pad with at least two chambers and each chamber receives, through a conduit, a fluid from a source (a "fundamental compression therapy pad design"). The fluid can (a) return to the source through a return conduit or the original conduit ("recirculation systems"), (b) be directed toward a receiving unit (not the source) through a return conduit ("receiving system"), or, alternatively, (c) permeate through apertures in the chambers (normally using air as the fluid and commonly referred to as a "low air-loss system"). The alternative method is preferred if the fluid is a gas; and the former methods are desired if the fluid is a liquid (like an aqueous fluid or a non-aqueous fluid) or a gas (like air). In any case, the fluid is pressurized. The fluid pressure in each chamber can be the same or different, depending on the desired result. For example, the fluid in:                (a) chamber 1 is 50 mm Hg, chamber 2 is 50 mm Hg and so on; (Uniform pressure)        (b) chamber 1 is 80 mm Hg, chamber 2 is 40 mm Hg, and chamber 3 is 20 mm Hg; (Sequential downward pressure)        (c) chamber 1 is 60 mm Hg, chamber 2 is 40 mm Hg, chamber 3 is 60 mm Hg, and chamber 4 is 20 mm Hg; (Alternating Uniform/Sequential Downward Pressure)        (d) chamber 1 is 50 mm Hg, chamber 2 is 30 mm Hg, chamber 3 is 50 mm Hg, and chamber 4 is 30 mm Hg; (Alternating distinct uniform pressure) or        (e) combinations thereof.The fluid can also have a desired temperature. As disclosed in U.S. Pat. No. 2,531,074 to Miller at col. 1, lines 50-56; DVT apparatus can control the fluid temperature. The fluid temperature, however in the cited references, is uniform in each chamber of the therapy pad.
The fluid receiving cells can be made of a single material or a plurality of materials. Whatever number of materials are used, the material that contacts the patient's skin should be of a material or combination of materials that effectively transfers thermal energy to the patient or receives thermal energy from the patient (hereinafter "Transfer Material"). Examples of such transfer materials that have been used in the past include and are not limited to polymeric materials like polyethylene, polymeric materials with metallic materials (like rivets) positioned on and within the polymeric material, metallic-polymeric materials, and metallic materials.
All of the above variations of (a) fluid pressures, (b) recirculation systems, (c) constant fluid temperature in each chamber, (d) air-loss systems, (e) compression DVT systems, and (f) fundamental compression therapy pad designs, revert at least to the late 1970's.
Hypo/Hyperthermia Control Devices
In this application, we need to also discuss hypo/hyperthermia blankets. One type of hyper/hypothermia blankets are forced-air blankets. Those blankets have been litigated for many years. One such case is Augustine Medical, Inc. v. Gaymar Indus., Inc. (the assignee of this application), 181 F. 3d 1291, 50 USPQ2d 1900 (Fed. Cir. 1999). In that case, Judge Radar concluded that Gaymar's forced-air blankets did not infringe any of Augustine's patents at issue, and wrote, "Convective thermal blankets inflate to direct warm (or cool) air onto a person. Surgeons often use these blankets during and after an operation to prevent or treat hypothermia caused by surgical conditions. Hypothermia results when a patient's body temperature drops below a certain threshold. Surgery often presents the threat of hypothermia. A patient's body temperature may drop significantly during surgery because anesthesia prevents the patient's body from regulating its own temperature. Additionally, operating rooms—kept cool to accommodate the surgeon's working conditions and to reduce the spread of germs—can chill patients. Moreover, surgery often calls for administration of cool intravenous fluids at a time when the patient's body cavity is open.
A convective thermal blanket over the patient is thus necessary to prevent or treat hypothermia during and after surgery. Heated air from a warming unit inflates the blanket. Once inflated, the blanket directs heated air onto the patient through small holes (or "exit ports") in the undersurface of the blanket. With careful use, a convective blanket regulates patient temperature and prevents hypothermia . . . . [Gaymar's blankets] feature an inflatable quilt-like structure [, . . . ] attach two sheets of the same amount of flexible, lightweight material around their periphery and at various spots along their surfaces. In operation, heated air flows onto a patient's body from holes in the undersurface of [Gaymar's blankets], but [Gaymar's blankets] do not form a self-supporting or Quonset hut-like structure. Instead, [Gaymar's blankets] lie flat when inflated on a flat surface and rest substantially on a patient when in use . . . . Gaymar began selling forced-air blankets in March 1992." And one of those blankets is Gaymar's THERMACARE quilt.
Alternatively, other types of hypo/hyperthermia blankets are sold by Gaymar. An example of these blankets is Gaymar's DHP 600 hyper/hyperthermia blanket. That blanket operates differently from the forced-air blankets. Those blankets overlay a user and receive a fluid having a predetermined temperature. The fluid circulates through a cavity defined in the blanket that is to be positioned on a patient. The fluid (a) transfers its thermal energy to the patient and/or (b) receives the patient's thermal energy to control the patient's body core temperature. A description of those blankets is set forth in U.S. Pat. No. 6,375,673, which is hereby incorporated by reference in this application and which is licensed to the assignee of this application.
These blankets are extremely effective in altering the body core temperature of a patient. A problem with these devices is that some people claim those prior art hypo/hyperthermia blankets are bulky and difficult to use because those blankets cover too much of the patient. To address that problem, applicants have found a solution. The solution is set forth in the present application.
Negative Therapy Devices
Stanford University is the assignee of U.S. Pat. Nos. 5,683,438; 6,602,277; 6,673,099; 6,656,208; 6,966,922; 7,122,047; and 6,974,442. These patents disclose devices that create a negative pressure about a portion of a patient's body having a venous plexus. A venous plexus is a vascular network formed by numerous anastomoses between veins. The venous plexus is normally located at the patient's foot area and hand area. The negative pressure is applied, and simultaneously thermal energy (cold or warm) is applied to the venous plexus area that is subject to negative pressure.
