Organic Syntheses Part 1

Organic Syntheses.

by James Bryant Conant, Editor.

INTRODUCTION TO THE SERIES

THE publication of this series of pamphlets has been undertaken to make available in a permanent form complete detailed directions for the preparation of various organic chemical reagents.

In announcing this purpose it may be well to mention at the outset some of the difficulties in the way of the research chemist, which it is hoped this series will be able to overcome. The cost of chemicals is prohibitive to the majority of chemists; this was true before the war when Kahlbaum's complete supply was available, and to-day with our dependence on domestic stocks, this cost has increased.

The delay in obtaining chemicals, especially from abroad, even if the expense need not be considered, is an important factor.

These difficulties have therefore thrown the research chemist on his own resources. The preparation of materials for research, always time consuming and annoying, is made increasingly so by the inexactness of the published information which so often omits essential details.

Because of this, much needless experimentation is necessary in order to obtain the results given in the published reports.

As the additional information thus acquired is seldom published, duplication of such experiments occurs again and again,-- a waste of time and material. It is hoped these difficulties may be remedied by the publication of this series of pamphlets.

In other words, the authors hope to make this a clearing house for the exchange of information as to methods of preparation of some of the most needed organic chemical reagents.

On account of the impossibility of obtaining the less common organic chemicals in the United States during the past few years, university laboratories have had no option but to prepare their own supplies. At the University of Illinois, for instance, a special study has been made of this field, and methods for the production of various substances have been investigated.

As a result, reliable methods and directions have been developed for producing the materials in one-half to five pound lots.

Such work as Illinois has done is now being given an even more extensive scope at the Research Laboratory of the Eastman Kodak Company. It is felt that the results from these various laboratories should be available to all chemists and it is hoped that they eventually will be completely incorporated in these pamphlets.

The organic chemicals herein discussed have been quite arbitrarily chosen, being those which have been needed in various research laboratories in the last years and for which the directions happen now to be ready for publication. The methods are in only a few cases new ones; they are in general the most satisfactory to be found in the literature. Only such details have been added as will enable a man with a reasonable amount of experience in organic chemistry to duplicate the results without difficulty.

To be absolutely sure that each set of directions can be repeated, every experiment has been carried out in at least two laboratories.

Only after exact duplication of the results in both laboratories are the directions considered ready for publication.

The names of the chemists who have studied the various experiments are given so that further information concerning any obscure point can be obtained if any question arises in using these directions.

And finally, in describing the experiments, special attention has been given to the explanation of why it is necessary to follow the directions carefully, and what will happen if these directions are not followed.

Although the main object in this series is to give the most convenient laboratory methods for preparing various substances in one-half to five pound lots, an attempt has also been made to have these processes as far as possible adaptable to large scale development.

For example, extractions have been avoided wherever possible, cheap solvents have been sub-st.i.tuted for expensive ones, and mechanical agitation, a procedure extremely important in the success of many commercial processes, has usually been specified.

The apparatus used is always carefully described and wherever necessary an ill.u.s.tration is given. Accompanying each preparation there will be found a bibliography containing references to all the methods for the production of the substance described in the literature.

This is given in order to aid any future investigator who may wish to study or improve the methods of preparation.

It is not claimed that the methods are, in every case, completely perfect, but only that the yields are very satisfactory and allow the production of the substances at a reasonable cost.

It is hoped therefore that the pamphlets will benefit not only the scientific research man of the university, but also the technical chemist who desires to develop the preparation of one of these substances to a large scale process of manufacture.

The editors trust also that this work may be used to advantage as a preparation manual in intermediate or advanced courses in organic chemistry in university laboratories, and that it will aid small colleges in the production of necessary reagents which they are often financially unable to purchase.

The pamphlets are to be edited by the following committee: Roger Adams, University of Illinois, Urbana, Illinois; J. B. Conant, Harvard University, Cambridge, Ma.s.sachusetts; H. T. Clarke, Eastman Kodak Company, Rochester, New York; Oliver Kamm, Parke, Davis Company, Detroit, Michigan; each to act for one year as editor-in-chief and the other three to a.s.sist him as a.s.sociate editors. A new number of the series will appear annually, and every five years the data will be rearranged, revised, corrected, and then published in book form.

The number of preparations to be completed yearly is not fixed.

There will be, it is certain, about twenty; and it is hoped, as the interest is stimulated in this work, that this number may increase considerably. The editors especially desire to solicit contributions from other chemists, not only in this country but abroad.

Whenever a compound is thoroughly and extensively studied in connection with some research, it is hoped that complete directions for its preparation will be a.s.sembled and sent to the editor.

He will then have them checked and published in a subsequent number.

Directions for the preparation of substances already on the market are needed to make this work complete and will be gladly accepted.

It will, of course, be recognized that an occasional mistake or omission will inevitably be found in such a pamphlet as this which contains so many references and formulae. The committee on publication will therefore deem it a favor if they are notified when any such error is discovered. It is hoped also that if any chemist knows a better method for the preparation of any of the compounds considered, or if anyone discovers any improvements in the methods, he will furnish the authors with such information. Any points which may arise in regard to the various preparations will be gladly discussed.

In conclusion, the editors are ready to do all they can to make this.

work successful, and welcome suggestions of any kind.

