‘ lxnljllijiljniliflnimiil‘ QM.) LIBRARY Michigan State University This is to certify that the thesis entitled PREPARATION AND APPLICATION OF DI-GRIGNARD REAGENTS presented by Ching-Hahn Suh has been accepted towards fulfillment of the requirements for Masters degreein Science M «UL-«S— Date April 30, 1986 0-7639 MS U is an Affirmative Action/Equal Opportunity Institution PLACE IN RETURN BOX to roman this checkout from your record. TO AVOID FINES roturn on or baton am duo. DATE DUE DATE DUE DATE DUE Hm g-Lj Ill—[:3 f—T—T—T MSU I: An Affirmative Adlai/Emmi Opportunity Intuition Mani-9.1 PREPARATIOI AND APPLICATION OF DI-GRIGNARD RBAGEITS BY Chins-Hahn Suh A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree or MASTER OF SCIENCE Department of Chemistry 1986 © 1987 CHING-HAHN SUH All Rights Reserved ABSTRACT PREPARATIOI AND APPLICATION OP DI‘GRIGNARD REAGEITS BY Ching-Hahn Suh The following three types of di-Grignard reagents are prepared: 1. di~Grignard reagents from di-haloarenes; 2. di-Grignard reagents from 1,2,”,5-tetrahalobenzenes; 3. 1,N-di-Grignard reagents from hexahalogenobenzenes. Three conventional methods (direct preparation, exchange and entrainment) have been reviewed. Two new methods have been studied: 1.4 a combination of-the direct, exchange and entrainment methods; 2. a combination of the exchange and entrainment methods. They both show better results than conventional methods. Some limited applications of these di~Grignard reagents to synthesis have been carried out. ACKIOHLBDGHEIT I thank the Department of Chemistry of Michigan State University for supporting my research. ii TABLE OF CONTENTS ACKNOHLEDGEMENTS O I O O O O O O O O O O O O O O O O I O O 0 LIST OF TABLES O O O O O O O O O O O O O O O O O O O O O O 0 LIST OF FIGURES O O O O O O O O O O O O O O O O I O O O O 0 INTRODUCTION 0 O O O O O O O O O O O I O O O O O O O O O O O I. II. III. PREPARATION OF DI-GRIGNARD REAGENTS . . . . . . . . . A. Di-Grignard Reagents Generated from Di-Haloarenes B. Di-Grignard Reagents Generated from 1,2,A,S-Tetrahalogenobenzenes . . . . . . . . . . C. Di-Grignard Reagents Generated from Hexahalogenobenzenes . . . . . . . . . . . . . . . DISCUSSION OF PREPARATION METHOD OF DI-GRIGNARD REAGENTS 0 O O O O O O I O O O O O O O I O 0 O O O O A. Direct Reaction of Hexahalogenobenzene with Magnesium . . . . . . . . . . . . . . . . . . . . 8. Ease of Formation, Stability and Reactivity of .Di-Grignard Reagents . . . . . . . . . . . . . . C. Exchange Method . . . . . . . . . . . . . . . . . D. Entrainment Method . . . . . . . . . . . . . . E. Combination of Direct Preparation, Exchange and Entrainment . . . . . . . . . . . . . . . . . F. Combination of Exchange and Entrainment . . . . . APPLICATIONS OF DI-GRIGNARD REAGENTS . . . . . . . . A. Addition of Di-Grignard Reagents to Ethylene Oxide B. Addition of Di-Grignard Reagents to Benzaldehyde . iii Page 11 vi 10 10 17 19 20 22 2A 25 25 26 C. TABLE OF COITEITS (cont'd) Page Reaction of Di-Grignard Reagents with Acetyl Chloride O O O O O O O I O I O O O O I C O O O I O O O 28 Reaction of Di-Grignard Reagents with Benzoyl Chloride O O O O O O O O I I O O O O O O O O O O O O O O 28 Preparation of Mono-. Di- or Tri-Grignard Reagents from 1.3.5-Tribromobenzene by Temperature Control and Quenching Experiments . . . . . . . . . . . . . . . 36 iv LIST OF TABLES Page Di-Grignard Reagents from Di-Haloarenes . . . . . . . . . . . 5 Di-Grignard Reagents from 1,2,u,5-Tetra- halogenobenzenes . . . . . . . . . . . . . . . . . . . . . . 7 Di-Grignard Reagents from Rexahalogenobenzenes . . . . . . . 9 Products of Di-Grignards Reacting with Ethylene Oxide . . . . 11 Diols from Reaction of Di-Grignards with Benzaldehyde . . . . 27 Diketones from Reactibn of Di-Grignards with Benzoyl Chloride O O O O O 0 O 0 O O O I O O O O O O O O O O O O O O 29 10. 11. 12. 13. 1A. 15. 16. 17. LIST OF FIGURES Cyclization from a, m-Alkane Di-Grignards . . . . . . Metallocyclic Complexes from a. m-Alkane Di-Grignards Metallocyclic Complexes from o-C6Hu(CH2MgCI)2 . . . . Trapping of Arynes with Alkyl Grignard . . . . . . . R Values of the Products of Di-Grignards Reacting with EEhylene oxide 0 O O O O O O O O I O O O O O O O O O H1 NMR of 3,6-Dichloro-2.5-dibnomo-1,u- bis(2-hydroxyethyl)benzene . . . . . . . . . . . . . Mass Spectrum of 3,6-Dichloro-2,S-dibromo-1,u- bis(2~hydroxyethy1)benzene . . . . . . . . . . . . . H1 NMR of 3,6-Dichloro-2,S-dibromo-1- (2-hydroxyethyl)benznen . . . . . . . . . . . . . . . Mass Spectrum of 3,6-Dichloro-2,S-dibromo-i- (2-hydroxyethyl)benzene . . . . . . . . . . . . . . . H1 NMR of 3,6-Dichloro-2,H.5-tribromo-1- (2-hydroxyethyl)benzene . . . . . . . . . . . . . . . Mass Spectrum of 3,6-Dichloro~2,H.5-tribromo-1- (2-hydroxyethyl)benzene . . . . . . . . . . . . . . . Mass Spectrum of 2,A-Dichloro-1.S-dibenzoylbenzene . IR Spectrum of 2,A-Dichloro-1,S-dibenzoylbenzene . . H1 NMR of 2,A-Dichloro-1.S-dibenzoylbenzene . . L . . H1 NMR of Benzophenone . . . . . . . . . . . . . . . Mass Spectrum of 2,5-Dichloro-3,6-dibromo- 1,H-dibenzoylbenzene . . . . . . . . . . . . . . . . IR Spectrum of 2,5-Dichloro-3,6-dibromo- 1,4-dibenzoylbenzene . . . . . . . . . . . . . . . vi Page 12 .13. 13 1“ 15 16 16 3O 31 31 32 33 33 18. 19. 20. 21. 22. .23. 