Applying a negative pressure condition to a portion of the body (a) lowers the vasoconstriction temperature and/or (b) increases vasodilation in the body portion that is enclosed. The negative pressure conditions may be provided using any convenient protocol. In many embodiments, the negative pressure conditions are provided by enclosing a patient's venous plexus area in a sealed enclosure, where the pressure is then reduced in the sealed enclosure thereby providing the desired negative pressure. In many of the embodiments, the negative pressure is allowed to leak to the ambient environment through a seal so it does not create a tourniquet effect. A tourniquet effect is undesirable because it terminates the blood flow which is contrary to the intent of Stanford's negative pressure, thermal energy device.
Negative pressure includes conditions where a pressure is lower than ambient pressure under the particular conditions in which the method is applied, e.g., 1 ATM at sea level. The magnitude of the decrease in pressure from the ambient pressure under the negative pressure conditions in one example is at least about 20 mmHg, preferably at least 30 mmHg, and more preferably at least about 35 mmHg, where the magnitude of the decrease may be as great as 85 mmHg or greater, but preferably does not exceed about 60 mmHg, and more preferably does not exceed about 50 mmHg. When the method is performed at or about sea level, the pressure under the negative pressure conditions generally may range from about 740 to 675 mmHg, preferably from about 730 to 700 mmHg and more preferably from about 725 to 710 mmHg.
In practicing the exemplary methods, the negative pressure conditions during contact with the patient's skin may be static/constant or variable. Thus, in certain examples, the negative pressure is maintained at a constant value during contact of the surface with the low temperature medium. In yet other examples, the negative pressure value is varied during contact, e.g., oscillated. Where the negative pressure is varied or oscillated, the magnitude of the pressure change during a given period may be varied and may range from about 85 to 40 mmHg, and preferably from about 40 to 0 mmHg, with the periodicity of the oscillation ranging from about 0.25 sec to 10 min, and preferably from about 1 sec to 10 sec.
The negative pressure is applied to the certain venous plexus area to create vasodilation. That vasodilation results in the thermal energy (1) effectively transferring its thermal energy to the patient to warm the patient's body core temperature, or (2) effectively receiving the patient's thermal energy to cool the patient's body core temperature.
Stanford University disclosed that the thermal energy can be provided from outside the enclosure—for example a heat lamp—if the enclosure allows such thermal energy to penetrate through it or within the enclosure. Within the enclosure, the thermal energy can be provided by an electric thermal blanket or pad; or a conductive conduit or pad that allows a fluid having a desired temperature to flow through it. In both internal thermal energy providing embodiments and variations thereof, the patient's venous plexus is applied to the thermal energy providing device to transfer thermal energy to the patient and/or receive thermal energy from the patient.
"Third Space" in the Human Body
Current scientific literature reveals that inflammatory mediators initiate a biochemical chain of events that increase capillary permeability. These mediators include pharmacologically active amines such as histamine and 5-hydroxytryptamine, polypeptides such as bradykinin, kallikrein and leukotoxine, the prostaglandins, and various complements including derivatives thereof. These mediators act specifically on the junction of the endothelial cells of capillaries so that the junctions cannot contain colloids such as serum albumin within the vessel. The serum albumin escapes into the interstitium creating a nonfunctional "third space", the volume of which increases proportionally to albumin leakage and the presence of cytokines as well as proteolytic enzyme activities within the matrix. This leakage further widens capillary membrane-mitochondrial distances creating problems of poor diffusion and transport between the circulatory system and the functional cells resulting in cellular anoxia, a cellular energy deficit, and acidosis, and possibly leading to sequential organ failure.
In the past, the problem of the creation of the third space has been approached through pharmacological means. The present invention approaches the problem by controlling the patient's temperature, applying compression therapy to the patient and/or applying pressure therapy to the patient.


The invention relates to the production of (R)-enantiomeric, optically active cyanohydrins by reacting an aldehyde or a ketone with a cyanide group donor in the presence of (R) oxynitrilase, wherein a reaction mixture comprising a) an aldehyde or a ketone dissolved in an organic solvent; said organic solvent is immiscible or only slightly miscible with water, b) any aqueous R)-oxynitrilase solution and c) a cyanide group donor is stirred in such away that an emulsion is formed which remains intact until the end of the enzymatic reaction. After the enzymatic reaction has terminated, the (R)-cyanohydrin is isolated from the reaction mixture.

Cyanohydrins are of importance, for instance, for the synthesis of alpha-hydroxyacids, alpha-hydroxyketones, beta-aminoalcohols, which are used to produce biologically active substances, for example active pharmaceutical substances, vitamins or pyrethroid compounds.
A cyanohydrin can be produced by addition of hydrocyanic acid (HCN) to the carbonyl group of an aldehyde or of an unsymmetrical ketone, enantiomeric mixtures of unsymmetrical cyanohydrins being formed.
Since in a biologically active enantiomeric mixture usually only one of the two enantiomers is biologically active, there has been no lack of attempts to find a method for producing the (R)-enantiomer of an optically active cyanohydrin in the highest possible optical purity.
Many methods are based on adding HCN to the carbonyl group in the presence of a chiral catalyst, for example an oxynitrilase.
The enantiomeric purity of the cyanohydrin to be synthesized depends to a great extent on how much the competing chemical reaction and racemization can be suppressed.
As is disclosed by J. Am. Chem. Soc. 1991, 113, pp. 6992-6996, particularly in the case of methods employing an aqueous system it is difficult, because of this competing reaction, to achieve high enantioselectivity and enantiomeric purity.
