This dissertation has been microfilmed exactly as received Mic 60-6372

HELLING, John Frederic. THE CHEMISTRY OF SOME NEW FUNCTIONAL DERIVATIVES OF FERROCENE.

The Ohio State University, Ph.D., 1960 Chemistry, organic

University Microfilms, Inc., Ann Arbor, Michigan THE CHEMISTRY OF SOME NEW FUNCTIONAL

DERIVATIVES OF FERROCENE

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The ( M o State University

By

JOHN FREDERIC HELLING, B.A.

******

The Ohio State University I960

Approved by

Adviser Department of Chemistry ACKNOWLEDGMENT

The intellectual stimulation and the guidance of Dr. Harold

Shechter during this investigation are gratefully acknowledged. His imaginative ideas challenge the unknown; his enthusiasm is infectious.

Translations of several Russian papers have been generously pro­ vided by Dr. Kenneth Rinehart, Jr., of the University of Illinois and

Dr. Marvin Rausch of the Monsanto Chemical Company.

Thanks go to Dr. A. C. Haven, Jr., Dr. S. N. Boyd, and Dr. J. D.

Brady of E. I. du Pont de Nemours for gifts of ferrocene.

I am grateful for fellowships supported by the National Science

Foundation and E. I. du Pont de Nemours. The opportunity to serve as

DuPont Teaching Fellow has been of inestimable value to me in develop­ ing a better understanding of chemistry.

ii TABLE OF CONTENTS

Page

I. SUMMARY...... 1

II. BACKGROUND...... 3

III. DISCUSSION OF RESULTS...... 8

A. Nitroferrocene...... 8

B. Haloferrocene...... 15

IV. EXPERIMENTAL...... 23

A. General Information...... 23

B. Synthesis and Reactions ofNitroferrocene ...... 23

Nitroferrocene...... 23

Catalytic Reduction of Nitroferrocene ...... 2$

Lithium Aluminum hydride Reduction of Nitroferrocene...... 26

C. Unsuccessful Routes to Nitroferrocene. . 27

Reaction of FerrocenyUithium and Amyl Nitrate ...... 27

Sodium Nitrocyclopentadienide...... 28

Reaction of Sodium Nitrocyclopentadienide and Ferrous I o n ...... 28

Acetylferrocene ...... 29

Reaction of Acetylferrocene and Ifydrazoic A c i d ...... 29

O-Benzylhydroxylaraine...... 30

AnrLnof erroc en e ...... 30

Oxidation of Aminoferrocene ...... 30

iii TABLE OF CONTENTS (CONTD.)

Page

IV. EXPERIMENTAL (CONTD.)

D. Synthesis and Reactions of Haloferrocenes ...... 31

Chloromercuriferrocene ...... 31

Iodoferrocene ...... 32

_ Ferrocenylboronic Acid and 1,1’- Ferrocenylenediboronic Acid ...... 33

Bromoferrocene...... 3h

Chloroferrocene ...... 35

1,1*- Dibromoferrocene ...... 35

Ferrocenylmagnesium Bromide (Methyl Iodide as Entrainer) ...... 35

Ferrocenylmagnesium Bromide (Trace Amount of Methyl I o d i d e ) ...... 37

Ferrocenylmagnesium Iodide (Methyl Iodide as Entrainer)...... 37

Ferrocenylmagnesium Iodide (Trace Amount of Methyl I o d i d e ) ...... 38

Ferrocenylmagnesium Chloride...... 38

Attempted Reaction of Bromoferrocene and Methylmagnesium Iodide...... 39

Reaction of Ferrocenylmagnesium Bromide and Cobaltous Chloride ...... 39

Reaction of 1,1’- Dibromoferrocene with Magnesium ...... HO

Coupling of Iodoferrocene with Magnesium...... k2

Reaction of Iodoferrocene and Butyllithium ..... U3

Reaction of Iodoferrocene and Sodium Amide...... U3

Reaction of Ferrocenylmagnesium Bromide and Amyl Nitrate...... Uit.

iv TABLE OF CONTENTS (CONTD.)

