EXCHANGE THE SYNTHESIS OF DI-ARYL THIOPHENES, DI-ARYL SELENOPHENES, AND RELATED COMPOUNDS BY PILAR PEREZ HERRERA, Pn.G., B.S., M.A. DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Faculty of Pure Science of Columbia University NEW YORK CITY 1922 THE SYNTHESIS OF DI-ARYL THIOPHENES, DI-ARYL SELENOPHENES, AND RELATED COMPOUNDS BY PILAR PEREZ HERRERA, Pn.G., B.S., M.A. DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Faculty of Pure Science of Columbia University NEW YORK CITY 1922 &itfg$ClX3 TO MY MOTHER ACKNOWLEDGMENT It gives the author great pleasure to express in this place her appre- ciation and gratitude to Professor Marston Taylor Bogert, at whose suggestion the following investigation was undertaken, for his kindly supervision and thoughtful advice. P. P. HERRERA. Organic Research Laboratories Havemeyer Hall, Columbia University, July, 1922. CONTENTS PAGE DEDICATION 3 ACKNOWLEDGMENT 5 ABSTRACT OF THE DISSERTATION > . . . . 9 GENERAL INTRODUCTION 12 PART I DI-ARYL THIOPHENES 13 Historical Review of Previous Work 13 General Discussion 14 Experimental Part 15 1. Preparation of Aniline Zinc Chloride 15 2. Preparation of Acetophenon-Anil 15 3. Para Toluidine Zinc Chloride 15 4. Ortho Toluidine Zinc Chloride 15 5. Acetophenon-p-Tolil 15 6. Acetophenon-o-Tolil 16 7. 2,4-Diphenyl Thiophene 16 (a) From Acetophenon-Anil 16 (b) From Acetophenon-o-Tolil 17 (c) From Acetophenon-p-Tolil 17 8. 5-HgCl-2,4-Diphenyl Thiophene 18 9. Nitration of 2,4-Diphenyl Thiophene 18 PART II DI-ARYL SELENOPHENES 21 Historical Part 21 Discussion 21 Experimental Part 21 1. 2,4-Diphenyl Selenophene 21 (a) From Acetophenon-Anil 21 (b) From Acetophenon-p-Tolil 22 (c) From Acetophenon-o-Tolil 23 2. 5-HgCl-2,4-Diphenyl Selenophene 23 3. Para Methyl Acetophenon-Anil 23 4. 2,4-Di-p-Tolil Selenophene 24 5. Methyl Ester of Orthoformic Acid 25 6. Ethyl Ester of Orthoformic Acid 25 7. Acetophenone Dimethyl Acetale 25 8 Contents 8. Acetophenone Diethyl Acetale 25 9. An attempt to condense Acetophenone Diethyl Acetale with Benzaldehyde 25 10. Chalcone or Benzalacetophenone 25 11. An attempt to prepare Acetophenon-Guanidine-Anil. ... 25 BIBLIOGRAPHY 29 VITA 31 ABSTRACT OF THE DISSERTATION 1. Purpose of the Research. To make some further contributions to the chemistry of organic selenium compounds and to develop a satisfactory method for preparing di-aryl thiophenes and selenophenes in a pure state free from isomers. 2. What was attempted. An attempt was made to study the reaction of acetophenon-anil when fused with sulphur or selenium. There are three possibilities which may result from such a fusion, the sulphur combining with the anil molecule according to the following equations: (a) C - N \/\ ^ N CH 2 H S 2 >H 2 ST + CH 2 ace tophenon-anil /3-phenyl-benzo- p-thiazine This compound was prepared by linger (i) * from amino thiophenol and co-brom acetophenone. It crystallizes in pale sulphur yellow, double refractive cubes m.p. 233. (b) = N I CH 2 .1. . . H * +S 2 -> H 2 S C = N - CH acetophenon-anil V S 3-phenylimino- thionaphthene- 2,3 dihydride * Figures in parentheses refer to bibliography, p. 29. ***"** C * 1 * " 10 The Synthesis of Di-Aryl Thiophenes This compound has never been prepared. (c) Aniline splits off and the sulphur combines with the acetophenone part of the molecule. C,H 4 C CH NC.H,; H,: H, -|- S > 2 C.H JSTH, + C JI ft C CH II II N C.H,: HC C HC - C C,H, S 2, 4-diphenyl thiophene or the HS present decomposes the acetophenon-anil first into thio- acetophenone which then forms the diphenyl thiophene as described by Baumann and Fromm (2) according to the following equations: CH 4 C - NCH t + H^ - > Cja^NHj-K CeH.CSCH, I CH, thio-acetophenone acetophenon-anil CJLCSCH, -- > S + C.H.CH . CH, thio-acetophenone styrol 2 CJI*CH = CH 2 -f 3 S -> 2 H,S + CeH 6 C - CH II II styrol HC C C,H 6 S _ ^.' 