One way of suppressing the competing chemical reaction and racemization is disclosed in EP-A-0 326 063, according to which optically active (R)-cyanohydrins are said to be obtained by reacting aliphatic, aromatic or heteroaromatic aldehydes or ketones in an aqueous environment with hydrocyanic acid in the presence of (R)-oxynitrilase (EC 126.96.36.199) from Prunus amygdalus, by employing acidic conditions, in particular pHxe2x89xa64.5, at temperatures such that the competing chemical reaction and racemization are negligible compared with the enzymatic synthesis. Reference is made here to the increased activity losses of the biocatalyst under these conditions and the examples show favoring of low temperatures in the range from 5 to 8xc2x0 C.
Since the enzymes are water-soluble proteins and the substrates, in contrast, are only sparingly water-soluble compounds, the use of water-miscible organic solvents to improve the solubility of the substrate and the product has been proposed.
Thus, for example, Effenberger et al. (Angew. Chem. 99 (1987) pp. 491-492) studied enzymatic cyanohydrin formation in aqueous alcoholic systems varying the pH, temperature and concentration with a view to optimum suppression of the competing reactions. However, the stereochemical purity of the desired end products was frequently unsatisfactory. As an improvement it was proposed to carry out the enzymatic reaction of oxo compounds with hydrocyanic acid in organic water-immiscible solvents in order to suppress the chemical reaction. In this case, preferably ethyl acetate and support-immobilized (R)-oxynitrilase were employed. Although in this manner products of high optical purity were obtained, as a result of the enzyme immobilization, a considerable loss of enzyme activity was observed. In addition, it was found that the non-enzymatic reaction which leads in the aqueous phase, by addition of hydrocyanic acid to the starting compound, to racemic cyanohydrins, causes an unwanted decrease in enantiomeric purity of the product.
In J. Am. Chem. Soc. 1991, 113, pp. 6992-6996 the problems associated with the use of free hydrocyanic acid are avoided by a transcyanation in the presence of hydroxynitrilase using acetone cyanohydrin in a two-phase reaction mixture consisting of an aqueous buffer solution and a water-immiscible solvent. The disadvantage in this case is that the volume of organic solvent, and as a result of the entire reaction mixture, is somewhat large in relation to the amount of aldehyde used. In addition, an extremely long reaction time and a large amount of enzyme are required. Finally, the optical purity of the cyanohydrins is also generally inadequate for enantiospecific synthesis of the target products.
As an improvement, EP-A1-0 547 655 proposes a method in which optically active cyanohydrins are produced from aldehydes or ketones and hydrocyanic acid in a two-phase system consisting of a homogeneous aqueous solution of the hydroxynitrilase and a suitable organic solvent which is at least essentially immiscible with water, the aqueous solution being buffered by an acetate buffer at a concentration of 0.005 to 0.1 mol per liter, and the ratio of organic phase to aqueous phase being between 5:1 and 1:5. The reaction system is stirred during the enzymatic reaction, the two-phase system being maintained.
Despite the reaction at a pH of about 4.5, the chemical reaction, however, cannot be suppressed completely, even in this two-phase system of organic substrate solution and aqueous enzyme solution. A disadvantage with this method is that the ee values of the cyanohydrins could only be improved by using large amounts of enzyme.
It was an object of the invention to find an improved method for the production of optically active cyanohydrins which ensures high enantiomeric purity with at the same time low enzyme and time requirements.
It has now unexpectedly been found that it is possible to react a multiplicity of carbonyl compounds, for instance aliphatic, alicyclic, unsaturated, aromatically substituted aliphatic, aromatic and heteroaromatic aldehydes and ketones, to give the corresponding cyanohydrins with high yield and at high optical purity in a more concentrated procedure, with lower enzyme usage and in with shorter reaction times, compared with the prior art, if the reaction is carried out in an emulsion. Unexpectedly, the enzyme activity remains stable under emulsion conditions which lead, with many proteins, to deactivation, such as in the case of high stirring energy.
The present invention therefore relates to a method for the production of (R)-enantiomers of optically active cyanohydrins by reacting an aldehyde or a ketone with a cyanide group donor in the presence of an (R)-oxynitrilase which is characterized in that a reaction mixture of
a) an aldehyde or ketone dissolved in an organic, water-immiscible or only slightly water-miscible diluent,
b) an aqueous (R)-oxynitrilase solution and
c) a cyanide group donor is stirred in such a manner that an emulsion forms which is maintained up to the end of the enzymatic reaction, whereupon, after the enzymatic reaction is terminated, the corresponding (R)-cyanohydrin is isolated from the reaction mixture.
The starting materials used in the inventive method are an aldehyde or a ketone, a cyanide group donor, an aqueous solution of an (R)-oxynitrilase and an organic water-immiscible or only slightly water-miscible diluent.
Aldehydes are taken to mean here aliphatic, aromatic or heteroaromatic aldehydes. Aliphatic aldehydes are taken to mean saturated or unsaturated, aliphatic, unbranched, branched or cyclic aldehydes. Preferred aliphatic aldehydes are unbranched aldehydes having, in particular, 2 to 30 carbon atoms, preferably 2 to 18 carbon atoms, which are saturated or are monounsaturated or polyunsaturated. The aldehyde can have not only Cxe2x80x94C double bonds but also Cxe2x80x94C triple bonds. The aliphatic, aromatic or heteroaromatic aldehydes can, in addition, be unsubstituted or be substituted by groups inert under the reaction conditions, for example by unsubstituted or substituted aryl or heteroaryl groups, such as phenyl, phenoxy or indolyl groups, by halogen, hydroxyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, ether, alcohol, carboxylic ester, nitro or azido groups.
Examples of aromatic or heteroaromatic aldehydes are benzaldehyde and variously substituted benzaldehydes, for instance 3,4-difluorobenzaldehyde, 3-phenoxybenzaldehyde, 4-fluoro-3-phenoxybenzaldehyde, hydroxybenzaldehyde, methoxybenzaldehyde, in addition furfural, methylfurfural, anthracene-9-carbaldehyde, furan-3-carbaldehyde, indole-3-carbaldehyde, naphthalene-1-carbaldehyde, phthaldialdehyde, pyrazole-3-carbaldehyde, pyrrole-2-carbaldehyde, thiophene-2-carbaldehyde, isophthalaldehyde or pyridinealdehydes, thienylaldehydes, etc.
