undergraduate laboratory course in aromatic chemistry based on sequence syntheses

3
LABORATORY COURSE IN AROMATIC .CHEMISTRY BASED ON SEQUENCE SYNTHESES MANUEL M. BAIZER Brooklyn College, Brooklyn, New York Om OF THE features of the laboratory course in aro- matic chemistry which students at this college find most attractive is the "sequence synthesis" assignment. Beginning with the fourth or fifth laboratory period, t,he student undertakes, in addition to his regnlarly scheduled experiments, a series of syntheses in which the product of the first reaction is the starting mate- rial for t.he second reaction, etc. The'"sequence syn- thesis" runs to the end of the semester. Allocation of time for this work is arranged by the student himself so that it does not interfere with his other preparations. The product chosen as the final objective of the ex- bended synthesis derives interest not only from the fact that it is relatively difficult to prepare but generally also because it finds application in one of the several branches of Applied Chemistry. The following are typical sequences that have been fonnd suitable for inclusion in our course: (I) Ht:nzyl chloride --t benzyl cyanide - p-nitl.ophenyhcetic acid --r p-aminophenylacetic acid - p-bromoph$nyl- scetieseid (2) Sitrobenzene - hydraeohonzene + henzidine + Congo Red (3) Tolueno - saccharin (1) Phenol --t ooumarin (5) p-Sitrotoluene + esters oi p-aminobenzoic aeid In contrast to the usual one-step "prep" these syn- theses are lengthy projects. The student is stimu- lated to exert his best efforts in order t,hat at the end of the semester he may, with pride, present a ponder- able sample of a chemical which he has literally wrested from a maze of products and by-products that threat- ened to engulf him. He has had to think of timing his work carefully. He has generally had to consult references other than his own text and laboratory manual; he may even have had the new experience of consulting original papers. He has very likelv encountered reaction types which would otherwise not have come within his ken in an undergraduate lahora- tory. One incidental but important experience that is an outgrowth of the "sequence synthesis" is the practice of paying more than usual attention to the properties of intermediates so that they may be properly stored until needed. Many of the advantages of interest and selfdisciplinc that accrue to a student from carrying through a "se- quence synthesis" can be gained from a laboratory course in aromatic chemistry in which all the prepara- tions are part of a small number of major sequences. The starting material for each of these sequences in this plan is benzene, so that in effect all aromatic products are totally synthesized from the parent hydro- carbon. (One need not approach any more closely the popular starting materials, "coal, air and water.") A variety of undergraduate laboratory courses in aromatic chemistry can be devised in which the pre- parative experiments are based on sequence syntheses. They must all be designed, however, to include san- plings of the cornmoil aromatic reaction types (such as Friedel-Crafts reaction, nitration, etc.) and to afford practical instruction in a number of standard manipu- lative skills (e. g., vacuum distillation, recrystalliza- tion, use of mechanical stirring, etc.). The scheme proposed below has the virtue of re- quiring possihly the least modification of currently t r , IiUitrobenzene I -m-Dinitrobenzene 4 11,'. I ( XXI ' m-Phenyl$ned~nminc 1 XXII I . Benzidine 13cneddehyde Diphenjl- 4 Reneonitrile 4 methanr Quinaline Benzaldchyde I XVII Sie?tinic acid XIS L-Phenylhydrazine .kcetanilid Cinnamic acid Benzylaloohol + Sulfanilamide 1 VI x ' ' 1 knzoic XIV xid prontos,lt --------- ........ : ........... -' Benzoin 111 4 xv Bend ~he*nol [ , 7 svrrr , XVI B~nzilio acid Salicylaldehyde .%nisolr 4 xx XI Diphenylaeet~c acid Coumarin X6

Upload: manuel-m

Post on 19-Feb-2017

213 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Undergraduate laboratory course in aromatic chemistry based on sequence syntheses

LABORATORY COURSE IN AROMATIC .CHEMISTRY BASED ON SEQUENCE SYNTHESES

MANUEL M. BAIZER Brooklyn College, Brooklyn, New York

Om OF THE features of the laboratory course in aro- matic chemistry which students a t this college find most attractive is the "sequence synthesis" assignment. Beginning with the fourth or fifth laboratory period, t,he student undertakes, in addition to his regnlarly scheduled experiments, a series of syntheses in which the product of the first reaction is the starting mate- rial for t.he second reaction, etc. The'"sequence syn- thesis" runs to the end of the semester. Allocation of time for this work is arranged by the student himself so that it does not interfere with his other preparations. The product chosen as the final objective of the ex- bended synthesis derives interest not only from the fact that it is relatively difficult to prepare but generally also because it finds application in one of the several branches of Applied Chemistry.