2, 4-diphenyl thiophene C JI.CH = CH, + H,S - > S -f C .H, C^I. styrol ethyl benzol 3. The Method of Attack. Equal moles of acetophenon-anil and sulphur (or selenium) were fused at a temperature above 200 C. yielding 2, 4-diphenyl thiophene (or selenophene). To prove that this is not a reaction peculiar to aceto- phenon-anil, two things were necessary: (a) To show that similar combinations of acetophenone with other Di-A ryl Selenophenes, and Related Compounds 1 1 primary aromatic amines, like the toluidines for example, will give the same reaction. (b) That a homologue of acetophenone like para methyl acetophenone may be substituted for acetophenone itself. 4. In how far were the attempts successful. (a) The fusion of acetophenon-anil, acetophenon-o-tolil and aceto- phenon-p-tolil with sulphur (or selenium) gave the same compound, that is, 2,4-diphenyl thiophene (or selenophene), the difference being as fol- lows: in the case of the anil, aniline was the by-product while in the case of the tolils, toluidine was the by-product. (b) Para methyl acetophenon-anil when fused with metallic selenium gave 2,4-di-p-tolil selenophene. 5. What contribution actually new to the science of chemistry has been made. (a) A resume of previous work on the selenophenes and di-aryl thio- phenes has been given. (b) A general method for the preparation of 2,4-di-aryl thiophenes and selenophenes free from isomers and in good yield is given. (c) The following new compounds have been prepared: Acetophenon-o-Tolil 2,4-Diphenyl Thiophene * 5-HgCl-2,4-Diphenyl Thiophene 2,4-Diphenyl Selenophene 5-HgCl- 2,4-Diphenyl Selenophene Para Methyl Acetophenon-Anil 2,4-Di-p-Tolil Selenophene Acetophenon-Dimethyl Acetale * * Not a new compound but prepared by a different method. GENERAL INTRODUCTION The plan adopted for numbering the positions on the thiophene and selenophene nuclei is indicated in Formulas I and II so that S or Se is always in position (I). This is in agreement with the system adopted in the new (2nd) edition of Meyer- Jacobson's " Lehrbuch der Organischen Chemie." (3) (4) (5) (3) (4) or () (s) S Se (i) d) I (3) on (a) (a') 03'; or (a) (a') S Se II (a) Although acetophenon-anil has served as a starting material through- out this work, the problems involved are essentially different and there- fore it was deemed advisable to present the subject in two parts: I. Di-Aryl Thiophenes. II. Di-Aryl Selenophenes. PART I DI-ARYL THIOPHENES In 1888 Kopf and Paal (4) in connection with some work on phenacyl- benzoyl acetic ether, obtained from diphenacyl and phosphorous penta- /C(C,H 6 ) = CH sulphide at i6o-i8o a, a'-diphenyl thiophene, S\^ | white X C(C6H 6 ) = CH shiny flakes melting at i52-i53. The yield is approximately 60-70% of the theory. In 1895 Baumann and Fromm (5) by heating cinnamic acid with sulphur at 240 obtained a mixture of 2,4-diphenyl thiophene m.p. H9-i2o and 2,5-diphenyl thiophene m.p. 152-! 53; and by heating styrol with sulphur at 230 they obtained a mixture of ethyl benzol b.p. I 33~ I 34> 2,4-diphenyl thiophene m.p. 119, and 2,5-diphenyl thiophene m.p. i52-i53. The same authors (6) found that by distilling trithio- acetophenone they obtained ethyl benzol and a mixture of 2,4- and 2,5- diphenyl thiophenes. The fact that when anhydrotriacetophenon disul- phide (7) is heated it yields 2,4-diphenyl thiophene together with some styrol and hydrogen sulphide according to the following reaction, >H 2 S+C 8 H 8 +S< V I S - C = CH styrol X C(C 6 H 6 ) = CH 2,4-diphenyl C 6 H 6 thiophene anhydro-triacetophenon disulphide proves the constitution of 2,4-diphenyl thiophene. No 2,5-diphenyl thiophene was formed. Baumann and Fromm (8) also found that when acetophenone in alcoholic solution is saturated with hydrogen sulphide in the presence of ammonia and allowed to stand for 14 days they obtained besides ethyl benzol and styrol, a mixture of 2,4- and 2,5-diphenyl 14 The Synthesis of Di-Aryl Thiophenes thiophenes and free sulphur. The yield of 2,4-diphenyl thiophene ob- tained is i% of the theory. In 1909 Willgerodt and Merk (9) obtained by heating in a tube at 210, 3 g. of acetophenone, 3 cc. of water and 5 g. of solid colorless am- monium sulphide, phenyl acetamide, phenyl acetic acid, ethyl benzol, 2,4-diphenyl thiophene m.p. 124 and 2,$-diphenyl thiophene m.p. 150.5. It is apparent therefore, that although the di-aryl thiophenes have been prepared before, yet up to the present, no entirely satisfactory method has been developed for preparing them in a pure state. Hereto- fore, there always resulted a mixture of the two isomers and the yield obtained was very small. We have found, however, that by fusing acetophenon-anil with sulphur at a temperature of 220 to 240 C., we get a very satisfactory yield of 2,4-diphenyl thiophene m.p. 124 C. (u.c.) or 122.5 (cor.), inasmuch as no isomers or other compounds such as styrol and ethyl benzol are formed, the amount of pure product obtained being 28% of the theory. The compound is identical with Baumann and Fromm's (10) 2,4-diphenyl thiophene melting at 119-! 