Ketones are aliphatic, aromatic or heteroaromatic ketones in which the carbonyl carbon is unequally substituted. Aliphatic ketones are taken to mean saturated or unsaturated, unbranched, branched or cyclic ketones. The ketones can be saturated or monounsaturated or polyunsaturated. They can be unsubstituted, or substituted by groups inert under the reaction conditions, for example by unsubstituted or substituted aryl or heteroaryl groups such as phenyl or inolyl groups, by halogen, ether, alcohol, carboxylic ester, nitro or azido groups.
Examples of aromatic or heteroaromatic ketones are acetophenone, indolylacetone, etc.
Aldehydes and ketones which are suitable for the inventive method are known or can be produced by conventional means.
The cyanide group donor added is hydrocyanic acid. The hydrocyanic acid here can also be released shortly before the reaction from one of its salts, for instance NaCN or KCN, and added to the reaction mixture without solvent or in dissolved form.
Suitable oxynitrilases are (R)-oxynitrilases, for example, from Prunus amygdalus, Prunus laurocerasus or Prunus serotina. Preferably, the oxynitrilase used is oxynitrilase from Prunus amygdalus.
The enzyme is distinguished by a high resistance to solvents. Therefore, there is the possibility of using for the enzymatic reaction various organic solvents which permit the formation of an emulsion which has a beneficial action on the productivity of the respective process.
The oxynitrile lyase can be used in the purified or unpurified form, as such or immobilized.
The organic diluent used can be water-immiscible or only slightly water-miscible aliphatic or aromatic hydrocarbons which may be halogenated, alcohols, ethers or esters or mixtures thereof. Examples of these are diethyl ether, diisopropyl ether, dibutyl ether, methyl tert-butyl ether, ethyl acetate, propyl acetate, toluene, xylene, cyclohexane, trichloroethane, chlorobenzene, etc.
Preferably, methyl tert-butyl ether (MTBE), diisopropyl ether, dibutyl ether and ethyl acetate or a mixture of MTBE and toluene are used.
About 0.2 to 20 g of diluent and 10 to 2000 IU of activity of oxynitrilase, preferably about 50 to 1000 IU, are added per g of aldehyde or ketone.
One IU (International Unit) is that amount of an enzyme preparation which catalyzes the formation of one micromole of product per minute. The required amount of the respective oxynitrilase is best determined in an activity assay, for example by the activity assay of Sigma, similar to that of Jorns et al. J. Biolog. Chem. 254, pp. 12145-12152, 1979.
At least 1 mole, preferably 1 to 5 moles, particularly preferably 1 to 2 moles, of cyanide group donor are added per mole of aldehyde or keto group used. In the inventive method the aldehyde or the ketone is dissolved in the organic diluent. To this solution the enzyme is added in the form of an aqueous buffer solution. The pH of this solution is to be in this case less than 7, preferably between 3 and 6.5.
The resultant reaction mixture is stirred at temperatures of 0 to about 30xc2x0 C., preferably 5 to 25xc2x0 C., in such a manner that an emulsion forms. The stirrer speed (N) required for this depends on what is termed the power number of the stirrer used (Po), its diameter (d), the reaction volume (V) and the density (xcfx81) of the reaction medium. From these factors may be calculated the stirrer energy (P/V), that is to say the stirrer power per unit of reaction volume (volume of the reaction mixture, not of the apparatus).       P    /    V    =                    P        0            ·      ρ      ·              N        3            ·              d        3              V
Preferably, the stirrer energy in the inventive process is, greater than 500 W/m3, particularly preferably greater than 1000 W/m3. By way of comparison, in the case of previously known methods which operate in an aqueous, organic or two-phase system, for instance according to EP-A1-0 547 655, stirrer energies merely of approximately 100 W/m3 are achieved.
If the reaction mixture is an emulsion, the cyanide group donor is added. The emulsion is maintained until the end of the reaction. The course of the reaction can be followed, for example, photometrically via the decrease in aldehyde or ketone content.
Depending on the starting material, measurements are made at the wavelength at which the starting material absorbs and the resultant cyanohydrin does not absorb. The absorption of the reaction mixture thus decreases in proportion with increasing conversion.
However, all components may first be mixed and then the resultant reaction mixture may be stirred in such a manner that an emulsion is obtained.
When a salt of hydrocyanic acid is used, the hydrocyanic acid can first be released from a solution of the salt by adding, for example, H2SO4 or H3PO4. The pH of this solution of hydrocyanic acid should be less than 7, preferably between 4 and 6.5.
The aqueous enzyme solution, the organic diluent and the aldehyde or the ketone are then added to the hydrocyanic acid solution, the reaction is started and if appropriate the pH is readjusted.
Here also, it must be ensured that the reaction mixture is stirred in such a manner that an emulsion forms which in turn remains until the end of the reaction.
For workup of the reaction mixture and to isolate the cyanohydrin formed, customary methods are used which first break the emulsion, for example filtration, centrifugation or coalescence. The resultant phases are then separated, if appropriate with addition of demulsifiers, and the product-containing phase is worked up.
To obtain the corresponding cyanohydrin, depending on the end product, known methods such as filtration, distillation, extraction or crystallization are employed. The cyanohydrins thus obtained can, if appropriate, be stabilized by adding an acid before further processing.