Page

IV. EXPERIMENTAL (CONTD.)

E. Miscellaneous Preliminary Results......

Reaction of Ferrocenyllithium and Acetone Cyanohydrin Ni t r a t e ...... 1|5

Reaction of Ferrocenylmagnesitim Bromide and DinitrogenTetroxide ...... U6

APPENDIX ...... U7

AUTOBIOGRAPHY...... SO

v LIST OF TABLES

Table Page

I. Reactions of Haloferrocenes and Magnesium...... 17

LIST OF FIGURES

Figure Page

I. Infrared Spectrum of Nitroferrocene...... U8

II. Ultraviolet Spectrum of Nitroferrocene...... U9

vi I. SUMMARY

Nitroferrocene was prepared in 2% conversion by addition of dinitrogen tetroxide in ethyl ether at -70° to ferrocenyllithium in ethyl ether at -70°. The structure was established by catalytic hydro­ genation to aminoferrocene with Raney nickel as catalyst. Reduction of nitroferrocene with lithium aluminum hydride gave aminoferrocene and azoferrocene.

No ferrocene derivatives were isolated from reaction of ferro- cenyllithium and amyl nitrate. Reaction of ferrocenyllithium and acetone cyanohydrin nitrate gave cyanoferrocene and several unidenti­ fied ferrocene derivatives. Nitroferrocene was not detected.

Oxidation of aminoferrocene with peroxytrifluoroacetic acid caused the destruction of the ferrocene nucleus. Reaction of ferrous ion and nitrocyclopentadienide ion did not produce 1,1'- dinitroferrocene.

Grignard reagents were prepared by controlled reactions of magnesium with chloroferrocene, bromoferrocene, iodoferrocene, and

1,1'- dibromoferrocene, respectively, in tetrahydrofuran. Effective techniques involving methyl iodide and ethylene bromide have been developed. Ferrocenyl Grignard reagents decompose at elevated temper­ atures to give ferrocene and biferrocenyl. Ferrocenylmagnesium bromide reacts with cobaltous chloride to give biferrocenyl in 80# conversion.

These coupling and reduction reactions may be attributed to ferrocenyl radicals.

Similarly, butyllithium reacts with iodoferrocene to give ferro-

1 cene and biferrocenyl, in addition to ferrocenyllithium. Reaction of iodoferrocene and sodium amide in liquid ammonia yields azoferro­ cene.

Reaction of acetylferrocene and hydrazoic acid in trichloroacetic acid containing a trace of sulfuric acid produced nearly the theoretical amount of nitrogen hut no ferrocene derivative remained.

Helds of ferrocenylboronic acid and 1,1*- ferrocenylenediboronic acid from the published reaction of ferrocenyllithium and butyl borate have been increased considerably by use of ethyl ether- tetrahydrofuran

as a solvent for preparation of ferrocenyllithium. The known reaction

of ehloromercuriferrocene and iodine is better performed in methylene

chloride rather than in hot xylene as previously reported. II. BACKGROUND

The unexpected discovery that biscyclopentadienyl iron (l, 2),

(1) T. J. Kealy and P. L. Pauson, Nature, 168, 1039 (l95l).

(2) S. A. Miller, J. A. Tebboth, and J. F. Tremaine, J. Chem. Soc., 632 (1952). ferrocene, possesses aromatic character (3) has prompted many chemists

(3) R. B. Woodward, M. Rosenblum, and M. C. Whiting, J. Am. Chem. Soc., 7U, 3H58 (1952). to undertake extensive investigations of its properties. Initially it was found that in spite of its formal unsaturation, ferrocene would not undergo BLels-Alder addition to maleic anhydride and could not be hydrogenated under conditions usually satisfactory for catalytic hydro­ genation of olefins (3). Furthermore, the unusual thermal stability of ferrocene, the presence of a single C-H stretching frequency in its infrared spectrum (U), and a number of other physical measure-

(U) G. Wilkinson, M. Rosenblum, M. C. Whiting, and R. B. Woodward, J. Am. Chem. Soc., 7U, 2125 (195U). raents (5) suggested the now-familiar sandwich structure (U). The

(5) For the most recent and informative review of the chemistry of metallocenes see A. N. Nesmeyanov and E. G. Perevalova, Uspekhi Khimii, 27, 3 (1958). equivalence of carbon atoms in ferrocene and the presence of six

3 delocalized, electrons in each ring bear a striking resemblance to benzene.

Early experiments showed that ferrocene could be acylated under typical Friedel-Crafts conditions (3). Since then ferrocene has been found to 'undergo numerous substitution reactions similar to those of benzene. In ease of electrophilic substitution ferrocene surpasses anisole (6).