2”. LIST OF FIGURES (cont'd) H1 NMR of 2,5-Dichloro-3,6-dibromo-1,fl- dibenzoylbenzene . . . . . . . . . . . . . . . . . IR Spectrum of 2,5-Dichloro-1,u-dibenzoylbenzene H1 NMR of 2.5-Dichloro-1,A-dibenzoylbenzene . . . . Mass Spectrum of 2,5-Dichloro-1,u-dibenzoylbenzene Mass Spectrum of S-Bromo-1,3-dibenzoylbenzene . . . H1 NMR of S-Bromo-1,3-dibenzoylbenzene . . . . . . IR Spectrum of S-Bromo-i.3-dibenzoy1benzene . . . . vii Page 3U 35 35 36 38 39 39 INTRODUCTIOI The history of di-Grignard reagents is long. In 193", Grignard prepared the first two di-Grignard reagents by the entrainment method:t A-BrC6HuMgBr + CZHSBr + Mg --9 1'"-(BrH8)2C6HH ---9 C6H6 Molar Ratio: 1 : 2 excess ‘ #01 h-BrC6HuCR2MgBr + CZHSBr + Mg --—9 u-BngcéfluCRzMgBr ---9 CH3C6H5 35$ Molar Ratio: 1 : 2 excess In 1971, Tamborski‘ et. a1. prepared the di-Grignard 2.3.5.6- tetrabromo-1,u-bis (magnesium bromide)benzene by exchange of CH3CH2MgBr or C68 MgBr with hexabromobenzene.2 The yields were 51: and 2% 5 respectively. In 1976, Whitesides and Gutowski prepared several o.m-a1kane di- Grignard reagents by the direct method. They used silver triflate (AgOSO CF3) to oxidize the di-Grignard, thus providing a practical 2 synthesis for four-, five- and six-membered carbocyclic rings.3 For example, “A “‘“THF I 90 431': (1:01 reflux I 0:)”: O] (61%) Figure 1. Cyclization from o.mrAlkane Di-Grignards They also used a,w-alkane di-Grignard reagents to synthesize metallocyclic complexes." For example, Ph3P 1.3mm: ) MgBr \ A (coletCIz 2 “ —> Pt (c112)n 2. Ph 9 / \J 3 Ph P 3 cod-cyclo-octa-1,S-diene n-u,5,6 Figure 2. Metallocyclic Complexes from e.u~Alkane Di-Grignards In 1978. Clark and O'Reilly prepared p-bis-(Magnesium bromide)benzene by the direct method. and used it in a reaction with ethylene oxide, and a 50% yield of 1,fl-bis (2-hydroxyethyl)benzene was obtained.5 In 1982, Raston, et. al. prepared the di-Grignard reagent 0: C6Ru(CH2MgCl)2 from o-bis(chloromethyl)benzene by the direct method. and they used the di-Grignard in synthesis of a metallocyclic complex.6 an M9 - NgCl mum!) A mu“) Cl THF Noel Figure 3. Metallocyclic Complexes from o~csfln(CHZHgCI)2 In 198“, they prepared the di-Grignard reagent 1,1'-bis(methylene magnesium chloride)biphenyl from 1,1'~bis(chloromethyl)biphenyl by the direct method.7 More recently, they published an improved method for benzylic type di-Orignards by using as the Mg source the 1:1 adduct of magnesium with anthracene.8 Yields are 92-96%. In this thesis, the preparation of the following three types of di-Grignard reagents is described: A. Di-Grignard Reagents Generated from Di-haloarenes. B. Di-Grignard Reagents from 1,2,",5-Tetrahalobenzenes. C. 1,u-di-Grignard Reagents from Hexahalobenzenes. Three conventional methods (direct preparation. exchange and entrainment) have been reviewed. Two new methods have been studied: 1. a combination of the direct. exchange and entrainment methods: 2. a combination of the exchange and entrainment methods. They both show better results than conventional methods. These methods, and their applications, are described in Section I of this thesis. I. PBEPARATIOI OP DI-GBIGIABD REAGEITS A. Di-Grignard Reagents Generated from Di-Haloarenes .In the following preparation of di-Grignard reagents by the direct method, magnesium can be used in stoichiometric amounts or in excess. Products were analyzed by G.C. and compared with authentic samples. Experimental Procedure To a dried. Ar protected three-necked round-bottomed 250-mL flask was added Mg powder (0.393, 16 mmole or a little excess), THE 10 mL and BrCRZCHZBr (0.2 mL, 2.32 mmole). The mixture was magnetically stirred at r.t. for 15 minutes. A solution of 6 mmole of the di-haloarene in 50-70 mL TRF was added dropwise over 30 min. and the solution was then heated at reflux for 6-8 hrs. During this period, vigorous stirring was important. Then a grey-white precipitate of the di-Grignard reagent can be noted. The solution was cooled to 0°C and 10 mL of dilute hydrochloric acid (51). or 20 mmole 12 or Br2 was added, and the mixture was stirred for a few minutes. Isolation After distilling most of the THF, the residue was extracted with 50 mL CHCI . The solution was washed successively with dilute 3 hydrochloric acid and water, and dried ("3230u)' am oo— oa oo— - weirdflfluqxrta sa/HHHHHLJ .9. .©_ 8 8. H©H N. s é... om cop 8 8M 3 8. g o~:-_uz 3. © © . .. .0. 5 Eu; 3 an»: 332.. 202 2835-5 3232 253m twee—om. .ud 5‘ 5:25 we 8:333 8:283:13 I9: Sconces cauqéua .. 032. uflsmom B. Di-Grignard Reagents from 1,2,A,S-Tetrahalogenobenzenes Preparations of the following di-Grignard reagents were carried out using a large excess of magnesium, and ethylmagnesium bromide. The yields of products were determined by G.C. analysis, and products were identified by comparison with authentic samples. Experimental Procedure To a dried, Ar-protected three-necked round-bottomed 250-mL flask was added magnesium powder (1g, no mmole). THP (no mL). and CRBCHZBr (1.2 mL, 15 mmole). The mixture was rigorously stirred at r.t. for 30 minutes. A solution of 6 mmole 1,2,n.5-tetrahalogenobenzene in 80 mL THE was added dropwise over 0.5-1 hr at 0°C, and the mixture was stirred for 1-2 hrs at 0°C. The reaction was quenched by adding 20 mL of dilute hydrochloric acid at 0°C. Isolation A See description in the former section. Observation Those 1,2,A.S-tetrahalogenobenzenes that contain iodine usually give greyish white precipitate during the reaction. oev «new a _ a .u so / 63 SO 38 a a 3 £3: a a x x as 2.3 b” u _ Ann. .