Method for the production of optically active cyanohydrins using r-oxynitrilase

DSM Fine Chemicals Austria Nfg GmbH and Co KG


Illustrated and described is an ultrasonic flowmeter for flowing media, that operates according to the transit time method, with a measuring tube and at least one transmitting and/or receiving head, in connection with which the transmitting and/or receiving head has a housing and an ultrasonic transducer with which ultrasonic signals can be emitted into the flowing medium and ultrasonic signals can be received from the flowing medium. The ultrasonic flowmeter for flowing media is characterized in that a damping device with at least one damping element is arranged around the sides of the housing of the transmitting and/or receiving head and at least partly adjacent to it, and the damping device is provided in a recess of the measuring tube.

The invention relates to an ultrasonic flowmeter for flowing media, that operates according to the transit time method, with a measuring tube and at least one transmitting receiving head, in connection with which the transmitting and/or receiving head has a housing and an ultrasonic transducer by which ultrasonic signals can be emitted into the flowing medium and ultrasonic signals can be received from the flowing medium.
In industrial flow measuring of flowing media, i.e. of flowing liquids or flowing gases, the use of ultrasonic flowmeters has been gaining importance in recent times. In this connection, it is particularly advantageous, as is also the case with magnetic-inductive flowmeters, for the flow measuring to be able to take place in such a way that nothing needs to be inserted into the flow, such that the flow is not disturbed by the measurement.
In the case of ultrasonic flowmeters, as regards the measuring process a distinction is made above all between the transit time method, on the one hand, and the Doppler method, on the other hand. In this connection, the precision achievable with the transit time method is considerably greater than with the Doppler method. For this reason, ultrasonic flowmeters are preferably used that operate according to the transit time method, namely in particular according to the transit time difference method.
The transit time of an ultrasonic signal along the measuring path from the ultrasonic transducer emitting ultrasonic signals to the ultrasonic transducer receiving the ultrasonic signals in a liquid results from the acoustic velocity in the liquid or in the gas carried along in the liquid/gas as well as from the flow rate of the liquid and/or the gas carried along. The concerned principle of ultrasonic flow measuring according to the transit time method is derived from this. In the transit time difference method, ultrasonic signals are alternately or simultaneously transmitted upstream and downstream in the liquid and/or in the gas. Due to the different propagation rates, with the same length measuring path upstream and, respectively, downstream, the signals reach the ultrasonic transducers operating as receivers at different transit times. In this connection, the transit time difference of the two sound waves is directly proportional to the flow rate of the flowing medium.
For an ultrasonic flowmeter of a flowing medium, a measuring tube carrying the flowing medium and at least one ultrasonic transducer, preferably two ultrasonic transducers arranged staggered in the flow direction, and a control and evaluation circuit for determining the transit time of the ultrasonic signals are required. In addition, the control and evaluation circuit can calculate the flow rate, the flow volume and other parameters of the flowing medium from the transit time.
However, in ultrasonic flow measuring of a flowing medium there is not only the transfer, i.e. the emitting and receiving of ultrasonic signals that have run through the flowing medium, but also of ultrasonic signals that make their way beyond the measuring tube from the ultrasonic transducer emitting ultrasonic signals to the ultrasonic transducer receiving ultrasonic signals. This leads to a disturbance signal that considerably hinders the ultrasonic flow measurement under certain circumstances. The ultrasonic signal transferred beyond the measuring tube is particularly disruptive in particular because it is at least partially a coherent signal that cannot be treated as normal noise during the suppression.
To solve this problem, various suggestions have been made in the past to avoid the transfer of ultrasonic signals from the transmitting ultrasonic transducer to the receiving ultrasonic transducer beyond the measuring tube. In this connection, for example, it has been proposed to isolate the oscillating ultrasonic transducer from the measuring tube as much as possible in terms of vibration by means of rubber seals or similar devices for example. Similar approaches consisted in filling the space in which the ultrasonic transducer is arranged as far as possible with a damping material such as wax, rubber or plastic. In this respect, U.S. Pat. Nos. 4,410,825, 4,945,276 and 5,515,733 are referred to as examples.
Consequently, the invention is based on the technical problem of developing the known ultrasonic flowmeters in such a way that disturbances of ultrasonic flow measurement on a flowing medium due to ultrasonic signals transferred beyond the measuring tube are largely avoided.
The technical position deduced and described in the foregoing is solved according to the invention in that a damping device with at least one damping element is arranged around the sides of the housing of the transmitting and/or receiving head and at least partly adjacent to it, and the damping device is provided in a recess of the measuring tube.
According to the invention, the housing of the transmitting and/or receiving head in which the oscillating ultrasonic transducer is arranged is thus not directly connected with the measuring tube, but rather by means of a damping device, in such a way that the ultrasonic signals are fed into the measuring tube only through the damping device. The transition from the housing into the damping device, which is indeed connected mechanically with the housing but is not designed in one piece with it according to the invention, leads to a considerable reduction of the ultrasonic signal when it goes through the boundary surface between the housing and the damping device. In addition, signal coherence is also considerably reduced due to the dispersion of the sound at the boundary surface.
The inside of the measuring tube can already be sufficiently sealed off from the surroundings by the contact of the housing with the damping element as well as by the contact of the damping element with the measuring tube. If greater demands are made on the tightness of the ultrasonic flowmeter, however, the ultrasonic flowmeter according to the invention is preferably further developed by providing a seal between the housing and the damping device, on the one hand, and between the damping device and the measuring tube, on the other hand.
The housing can be inserted or slid into the damping device, for example, by having a recess designed in the damping device in conical shape corresponding to the outside of the housing. The housing preferably has an external screw thread and the damping device an internal screw thread, however, in such a way that the housing can be screwed with its external thread into the internal thread of the damping device. This enables the damping device to be particularly firmly seated in the housing, with the screwing having an additional sealing effect. In addition, the boundary surface between the housing and the damping device is substantially enlarged by the screwing, which has a positive effect on the damping of the ultrasonic signal penetrating the boundary surface and helps to reduce its coherence.