(6) P. L. Pauson, Quart. Rev., 9j 391 (1955).

In contrast to benzene, ferrocene cannot be nitrated or halo- genated directly and cannot be sulfonated in concentrated sulfuric acid. Halogens, nitric acid, and sulfuric acid oxidize ferrocene to the ferricinium cation (3)* a stable species which does not undergo electrophilic substitution. When warned with bromine in carbon tetra­ chloride, ferrocene is converted to pentabromocyclopentane (7).

(7) A. N. Nesmeyanov, E. G, Perevalova, and 0. A. Nesmeyanova, DolcLady Akad. Nauk SSSR, 100, 1099 (1955).

Chlorine effects cleavage at room temperature to give pentachlorocyclo- pentane (7). Iodine forms an adduct with ferrocene, FeCC^H^^’lO I2, which, in water, produces the ferricinium ion (7).

As a result of the sensitivity of ferrocene to oxidation, many of its derivatives must be prepared by indirect routes. The most important intermediates in these synthetic paths result from metalla- 5 tion of ferrocene with butyllithium (8, 9), phenyls odium (10),

(8) R. A. Benkeser, D. Goggin, and G. Schroll, J. Am. Chem. Soc., 76, 1*025 (195U).

(9) A. N. Nesmeyanov, E. G. Perevalova, R. 7. Golovnya* and 0. A. Nesmeyanova, Doklady Akad. Nauk SSSR, 97 , 1*59 (1951*).

(10) A. N. Nesmeyanov, E. G. Perevalova, and Z. A. Beinoravichute, Doklady Akad. Nauk SSSR, 112, 1*39 (1957). amylsodium (11), or mercuric acetate (9). Butyllithium and mercuric

(ll) A. N. Nesmeyanov, E. G. Perevalova, Z. A. Beinoravichute, and I. L. Malygina, Doklady Akad. Nauk SSSR, 120; 1263 (1958). acetate give mixtures of mono- and di-metallated derivatives. Phenyl- sodium and amylsodium yield disodioferrocene almost exclusively, under the conditions reported.

At the time this investigation was begun, nitroferrocene was unknown. g-Nitrophenylferrocene (12) was known and indicated that the

(12) V. Weinmayr, J. Am. Chem. Soc., 77, 3012 (1955). nitro group is compatible with a ferrocene nucleus. However, it had also been reported that ferrocene is oxidized to the ferricinium cation by nitrobenzene in hydrogen fluoride (13). The known stability of the

(13) 7. Weinmayr, J. Am. Chem. Soc., 77, 3009 (1955). nitrocyclopentadienide ion in water (ll*) aroused speculation as to

(ll*) J. Thiele, Ber., 33, 666 (1900). whether this ion would coordinate with ferrous ion to give a ferrocene system. A search for a satisfactory synthesis of nitroferrocene was undertaken in order to determine whether or not it was a stable compound. A subsequent study of its chemical properties was planned.

The program was extended to include investigation of same reactions of haloferrocenes after publication of some excellent synthetic routes to these compounds. Iodoferrocene may be prepared from chloromercuriferrocene and iodine in hot xylene (7). A mixture of mono- and dilithioferrocene reacts with butyl borate in ethyl ether at -70° to produce ferrocenylboronic acid and 1,1'- ferrocenylenedi- boronic acid (15>). Reaction of ferrocenylboronic acid with aqueous

(15) A. N. Nesmeyanov, V. A. Sazonova, and V. N. Drozd, Doklady Akad. Nauk SSSR, 126, 100U (1959). cupric bromide or cupric chloride gives the corresponding haloferro- cene (l£). Reaction of 1,1'- ferrocenylenediboronic acid with cupric bromide or cupric chloride yields the corresponding 1,1'- dihaloferro- cene (15). Pure haloferrocenes are obtained in good conversions by these routes.