«oo o .9 gems” Hun a H 88 :3 A 25¢ S 3Q 7Q 3 L”, H “lbw ”a .umwm— a a. e 33 O A358 Q .Q. .HH...Q. _ . _ a . Q .u o n 83 o :8 on .5. 5. d. ’5 .6 a a a m < 8.2.3.6 233.5 m < 22.3.5 223.5 .G 58; -88.. so: -5 -88. 3.232 A: 83833 A3 839:. 338%; Co 339:. cc 333.535 9.5.33 32353.: noconczocomoumfihaeklm.t.m. — I9...— nacomnoz 6.3.5751:— .~ manna. pflsnmm mam M... a udfigflnh Ewup a: w‘m' IQ? Figure A. Trapping of Arynes with Alkyl Grignard Similar processes occurred with 1,3-dichloro-u,6-bis (magnesium bromide)benzene. C. Di-Grignard Reagents Generated from Hexahalogenobenzenes The method of preparing the following di-Grignard reagents was exactly the same as that described above. The yields of products were determined by G.C. analysis, and products were identified by comparison of retention time with those of authentic samples. Experimental Procedure To a dried, Ar-protected three-necked round-bottomed 500 mL flask was added Mg powder (1g, A0 mmole), THF (“0 mL) and CH3CR2 10 mmole). The mixture was rigorously stirred at r.t. for 30 minutes. Br (0.8 mL, A solution of A mmole hexahalogenobenzene in 100 mL TRF was added dropwise over 1-1.5 hrs at 0°C, and followed by additional stirring for 2 hrs at 0°C. The reaction was quenched with 20 mL of dilute hydrochloric acid at 0°C. A m .5 node .3 so? I a .- U m H .5? A2,. o 3: o o 9..- .MH .. ES 3: .6 a... .5 a .- uwn .. .5. v.35 .75 225 T5 .225 75 P38 r5 .8 so: -28: soc“. -5 .25: «3:: 333.535 3 32: Heaven. ngogzgogumzmwce. IPC 3.830: 9.33.513 .m 033. udsmmm 11. DISCUSSION OF PREPARATIOI METHOD OF DI-GRIGNARD REAGENTS A. Direct Reaction of Hexahalogenobenzene with Magnesium In the following experiments, the hexahalogenobenzene reacts with a large excess of magnesium powder and 1,2-dibromoethane as an entrainer, under different temperature (T), and different time periods (t) sequence control. The yields of mono- or di-Grignard reagents were determined by ethylene oxide quenching. . .In all runs, there was no or only a trace of 3,6-dichloro~2,u,5- tribromo-1-(2-hydroxyethyl)benzene. Experimental Procedure To a dried, Ar-protected three-necked 100-mL round-bottomed flask was added Mg powder (0.2g. 8 mole). THF (:40 1nL), BrCHZCHZBr (0.2 mL, 2.32 mmole), and the mixture was stirred magnetically at r.t. for 15 mins. A solution of 1 mmole (0.“62g) 1,2,”,5-tetrabromo-3,6- dichlorobenzene in 35 mL THF was added dropwise over 30 mins at T , and 1 the mixture was stirred for t1 at T1. Ethylene oxide (0.5 mL, 10 mmole) in 5 mL THF or ether was added at T and the mixture was 2’ stirred for t2 at T2, and then for t3 at T3. Finally. the solution was cooled to 0°C, and 10 mL of dilute hydrochloric acid (5%) was added. Observation The color of the Grignard reagents solution was dark brown. When ethylene oxide was added, the color changes to light brown. If the solution was heated over 65°C for several hrs, a reddish brown color In 11 S 2. a... Sm m 8 m o m 3 m cm SN a... E m S m o m 3 a a S. “8 3 m 3 m a e am 3m 3m 3 m .3 m mu m 3N as Rm 3 a 2 m 2 s an; gm 3 “a m 2 m m. m a... a8 a... a m 3 S m. N as 2: S o z o _ :33 o :5 8L :5 8,; :5 8L :3. 3:... .33 mu m Nd NH 5 : oeuuo ocodhgum no“: neuuomo: monocuuLUIun no nuosuocm .2 onamfi yasmom 12 was observed. When the mono-adduct became di~adduct. a greyish yellow precipitation deposited around the edge of container. Isolation After distilling most of THF, the residue was extracted with 50 mL CHCl The extract was washed successively with dilute hydrochloric 3. acid and water, and dried over Nazsou. For product isolation by chromatography. a silica gel column was used. with a mixed solvent eluent of CH Cl :CHCl (1:1). The R values (on 0.2 m m MN silica gel 2 2 3 r N-H R/Uvzsu plates) are: ‘°h°h" Cfiflflfli anneal CWfifldll IP IF : , 0.17 0.28 0.33 0.72 0.72 (A) (B) (C) Figure 5. REhValues of the Products of Di-Grignards Reacting with B ylene Oxide Identification The following three adducts were all previously unknown compounds. (A) 3.6-dichloro-2,5-dibromo-1,u-bis(2-hydroxyethyl)benzene: yellowish needles, m.p. 102-10u°C; MS:m/e (relative intensity) 392(M+, 12). 3"“(100). 331(53). 311(15). 295(13). 283(18). 265(52). 252(30). 229(13). 216(22). 170(23). 1u9<20). 136(3n); H‘ NMR (cool 3 3):63.u8(t, J's 9 Hz, an), 3.59-3.79(m, an), 1.28(t, 3J's u Hz, 23). Anal. Calcd for C1OH1OOZBr2C12:C, 30.57; H, 2.57. Found: C, 30.63; H, 2.59. 13 Figure 6. n‘ m of 3,6-Dichloro-2.5-dibr0lo-1,!-bis (Z-hydroxy- ethyl)benzene l...‘ ‘ { i132 4 h 4 b b 3.0-4 . 1 ‘ F 1 m . m 20 < 73 a n p “5‘ ‘.!w :I ’ “ | ’H'\ ‘( .r I r ad to II 1 in no no no 23 an Iowa "" 1m . i r L x ‘S ”0" h 1 b 1 " D J . . i .- 31 ' H [1' b | 1 a " E in” . In I""[""Y""""" """"""" I """" Wt an an an up as an an Jo «a «o 'Pigure 7. HS Spectrum of 3,6-Dichloro-2,5-dibro-o-1,h-bis(2-hydroxy- ethyl)benzene 14 The protons of a- and B-CH2 absorb at 63.u8 and 63.59-3.79 3 respectively. and protons of a-CH2 is split into a triplet ( J's 9 Hz). Protons of 8-08 is split by those of a-CH and hydroxyl into a 3 2 2 multiplet. The addition of 020 produces 63.69(t, 63.u8(t, 3J's 9 Hz, ha). The a-cnz (63.69) is more deshielded than the J's 9 Hz, RH). a-CHZ (63.”8). The OR proton is at 61.28, and is split by protons of B-CH into a triplet peak (3J's H Hz). Mass spectrum; 392:molecular 2 ion; 3uu (base peak):M-(CH20H and 0H): 331:H-(CHZOH and CHOH); 295:M~ (20H OH and Cl); 283:M-(CH20H, CH CH OH and C1); 265:M-(CH20H, OH and 2 2 2 Br); 252:M-(2CH 0H and Br). 