The size of the boundary surface through which the ultrasonic signals must pass in order to make their way from the ultrasonic transducer into the measuring tube can be further increased by the damping device having several damping elements nested into each other and at least partially contiguous. In this way, the ultrasonic signal must penetrate several consecutive boundary layers on its way from the ultrasonic transducer in order to arrive in the measuring tube.
The damping elements themselves can be sealing, if they are firmly inserted or screwed into each other, for example. However, a seal is preferably attached between each of the damping elements.
The measuring tube, the housing and the damping device with the damping elements can be made of numerous materials that only need to meet the requirements of a corresponding pressure resistance and a chemical resistance to the flowing medium. However, the measuring tube, the housing and at least one damping element preferably consist of a metal, preferably special steel.
Contiguous components, i.e. the measuring tube, the housing or the damping elements which are both designed of metal are preferably provided with sealing by being welded together.
It is also provided for, however, to have at least one damping element made of plastic, which leads to an additional damping of the ultrasonic signal due to an increased absorption of the ultrasonic signal in the plastic. Furthermore, a damping element designed of plastic that is provided firmly and tightly between two metal components can be used at the same time as a seal.
In particular when using at least one damping element of plastic, at least one of the seals is preferably rubber or plastic, with O-ring-seals of Viton being particularly useful.
A particularly reduced transmission of the ultrasonic signal to the measuring tube through the damping device is achieved when the damping device is attached to the measuring tube only on its side facing away from the ultrasonic transducer. With such a construction, before the ultrasound can penetrate the measuring tube, it must pass through the entire length of the housing and/or the damping device, thus resulting in an increased sound damping.
The damping device can be arranged directly in a recess of the measuring tube, but it is preferable for the measuring tube to have a connecting piece in which the damping device is mounted. In this connection, it is particularly preferable to arrange the damping device in the connecting piece at a distance from its inner wall in such a way that the above-described effect occurs, namely that the ultrasound must pass through the entire length of the housing and/or the damping device before it enters the connecting piece or the measuring tube. In this respect, a particularly advantageous arrangement is achieved when the damping device is connected with the connecting piece only at its free end. If the connecting piece and at least the outermost damping element are both made of metal, there is preferably a connection of the outermost damping element with the connecting piece by a weld seam that has a sealing effect at the same time.


A process for preparing caprolactam by reacting 6-aminocapronitrile with water in the presence of catalysts comprises using a starting mixture of 6-aminocapronitrile and the tetrahydroazepine derivative of the formula

The present invention relates to an improved process for preparing caprolactam by reacting 6-aminocapronitrile with water in the presence of catalysts.
On heating or storage at room temperature, 6-aminocapronitrile forms a brown tetrahydroazepine derivative (THA derivative I) of the formula
THA derivative I shall also encompass its tautomeric form
EP-A-497,333 describes the direct polymerization of polycaprolactam starting from 6-aminocapronitrile. The problem to be solved in the process mentioned was the removal of tetrahydroazepine (xe2x80x9cTHAxe2x80x9d) before the polymerization step, since tetrahydroazepine leads to discoloration of the polymer obtained on polymerizing caprolactam in the presence of tetrahydroazepine. EP-A-497,333 proposes solving the problem by means of a treatment with a basic compound such as an alkali metal hydroxide or an alkali metal alkoxide. Following the treatment, 6-aminocapronitrile can be conveniently separated from the reaction mixture by distillation, which is not possible without such a treatment. EP-A 502,439 solves the problem of removing THA in the presence of 6-aminocapronitrile by treatment with sodium borohydride. Here too 6-aminocapronitrile can be readily separated from the reaction mixture by distillation after the treatment.
DE-B-25 42 396 and DE-B-25 42 397 describe the conversion of gamma-aminobutyronitrile into a mixture comprising 2-(N-gamma-cyanopropyl)amino-deltal-pyrroline (xe2x80x9cCAPxe2x80x9d) and 2-amino-deltal-pyrroline (xe2x80x9cAPxe2x80x9d), and also the further hydrolysis of the isolated CAP to 2-pyrrolidone in the absence of catalysts. Neither reference indicates whether the corresponding THA derivative I can be converted into caprolactam in a similar manner in liquid phase in the presence of heterogeneous catalysts. Furthermore, in the cited DE references CAP is first isolated as a pure substance before it is hydrolyzed. It might therefore be expected that the use of mixtures comprising THA derivative I would promote the formation of undesirable by-products. It is also known that five-membered rings are easier to form than seven-membered rings (see Rxc3x6mpp Chemie Lexikon, 9th edition, editors Falbe and Regitz, Georg Thieme verlag, New York). Altogether and on the basis of experience with THA it might therefore be expected that THA derivative I would lead to discolored caprolactam in the cyclization of 6-aminocapronitrile and to discolored polycaprolactam in the direct conversion of 6-aminocapronitrile into polycaprolactam, unless separated off before the cyclization and before the polymerization step.
It might further be expected that THA derivative I would reduce the lifetime of the catalyst used in the polymerization, since it was known from U.S. Pat. No. 5,162,567 that heating THA produces high boilers, ie. compounds or mixtures with a higher boiling point than 6-aminocapronitrile (accordingly making it easy to remove the 6-aminocapronitrile). High boilers, however, tend to form polymeric or oligomeric decomposition products which can form deposits on catalyst surfaces and so reduce not only the lifetime but also the activity of the catalysts.
It is an object of the present invention to provide a process for cyclizing 6-aminocapronitrile to caprolactam wherein THA derivative I reduces neither the lifetime nor the activity of the cyclization catalyst, nor leads to a caprolactam-containing reaction mixture whose UV number is equal to or higher than that prior to the cyclization step. Preferably the post-cyclization UV number should be smaller than pre-cyclization as a function of the pre-cyclization THA derivative I content. Furthermore, any THA derivative I present in the reaction mixture for the direct polymerization of 6-aminocapronitrile shall be easy to remove or it shall be possible to conduct the reaction in such a way that THA derivative I is eliminated.