20. This method proves to be generally applicable for the preparation of 2,4-di-aryl thiophenes and selenophenes. EXPERIMENTAL PART 1. ANILINE ZINC CHLORIDE, (C 6 H 6 NH 2 ) 2 . ZnCl 2 . This compound was made following the directions of Lachowicz and Bandrowski (i i). It was found necessary to add just enough HC1 to the aqueous solution of zinc chloride to get it in solution. 2. ACETOPHENON-ANIL, C^C ^5,' N IM^ells This compound was prepared according to Reddelien's (12) method. The reaction proceeds as described and the yield, melting point, and boiling point coincide with those given. Bogert's (13) apparatus was used to separate all the unchanged aceto- phenone from the anil. 3. PARA TOLUIDINE ZINC CHLORIDE, (p) (C 6 H 4 <^ 3 ) 2 . ZnCl 2 This compound was prepared by adding to a solution of 13.6 g. (o.i mole) of ZnCl 2 in 100 cc. of 95% alcohol a solution of 21.4 g (0.2 mole) of (p) toluidine in 100 cc. of 95% alcohol. Fine white needles. Yield, 32 g. or 91.4% of the theory. 4. ORTHO TOLUIDINE ZINC CHLORIDE, (o) (C 6 H 4 <( 3 ) 2 . ZnCl 2 Prepared in the same way as (p) toluidine zinc chloride. White fine needles. Yield, 31 g or 88.6% of the theory. 5. ACETOPHENON-P-TOLIL, N \/\ CH 3 \/ -CH 3 Prepared according to Reddelien's method (14). Light yellow oil, not very viscous, which when exposed to the air soon turns brown. Yield, 33-7% of the theory. i6 The Synthesis of Di-Aryl Thiophenes CH, 6. ACETOPHENON-O-TOLIL, C = N CH, x\ \x Mix 380 g. of acetophenone, 475 g. of (o) toluidine and 19 g. of (o) toluidine zinc chloride in a round bottom flask and heat in an oil bath at a temperature of 1 70-! 80 C. for i hour. Allow to cool, add chloroform to the melted oil and filter off the (o) toluidine zinc chloride salt. Dis- till the filtrate up to 220 C. and the rest is distilled under diminished pressure. The main portion distilling at 2io-220 .,57 mm. pressure is a light yellow oil which does not solidify. Yield, 323 g or 48.8% of the theory. Light yellow oil not very viscous, which when exposed to the air soon turns brown. 7. 2,4-DIPHENYL THIOPHENE, CH 6 C CH II II HC C . C.H 8 \> S (a) From Acetophenon-Anil. A mixture of 60 g. of acetophenon-anil (0.3 mole) and 20 g. of powdered roll sulphur (0.3 mole) was placed in a distilling flask provided with an air condenser and kept at a temperature of 220 to 240 C. for thirteen hours. Aniline distilled off and some H 2 S was evolved. The melt was distilled under diminished pressure. The main portion distilling at 260- 265 C., 36 mm. pressure, was a yellow oil which solidified in the receiver to a yellow crystalline mass. The solid distillate was recrystallized from absolute alcohol to constant melting point a little norite being added to the alcoholic solution. Absolute purity requires two or three recrystalliza- tions from absolute alcohol. White shiny plates, melting at 122.5 C. (cor.) were obtained. Yield, 10 g. or 28% of the theory. Easily soluble in chloroform, ether, and acetone; soluble in hot petro- leum ether, benzol, alcohol, and glacial acetic acid; insoluble in water, HC1, and alkali. It gives a yellow color with concentrated H 2 SO< and a red color with concentrated nitric acid. It does not form an Di-Aryl Selenophenes, and Related Compounds if addition product with methyl iodide. With concentrated sulphuric acid and isatin (Indophenin Test [15] ) a bluish green dye is precipitated. With Laubenheimer's Test (16), a green dye is precipitated, which is soluble in ether, alcohol, benzol, and glacial acetic acid with cherry red coloration. With nitrososulphuric acid (Liebermann's Reaction [17] ) we get a green then dark red coloration of the sulphuric acid. Qualitative analysis showed the presence of C, H, and S but no nitro- gen. It was analyzed for C and H by Fisher's (18) method and for S by Carius' (19) method. Analysis : Calculated for C 16 H 12 S: C = 81.3%, H = 5.08%, S = 13.54% Found T 1 8l ' I9% ' H ! 