2 (B) 3.6-dichloro-2.5-dibromo-1~(2-hydroxyethyl)benzene: . yellowish needles, m.p. 1u3-1HS°C; MS:m/e (relative intensity) 3u8(M+. 17). 318(62). 283(26). 269(63). 239(97). 203(fl8). 157(86). 121(91). 1 85(100); H NMR (CDCl ):63.u8(t. 3J'8 9 Hz, 2H), 3.90(t, 3J's 9 Hz, 3 . 2H), 1.28(t, 3J's u Hz, 1H). 7.69(s, 1H). Anal. Calcd for 08H608r2012:c, 27.5”; H. 1.73. Found: C, 27.99; H. 1.90. .1 . d 1.4,. 7 AT - 7 47 I I 7 z .1 Figure 8. n1 m of 3.6-Dichloro-2.S-dibro-o-1-(2-hydroxyethyl)benzene 15 121 A I V fi‘v ' Figure 9. H3 Spectrum of 3.6-Dichloro-2,5-dibro-o~1~(2-hydroxy- ethyl)benzene The protons of a- and B-CH are at 63.h8 and 3.90 respectively, and 2 each group of protons is split by the other into a triplet (3J's 9 Hz). The B-CH (63.90) is more deshielded than the a-CH2 (63.u8). The DH 2 proton at 61.28 is a triplet, split by protons of B-CH (3J's u Hz). 2 The aromatic proton at 67.69 appears as a singlet. Mass spectrum; 3h8zmolecular ion; 318:M-CHOH; 283zM-(CHOH and Cl); 269:M-(CHCH20H and C1); 239:M-(CHOH and Br); 203:M~(CH20H, C1 and Br). (C) 3.6-dichloro-2,n.5-tribromo-1-(2-hydroxyethyl)benzene: yellowish needles, m.p. 150-152°C; MS:m/e (relative intensity) "28(M+, 30). 398(9"). 3h7(100), 317(90). 269(27). 237(98). 203(27). 121(32). 16 85(37). ”C(68); H‘ NMR (cool ):63.u8(t,‘3J's 9 Hz, zn). 3.90(t, 3J's 9 3 Hz, 2H), 1.28(s, 1H). Anal. Calcd for 68H508r3C12:C, 22.u6; H, 1.18. J L. liiil-iii--.iLllliLllllLlli.Liliii-lililiilill 1 1 L k a I 2.. l 0 Figure 10. n1 was of 3,6-picnioro-2.n.5-tribre-o-1~(2-nydroxy- ethyl )benzene 1...! 217 m A v fi r f ' V j V " " 113 Figure 11. HS Spectrum of 3,6-Dichloro-2,I,5-tribrono-1~(2-hydroxy~ ethyl)benzene 17 The protons of a- and B-CH are at 63.UB and 3.90 respectively, and 2 each group of protons is split by the other into a triplet (3J's 9 Hz). The B-CH2 (63.90) is more deshielded than the a-CH2 (63.n8). The DH proton at 61.28 is a broadened singlet. Mass spectrum interpretation; n28:molecular ion; 398:M*CHOH; 3H7:M-(CH2CH OH and C1): 317:H-(CH20H 2 and Br); 269:M-(CH2CH OH, Br and Cl); 237:M-(CH20H and ZBr). 2 B. Ease of Formation, Stability and Reactivity of Di-Grignard Reagents Ease of Formation From the results shown in the above sections, we get a relative rate of polyhalogeno benzene reacting with Mgz~I > -Br > -Cl: the order is identical to the situation of mono-halogeno benzene: C6H I > C H Br 5 6 5 9 > C6H Cl > CGHSF,9 and of alkyl halides: RI > RBr > RC1. Even in the 5 exchange method of preparing di-Grignard reagents, we have the same order. For example, no significant yield of p-bis(magnesium bromide)benzene was obtained from u-chlorobromobenzene: instead, only u-chlorophenylmagnesium bromide was formed (exchange at Br, but not at Cl). Stability Di~Grignard reagents generated from di~haloarenes usually show good stability in the temperature range 0-80°C, and can exist for more than 2” hrs, no significant change to the yields of quenching experiments (see Section III, A.). Di-Grignard reagents prepared from polyhalogenobenzene are usually stable at 0°C for h-6 hrs: later they begin to decompose slowly, producing arynes. Data table in the former section shows that total yields of products, intermediates and recovered starting material decrease when reaction time increases, while the yields of by-products 18 polyethyl substituted benzene or polyhalogenobenzene increase. Electron~withdrawn groups stablize di-Grignard reagents, but electron- donating groups destablize di-Grignard reagents. For example, 2,5-bis (magnesium bromide)-3,6~dibromo-p-xylene decomposes at 0°C, whereas 3,6-bis(magnesium bromide)-p~dibromobenzene is stable at 0°C. The methyl substituents destabliize the former reagent. The stronger the electron-withdrawing group is, the more stable is the di-Grignard reagent. Thus 2,5-bis (magnesium bromide)-3,6-dichloro-p-xylene at 0°C is more stable than the corresponding 3,6-dibromo compound. This rule is also applyable to mono-Grignard reagents made from polyhalogenobenzenes. The more electron-withdrawing groups a mono- or di-Grignard reagent contains, the more stable is the reagent. _For example, 2-(magnesium bromide)halogenobenzene (X-I, Cl, Br, F) decomposes at room temperature, but 2-(magnesium bromide)-1,u,5- tribromobenzene (with two more halogens on the aromatic ring) is stable, and 2-(magnesium bromide)‘3o6-dichloro~1,u,5‘tribromobenzene is stable even at 50°C. Temperature Effect and Reactivity 2,3,5,6~Tetrabromo-1,h-dichlorobenzene will not react with Mg at 0°C. At 15°C, a good yield of the corresponding mono-Grignard can be obtained, but no di-Grignard is formed. At room temperature, the halide reacts with Mg very rapidly, and over 70% of the mono-Grignard can be obtained within 2 hrs. The di-Grignard also forms rapidly, but decomposes rapidly to an aryne. The di-Grignard reagent from 2,3,5,6-tetrabromo-1,u- dichlorobenzene reacts very fast with one equivalent of ethylene oxide in the temperature range 0-30°C, but the resulting product will not react with a second equivalent of ethylene oxide in the same 19 temperature range, even overnight. At a temperature over 50°C, however reaction occurs. In contrast, the mono-Grignard derived from 2.3.5.6- tetrabromo-1,u-dichlorobenzene will not react with ethylene oxide in the temperature range 0-50°C, or even at higher temperatures; only trace amounts of the corresponding product results. This result means that the remaining Grignard moiety in the molecule u-(magnesium bromide)-2,5-dichloro-3,6-dibromoe1~(magnesium ethoxide)benzene is more reactive than mono-Grignard u-(magnesium bromide)-2.5-dichloro-1,3,6- tribromobenzene. So actually, the main products after isolation are diol and 2,5-dichloro-1,3,u-tribromobenzene, small amount of 3,6- dichloro-2,5-dibromo-1~(2-hydroxyethyl)benzene. Generally speaking, di-Grignard reagents are more reactive toward electrOphiles than mono Grignards, even at low temperature. 