Marbon solves synthesis, offers α-chloroacrylonitrile
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tine and the enzymes in six classes of vertebrates. These are man (mam- mal), chicken (aves), turtle (reptilia), frog (amphibia), perch (osteichthyes), and lamprey (cyclostomes). Dr. Van Pilsum and his coworkers have also confirmed the presence of creatine but absence of the enzymes in marine worms, sponges, sea urchins, and some other primitive creatures unrelated to the vertebrates. In checking how these lowly inverte- brates obtain their creatine, Dr. Van Pilsum and his associates exposed in- dividual bloodworms to very dilute so- lutions of carbon-14-labeled creatine. The worms readily take up the crea- tine. The rate of uptake is linearly re- lated to the square root of the weight of the worms. Earlier research by Dr. Stephens has shown that these worms can also take up labeled glycine and arginine. From this work the research group concludes that these worms must get their creatine from their surroundings. The worms lack the only known en- zymes for synthesizing creatine. They also lack the ability to convert two likely precursors—glycine and argi- nine—into creatine. In surveying primitive vertebrates the research group found that the hag- fish does not have creatine-producing enzymes. Dr. Van Pilsum explains that this indicates a major biochemical mutation between the hagfish and the lamprey. In other words, the genes of the lamprey and higher vertebrates contain the deoxyribonucleic acid code for creatine-producing enzymes. The genes of the hagfish and all lower ani- mal forms apparently do not. This finding correlates well with re- cent interpretations of the evolutionary relationship between these two ani- mals, Dr. Van Pilsum points out. They were formerly considered closely related. But some zoologists have re- cently proposed that the hagfish really represents a stock vastly more primi- tive than the lampreys. Norse markets methods, agents for resolution, racemization A new service to the chemical and drug industries—custom resolution and racemization of optical isomers— is being marketed by Norse Chemical Corp. The small specialty chemical house says it has developed unusual ion exchange techniques that will be of wide use in resolving many syn- thetic products, including drugs, vi- tamins, amino acids, fragrances, and flavors. The Cudahy, Wis., company is also offering commercial quantities of some resolving agents. In stressing the applications of the Willard C. Braaten Inactive may be an impurity techniques, president Willard C. Braaten points out that many syn- thetic drugs are used in the racemic form. But only one of the optical isomers usually has the desired phys- iological properties. The other, "in- active," isomer may be inert, it may have quite different physiological properties, or it may have serious side effects. In some cases such isomers are already removed. However, Mr. Braaten feels that the time may soon come when inactive isomers will be considered impurities and drug mak- ers will have to remove them. Mr. Braaten says the new tech- niques can first be used to identify how a racemic mixture should be re- solved. Norse can then produce a custom-designed resolving agent for separating the isomers if this proves necessary. Norse may then resolve the product at its Cudahy plant on a production basis. Alternately, the company will supply the customer with the resolving agent and help him set up his own system to do the job. The racemization method converts one optical isomer either directly into its enantiomer or into a 50/50 racemic mixture of the two optical isomers. Mr. Braaten is reluctant to disclose details of his processes. But he says that they will resolve isomers at ef- ficiency levels of 60 to 90%. This is well above the 25 to 50% typically attainable with more traditional meth- ods that depend on fractional crystal- lization, he points out. The resolving agents the company is now offering are d- and Z-mandelic acid, d- and Z-malic acid, and d- and Z-phenylethylamine. Norse's price is $15 per pound for the mandelic acid and phenylethylamine isomers, and less for the malic. Marbon solves synthesis, offers a-chloroacrylonitrile a-Chloroacrylonitrile, a highly reactive monomer and chemical intermediate, is now commercially available from Marbon Chemical, Washington, W.Va. Several companies offered it briefly in development quantities a number of years ago but gave up on it, primarily because of a costly and inefficient syn- thesis. The compound is made by chlori- nating acrylonitrile to dichloropropio- nitrile, which is then dehydrohalogen- ated by cracking to a-chloroacryloni- trile and various by-products. After five years, Marbon scientists suc- ceeded in optimizing the a-chloroacryl- onitrile yield of the dehydrohalogen- ation. The company has been making the product in a pilot plant for about a year. Output from this plant is now available (under the tradename Alpha- Clan) at $1.50 per pound. As a hybrid of vinyl chloride and acrylonitrile, a-chloroacrylonitrile has chemical properties common to both compounds, including an activated carbon-carbon double bond and reac- tive chlorine and nitrile moieties. It readily polymerizes and copolymerizes with other unsaturated monomers. The presence of chlorine in the mol- ecule gives a-chloroacrylonitrile sev- eral advantages over acrylonitrile, Marbon says. For example, fiber made from a copolymer of acryloni- trile and Alpha-Clan has 40% higher dye uptake than does acrylic fiber. The chlorine site adds greatly to the cross-linking ability of Alpha-Clan copolymers. Small amounts of Alpha- Clan (less than 15%) improve the curing properties of acrylic latexes and plastics. The chlorine site also imparts to polymers resistance to heat, fire, oil, water, and oxidation. For example, Alpha-Clan homopolymer is being studied for use in solution-deposited coatings and films having these prop- erties. Also, Marbon is studying the grafting of a-chloroacrylonitrile to cel- lulose fiber to make it water-repellent. Alpha-Clan undergoes several reac- tions which may make it a useful in- termediate. The carbon-carbon dou- ble bond can take part in a Diels- Alder reaction, yielding highly chlori- nated cyclic adducts which have been used as insecticides. The nitrile group is affected by acid hydrolysis. With 85% sulfuric acid, a-chloroacrylamides are pro- duced. Concentrated hydrochloric acid gives a-chloroacrylic esters. These products can be useful mon- omers—a-chloromethyl methacrylate has properties common to vinyl chlo- ride and methyl methacrylate. 14 C&EN MAY 1, 1967
Transcript of Marbon solves synthesis, offers α-chloroacrylonitrile
tine and the enzymes in six classes of vertebrates. These are man (mammal) , chicken (aves), turtle (reptilia), frog (amphibia), perch (osteichthyes), and lamprey (cyclostomes). Dr. Van Pilsum and his coworkers have also confirmed the presence of creatine but absence of the enzymes in marine worms, sponges, sea urchins, and some other primitive creatures unrelated to the vertebrates.