4 ' 89% ' S I3 ' 6 ? % F Und C = [ 81.03% H = I 4-88% S - | I3 .8o% No styrol, ethyl benzol, or isomeric 2,5-diphenyl thiophene were en- countered. (b) From Acetophenon-o-Tolil. A mixture of 149 g. of acetophenon-o-tolil and 46 g. of powdered sulphur roll was placed in a distilling flask provided with an air con- denser and heated in an oil bath at a temperature of 24o-25o C. for 19 hours. The reaction started at 240 C. 30 g. of (o) toluidine distilled off during the heating. When heated with acetic anhydride, (o) acet- toluide(2o), CH 3 C 6 H 4 NHCOCH3, white needles m.p. 110 C. was obtained. The melt was distilled under diminished pressure. The main portion distilling at 26o-265 C., 36 mm. pressure was a yellow oil which solidi- fied in the receiver to a yellow crystalline mass. The solid distillate was recrystallized from absolute alcohol to constant melting point a little norite being added to the alcoholic solution. White shiny plates, m.p. 122.5 C. (cor.). Yield, 20 g. or 23.6% of the theory. It has the same crystalline structure and the same melting point as the 2,4-diphenyl thiophene obtained from acetophenon-anil. A mixture of the two compounds gave a melting point of 122.5 C- (cor.). (c) From Acetophenon-p-Tolil. 92 g. of acetophenon-p-tolil and 28.4 g. of powdered sulphur roll were placed in a distilling flask provided with an air condenser and heated in an oil bath at a temperature of 230^250 C. for 19 hours. The re- action started at 230 C. 10 g. of (p) toluidine were recovered during the heating. When tested with acetic anhydride, (p) acettoluide (21) i8 The Synthesis of Di-Aryl Thiophenes CHaCJIiNHCOCH,, lustrous white needles m.p. 148.3 C. (cor.) were obtained. The rest is the same as with acetophenon-o-tolil. White shiny plates m.p. 122.5 C. (cor.). Yield, 17 g. or 32.4% of the theory. It has the same melting point and the same crystalline structure as 2,4-diphenyl thiophene and a mixture of the two compounds gave a melting point of 122.5 C. (cor.). 8. 5-HgCl-2, 4 -DIPHENYL THIOPHENE, CJI, C CH II II HgCl C C CH* S Steinkopf and Bauermeister (22) prepared HgCl-2-phenyl thiophene from 2-phenyl thiophene and mercuric chloride. The analogous reaction was attempted in the case of 2,4-diphenyl thiophene. To a solution of i g. of 2,4-diphenyl thiophene in 200 cc. of 95% al- cohol add 10 g. of a 33% solution of sodium acetate and 50 g. of a cold saturated solution of mercuric chloride. Mix well and allow to stand. After two and a half days, 1.5 g. of 5-HgCl- 2,4-diphenyl thiophene in the form of white needles were obtained. After four days more, 0.5 g. more were obtained. The product was recrystallized from hot alcohol in which it is difficultly soluble, to constant melting point. White silky needles m.p. 223 C. (cor.). Yield, 1.5 g. or 75% of the theory. Easily soluble in hot chloroform and benzol, difficultly soluble in hot alcohol and glacial acetic acid, insoluble in ether. It gave a qualitative test for sulphur. Calculated for C,JH n SH g Cl: Hg = 42.57% Found Hg - 43-93% 9. NITRATION OF 2, 4 -DIPHENYL THIOPHENE. In a round bottom flask provided with a 3-hole stopper one hole con- taining a dropping funnel, another a tube connected to the water pump, and the third a capillary tube, place 5 g. of 2,4-diphenyl thiophene and 50 cc. of acetic anhydride. In the dropping funnel place 1.5 cc. of fuming nitric acid (sp. gr. 1.5) and 1.5 cc. of acetic anhydride. Immerse the flask in a freezing mixture in order to keep the temperature at o-5C. and very slowly, drop by drop, add the nitrating mixture at the same Di-Aryl Selenophenes, and Related Compounds 19 time drawing air into the flask. The reaction mixture turns brown. After all the nitrating mixture has been added, keep the flask in the freezing mixture