The following are typical sequences that have been fonnd suitable for inclusion in our course:

( I ) Ht:nzyl chloride --t benzyl cyanide - p-nitl.ophenyhcetic acid --r p-aminophenylacetic acid - p-bromoph$nyl- scetieseid

(2) Sitrobenzene - hydraeohonzene + henzidine + Congo Red

(3) Tolueno - saccharin (1) Phenol --t ooumarin (5) p-Sitrotoluene + esters oi p-aminobenzoic aeid

In contrast to the usual one-step "prep" these syn- theses are lengthy projects. The student is stimu- lated to exert his best efforts in order t,hat a t the end of the semester he may, with pride, present a ponder- able sample of a chemical which he has literally wrested from a maze of products and by-products that threat- ened to engulf him. He has had to think of timing his

work carefully. He has generally had to consult references other than his own text and laboratory manual; he may even have had the new experience of consulting original papers. He has very likelv encountered reaction types which would otherwise not have come within his ken in an undergraduate lahora- tory.

One incidental but important experience that is an outgrowth of the "sequence synthesis" is the practice of paying more than usual attention to the properties of intermediates so that they may be properly stored until needed.

Many of the advantages of interest and selfdisciplinc that accrue to a student from carrying through a "se- quence synthesis" can be gained from a laboratory course in aromatic chemistry in which all the prepara- tions are part of a small number of major sequences. The starting material for each of these sequences in this plan is benzene, so that in effect all aromatic products are totally synthesized from the parent hydro- carbon. (One need not approach any more closely the popular starting materials, "coal, air and water.")

A variety of undergraduate laboratory courses in aromatic chemistry can be devised in which the pre- parative experiments are based on sequence syntheses. They must all be designed, however, to include san- plings of the cornmoil aromatic reaction types (such as Friedel-Crafts reaction, nitration, etc.) and to afford practical instruction in a number of standard manipu- lative skills (e. g., vacuum distillation, recrystalliza- tion, use of mechanical stirring, etc.).

The scheme proposed below has the virtue of re- quiring possihly the least modification of currently

t r , IiUitrobenzene I

-m-Dinitrobenzene 4 11,'.

I ( XXI ' m-Phenyl$ned~nminc 1 XXII I . Benzidine 13cneddehyde Diphenjl- 4 Reneonitrile 4 methanr Quinaline

Benzaldchyde I XVII Sie?tinic acid

X I S

L-Phenylhydrazine

.kcetanilid

Cinnamic acid Benzylaloohol + Sulfanilamide

1 VI x'' 1 knzoic XIV x i d

prontos,lt ---------........ : ........... -' Benzoin 111 4 xv

B e n d ~he*nol [, 7 svrrr

, XVI B~nzilio acid

Salicylaldehyde .%nisolr 4 xx XI Diphenylaeet~c acid

Coumarin X 6

Page 2: Undergraduate laboratory course in aromatic chemistry based on sequence syntheses

JUNE, 1948 337

accepted course plans, since a large number of the his sequences with relatively large-scale laboratory syutheses present.ed in widely used lahoratory manuals "prepsn-which, incidentally, utilize inexpensive ma- derive from either nitrobeuzene or henzaldehyde. terials-and in the course of the semester he will gain

A listing of these experiments is presented below experience in the use of progressively smaller quanti- giving experiment number, name of the reaction illus- ties of material and appropriately scaled apparatus. trated, and reference to detailed direct,ions which can His manipulative skill will be increasingwith practice .be adapted to the requirements of this course: while at the same time his need for exercizing' that

skill will be continuously sharpened by the knowledge . . -- that small losses of product become ever more im-

Erperimenl .Vumber Reaction Illustralion Reference portant on a percentage basis and that only the in-

telligent application of the laboratory arts will as- I ; 1: Nitrat,ion

11; I1 Reduction of -NO1 to -N& 4) sure him of achieving the final product of a sequence. I11 Diszotisation and hydrolysis ( i d If a student occasionally succeeds in obtaining only IV Acetylation of -NH2 ( 1 4 disappointing yields, he may have to conclude his se- V Chlorosulfonation and ammonolysis ( l e )

VI Diaaotiaation and coupling; formation (4) quences by experiments on a semi-micro scale. It, is of anaso dye not to be inferred, of course, that instruction in semi-

VII Chloromethylation VIII Friedel-Crafts reaction

(6) ( I f )

micro techniques is offered as a reward for poor success IX Controlled sidechain oxidation (6,; 6b) in ~ynthesis. The instructor may wish to include one X Canniaaaro reaction (19) or more small-scale syntheses a t the end of the semester

XI; XI' Perkin resetion XI1 Reimer-Tiemsnn resetion

(Ih; ') as an integral part of the program, and with this pur- XI11 Skraup synthesis

( 8 4 ( l i ) pose in mind he will suitably calculate the quantity of

XIV Benzoin condensation XV Oxidation of a secondary alcohol

( I A , starting material he dispenses a t the start. XVI Benzilic acid rearrangement

(Ik) (11) Alternatively, the instructor may desire that all t,he

ICVII Side-chain oxidation; decarboxylation (9%) preparations be made on approximately the same SVIII Formation of a phenolic ether ( 9 4

XIX Reduction of a, diazonium compound (Im) - scale. In that case the student (or class) prepares X X Reduction of a secondary alcohol (10) each chemical in the sequences chosen but not the total

XXI Controlled reduction of -NO2; hen& (9c) quantity that is required for the subsequent step. The dine rearrangement

XXII Sandmeyer reaction (8b) balance is supplied from stock, and the student will SXIII Stephen reaction ( 1 1 ~ ; l i b ) readily adjust to the idea that if he had scaled up

earlier experiments he would indeed have prepared all his compounds from one sample of benzene.