Nesmeyanov and Perevalova reported that iodoferrocene had unusually low reactivity (5). It resisted attempts to form ferrocenyl­ magnesium iodide by reaction with magnesium in ethyl ether (7). It did not react with potassium acetate or potassium hydroxide in methanol at

100° (5). Nothing was reported concerning reactions of other halo­ ferrocenes. These facts suggested that unusual conditions might be necessary for replacement of halogen on a ferrocene nucleus. Research was under­ taken to determine some of these conditions. IU. DISCUSSION OF RESULTS

A. Nitroferrocene

Direct nitration, the usual method for attaching nitro groups to aromatic rings, is not applicable to the synthesis of nitroferrocene because of the ease with which ferrocene is oxidized to the ferricinium ion by nitric acid, alone (3) or in acetic anhydride. Oxidative decomposition of aminoferrocene during attempted diazotization, noted previously (?) and in the present work, precludes replacement of the diazonium group with the nitro group.

Although ferrocene is readily oxidized under acidic conditions, aqueous solutions of the ferricinium ion regenerate ferrocene when made alkaline (16). In view of this, it seemed likely that alkaline

(16) E. 0. Fischer and ¥. Pfab, Z. Naturforsch., 7b, 377 (l9?2). conditions would be required for successful nitration of ferrocene.

Lithioferrocene was reacted with dinitrogen tetroxide, amyl nitrate, and acetone cyanohydrin nitrate. In all of these reactions, the excess butyllithium required for installation of ferrocene is an undesirable competitor for the nitrating agent. Both butyllithium and lithioferrocene can react with products of the initial reactions.

Furthermore, dilithioferrocene is always present and increases the number of products possible.

Despite these unavoidable complications, nitroferrocene was isolated in 2% conversion from the reaction of lithioferrocene and

8 9 dinitrogen tetroxide in ethyl ether at -70° (Equation l).

ether_ ^70°

Fe

This is the first reported example of the synthesis of a nitro com­ pound from dinitrogen tetroxide and an organolithium reagent (17).

(17) A summary of the reactions of dinitrogen tetroxide with organic compounds is given by J. L. RLebsomer, Chem. Rev., 36, 15>7 (19U5).

The reaction was successful only when dinitrogen tetroxide in ethyl ether cooled to -70° was added to lithioferrocene in ethyl ether at

-70° (mole ratio - butyllithium: ferrocene: dinitrogen tetroxide::

1.25: Is l). Under these conditions the highest conversion to nitro­ ferrocene and the highest recovery of ferrocene were obtained. Ferric hydroxide was identified as an insoluble by-product by its solubility in hydrochloric acid to give a blood-red solution following treatment

•with ammonium thiocyanate. Another oxidation product, the ferricinium ion, was observed in the water washing of the reaction mixture.

Treatment of the water washing with sodium bisulfite gave ferro­ cene (12, 13).

Numerous attempts were made to improve the yield by varying the

conditions. Higher conversion of ferrocene uo lithioferrocene is 10 effected with a large excess of butyllithium (8, 9, 18). Preparation

(18) D. W. Mayo, P. D. Shaw, and M. Rausch, Chem. and Ind., 1388 (1957). of lithioferrocene in tetrahydrofuran-ethyl ether (1:1 by volume) (18) is known to give much higher conversion than preparation in ethyl ether alone. Lithioferrocene prepared in tetrahydrofuran-ethyl ether yielded no nitroferrocene when treated with dinitrogen tetroxide (mole ratio - butyllithium: ferrocene: dinitrogen tetroxide:: 3* Is U). Only oxidation products were formed.

To minimize the side-reactions induced by excess organometallic compounds, inverse addition of lithioferrocene to dinitrogen tetroxide was. tried. Again nitroferrocene was not produced. This procedure caused immediate, nearly quantitative formation of a red-brown precipi­ tate. No ferrocene remained; only a trace amount of ferricinium ion was detected. The red-brown solid exploded when heated with a flame.

It was thought to contain the nitrocyclopentadienide ion. An attempt to substantiate this hypothesis by comparison of the ultraviolet spectra of the -unknown solid and sodium nitrocyclopentadienide in water was inconclusive. The spectra of the two compounds, although similar, have no absorption maxima in the region 225-500 rn^i and only- one small shoulder.

The variables, order of addition, solvent, and mole ratio, were not exhaustively studied. From the results obtained, excess dinitrogen tetroxide (inverse addition) appears to be more harmful than 11 excess organometallic compounds (normal addition). Whether or not tetrahydrofuran promotes side reactions has not been established definitely. It seems unlikely that good conversion to nitroferrocene can be achieved by this reaction. This synthesis of nitroferrocene was published in 1959 (19).

(19) J. F. Helling and H. Shechter, Chem. and Ind., 1157 (1909).