for 5 minutes longer then pour the reaction product into ice water, stir thoroughly, and allow to cool. A reddish oil which soon solidifies to a reddish brown crystalline mass is obtained. It does not distill with steam. It was filtered off, dried, and powdered. It is insoluble in water, alkali, petroleum ether, ethyl alcohol and methyl alcohol. Easily soluble in ether, chloroform, benzol, acetone, toluene and ethyl acetate but does not crystallize from any of these solvents. Soluble in hot glacial acetic acid. At 8o-85 C., it begins to decompose and at iio-ii5 C. it forms a brown liquid. When pulverized it forms a yellowish brown powder. The product obtained was not pure enough for combustion. PART II DI-ARYL SELENOPHENES Up to the present, very little work has been done on selenophene com- pounds. The first compound of this class was prepared by Paal (23) in 1885. By heating ace tony lace tone with phosphorous pentaselenide at 180, he obtained selenoxene or 2,5-dimethyl selenophene. In 1894, Zoppellari (24), in connection with his work on "Atomic Re- fraction of Selenium," determined the vapor density and the percentage of carbon and hydrogen in selenoxene. In 1909, Foa (25) prepared selenophene itself by heating in a com- bustion tube 52.9 g. of sodium succinate and 100 g. of phosphorous triselenide. He obtained a yellowish liquid boiling at i47-i49, 250 mm. pressure. The yield was very small. Our method for the synthesis of 2,4-diphenyl thiophene having proved successful and in view of the fact that selenium reacts very similar to sulphur, it was decided to apply the same method for the preparation of di-aryl selenophenes. A good yield of 2,4-diphenyl selenophene melt- ing at 112.3 C. (cor.) was obtained by fusing acetophenon-anil and metallic selenium at a temperature of 280 to 295 C. It will be noted that as far as possible we endeavored to duplicate our sulphur compounds with selenium compounds and in every instance obtained the desired results. EXPERIMENTAL PART i. 2,4-DI-PHENYL SELENOPHENE, C 6 H 5 C CH II II HC C C 6 H 5 \/ Se (a) From Acetophenon-Anil. A mixture of 60 g. of acetophenon-anil (0.3 mole) and 48.6 g. of metallic selenium (0.3 mole) was placed in a distilling flask provided with an air condenser and heated in a KNO 3 bath at a temperature of 280 to 295 C. for 1 6 hours. The reaction started at 280 C., at which temperature aniline distilled off. About 30 cc. of aniline were obtained. When treated with acetic anhydride we obtained acetanilide (26) m.p. 112.7 C. (cor.). 22 The Synthesis of Di-Aryl Thiophenes The melt, a solid crystalline mass, was distilled under diminished pressure. The main portion distilled at 270 to 280 .,31 mm. pres- sure, and was a reddish oil which solidified in the receiver. It was re- crystallized from absolute alcohol to constant melting point a little norite being used. Shiny colorless scales m.p. 112.3 C. (cor.). Yield, J 3 g- r 3% of the theory. Easily soluble in chloroform, ether, benzol, and acetone; soluble in hot alcohol and glacial acetic acid; insoluble in water, NaOH solution and HCL. With concentrated HNOi it gives a dark red coloration, and is oxi- dized. It dissolves in concentrated H^O 4 with an orange-yellow colora- tion. With isatin and cone. H,SO4 (Indophenin Test [27] ) it gives a brown color. By adding water the dye is precipitated as a brown mass. With Laubenheimer's Test (28) it gives a green color. On adding water the dye is precipitated in the form of green flocks soluble in ether, al- cohol, and glacial acetic acid with orange-yellow color; in benzol, with deep orange color; in cone. HjSO 4 , with violet red color. With Lieber- mann's Test (29), it gives a green then a brownish black color. Qualitative analysis showed the presence of C, H, and Se. Analysis: Calculated for C,,H,,Se: C - 67.77%, H 4.27% Found C - 67.74%, H - 4-30% (b) From Acetophenon-p-Tolil. A mixture of 125 g. of acetophenon-p-tolil (0.6 mole) and 95.4 g. of metallic selenium (0.6 mole) was placed in a distilling flask provided with an air condenser and heated in a KNOi bath at a temperature of 27o-290 C. for 23 hours. About 50 g. of (p) toluidine