RESEARCH
Transcript of RESEARCH
R E S E A R C H
The Function of α Screening Laboratory.
Dropping the chemical blind alleys. . .
To work rapidly through a store of research ideas. . .
KARL M. HERSTEIN, Herstein Laboratories, Inc., New York, Ν. Υ.
Passing the promising prospects on to specialists
Y O U R PRODUCT is a basic foodstuff with a 30-year hisjtory of extreme market stability. If your product is to expand, it must find new markets. The chemical industry is an interesting possibility, since 14 fields of organic chemistry consume materials in large enough quantities to make a successful application significant in terms of sales.
A limited number of the possibilities can be handled by research organizations with t he experience, technology, and equipment for a particular field. A stock of ideas, however, remains in which no obvious path of progress appears; a growing number of ideas—apparently sound chemically and economically—await evaluation.
This was the situation facing the Sugar Research Foundation when it was organized 13 years ago. The foundation solved the problem by going to a screening laboratory.
The usefulness of a screening laboratory depends on its ability to work through this stock of ideas. I t must have personnel and facilities to enable it to work competently and rapidly on many ideas. With unlimited time and money, each idea could be given to a separate group for prolonged study. In the absence of these pleasant but nonexistent conveniences, the screening
laboratory functions, so that from its results a decision can be made whether to apply intensive study or to discontinue work on each idea that has passed through its operation.
The Sugar Research Foundation came to the Herstein Laboratories with its problem. During the past three years 22 projects have been undertaken; two to eight have been in progress concurrently.
The first project, which is sporadically active, concerns dental caries. A reason frequently given for
limiting consumption of products high in sugar is fear of tooth decay.
If dental enamel were made hydrophobic by treatment with a suitable reagent such as a silicone, surface attack by mouth fluids would decrease. In vitro tests were made by applying about 10 silicones and fluorine-containing compounds in aqueous and nonaqueous solvents to human teeth. After treatment, the teeth were exposed to dilute lactic acid, and the susceptibility to attack estimated by colori-metric determinations of the dissolved phosphate ion. The nonenamel tooth surfaces Λ ;re protected by application
of nitrocellulose lacquer. Considerable variatioris i n protective action were found, and t h e project was transferred to The University of Toronto school of dentistry for further study.
Ammonia can b e fixed by a variety of natural substances—including carbohydrates, pectins, or lig-
nin—and the resulting products utilized b y cattle as protein equivalent. W e have ^worked intermittently- on this p r o b l e m for almost three years. Research began with comparative study of the "binding of ammonia from aqueous solution and at room temperature b y sucrose, invert sugar, molasses, inver ted molasses, and dextrose. Later, ammoniation of bee t pulp was investigated. In view of the marked success of t h i s research, patent applications have b>een made. At present, bagasse i s beiixg tested as a carrier of available ni trogen,
Continuation of earlier work by another laboratory on the reaction of sucrose with ethylene ox
ide l e d to study of the reaction of sucrose -with propylene oxide. The idea was t o produce a bread-softening agent. One mole of sucrose by this reaction
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could be bound with as many as 48 moles of propylene oxide. The materials did not appear to be particularly good bread-softening agents, so this project was screened out.
A most tempting field is synthetic plastics because of its large size and the wide variety of products
it consumes and produces. One possibility for sugar to enter this field is by reaction with urea. Sucrose carbamates alone did not appear to be promising. However, the reaction product from sucrose, urea, and formaldehyde can form a clear, colorless, hard resin of considerable promise. This project led to the decision to set up a project on the entire problem of plastics from sucrose. It is now in active prosecution at the Bjorksten Research Laboratories.
The reductive aminoly-sis of sucrose is regarded as one of the three most significant recent develop
ments in sucrochemistry, the other two being sucrose detergents and the south Puerto Rico plant producing furfural from bagasse. This reaction produces 2-methylpiperazine chiefly, along with other heterocyclic and aliphatic nitrogen compounds. To speed up the rate of data collection, the screening laboratory was called on. W e were able to convert over 90% of the sucrose carbon to distillable products and to discover a number of effects of reaction variables on the yields. Since the main product, 2-methylpiperazine, was of special interest as a precursor of high polymers, a quantity was prepared by condensation of equal moles of propylene oxide with ethylenediamine, followed by cyclization with splitting out of water. As a means of identification we found that amine salts of o-chloro-benzoic acid are well characterized and have sharp melting points in a convenient range. Part of the job, of course, was to supply samples of 2-methylpiperazine to interested prospective users.