In checking how these lowly invertebrates obtain their creatine, Dr. Van Pilsum and his associates exposed individual bloodworms to very dilute solutions of carbon-14-labeled creatine. The worms readily take up the creatine. The rate of uptake is linearly related to the square root of the weight of the worms. Earlier research by Dr. Stephens has shown that these worms can also take up labeled glycine and arginine.
From this work the research group concludes that these worms must get their creatine from their surroundings. The worms lack the only known enzymes for synthesizing creatine. They also lack the ability to convert two likely precursors—glycine and arginine—into creatine.
In surveying primitive vertebrates the research group found that the hag-fish does not have creatine-producing enzymes. Dr. Van Pilsum explains that this indicates a major biochemical mutation between the hagfish and the lamprey. In other words, the genes of the lamprey and higher vertebrates contain the deoxyribonucleic acid code for creatine-producing enzymes. The genes of the hagfish and all lower animal forms apparently do not.
This finding correlates well with recent interpretations of the evolutionary relationship between these two animals, Dr. Van Pilsum points out. They were formerly considered closely related. But some zoologists have recently proposed that the hagfish really represents a stock vastly more primitive than the lampreys.
Norse markets methods, agents for resolution, racemization
A new service to the chemical and drug industries—custom resolution and racemization of optical isomers— is being marketed by Norse Chemical Corp. The small specialty chemical house says it has developed unusual ion exchange techniques that will be of wide use in resolving many synthetic products, including drugs, vitamins, amino acids, fragrances, and flavors. The Cudahy, Wis., company is also offering commercial quantities of some resolving agents.
In stressing the applications of the
Willard C. Braaten Inactive may be an impurity
techniques, president Willard C. Braaten points out that many synthetic drugs are used in the racemic form. But only one of the optical isomers usually has the desired physiological properties. The other, "inactive," isomer may be inert, it may have quite different physiological properties, or it may have serious side effects. In some cases such isomers are already removed. However, Mr. Braaten feels that the time may soon come when inactive isomers will be considered impurities and drug makers will have to remove them.
Mr. Braaten says the new techniques can first be used to identify how a racemic mixture should be resolved. Norse can then produce a custom-designed resolving agent for separating the isomers if this proves necessary. Norse may then resolve the product at its Cudahy plant on a production basis. Alternately, the company will supply the customer with the resolving agent and help him set up his own system to do the job. The racemization method converts one optical isomer either directly into its enantiomer or into a 50/50 racemic mixture of the two optical isomers.
Mr. Braaten is reluctant to disclose details of his processes. But he says that they will resolve isomers at efficiency levels of 60 to 90%. This is well above the 25 to 50% typically attainable with more traditional methods that depend on fractional crystallization, he points out.
The resolving agents the company is now offering are d- and Z-mandelic acid, d- and Z-malic acid, and d- and Z-phenylethylamine. Norse's price is $15 per pound for the mandelic acid and phenylethylamine isomers, and less for the malic.
Marbon solves synthesis, offers a-chloroacrylonitrile
a-Chloroacrylonitrile, a highly reactive monomer and chemical intermediate, is now commercially available from Marbon Chemical, Washington, W.Va. Several companies offered it briefly in development quantities a number of years ago but gave up on it, primarily because of a costly and inefficient synthesis.
The compound is made by chlorinating acrylonitrile to dichloropropio-nitrile, which is then dehydrohalogen-ated by cracking to a-chloroacrylonitrile and various by-products. After five years, Marbon scientists succeeded in optimizing the a-chloroacrylonitrile yield of the dehydrohalogen-ation. The company has been making the product in a pilot plant for about a year. Output from this plant is now available (under the tradename Alpha-Clan) at $1.50 per pound.
As a hybrid of vinyl chloride and acrylonitrile, a-chloroacrylonitrile has chemical properties common to both compounds, including an activated carbon-carbon double bond and reactive chlorine and nitrile moieties. It readily polymerizes and copolymerizes with other unsaturated monomers.
The presence of chlorine in the molecule gives a-chloroacrylonitrile several advantages over acrylonitrile, Marbon says. For example, fiber made from a copolymer of acrylonitrile and Alpha-Clan has 40% higher dye uptake than does acrylic fiber.
The chlorine site adds greatly to the cross-linking ability of Alpha-Clan copolymers. Small amounts of Alpha-Clan (less than 15%) improve the curing properties of acrylic latexes and plastics.
The chlorine site also imparts to polymers resistance to heat, fire, oil, water, and oxidation. For example, Alpha-Clan homopolymer is being studied for use in solution-deposited coatings and films having these properties. Also, Marbon is studying the grafting of a-chloroacrylonitrile to cellulose fiber to make it water-repellent.
Alpha-Clan undergoes several reactions which may make it a useful intermediate. The carbon-carbon double bond can take part in a Diels-Alder reaction, yielding highly chlorinated cyclic adducts which have been used as insecticides.
The nitrile group is affected by acid hydrolysis. With 85% sulfuric acid, a-chloroacrylamides are produced. Concentrated hydrochloric acid gives a-chloroacrylic esters. These products can be useful monomers—a-chloromethyl methacrylate has properties common to vinyl chloride and methyl methacrylate.
14 C&EN MAY 1, 1967