was recovered. When heated with ace tic anhydride it gave (p) acettoluide (30), CH,CeH 4 - NHCOCH,, lustrous white needles m.p. 148.3 C. (cor.). The melt was distilled under diminished pressure. The main portion distilled at 27o-28oC., 31 mm. pressure and was a reddish oil which solidified in the receiver to a reddish crystalline mass. It was recrystal- lized from absolute alcohol to constant melting point, a little norite being added. Shiny colorless scales m.p. 112.3 C. (cor.). Yield, 25 g. or 29.3% of the theory. It has the same crystalline structure and the same melting point as 2,4-diphenyl selenophene and a mixture of the two compounds gave a melting point of 112.3 C. (cor.). Di-Aryl Selenophenes, and Related Compounds 23 (c) From Acetophenon-o-Tolil. 173 g. of acetophenon-o-tolil and 132 g. of metallic selenium powder were placed in a distilling flask provided with an air condenser and heated in a KNO 3 bath at a temperature of 2'jo-2go C. for 23 hours. 79 g. of (o) toluidine were recovered during the heating. When tested with acetic anhydride it gave (o) acettoluide (31), CHjC^NHCOCH,, color- less needles m.p. 1 10 C. The rest is the same as with acetophenon-p-tolil. Colorless shiny scales m.p. ii2.3C. (cor.). Yield, 27 g. or 23% of the theory. It has the same melting point and the same crystalline structure as 2,4-diphenyl selenophene. A mixture of the two compounds gave a melting point of 112.3 C. (cor.). 2. 5-HgCl-2, 4 -DIPHENYL SELENOPHENE, CH 6 C C - H II II HgCl C C C& 6 \/ Se To a solution of 5 g. of 2 ,4-diphenyl selenophene in i li ter of 95% alcohol, add 50 g. of a 33% solution of sodium acetate and 250 g. of a cold satu- rated solution of mercuric chloride. Shake well and allow to stand. After 20 hours, 8 g. of 5-HgCl- 2,4-diphenyl selenophene were obtained in the form of colorless fine needles. After 24 hours more, 2 g. were obtained and after three and a half days, i g. more. It was recrystallized from 95% alcohol to constant melting point. Fine needles m.p. 224C. (cor.). Yield, 8 g. or 89% of the theory. Easily soluble in hot CHC1 3 , benzol, and glacial acetic acid. Diffi- cultly soluble in alcohol and ether. Insoluble in water. Qualitative analysis showed the presence of Se and Hg. A mixture of equal parts of CieHuSe.HgCl m.p. 224 C. (cor.) and CieHuS.HgCl m.p. 223 C. (cor.) gave a melting point of 219 C. (cor.). 3. PARA METHYL ACETOPHENON-ANIL, CH 3 / 24 The Synthesis of Di-Aryl Thiophenes 100 g. of (p) methyl acetophenone and 125 g. of aniline (redistilled) were placed in a round bottom flask and heated in an oil bath to 160 C. then 5 g. of aniline zinc chloride was added and the temperature raised to 1 80 for i hour. The melted oil was allowed to cool, chloroform was added and the aniline zinc chloride salt filtered off. The filtrate was distilled up to 200 C. and the remaining portion was distilled under diminished pressure. The main portion distilled at 22o-24o C., 53 mm. pressure. Yield, 46 g. or 29.5% of the theory. Light yellow oil not very viscous which when exposed to the air soon turns brown. 4. 2,4-DI-P-TOLIL SELENOPHENE, CH,CeH 4 C CH II II HC C C 6 H 4 CH S Se A mixture of 46 g. of (p) methyl acetophenon-anil (0.22 mole) and 35 g. of metallic selenium (0.22 mole) was placed in a distilling flask provided with an air condenser and heated in a KNO bath at a tem- perature of 26o-27o C. for n hours. The reaction started at 260 C. 13 g. of aniline distilled off during the heating. When tested with acetic anhydride it gave acetanilide (32), white leaflets m.p. 112.7 C. (cor.). The melt, a solid mass, was distilled under diminished pressure. The main portion distilled at 26o-28o C., 38 mm. pressure and was a red- dish oil which solidified in the receiver. It was recrystallized from ab- solute alcohol to constant melting point a little norite being added to the alcoholic solution. Beautiful colorless shiny leaflets m.p. 136.3 C. (cor.). Yield, 7 g. or 20.5% of the theory. Easily soluble in CHC1 8 , ether, benzol, and acetone; soluble in hot alcohol and glacial acetic acid; insoluble in water, NaOH solution and HC1. It dissolves in cone. H 2 SO 4 