They feel that the success of the series will undoubtedly depend upon the cooperation of others, and as its success promises to be important to research chemists, the editors urge all interested to a.s.sist. THE EDITORS

TABLE OF CONTENTS PAGE I. BENZALACETOPHENONE...........................1 II. BENZYL BENZOATE.............................5 III. BENZYL CYANIDE.............................9 IV. a, g-DICHLOROACETONE..............13 V. _p_-DIMETHYLAMIn.o.bENZALDEHYDE..................17 VI. ETHYL OXALATE...............................23 VII. ETHYL PHENYLACETATE........................27 VIII. GLYCEROL a, g-DICHLOROHYDRIN....29 IX. GLYCEROL a-MONOCHLORORYDRIN............33 X. HYDRAZINE SULFATE............................37 XI. MESITYLENE..................................41 XII. METHYL RED.................................47 XIII. _p_-NITROBENZOIC ACID.......................53 XIV. _p_-NITROBENZYL CYAI~DE......................57 XV. _p_-NITROPHENYLACETIC ACID....................59 XVI. NITROSO-b-NAPHTHOL....................61 XVII. PHENYLACETIC ACID.........................63 XVIII. PHENYLACETYLENE..........................67 XIX. PHENYLHYDRAZINE............................71 XX. PHTHALIMIDE.................................75 XXI. QUINOLINE..................................79 XXII. QUINONE...................................85 XXIII. SODIUM _p_-TOLUENESULFINATE................89 XXIV. 1,3,5-TRINTROBENZENE......................93 XXV. 2,4,6-TRINTROBENZOIC ACID..................95 INDEX.....................................99

ORGANIC SYNTHESES

I

BENZALACETOPHENONE

C6H5CHO + C6H5COCH3 + (NaOH)--> C6H5CH=CHCOC6H5 + H2O

Prepared by E. P. KOHLER and E. M. CHADWELL. Checked by H. T. CLARKE and R. P. LEAVITT.

1. Procedure

A SOLUTION of 218 g. of sodium hydroxide in 1960 g.

of water and 1000 g. of 95 per cent alcohol are introduced into a 5500-cc. bottle which is loosely covered with a perforated disk of cardboard, supplied with an effective stirrer, and supported in a larger vessel so as to permit cooling with cracked ice.

Into the alkaline solution, 520 g. of pure acetophenone is poured, the bottle is rapidly surrounded with cracked ice, and the stirrer started; 460 g. of benzaldehyde (U. S. P.) are then added at once.

The temperature of the mixture should not be below 15'0 and it should not be allowed to rise above 30'0 during the reaction.

If it tends to do so, the stirring is not sufficiently vigorous.

It is advantageous, though not essential, to inoculate the mixture with a little powdered benzalacetophenone after stirring for half an hour. After two to three hours, the mixture becomes so thick that the stirring is no longer effective. The stirrer is then removed and the mixture left to itself in an ice-box for about ten hours. The mixture now is a thick paste composed of small shot-like grains suspended in an almost colorless liquid.

It is cooled in a freezing mixture and then either centrifuged or filtered on a large Buchner funnel, washed with water until the was.h.i.+ngs are neutral to litmus, and finally washed with 200 cc.

of alcohol, which has previously been cooled to 0'0. After thorough drying in the air, the crude product weighs about 880 g.

(yield 97 per cent of the theoretical amount) and melts at 50-54'0.

It is sufficiently pure for most purposes but tenaciously holds traces of water. It is most readily purified by recrystallization from four to four and a half times its weight of 95 per cent alcohol.

Eight hundred and eighty grams of crude product give 770 g.

(85 per cent of the theoretical amount) of light-yellow material (m. p. 55-57'0) and 40-50 g. that require recrystallization.

2. Notes

The acetophenone should be as pure as possible (m. p.

20'0). Commercial acetophenone contains variable quant.i.ties of impurities which reduce the yield. By distilling commercial acetophenone with the help of a good still-head (preferably under diminished pressure) and using only the fraction which boils at 201-202'0 (76-77'0/10 mm.) greater quant.i.ties of benzalacetophenone can be obtained than by using the entire sample.

Commercial benzaldehyde can be used in place of the purer product, but the amount used must be increased to make up for the impurities which are present.

If the temperature is too low, or the stirring too slow, the product separates as an oil, which later solidifies in large lumps.

If the temperature is allowed to rise above 30'0, secondary reactions diminish both the yield and the purity of the product.

The most favorable temperature is 25'0.

In recrystallizing benzalacetophenone, the alcohol should be saturated at 50'0. If the solution is saturated above this temperature, the benzalacetophenone tends to separate as an oil. The solution should be allowed to cool gradually, and should finally be chilled in a freezing mixture. 3. Other Methods of Preparation

The methods for producing benzalacetophenone are: the action of acids on a mixture of benzaldehyde and acetophenone or on a solution of these substances in glacial acetic acid;[1] the condensation of benzaldehyde and acetophenone with a 30 per cent solution of sodium methylate at low temperatures;[2] the action of sodium hydroxide on an alcoholic solution of benzaldehyde and acetophenone.[3]

The methods based on the use of acids as condensing agents were not considered, because Claisen, who devised them, abandoned them after he found that alkaline condensing agents gave better results.

The preliminary experiments showed that condensation with sodium methylate takes a long time and gives a product which it is difficult to handle in large quant.i.ties. The method devised by Kostanecki and Rossbach[3] has therefore been developed.

[1] Ber. 14, 2463 (1881).

[2] Ber. 20, 657 (1887).