We have found that this object is achieved by a process for preparing caprolactam by reacting 6-aminocapronitrile with water in the presence of catalysts, which comprises using a starting mixture of 6-aminocapronitrile and the tetrahydroazepine derivative of the formula
and conducting the reaction in liquid phase in the presence of a heterogeneous catalyst.
The present invention also provides tetrahydroazepine derivative I, a process for its preparation, and the use of THA derivative I for preparing caprolactam.
The reaction of the present invention is carried out in liquid phase in the presence of heterogeneous catalysts at temperatures from generally 140 to 320 xc2x0 C., preferably from 160 to 280xc2x0 C.; the pressure is generally within the range from 41 to 250 bar, preferably from 5 to 150 bar, care having to be taken to ensure that, under the conditions employed, the reaction mixture is predominantly (ie. without the catalyst, which is present in solid phase) liquid. The residence times are generally within the range from 1 to 120, preferably from 1 to 90, in particular from 1 to 60, min. In some cases residence times from 1 to 10 min will prove completely adequate.
The amount of water used is generally at least 0.01 mol, preferably from 0.1 to 20 mol, in particular from 1 to 5 mol, per mole of THA derivative I.
Advantageously THA derivative I is used in the form of a from 1 to 50% strength by weight, in particular from 5 to 50% strength by weight, particularly preferably from 5 to 30% strength by weight, solution in water (in which case the solvent is then also the reactant) or in water-solvent mixtures. Examples of suitable solvents are alkanols such as methanol, ethanol, n- and i-propanol, n-, i- and t-butanol and polyols such as diethylene glycol and tetraethylene glycol, hydrocarbons such as petroleum ether, benzene, toluene, xylene, lactams such as pyrrolidone or caprolactam or alkyl-substituted lactams such as N-methylpyrrolidone, N-methylcaprolactam or N-ethylcaprolactam and also carboxylic esters, preferably of carboxylic acids having from 1 to 8 carbon atoms. Ammonia too can be present in the reaction. It is of course also possible to use mixtures of organic solvents. Mixtures of water and alkanols in a water:alkanol weight ratio of 1-75:25-99, preferably 1-50:50-99, have been determined to be particularly advantageous in some cases.
The THA derivative I content in the 6-aminocapronitrile of the starting mixture can be within the range from 0.01 to 95% by weight, in particular from 0.1 to 50% by weight, particularly preferably from 0.5 to 20% by weight.
The starting mixture customarily has, depending on the level of THA derivative I, a UV number (sum of all absorbances of a 10% by weight solution in ethanol at wavelengths from 280 to 400 nm, based on a path length of 5 cm) within the range from 5 to 40,000.
The starting mixture is obtainable by heating 6-aminocapronitrile with or without solvent. From experience to date, the temperature can be within the range from 20 to 280xc2x0 C., in particular within the range from 50 to 250xc2x0 C., particularly preferably within the range from 100 to 230xc2x0 C. The reaction times are customarily within the range from 10 minutes to 20 hours. As expected, shorter reaction times are possible at higher temperatures. The reaction can be carried out at pressures within the range from 100 kPa to 25 MPa, preferably from 500 kPa to 20 MPa. It can further be advantageous to carry out the reaction in the presence of acidic homogeneous or heterogeneous catalysts such as mineral acid, carboxylic acids, sulfonic acids, titanium dioxide, aluminum oxide, acid ion exchangers or Lewis acids.
If desired, pure THA derivative I can be obtained for example by distillation of unconverted 6-aminocapronitrile, solvents and any by-products.
Examples of suitable heterogeneous catalysts include: acidic, basic or amphoteric oxides of the elements of the second, third or fourth main group of the periodic table, such as calcium oxide, magnesium oxide, boron oxide, aluminum oxide, tin oxide or silicon dioxide as pyrogenic silica, as silica gel, diatomaceous earth, quartz or mixtures thereof, also oxides of metals of secondary groups two to six of the periodic table, such as titanium oxide, amorphous, as anatase and/or rutile, zirconium oxide, zinc oxide, manganese oxide or mixtures thereof. It is also possible to use oxides of the lanthanides and actinides, such as cerium oxide, thorium oxide, praseodymium oxide, samarium oxide, rare earth mixed oxide, or mixtures thereof with the aforementioned oxides. Further catalysts can be, for example:
vanadium oxide, niobium oxide, iron oxide, chromium oxide, molybdenum oxide, tungsten oxide or mixtures thereof. Mixtures between the oxides mentioned are also possible. It is also possible to use sulfides, selenides and tellurides such as zinc telluride, tin selenide, molybdenum sulfide, tungsten sulfide, sulfides of nickel, of zinc and of chromium.
The aforementioned compounds may be doped, ie. contain, compounds of main groups 1 and 7 of the periodic table.
Also suitable are zeolites, phosphates and heteropolyacids and also acidic and alkali iron exchangers such as, for example, Naphion(copyright).
If desired, these catalysts may contain up to 50% by weight each of copper, tin, zinc, manganese, iron, cobalt, nickel, ruthenium, palladium, platinum, silver or rhodium.
The catalysts can be used as solid catalyst or supported catalyst, depending on the composition of the catalyst. For instance, titanium dioxide can be used in the form of a titanium dioxide extrudate or in the form of a thin layer applied to a carrier. Any method described in the literature is suitable for applying TiO2 to a carrier such as silicon dioxide, aluminum oxide or zirconium dioxide. For instance, a thin layer of TiO2 can be applied by hydrolysis of organotitaniums such as titanium isopropoxide or titanium butoxide, or by hydrolysis of TiCl4 or other inorganic Ti-containing compounds. Sols which contain titanium dioxide are also suitable.
Particular preference is given to catalysts which contain no constituents that are soluble under the conditions of the reaction.