with red coloration. It is oxidized by cone. HNO 3 . With isatin and cone. H 2 SO 4 (Indophenin Test [33]) it gives a bright red coloration. With Laubenheimer's Test (34) a green dye is precipitated. The dye is soluble in ether with orange yellow coloration; in alcohol, benzol and glacial acetic acid with orange color; in cone. H 2 SO 4 with brown coloration. On addition of H 2 O to the H 2 SO 4 solution, the green dye is reprecipitated. With Liebermann's Test (35) it gives a dark green coloration of the H 2 SO 4 . Di-Aryl Selenophenes, and Related Compounds 25 Qualitative analysis showed the presence of C, H, and Se but no N. Analysis: Calculated for C 18 H 16 Se: C = 69.45%; H = 5.14% Found C = 69.40%; H = 5.39% 5. METHYL ESTER OF ORTHOFORMIC ACID, HC(OCH 3 ) 3 . 72 g. of finely cut metallic sodium are mixed with 600 cc. of absolute ether and to this add slowly, while cooling with ice, 100 cc. of absolute methyl alcohol. Stopper the flask with a CaCl 2 tube and allow to stand for one day. Cool with ice, carefully add 86.6 g. of chloroform and then heat for a time in a flask provided with a reflux condenser. Filter off the NaCl formed, evaporate the ether on a water bath, and distil the rest under diminished pressure. The main portion distills at 45 C., 65 mm. pressure. A pleasant smelling liquid, slightly soluble in water, and inflammable. Yield, 22.2 g. or 28% of the theory. 6. ETHYL ESTER OF ORTHOFORMIC ACID, HC(OC 2 H 6 ) 3 . Prepared according to Bender and Erdmann (36). OCH 3 1 7. ACETOPHENONE DIMETHYL ACETALE, CeH 6 C CH 3 OCH 3 Mix 22 g. of methyl ester of orthoformic acid, 16.2 g. of acetophenone and 18.9 g. of absolute methyl alcohol with 5 drops of cone. HC1 in a flask fitted with a CaCl 2 tube and heat the mixture to 40 C. with fre- quent shaking. The odor of acetophenone disappears and is replaced by the pleasant flowery odor of the acetale. Allow to stand for 16 hours. Make the mixture alkaline with a drop of alcoholic sodium methylate, distill the alcohol and the residue is distilled under diminished pressure. The main portion distills at 90 C., 20 mm. pressure. Yield, 20 g. or 89.3% of the theory. Colorless liquid with flowery odor. 8. ACETOPHENONE DIETHYL ACETALE, CH 6 C(OC 2 H 5 ) 2 CH3 Prepared according to Claisen (37). 9. AN ATTEMPT TO CONDENSE ACETOPHENONE DIETHYL ACETALE WITH BENZALDEHYDE. An attempt was made to condense acetophenone diethyl acetale with 26 The Synthesis of Di-Aryl Thiophenes benzaldehyde with a view of getting a substituted chalcone according to the following equation: CH5C(OC,H),CH |H7+O"| HCCH 5 > H 2 O + c 8 H 6 c(oc,H 4 ) 2 CH= CHC.HS (a) 3 g. of acetophenone diethyl acetale, 1.6 g. of benzaldehyde (re- distilled) and 0.5 g. of a 20% sodium ethylate solution were mixed in a corked flask and allowed to stand for a day in a freezing mixture. A light yellow gelatinous mass was obtained. Soluble in hot 95% alcohol; insoluble in ether, CHCU, petroleum ether and anhydrous ethyl acetate. Heated in a dry test tube it forms an oil. Easily hydrolized with water. It could not be crystallized. It behaves very much like chalcone. (b) 2 g. of acetophenone diethyl acetale, i g. of benzaldehyde (re- distilled) and i cc. of 10% sodium ethylate solution were mixed and heated under pressure between ioo-io5 C. for i hour. A solid yellow- ish mass was obtained. It was washed with ether and dried in a vacuum. It had the same properties as (a). (c) 2 g. of acetophenone diethyl acetale, i g. of benzaldehyde (redis- tilled), 10 g. of 95% alcohol and i cc. of 10% NaOH solution were mixed and allowed to stand in a corked flask for one day. No change occurred. The mixture was poured into a beaker and evaporated in a dessicator under reduced pressure. A solid mass which behaved like (a) was obtained. 10. CHALCONE OR BENZALACETOPHENONE, CeH.COCH . CHCJI,. Prepared from acetophenone and benzaldehyde according to Claisen (38) . 1 1 . AN ATTEMPT TO PREPARE ACETOPHENON-GUANIDINE- ANIL, \_NH Attempts were made to prepare this compound from acetophenone and guanidine carbonate as follows: C.H.C = 10+H.JN _ ^ HiCO ,>H ! o+ K.CO.