0n the other hand, to increase reactivity of mono-Grignard, generated from di- Grignard reacting with one equivalent of reactant, we may elevate the temperature, or mix in some sort of low basic solvent, that has low coordination ability, together with adding reactant. For example, adding ethylene oxide, mixed with ether or cyclohexane (1/3 volume of di-Grignard solution), in di-Grignard solution (THF), we can change mono-alkoxide to di-alkoxide at lower 'temperature 35-fl0°C, within shorter time. C. Exchange Method Here the conventional method for preparing a di-Grignard from a polyhalogenobenzene is followed, using CH3CH2MgBr as the exchanger. The yield of di-Grignard is examined by ethylene oxide quenching. 20 Procedure To a dried, Ar-protected three-necked 100-ml round-bottomed flask was added 1 mmole (0.”62g) 2.3.5.6-tetrabromo-1,u-dichlorobenzene and THE (35 mL). The mixture was stirred magnetically, and a solution of 2 mmole CH3CH2MgBr in 10 mL ether or THF was added by dropwise over 30 mins at 0°C. After stirring for 3 hrs at 0°C, 10 mmole ethylene oxide in 5 mL ether was added and the mixture was stirred at 0°C for 2 hrs, at r.t. for 1 hr, and then at 50°C for 5 hrs. The reaction was quenched by adding 5 mL diluted hydrochloric acid at 0°C. The products were isolated by the procedure described in section II, A. The by-product CHBCHZCHZCHZOH’ formed from ethylmagnesium bromide and ethylene oxide, can be removed in the diluted aqueous hydrochloric acid layer. Observation and Results The color of the reaction solution was light yellow from the beginning to the end, much different from the color in direct preparation method (dark brown). The reaction products were 3,6-dichloro-2,5-dibromo-1,u-bis(2- hydroxyethyl)benzene (53). 3,6-dichloro-2,5-dibromo-1~(2- hydroxyethy1)benzene (21), 2,5-dichloro-1,3,u-tribromo-benzene (76%), and recovered starting material (121). D. Entrainment Method The conventional method was used to prepare the di-Grignard reagent of hexahalogenobenzene. The yield was examined by ethylene oxide quenching. Ethylene dibromide and ethyl bromide was used as the entrainers. 21 Procedure To a dried, Ar-protected three-necked 100-mL round-bottomed flask was added Mg powder (0.2g, 8 mmole), THF (4 mL), BrCHZCHZBr (0.2 mL, 2.32 mmole). The mixture was magnetically stirred at r.t. for 15 minutes. A solution of 1 mmole (0.h62g) 1.2.0.5-tetrabromo-3,6- dichlorobenzene and u mmole CH3CHZBr, both in 35 mL THF was added dropwise over 30 mins at 15°C. Rapid stirring was continued for 5 hrs at 15°C, after which 0.5 mL ethylene oxide (10 mmole) was added. After stirring at 15°C for 1 more hr, the mixture was heated at 50°C for 5 hrs. The reaction was quenched by adding diluted hydrochloric acid at 0°C. .Isolation is same as the procedure described in II, A. Result There was obtained 3,6-dichloro-2,5-dibromo-1,u-bis(2- hydroxyethyl)benzene (10$). 3.6-dichloro-2,5-dibromo-1-(2- hydroxyethyl)benzene (5%). 2,5-dichloro-1,3,u-tri-bromobenzene (601). and recovered starting material (5%). Observation and Discussion The color of the reaction solution from the time of adding the solhtion until the end was light yellow, Just as in the exchange method. It seems likely that the so-called CH3CHZBr entrainment method ‘is actually the same as the exchange method, Judging from the results. As an entrainer, BrCH CH Br functions through the reaction: 2 2 BrCHZCHZBr + Mg ---9 MgBr2 + CHZ-CH2 The entrainer cleans the surface of the Mg, so that the halide can react with Mg successfully. In the direct preparation method described 2CHZBr beforehand. Only the mono-Grignard product was obtained at 15°C: that above, the surface of the Mg was cleaned by washing with BrCH is, the mono-Grignard does not react further with Mg below r.t. 22 Di-Orignard can be obtained below room temperature only by exchange. So the likely reaction course is that the CH3CHzBr reacts with the Mg 3CHZMgBr: then CHBCHzMgBr exchanges with substrate. Three aspects of the preparation can be mentioned: 1. the higher yield first, to give CH of di-Grignard reagent than in the exchange method (at 0°C) arises from the higher reaction temperature (15°C): 2. for the same reason, a portion of the di-Grignard reagent decomposed: 3. adsorption of CH3CHZBr rather than 1,2,u,5-tetrabromo-3,6-di-chlorobenzene on Mg surface is favored. In both methods, exchange and entrainment, CHBCHZBr is regenerated after exchange of CH3CH2MgBr with hexahalogenobenzene. Perhaps the regenerated CHBCHzBr reacts with Mg again, consequently resulting in a second generation of CH CHZMgBr, and 3 the cycle is repeated. The following two procedures are designed based on this possibility. E. Combination of Direct, Exchange