Obviously more experiments are included here than The suggestions presented in this paper apply only to can be performed by each student in a one-semester the preparative aspects of a laboratory course in aro- course affording four hours of laboratory work per matic chemistry. It is assumed that the course in- week. The instructor will have to make adjustments cludes.numerous test-tube experiments which illustrate in the outline to accommodate it to his requirements. qualitatively characteristic reactions of the various He may wish to cut short one or more of the sequence aromatic types. No recommendation is made con- branches; he may, in order to include as many types of cerning the genesis of the aromatic reagents which synthesis as possible, reduce some to test-tube scale; he may be needed for these tests. may have a portion of the class work on one sequence The author intends to prepare a syllabus of experi- while another follows a different but closely related ments and to have his students a t this college assay the sequence.' This last procedure has much to recom- success of a sequence synthesis course. It is hoped mend it, for it introduces additional elements of variety that instructors elsewhere will be inclined to initiate and interest into the laboratory and permits a student similar plans and to report their findings. to observe the techniques and practices involved in It is a pleasure to acknowledge the friendly interest experiments which he has not the opportunity to per- of Professors Louis Sattler and Elise Tobin of this de- form himself. partment in this project.

A laboratory course based on sequence syntheses al- lows for interesting variations in the scale of opera- CITED tions. Here, too, the instructor will wish to exercise (I) ROBERTSON, G. R., "Laboratory Practice oi Organic his own discretion and preference. He may give the Chemistry," Revised edition. Maomillan Co., New student (or class) one bottle of benzene a t the be- York, 1943. (a) p. 242; ( b ) p. 250; (c) p. 262; ( d ) p. ginning of the semester and announce that no addi- 251; (e) p. 324; (fl p. 300; ( g ) p. 279; (h) p. 282; ( i ) p.

331; ( j ) p. 280; (k) p. 281; (1) p. 281; (m) p. 276. tional starting material or other aromatic compound (2) A ~ ~ ~ ~ ~ , H., S. H. M ~ E ~ ~ ~ ~ ~ , AND N. W. K ~ ~ ~ ~ , rtpraC. will be ~upplied.~ The student will therefore start tice of Organic Chemistry," MoGraw-Hill Book Co.,

Inc., New York, 1940. (a) p. 225; (b) p. 101. For example, onehalf the class may prepare aniline while (3) WILLIUS, R. J., AND R. Q. BREWWER, "Laboratory

the other prepares m-phenylenediamine. The same division of Manual of Organic Chemistry,'' Van Nostrand Co., Xew work applies to the preparation of oinnamic acid and of coumarin. York, 1934, p. 119.

a In case of accident or other unusul circumstance this decree (4) RICHTER, G. H., "Laboratory Manual of Elementary Or- will have to be interpreted liberslly. (Cmtinued o n page 541)

Page 3: Undergraduate laboratory course in aromatic chemistry based on sequence syntheses

JUNE, 1948

LABORATORY COURSE IN AROMATIC CHEMISTRY BASED ON SEQUENCE SYNTHESES

(Continued from page 337)

ganic Chemistry," John Wiley & Sons, Inc., New York, (8) GATTERMAAN, L., AND H. WIELIND, "Lahomtory Methods 1940, p. 104. of Organic Chemistry," iVIacmillan Co., New York,

(5) F u s o ~ AND MCKEEVER, "Organic Reactions" (Adams, 1932. (a) p. 226: (b) p. 193. Editor-in-chief), John Wiley & Sons, Ino., New York, (9) FISHER, H. L., "hboratory Manual of Orgsnio Chenl- 1942, Val. I , p. 67. istry," 4th ed., John Wiley & Sons, Ino., New York,

(6) (a) ULLMANN, F., "EnzyklopBdie der Technisohon Chemie," 1938. (a) p. 215; (b) p. 193; (e) p. 180. 2nd ed., Urban and Sohwarzenberg, Berlin and Vienna, (10) MARVEL, C. S., F. D. H ~ G E R AND E. C. CAUDLE, "Organio 1928, Volume 11, p. 207; ( b ) LORGES, Rev. chirn. ind. , 34, Syntheses" (Gilman-Blatt, Eds.), 2nd ed., John Wiley & 52 (1925). Sons, Inc., New York, 1941, Coll. Vol. I, p. 224. .

(7) COHEN, J. B., "Practical Organic Chemistry," 4lacmillan (11) (a) STEPEEN, H., J. Chem. SOC., 1925, 1876; (b) J. W. Co., London. 1930, p. 221. Williams. J . A m . Chm,r.Soe.. 61, 2249 (1939).