Attempts to synthesize nitroferrocene by other routes were unsuccessful. Reaction of lithioferrocene and amyl nitrate in ethyl ether gave mainly ferrocene. Small amounts of tarry material and ferricinium ion were noted. This result is surprising in view of information later published by Grubert and Rinehart (20) concerning

(20) H. Grubert and K. L. Rinehart, Jr., Tetrahedron Letters, No. 12, 16 (1959). synthesis of nitroferrocene in low yield from lithioferrocene and n-propyl nitrate.

Reaction of lithioferrocene and acetone cyanohydrin nitrate, an effective alkaline nitration agent (21, 22), gave a complex mixture of

(21) W. D. Emmons and J. P. Freeman, J. Am. Chem. Soc., 77, U387 (1955).

(22) W. D. Emmons and J. P. Freeman, J. Am. Chem. Soc., 77, 1$391 (1955). ferrocene derivatives. No satisfactory method for isolation of the products was found. The absence of nitroferrocene in the mixture, however, was established by chromatography. Cyanoferrocene, an 12 unexpected, product, was identified.

Sodium nitrocyclopentadienide (lli) reacted with ferrous ion in water to give a dark precipitate the properties of which demonstrated that it was not a ferrocene derivative. It did not melt, dissolve in organic solvents, or show infrared absorption expected for 1,1'- dinitr of errocene. It was believed to be iron nitrocyclopentadienide.

Oxidation of aromatic amines with peroxytrifluoroacetic acid, is reported to be an excellent route to aromatic nitro compounds (23).

(23) W. D. Snmons, J. Am. Chem. Soc., 76; 31*70 (195U).

Complete destruction of the ferrocene nucleus was observed when amino­ ferrocene was reacted with peroxytrifluoroacetic acid. Aminoferrocene used for the oxidation reaction was synthesized by a published pro­ cedure, reaction of O-benzylhydroxylamine and lithioferrocene (2U),

(2l*) A. N. Nesmeyanov, E. G. Perevalova, R. V. Golovnya, and S. Shilovtseva, Doklady Akad. Nauk SSSR, 102, 535 (1955). which gives unsatisfactory conversion and is time consuming. In an attempt to find a more satisfactory route to aminoferrocene, acetyl­ ferrocene was reacted with hydrazoic acid in trichloroacetic acid containing a catalytic amount of sulfuric acid (25). Nearly quanti-

(25) P. A. S. Smith, J. Am. Chem. Soc., 70; 320 (19U8). tative formation of nitrogen was observed but no ferrocene derivatives remained. Later it was reported that aminoferrocene is best synthe- 13

sized by reaction of lithioferrocene and methoxyamine (20).

The structure of nitroferrocene was established by catalytic hydrogenation to aminoferrocene. Reaction of nitroferrocene with lithium aluminum hydride produced aminoferrocene and azoferrocene

(Equation 2).

(2)

Usually reduction of aromatic nitro compounds with lithium aluminum

hydride yields azo compounds only (26).

(26) N. G. Gaylord, "Reduction With Complex Metal Ifydrides," Interscience Publishers, Inc., New York, 1956, pp. 773-776.

Nitroferrocene is a stable, deep red, crystalline solid. It may

be purified by chromatography and vacuum sublimation and is soluble in

benzene, petroleum ether, chloroform, and acetone.

According to the findings of Brown (27) and of Kross and Fassel(28),

(27) J. F. Brown, Jr., J. Am. Chem. Soc., 77, 63i*l (1955).

(28) R. 0.Kross and V. A. Fassel, J. Am. Chem. Soc., 78, 1+225 (1956).

the asymmetric stretching frequencies of aromatic nitro compounds vary

directly with the electronic nature of other substituent groups as measured by Hammett o' constants. The greater the electron-donating

capacity of a substituent group, the lower the asymmetric stretching frequency. Comparison of the value measured for nitroferrocene

(lj>01 cm”l) with the frequencies recorded for a series of para substi­

tuted nitrobenzenes shows that it is intermediate between those of p-methoxynitrobenzene (15>10 cm"-*-) (28) and p-dimethylaminonitrobenzene

(lJU87 cm--*-) (29) and roughly equal that of p-aminonitrobenzene

(29) A. R. Katritzky and P. Simmons, Rec. trav. chim., 79, 361 (1960).