and Entrainment £222 In the following procedure, 1,2,n.5-tetrabromo-3,6-dichloro- benzene reacts with excess Mg at 15°C first, resulting in over 601 of the mono-Grignard (see I. A). Then 2 equivalents of CH3CH2HgBr are added, and exchange occurs. The regenerated CHBCHZBr may react with the excess Mg present: consequently exchange between the second generation of CHBCHzMgBr and the starting material or mono-Grignard may occur. Procedure To a dried, Ar-protected three-necked 100-mL round-bottomed flask was added Mg powder (0.2g, 8 mmole). THF (u mL), BrCH CH 2 2Br (0.2 mL, 23 2.32 mmole). The mixture was magnetically stirred at r.t. for 15 mins, after which a solution of 1 mmole (0."62g) 1,2,“,5-tetrabromo-3,6- dichlorobenzene in 35 mL THF was added dropwise over 30 mins at 15°C. After stirring for 2 hrs at 15°C, a solution of 2 mmole CHBCHZMgBr in 10 mL of ether was added dropwise at 0°C. The mixture was stirred for 3 hrs at 0°C. Ethylene oxide (0.5 mL, 10 mmole) in 5 mL ether was added. The mixture was stirred at 0°C for 2 hrs, at r.t. for 1 hr, and at 50°C for 5 hrs. The reaction was then quenched with diluted hydrochloric acid at 0°C. Isolation is same as the procedure described in II. A. 32.3.1122 There was obtained 3,6-dichloro-2,5-dibromo-1,H-bis*(2- hydroxyethyl)benzene (35$). 3.6-dichloro-2,5-dibromo-1-(2- hydroxyethyl)benzene (10%) and 2,5-dichloro-1,3,u-tribromobenzene (26$). Observation and Discussion The color of the solution was dark brown from the beginning to the end, Just as in the direct preparation method. The yield of di- Grignard is good, but still not ideal, and the procedure is not convenient. The regenerated CHBCHZBr did not seem to react with Mg again, resulting in a second generation of CH MgBr, as expected. 3CH2 Judging from the color of the solution and the low yield of di- Grignard, perhaps the 1,2,”,5-tetrabromo-3,6-dichlorobenzene adsorbed on the Mg makes the surface of the Mg inert. Consequently the CH3CHZBr could not react with Mg again. To overcome this disadvantage, one might drop the substrate into CH3CH2MgBr containing excess Mg. In this case, the surface of the Mg would be occupied by CH3CH28r first. After 24 exchange of CH3CH2MgBr with substrate, the regenerated CH CHZBr might 3 then react with Mg again. F. Combination of Exchange and Entrainment To a dried, Ar-protected three-necked 100 mL round-bottomed flask was added Mg (0.2g, 8 mmole), CH3CHzBr (0.15 mL, 2 mmole) and ether 10 mL, and the mixture was stirred at r.t. for 30 mins. A solution of 1 mmole 1,2,“,5-tetrabromo-3,6-dichlorobenzene in 35 mL THF was added dropwise over 30 mins at 0°C, and stirring was continued for 3 hrs. Ethylene oxide (0.5 mL, 10 mmole) in 5 mL ether was added at 0°C. Stirring was continued at 0°C for 2 hrs, at r.t. for 1 hr, and at 50°C for 5 hrs. The reaction was then quenched with diluted hydrochloric acid at 0°C. Isolation was same as the procedure described in II. A. 52-111; There was obtained 3,6-dichloro-2,5-dibromo-1,u-bis-(2~ hydroxyethyl)benzene (60$). 3,6-dichloro-2,5-dibromo-1-(2- hydroxyethyl)benzene (11%), and 2,5-dichloro-1,3,u-tribromo~benzene (15$). Observation and Discussion The color of the reaction solution was light yellow from the beginning to the end. The increased yield of bis-hydroxyethyi product may result from reaction of regenerated CH3CHZBr with excess Mg again, resulting in a second generation of CH3CH2MgBr which can further exchange. Of course, direct reaction of the polyhalogenobenzene with Mg is still possible. Thus we obtain a higher yield of di-Grignard reagent. This is the best new method and a relatively simple procedure. III. APPLICATIOI OF DI-GRIONARD REAGENTS Some limited applications of di-Grignard reagents to synthesis have been carried out and are described in the following sections. A. Addition of Di-Grignard Reagent to Ethylene Oxide Procedure and Result See I, C for the preparation of 2,5-dibromo-3,6-dichlorophenylbis *(magnesium bromide), and II. A for isolation of the products. After preparing the di-Grignard (fl mmole) by the method of combination of exchange and entrainment, there was added 2 mL ethylene oxide (“0 mmole) in 10 mL ether dropwise at 0°C. After stirring at 0°C for 2 hrs, 10 mL of dilute hydrochloric acid was added. The only product was the mono-adduct 3,6-dichloro-2,5-dibromo-1~(2-hydroxyethyl)benzene (751). In an alternative route, after adding the ethylene oxide the temperature was elevated to 50°C, and maintained there for 2 hrs. The mixture was then quenched with dilute hydrochloric acid at 0°C. The main product was the diol, 3,6-dichloro-2,5-dibromo-1,H-bis(2- hydroxyethyl)benzene (601). Discussion The advantage of the reaction can be seen by comparing the result with the di-Grignard reagent with that obtained using the di-lithium reagent, 2,5-dibromo-3,6-dichlorophenylbis(lithium). This reagent, prepared in toluene, is stable at -60°C, and in ether at -78°C. But 25 26 ethylene oxide does not react at these low temperatures, even overnight, and no addition occurs. Even when the solution was warmed to r.t. for several hours, neither the mono- or di-adduct was formed. See ASUPPLEMENT EXPERIMENTS about preparation of the di-lithium reagent from hexahalogenobenzene. B. Addition of Di-Grignard Reagents to Benzaldehyde Experimental Procedure See I. A for the preparation of the di-Grignard reagents. After preparing