Methionine is one of the dietary essential amino acids and is not synthesized by animals for their
own use. It is being manufactured in considerable volume as a food supplement, especially for poultry. It seemed possible that if a source of available
Karl A/I. Herstein, born in Elizabeth, N. J.3 was educated in the schools of Bayonne, N. J.? Washington, D. C , Brooklyn, Ν . Υ., and later at Columbia University. His bent for chemistry came from his father, a well known chemical economist. He has been president of Herstein Laboratories in New York for 20 years. Author of a leading text o n the chemistry and technology of wines and liquors, he describes himself as "almost a teetotaler," but insists that this has in no way interfered with his research on his book. H e is a former national councilor of the ACS and former chairman of the New York Chapter of the American Institute of Chemists.
methyl-mercapto groups could be supplied to the body, some of the methionine need could be served. We , therefore, prepared glucose dimethylmercap-tal, obtaining 70% yields. Part of the product was converted t o methylthio-glucoside. AVith slight modifications almost quantitative yields of the product were obtained. Samples of each product have been submitted to three other laboratories for nutritional and other studies. Preliminary testing indicates that these methylthio groups may not be metabolically available.
The surface coating industry is a very big consumer of organic chemicals. Since increasing the
number of unsaturated groups in the molecule produces more effective drying oils in the series methanol, ethylene glycol, glycerol, and pentaerythri-tol linseed esters, sucrose "octa-linseedate" was prepared. National Lead found the product an excellent drying oil.
Foster D. Snell, Inc., | made sucrose monof atty I acid esters by transesterifi-cation. Experiments are
now in progress to apply the transes-terification reaction in producing sucrose octa-linseedate. These esters have aroused exceedingly broad interest as surface active agents. There is every indication tha t they will b e easily competitive with other detergents now on the market and will have special features of value;. It is possible, for instance, that they may be available for use in foods. These compounds could decrease the problems of sewage disposal introduced by some of the present high-foaming materials. For personal use they are nonirritating to the skin and don't sting even if they
get into the eye. If sucrose ethers with generally similar surface active properties can be produced, they will be much less susceptible to alkaline degradation.
Although the reactions of acrylonitrile with over 400 different organic compounds have been tried,
no carbohydrate, not even sucrose, was included. W e prepared addition products containing from one to eight cy-anoethyl groups per sucrose unit. T h e nitrile group is known among other properties for its insecticidal activity, so attachment to a sugar molecule might lead to its direct absorption into the bloodstream of insects and thus to increased lethal effectiveness, as well as to a relatively low-priced insecticide. The product failed to meet these expectations. However, the carboxy-ethyl ethers of sucrose made by hydrolysis of the nitriles possess interesting sequestering powers. The sequestering agents have shown such high effectiveness that the work is now directed to broadening the knowledge of useful structures with a sugar basis.
Many desirable reactions of sucrose cannot b e performed in an aqueous medium. Data on
nonaqueous solvents for sucrose in the literature were rather scattered and completely inadequate. Therefore, a literature survey and a laboratory survey of nonaqueous solvents for sucrose were undertaken. About 45 literature references were found, each reporting at least one value for the solubility of sucrose in one or more of some 19 liquids. Most of these results have very litde pertinence for our work because, like water, t he liquids contain active hydrogens which might react, introducing further problems—hydroly-
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RESEARCH
sis, alcoholysis, a n d in other ways interfering wi th the desired reaction. T h e Literature results were mostly made a t only one temperature , and the methods of determination were questionable in some instances. At Herstein Labs, t he solubilities of sucrose in 14 solvents were determined at several temperatures. This information will b e a valuable aid to sucrochemical investigation.
T h e recent availability of perchloromethyl mer-captan suggested that its sucrose derivative might
b e an interesting and useful substance, for example as a herbicide. T h e product is a colorless, viscous sirup soluble in alcohol, acetone, and chloroform, partially soluble in water, a n d insoluble in benzene. However, on standing i t decomposed into a black, tarry residue . No more work is p lanned on this derivative.
Preliminary work on t he ammoniation of bagasse has given a number of promising indications, of
which one, possibly t h e least, is tha t a protein equivalent of well over 2 0 % can be produced by simple means. This may be a step in utilizing bagasse for cattle feed. If the work continues to b e successful, the project will be transferred to an animal husbandry depar tment for product evaluation.
At the present time, the three liveliest projects in Herstein Laboratories are the continued study of sequestering agents p repared from sugar, the ammoniation of bagasse, and the newest project, preparation of long chain monoethers of sucrose.
This incomplete listing of projects illustrates the wide variety of problems which fall to the lot of a screening laboratory. While numerous tools have been employed, the whole project has kept close to the preparat ion of specifically ordered materials and their chemical testing. Wherever broader testing in the biological field, or even in such a field as surface coatings was required, the products have been sent to specialists,
A screening laboratory therefore functions like a reconnaissance force; it must be prepared to overcome opposition—in this case, the obstinacy of nature—but it is not intended to do more than serve as a guide for the heavy artillery. η
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