In a further preferred embodiment, the reaction is carried out in a fixed bed reactor. A fixed bed process is customarily carried out with tablets or extrudates having diameters within the range from 1 to 10 mm. In principle, however, the reaction can also be carried out in suspension.
In a further preferred embodiment, the reaction is carried out in particular in the presence of a heterogeneous catalyst based on titanium dioxide, zirconium dioxide, cerium oxide or aluminum oxide.
Aluminum oxide is generally suitable in all modifications obtained by heating the precursor compounds aluminum hydroxide (gibbsite, boehmite, pseudoboehmite, bayerite and diaspore) at different temperatures. These include in particular gamma- and alpha-alumina and mixtures thereof.
The oxides can be used in pure form (purity of the respective oxide greater than 80% by weight), as a mixture of the abovementioned oxides, in which case the sum of the abovementioned oxides should be greater than 80% by weight, or as supported catalyst, in which case the abovementioned oxides can be applied to a mechanically and chemically stable carrier usually with a high surface area.
The pure oxides can be prepared by precipitation from aqueous solutions, for example titanium dioxide by the sulfate process or by other processes such as the pyrogenic production of fine alumina, titania or zirconia powders which are commercially available.
Mixtures of various oxides can be prepared in various ways. The oxides or their precursor compounds, which are convertible into the oxides by calcination, can be prepared for example by coprecipitation from solution. This generally brings about very good dispersion of the two oxides used. The oxide or precursor mixtures can also be precipitated by precipitating one oxide or precursor in the presence of a fine suspension of the second oxide or precursor. A further method consists in mechanically mixing the oxide or precursor powders, this mixture can be used as a starting material for producing extrudates or tablets.
Supported catalysts can be prepared by customary methods. For instance, the oxides can be applied to the support by simply impregnating the support with their sols. The sol volatiles are customarily removed from the catalyst by drying and calcining. Sols of this type are commercially available for titania, alumina and zirconia.
A further way of applying layers of the active oxides is the hydrolysis or pyrolysis of organic or inorganic compounds. For instance, a ceramic support can be coated with a thin layer of titanium dioxide by hydrolysis of titanium isopropoxide or other titanium alkoxides. Other suitable compounds include TiCl4, zirconyl chloride, aluminum nitrate and cerium nitrate. Suitable supports are powders, extrudates or tablets of the aforementioned oxides themselves or of other stable oxides such as silica. The supports used can be macroporous to improve the mass transport.
In a further particularly preferred embodiment, the catalyst used is titanium dioxide with an anatase content within the range from 100 to 5, preferably from 99 to 10%, by weight and a rutile content within the range from 0 to 95, preferably from 1 to 90%, by weight, based on the total amount of titanium dioxide. THA derivative I is preferably used for preparing caprolactam by heating it with water/solvent at a temperature within the range from 140 to 320xc2x0 C., preferably within the range from 160 to 280xc2x0 C., and a pressure within the range from 100 to 2500, in particular within the range from 500 to 2000, kPa in the presence of the abovementioned heterogeneous catalysts, preferably titania-containing, similarly to the abovementioned starting mixture, using a molar ratio of tetrahydroazepine derivative I to water within the range from 0.01:1 to 20:1, preferably from 0.5:1 to 20:1.
The abovementioned starting mixture as aqueous solution and THA derivative I alone can be directly converted into polycaprolactam by heating by known methods, for example described in EP-A-150,295.
The advantage of the process of the present invention is that it provides a convenient way of processing THA-derivative-I-containing reaction mixtures with 6-aminocapronitrile into caprolactam and, if desired, into polycaprolactam. The products and product mixtures thus obtained are free of troublesome THA derivative I. Thus there is no need for further process steps in the use of additional agents, compared with the removal of THA from corresponding reaction mixtures.
In certain circumstances it can even be advantageous to convert 6-aminocapronitrile in whole or in part into THA derivative I by preheating to temperatures from 20 to 280xc2x0 C. and to use the resulting mixture of THA derivative I and 6-aminocapronitrile for the cyclization over oxidic catalysts.

Abstract: and conducting the reaction in liquid phase in the presence of a heterogeneous catalyst. Also describes a process for preparing said tetrahydroazepine derivative I and its use for preparing caprolactam and polycaprolactam.


A mite repellant and/or miticide composition comprising at least one compound selected from the group consisting of jasmonoide, linear sesquiterpene alcohol and linear diterpene alcohol.

1. Field of the Invention
The present invention relates to a mite repellant and/or miticide composition having an excellent anti-mite effect on mites infesting houses.
2. Discussion of the Background
A great number of the mites inhabit places poor in air permeability, such as interiors of carpets, sofas, blankets, comforters and bedclothes or mattresses. The mites in houses can form the cause of allergic disease such as bronchial asthema and allergic rhinitis, and dermatisis, and so various exterminators have been developed.
As mite repellant and/or miticide compositions, are used various kinds of agents such as pyrethroids, carbamates and organophosphorus compounds. However, these agents are high in toxicity and are not preferable from the viewpoint of safety in houses, particularly, homes having children. These conventional mite repellant and/or miticide compositions have been particularly weak in effect in places poor in air permeability, such as interiors of carpets, sofas, blankets, comforters and bedclothes due to their low volatility even if the effect is achieved in a place on which such an agent is directly spread.
Since the dead bodies and excrements of mites are also allergens, there is a demand for development of an exterminator that not only directly kills mites, but also has a strong 4 repellent effect. Mite eliminators (Japanese Patent Application Laid-Open Nos. 104905/1988 and 87409/1998) containing linalool or carvone of a plant essential oil component that is considered to be comparatively high in safety have been proposed as mite repellents. However, the effects of these agents are also not sufficient.

Mite repellant and/or miticide composition

Abstract: The mite repellant and/or miticide composition according to the invention has excellent repellent effect, growth-inhibiting effect and mite repellant and/or miticide effect on mites inhabiting houses.