the di-Grignard reagents (6 mmole), the solution was cooled to r.t., and 1.5 mL benzaldehyde (15 mmole) in 10 mL THF was added dropwise. Stirring was continued at r.t. for 1 hr. In runs h and 5. it was necessary to heat the solution at u5°c for 1 hr. Isolation After distilling most of the THF, the residue was extracted with 50 mL CHC13. The solution was washed successively with dilute hydrochloric acid and aqueous sodium bisulfite. The excess benzaldehyde reacted with the NaHSO3 to give a water-soluble product. The organic phase was dried with NaZSOu. Further purification was done Cl as the eluent. by silica gel column, using CH2 2 27 Result Table 5. Dials from Reaction of Di-Grignards with Benzaldehyde Rm Halide . Product ie1d t m.p. °C Ref. 1 x x @4101: © -' '@ 86 170-172 10 (X=MJ) 2 m-@ so 123-125 11 3 ~’©k mg“ 82 154-156 12 ' © 1. I 65 197-200 13 Q G 70 296-298 14 Melting points agreed with those in the cited literature references. 28 C. Reaction of Di-Grignard Reagents with Acetyl Chloride Procedure See I. A for the preparation of the di-Grignard reagents. After preparing the di-Grignard reagents (6 mmole), the solution was cooled to 0°C, and 2.2 mL acetyl chloride (30 mmole) in 10 mL THF was added. The mixture was stirred at 0°C for 1 hr, then warmed to r.t. over 1 hr. Isolation and Result After distilling most of the THF, the residue was extracted with 50 mL benzene. The organic solution was washed with H 0, dried with 2 NaZSOu. Further purification was carried out by silica gel column, using CH2C12 as the eluent. The yields of 1,H-diacetylbenzene (A) and u,u'-diacetylbiphenyl (B) were 901 and 85% respectively. Melting points of the two compounds agreed with those cited in the literature references. For (A) m.p. is 108-11o°c (Lit.15 ‘6 111-3°C); for (B) m.p. is 192-19U°C (Lit. 192-3°C). D. Reaction of Di-Grignard Reagents with Benzoyl Chloride Experimental Procedure See I. A,B,C about the preparation of the di-Grignard reagents. After preparing the di-Crignard reagent (6 mmole for runs 1-6, u mmole for run 7), the solution was cooled to 0°C, and 2.“ mL benzoyl chloride (20 mmole) in 10 mL' THF was added. In runs 5-7, 3.5 mL benzoyl chloride (30 mmole) was added. The mixture was stirred at 0°C for 30 mins, then 10 mL H20 was added. In some cases, to complete the reactions more quickly, the solutions may be warmed to r.t., and stirred for approximately 10 mins after adding the benzoyl chloride. See description in former section about isolation. 29 Result Table 6. Diketones from Reaction of Di-Grignards with Benzoyl Chloride Run Halide Product ield x m.p. °c Ref. Q . I 1 “0‘“ £0"! so 157-159 17 (X23151) Q . 2 46 97-99 18 3 50 215-217 19 4 40 186-188 20 5 35 viscous 1iquid unknown 6 40 142-144 unknown 7 40 284 unknown 30 Melting points agreed with those in the cited literature references, for the products of runs 1-4, melting points (°C) in cited literature references are 159-160, 99.5-100, 218 and 189-190 respectively. The products of runs 5-7 are previously unknown. Identification of Unknown Compounds Carbon tetrachloride was used as the solvent for all of the following IR spectra. 2,4-Dichloro-1,S-dibenzoylbenzene: Colorless viscous liquid: MS:m/e (relative intensity) 354(M+, 1), 277(6), 214(2), 1 207(3). 172(2). 105(100). 77(65). 51(36): H NMR (CDCl ):67-”3(3. 1H). 3 7.81(s, 1H). 7.82(d, 3J's 10 Hz, uh), 7.6u(t, 3J's 10 Hz, an). 7.50(t, 3J's 10 Hz, 4H); IR shows carbonyl group at 1675 cm-1. Anal. Calcd for c20H1202C1230’ 67.63; H, 3.u1. Found: C, 66.81; H, 3.86. 169.6- “'5 '- $.01 77 Si ‘ 43 ‘ 53 x 63 71 u ,1 IVE ‘0 6. N 2...] D p . 1 1 1 u a ' ' ’ CD 1 0‘ n ¢0 ‘ 10.6- “k C v- :1 1 T . 4 m 7 b 11 3" 1 37 ll 'v'V‘l """"" l' """"" I """"" rV'Vf‘ '1' '1' 'VIfiT V"fir""""'""""$‘""""""' 11 E 240 266 239 398 2'1 346 - a“ n m Figure 12. MS Spectrum of 2,4-Dichloro—1,S-dibenzoylbenzene 31 MWfl1 “1111111 I'lllllll IT Ill 176171-1*1147fix1741llmqi - 1 .1-1- 7 I ‘ . 1 1 , 1 ; 11:1" 1 1 ‘ 1 ‘1: i1 Figure 13. IR Spectra of 2,4-Dichloro-1,5-dibenzoylbenzene p-H n-H YYYV ITYWTIYYYYTfiYfifiY [7717 [VYTTI’TTWT [jYfi B113 7.5 7.1! 6 5 SD 5.5 5.999" Figure 14. H1 NMR of 2,4-Dichloro-1.S-dibenzoylbenzene 32 'V’H~rffffivffivwvIfi1WVVfiVWYIWV'VYWVfoIYfiVVYVVT 918 616 1,0 6.. Figure 15. a‘ nun of Benzophenone 2,5-Dichloro-3,6-dibromo-1,u-dibenzoylbenzene: Colorless needles, m.p. 284°C; MS:m/e (relative intensity) 510(M+, 2), 432(2). 355(1), 300(1), 2u6(2), 105(base, 100). 77(61). 51(20): H1 NMR (CDCl ):67.88(d, 3J's 8 Hz, 18), 7.69(t, 3J's 8 Hz, 2H), 7.55(t, 3J's 8 3 Hz, AH): IR shows carbonyl group at 1688 cm-1. Anal. Calcd for C20H1OOZBrZC12:C, “6.83; H, 1.97. Found: C, ”6.72; H, 2.01. 33 mss mm om: 14161 no N 0242/5 14:16:” 9 3 6 M‘ I“ ' 1““ 9M 3 MI: CI. 03 RIC: 574464. 092 1'0 093 sumo - N 1W.O I” '— 6.“ Figure 16. rs Spectrum of 2,5-Dichioro-3.6-dibrono-1,I-dibenzoyi- benzene Figure 17. IR Spectrum of 2.5-Dichloro-3.6-dibromo-1,h-dibenzoyl- benzene 34 CH0, 9! (R 0 @W@ L «use 9-H P-H “'H Y777firfi[Y177I777TI7717[jTfiTTITYVYITji'[71' 1 SS 3111 8.5 an 7S 71' 6.5 E." Figure 18. H1 NMR of 2,5-Dichloro-3.6-dibromo-1,fi-dibenzoylbenzene 2,5-Dichloro-1.u-dibenzoylbenzene: Colorless needles, m.p. 1nz-1uu°c; MS:m/e (relative intensity) 3SN(M*, 1), 319(1), 277(2). 219(2). 211(2). 105(1001, 77(50), 51(32): H13 NMR (CDC13):67.83(d. 3J's 10 Hz, 4H). 7. 68(t, 3J's 10 Hz, 2H). 7. 