(l5oU cm--*-) (28, 30). From this information it may be concluded that

(30) All values were measured with solid compounds with the exception of that of p-dimethylaminonitrobenzene which was measured in chloroform. p-dimethylaminophenyl > ferrocenyl stf p-aminophenyl > p-methaxyphenyl

radical in electron density at the reaction site. Therefore, the order

of reactivity in electrophilic substitution reactions is expected to be

N, N-dimethylaniline > ferrocene s» aniline > anisole. In a competitive

Friedel-Crafts reaction, ferrocene is reported to be more reactive than anisole (6), thus substantiating the predicted order. No competitive

reactions have been performed with N, N-dimethylaniline or aniline and ferrocene. B. Haloferrocenes

Haloferrocenes were synthesized by known reactions. A number of advantageous modified procedures have been developed. Iodoferrocene is prepared from chloromercuriferrocene and iodine (7) (Equation 3).

CtjHcjF eCtjH^HgCl

The published procedure specifies hot xylene as the solvent, apparently because of the low solubility of chloromereuriferrocene in most organic solvents. A more convenient solvent was found to be methylene chloride in which chloromereuriferrocene is quite soluble. This change in reaction procedure increased the conversion slightly, 6k% to 70%, and simplified isolation of the product.

Synthesis of the boronic acids of ferrocene, intermediates for the preparation of haloferrocenes, is accomplished by reaction of mixed mono- and dilithioferrocene and butyl borate (l5) (Equation U).

(1) C ^ I i C ^ F e C ^ (2) (C^H9P)3B' (3) HgO, H*

The published procedure lists ethyl ether as the solvent. It was found that preparation of mono- and dili thiof errocene in tetrahydro­ furan-ethyl ether (lsl by volume) (18) and subsequent addition to butyl 16 borate in ethyl ether produced much higher conversions. Nesmeyanov et al. (15) obtained 26% ferrocenylboronic acid and 13% 1*1'- ferro- cenylenediboronic acid. The present modification yielded Uk% ferro­ cenylboronic acid, 18# 1,1'- ferrocenylenediboronic acid, and 29% ferrocene. Soxhlet extraction with ethyl ether was found to be a convenient method for separation of the dry acids (31).

(31) The boronic acids decompose if dried at elevated tempera­ tures.

Bromoferrocene and chloroferrocene were prepared from ferrocenyl­ boronic acid and the appropriate cupric halide (10) (Equation 0).

C^FeC^I^B(OH)2 + 2 CuX2 + HgO ------(£)

C^FeC^X 2 CuX «■ H3B03 V HX

1,1'- Dibromoferrocene was obtained by the analogous reaction of 1,1'- ferrocenylenediboronic acid and cupric bromide (10). Vacuum sublima­ tion was found to be convenient for purification of bromoferrocene, iodoferrocene, and chloroferrocene.

Chloroferrocene, bromoferrocene, and iodoferrocene (Table I) react with magnesium powder in tetrahydrofuran under controlled conditions to give Grignard reagents in satisfactory yields. 1,1'- Dibromoferrocene has been converted to its di-Grignard reagent ($9%). The yields of these reagents were determined by carbonation and isolation of the resultant carboxylic acids.

Reactions of haloferrocenes and magnesium to give Grignard reagents occur under oxygen-free, dry nitrogen when initiated with methyl iodide; TABLE I

Reactions of Haloferrocenes and Magnesium

Molar Reactant Ratio Time,b Conv. ,c,c* Recovery, $; Halof errocene3- Haloferrocene Mg CH^I Temp.,° hr. Haloferroc enee

Chloro 1 4 1 46-48f 4.0 15 79

Bromo 1 3 _g 38-42f 3.5 4911 y *

Bromo 1 4 1 37-3/ 2.0 84 11

Iodo 1 3 _g 11-12 2.5 ^7 44 Iodo 1 4 1 11-12 1.0 65 27

1,1*-Dibromo 5 2 33-34f 5.25 591 trace

aReactions were performed with 0.5-1.0 g. of the haloferrocene and 15-20 ml. of tetrahydrofuran. bTime after dropx-ri.se addition of halide. cConversion of haloferrocene to Grignard reagent; determined by addition of Dry Ice to give the carboxylic acid. “Optimum conditions for preparing the Grignard reagents were not determined. ®The recovered haloferrocene, on the basis of melting points and infrared spectra, contained ferrocene. *The halides in tetrahydrofuran were added at room temperature. ^Methyl iodide in trace amounts was used as the initiator. Biferrocenyl x-jas formed in 9$ conversion. ■••Conversion to 1,11-ferrocenedicarboxylic acid; ferrocenecarboxylic acid was also obtained in 16$ conversion.