+ CH, ' Di-Aryl Selenophenes, and Related Compounds 27 (a) Condensation with KOH. 12 g. of acetophenone were dissolved in just enough ethyl alcohol and mixed with a concentrated aqueous solution of guanidine carbonate. The mixture was made strongly alkaline with KOH solution and warmed for 2 hours on a water bath. The method did not work. Guanidine carbonate is insoluble in al- cohol. On addition of KOH, ammonia is liberated. (b) Condensation with ZnCl 2 . 12 g. of acetophenone, 22 g. of guanidine carbonate and i g. of ZnCl 2 were mixed and heated at 180 C. for > hour. The melt was extracted with 60% alcohol. On attempting to concentrate the alcoholic extract an oil separated. This oil was extracted with ether and distilled. Acetophenone was recovered. The residue from the ether extraction gave a solid mass on concen- tration. This was insoluble in alcohol and water but soluble in water acidified with HC1. It proved to be Guanidine. BIBLIOGRAPHY 1. Unger, Berichte, 30, 607, 2393 (1897). 2. Baumann and Fromm, Berichte, 28, 903 (1895). 3. Meyer- Jacobson, "Lehrbuch der Organischen Chemie," Vol. 2, Part 3, p. no. 4. Kopf and Paal, Berichte, 21, 3053, 3058 (1888). 5. Baumann and Fromm, Berichte, 28, 891, 893 (1895). Baumann and Fromm, Berichte, 30, in, 117 (1897). 6. Baumann and Fromm, Berichte, 28, 902 (1895). 7. Baumann and Fromm, Berichte, 28, 905 (1895). 8. Baumann and Fromm, Berichte, 28, 911 (1895). Manchot and Krische, Annalen, 337, 183-5 (1894). Manchot and Krische, Centralblatt (1905), I, 234. Fromm and Holler, Berichte, 40, 2979 (1907). Fromm and Holler, Centralblatt (1907), II, 791. 9. Willgerodt and Merk, Jour. Pr. Chem. (2) 80, 193 (1909). Willgerodt and Merk, Centralblatt (1909), II, 981-2. Willgerodt and Scholtz, Centralblatt (1910), I, 1969. 10. (See 5.) n. Lachowicz and Bandrowski, Monatshefte, p, 513 (i< 12. Reddelien, Berichte, 43, 2478 (1910). 13. Bogert, Jour. Ind. and Eng. Chem., 7, 785 (1915). 14. Reddelien, Annalen, 388, 185 (1912). Reddelien, Centralblatt (1912), I, 1462. Reddelien, Berichte, 46, 2716 (1913). Reddelien, Centralblatt (1913), II, 1667. 15. Baeyer, Berichte, 12, 1311 (1879). Meyer, Berichte, 16, 1478 (1883). Baeyer and Lazarus, Berichte, 18, 2637 (1885). Liebermann and Pleus, Berichte, 37, 2463 (1904). Liebermann and Krauss, Berichte, 40, 2499 (1907). Beilstein, II, 1617. 16. Laubenheimer, Berichte, 8, 224 (1875). Schleicher, Berichte, /p, 673 (1886). Oster, Berichte, 37, 3352 (1904). 17. Victor Meyer, Berichte, 16, 1473 ( l88 3)- 30 The Synthesis of Di-Aryl Thiophenes Liebermann, Bench te, 20, 3231 (1887). Schwalbe, Berichte, 37, 324 (1904). Liebermann and Pleus, Berichte, 37, 2461 (1904). Schwalbe, Centralblatt (1905), I, 1114. 18. Fisher, Lab. Man. of Org. Chem. 19. Gattermann, Practical Methods of Org. Chem. 20. Mulliken, "Identification of Pure Organic Compounds," Vol. 2. 21. (See 20.) 22. Steinkopf and Bauermeister, Annalen, 403, 66 (1914). 23. Paal, Berichte, 18, 2255 (1885). Beilstein, III, 770. Meyer- Jacobson, "Lehrbuch der Organischen Chemie," Vol. 2, Part 3, p. 145. 24. Zoppellari, Gaz. Chim. Italiana, 24, II, 399 (1894). 25. Foa, Gaz. Chim. Italiana, jp, II, 527 (1909). Foa, Centralblatt (1910), I, 837. Meyer- Jacobson, " Lehrbuch der Organischen Chemie," Vol. 2, Part 3, p. 145. 26. Mulliken, "Identification of Pure Organic Compounds," Vol. 2. 27. (See 15.) 28. (See 16.) 29. (See 17.) 30. (See 26.) 31. (See 26.) 32. (See 26.) 33. (See 15.) 34. (See 16.) 35. (See 17.) 36. Bender und Erdmann, Chemische Praparatenkunde, Vol. 2, 291. Alfred Deutsch, Berichte, 12, 116 (1879). 37. Claisen, Berichte, 40, 3908 (1007). 38. Claisen, Berichte, 20, 657 (1887). VITA Pilar Perez Herrera was born in Manila, Philippine Islands. She entered the University of the Philippines in 1912, receiving the degrees of Graduate in Pharmacy in 1915 and Bachelor of Science in 1916. From 1916 to 1918 she was assistant instructor in chemistry in the University of the Philippines. In 1918 she was granted a traveling fellowship of four years by the University of the Philippines. She entered Columbia University in the same year and in 1919 obtained her M. A. degree. 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