53(t. J's 10 Hz 4H). all the peaks are split further by 3-H and 6-H to doublet (J's 2 Hz) through long range coupling. 7.57(s, 2H); IR shows carbonyl group at 1682 cm-1. Anal. Calcd for C20H1202C12:C , 67.63; H, 3.41. Found: C, 67.86; H, 3.23. 35 m" ' “l"!"lnt'm Mlllllhh ||| llll' III "III II IIIIIIIIMI III If? . l I I. l ll'i 1 I “I ' III) ‘1, Ell! I‘LL - I '. ‘Il’ u - ___ , _ __. . Figure 19. IR Spectrum of 2.5-Dichloro-1J-dibenzoy1benzene CIQI @j‘ 1159 (um J L rjI¢II¢I f-‘I‘n-H Tfi[IIITIITIITjfifYIfiWTII—FT11I1fiT1[IIIIIII SS 30 35 8,0 15 70 SS 5. Figure 20. H1 m of 2,5-Dichloro-1J-dibenzoy1r 36 m..« m 1 I 4 I 20 2n 3 fit ""I' ‘ I """" 'V'V'hvv't' """" I """"" ""' PIE 240 26. 2“ 3a 33 3‘ u as Figure 21. HS Spectrum of 2,5-Dichloro-1,h-dibenzoylbenzene B. Preparation of Mono-, Di- or Tri-Grignard Reagents from 1,3,5~ Tribromobenzene by Temperature Control and Quenching Experiments In all of the following three experiments, the substrates reacted with Mg directly in THF, and the resulted Grignard reagents were quenched with iodine (H20 for exp. 1) or benzoyl chloride. For iodine quenching, yields of products were determined by GC-MASS. For benzoyl chloride quenching, products were isolated. Exp. 1: 1,3.5-Tribromobenzene reacted with Mg in THF at r.t., resulting mono-Grignard, 3,5-dibromo-1-(magnesium bromide)benzene absolutely. H O quenching gave 1,3-dibromobenzene (95“ benzoyl 2 chloride quenching gave 3,5-dibromo-benzophenone (60$). 37 Exp. 2: At IS-SO°C, corresponding mono- and di-Grignard reagents resulted. Iodine quenching gave 1,3-dibromo-5-iodobenzene (20%). and 1~bromo-3,5-diiodobenzene (76$); benzoyl chloride quenching gave 5- bromo-1,3-dibenzoylbenzene (”51). and 3.5-dibromo-benzophenone (15%). Exp. 3: At refluxing, corresponding di- and tri-Grignard reagents resulted. Iodine quenching gave 1-bromo-3.S-diiodobenzene (not), and 1,3.5-triiodobenzene (52$). Benzoyl chloride quenching gave S-bromo- 1,3-dibenzoylbenzene (30%), and 1,3,5-tribenzoylbenzene (25$). Experimental Procedure To a dried, Ar-protected three-necked round-bottomed ZSO-mL flask was added magnesium powder (0.53. 20 mmole). BrCHZCHZBr (0.2 mL, 2.32 mmole) and THE (10 mL). The mixture was stirred magnetically at r.t. for 10 minutes. A solution of 1,3,5-tribromobenzene (1.6g. 5 mmole) in 80 mL THF was added dropwise over 30 minutes at r.t. The mixture was rigorously stirred for 1 hr at r.t. for preparing mono-Grignard; for 8 hrs at "5-50°C for preparing di-Grignard; was refluxed for 8 hrs with rigorously stirring for preparing tri-Grignard, then cooled to 0°C. and H20 (20 mL) was added for exp. 1, or 7.623 iodine (30 mmole I2) in 10 mL THF were added for exp. 2 and 3, or a solution of 3.5 mL (30 mmole) benzoyl chloride in 10 mL THE was added (for all of the three experiments). After an additional 30 minutes at 0°C, the solution was quenched with 20 mL H20 at 0°C. See description about isolation in section III. C, for benzoyl chloride quenching, and section I. A, for iodine quenching. Identification 3.5-Dibromobenzophenone: 21 colorless needles, m.p. 7u-75°c, Lit 75°C. 1.3.5-Tribenzoylbenzene: colorless needles, m.p. 115-117°C, Lit22 118-119°C. S-Bromo-1,3- 38 dibenzoylbenzene: colorless viscous liquid, previously unknown compound. MS:m/e (relative intensity) 36U(M+, 5). 287(3). 285(2). 259(1). 152(3). 105(100). 77(fl9); H1 NMR (CDC13):68.1u-8.O7(m, 28). 7.87-7.7“(m. RH). 7.63“7.57(m, 2H). 7.52-7.35(m. 5H); IR shows carbonyl group absorption at 1725 and 1665 cm-1. Anal. Calcd for CZOH13Br02:C, 65.77: H. 3.59. Found: C, 66.07; H, 3.82. “NJ-I ‘” 2 ‘ us 1 23 1 1L_l .Li HE R? 1 no L¢L~*£RN-H---",fi.q-"-v-n,n 120 140 16. I“ 220 1 BY 8 f 0 Q2)” rij—rv ~ 2“ 2” 21” ME Whvvf‘VY'VIVVV'I'VVVIVIVV'VVVY'VV wv'vvvv'vvvvtvvvv'vvvvlvvvv'vvvv'vvv HIE 240 268 280 see 320 340 360 see 4“ ‘20 Figure 22. HS Spectrum of S-Bromo-I,3-dibenzoylbenzene 39 Figure 23. n1 m of S-Brouo-I,3~dibenzoylbenzene Figure 2!. IR Spectra of 5-Bro-o-1,3-dibenzoylbenzene LIST 0? REFERENCES 10. 11. 12. 13. 1H. 15. 16. 17. 18. 19. 20. 21. 22. REFERENCES Grignard, Compt. rend.. 1930 191, 1&60. Charles F. Smith. George J. Moore, and Christ Tamborski, ‘J; Organometal Chem., 1911.33, C21. George M. Hhiteside and F.D. Gutowski, J. Org. Chem., 1976 11. 2828. J.X. McDermott, J.F. White, and G.M. Whitesides. J. Am. Chem. Soc., 1976.28. 6521. Peter H. Clark and Eric J. O'Reilly, Q_g. Prep. Proced. Int. 1978 10, 173. C.L. Raston, et. al., J. Chem. Soc., Dalton Trans.. 1982 1959. C.L. Raston, et. al.. J. Chem. Soc., Dalton Trans.. 1988 331. C.L. Raston, et. al., J. Chem. Soc., Chem. Commun.. 198'. 1702. M.S. Kharasch and Otto Beinmuth "Grignard Reactions of Nonmetallic Substances;" Prentice-Hall: New York. 1958. Beilstein 6, 1OU7f, II 1017h, III 5797a. C. Kooistra, J.M.F. Van Dizk, P.M. Van Liev and H.M. Buck, Reel. Trav. Chim., 1973. 22, 961. Beilstein 6 III 5797a. Letsinger & Lansburg, J. Am. Chem. Soc., 1959 81. 935. Rio, Silllon, Compt. rend.. 1957 2”“, 623. Holsten. J., et. al. J. Org. Chem., 1957 33. 750. $103“, GOJO , et. a1 0 Jo OPE. Chemo ’ 1951 _2-2-0 750. Beilstein 7. 8293. I Inna, II 761h. Beilstein 7, 829b, I ”333, II 761f, III u298f. Beilstein 7. BIOg, I #52e, II 786f, III ””16c. Beilstein 7. 839d, II 780a, III u397e. Beilstein 7. II 361e. Beilstein 7, 8809, II 8U7d, III u7o1c, IV 28U7. 40 HICHIGAN STnTE UNIV. LIBRARIES 1|I"11111111111111111111111111ll1W1111111”11111111111111 31293013965540