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

2 8 6 2 C & E N J U N E I I , 1956

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-

J U N E I I . 1956 C & E N 2 8 6 3

Here are some applications where quality NaBH4 can benefit your processing

As α specific reducing agent To remove trace impurities As a deoxidizing agent

• To remove undesirable colors • To remove heavy metals From solution • To treat metal surfaces

These are just a few of many uses chemical processers a r e finding for this versatile product. Now available in commercial quantities from Callery Chemical Company, NaBKU has a number of characteristics that make it ideal for a variety of applications. I t reduces aldehydes, ketones, esters, nitriles, carboxylie acid and metal ions. It is soluble in water, alcohol, amines and dimethyl glycol ethers.

Perhaps there are processes in your operation where NaBH4 can improve your end-product. . . provide economies. Our staff is a t your service. We will be happy to apply our eight years of experience t o your particular problems.

OTHER CALLERY C H E M I C A L B O R O N C O M P O U N D S • Amine bonnes R3N:BH3 · Sodium Trialkoxyborohydride NaBH(OR)3 • Methyl Borate B(OCH3)3 · Trimethyoxyboroxine B203BCOCH3)3

• Sodium Tetramethoxyborate NaB(OCH3)4 Also—Potassium Metal and Sodium Potassium Alloy (NaK)

Available in drum or carload quantities

RY CHEMICAL C O M P A N Y C A L L E R Y , PA.

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

2 8 6 4 C & E N J U N E I I , 1 9 5 6