I 18 an attempt to use iodine as an initiator was unsuccessful. The rela­ tive reactivities of haloferrocenes are typical! iodo > bromo > chloro.

The rates of reaction and conversion to Grignard reagents are increased by use of methyl iodide or ethylene bromide (32) as entrainers.

(32) D. E. Pearson, D. Cowan, and J. D. Beckler, J. Org. Chem., 2U, SOU (19E>9).

Methylmagnesium iodide does not undergo exchange with bromoferrocene under conditions for preparing the Grignard reagent.

This procedure for preparation of ferrocenylmagnesium halides in high yields with ethylene bromide as an entrainer potentially permits the synthesis of many ferrocene derivatives. Primary advantages of the ferrocenyl Grignard reagent are the absence of side-reactions generated by excess organometallic compounds required in hydrogen exchange reactions and the absence of disubstitution products present whenever ferrocene is metallated directly.

Haloferrocenes also react with magnesium in tetrahydrofuran to

give biferrocenyl and ferrocene. Thus, reaction of iodoferrocene and magnesium at 25-30° for 3 hours in the presence of ethylene bromide as

entrainer yielded ferrocene (62%) and biferrocenyl (3h%). Bromoferro­

cene, magnesium, and methyl iodide at 38-U20 for 3.5 hours gave biferrocenyl (9%), ferrocene, and the ferrocenyl Grignard reagent. At

elevated temperatures the yields of Grignard reagents are substantially

reduced by formation of ferrocene and biferrocenyl. With iodoferrocene,

it was necessary to lower the temperature to 11-12° to minimize side-

reactions. Similarly, reaction of butyllithium and iodoferrocene in 19 ethyl ether at 0° and subsequent carbonation gave biferrocenyl (20%), ferrocene (60%), and ferrocenecarboxylic acid (17$). Beaction of ferrocenylmagnesium bromide with cobaltous chloride gave biferrocenyl in 80$ conversion (33). This reaction, useful for synthesis of

(33) Belated homolytic decomposition reactions of Grignard reagents are summarized and discussed by M. S. Kharasch and 0. Beinmuth, "Grignard Beactions of Non-metallic Substances," Prentice' Hall, Inc., New York, 195>U, pp. 116-137. biferrocenyl, presumably proceeds in a manner similar to that postu­ lated by Kharasch and Beinmuth (33) for related compounds (Equations

6-9).

C ^ F e C ^ M g B r + CoCl2 C ^ F e C ^ C o C l «- MgBrCl (6)

2 C^H^FeC^H^CoCl — » C ^ F e C ^ - C ^ F e C ^ + 2 CoCl (7)

CoCl + C ^ F e C ^ B r — > CoClBr -v- C^FeC^H^* (8)

X(C^FeC5Hu*) -^C^FeC^ ♦ C^FeO^ - C^FeC^ (9)

♦ polymers

Formation of biferrocenyl and ferrocene by decomposition of the ferrocenyl Grignard reagent may indicate that ferrocenyl radicals are generated readily (33) (Equation 10 )j dimerization of ferrocenyl radicals (Equation 11) or exchange with the solvent (Equation 12)

C^FeC^MgX C^FeC^* + *MgX (10) 20

2 C ^ F e t y y------> C^H^FeC^ - C^HjFeC^ (ll)

C ^ F e C y y + H - R ------=5*- CjjHjjFeCjJL + *R (1 2 )

may then give biferrocenyl and ferrocene. Formation of these products of radical reactions under relatively mild conditions is closely related to reactions of diferrocenylmercury and silver (3h) or

(3U) M. D. Rausch, J. Am. Chem. Soc., 8<2, 2080 (i960). palladium black (35) and ferrocenylboronic acid and ammoniacal silver

(35) 0. A. Nesmeyanova and E. G. Perevalova, Doklady Akad. Nauk SSSR, 126; 1007 (1959). oxide (15) to give the same products. Similarly, iodoferrocene and copper bronze (3ii) give biferrocenyl in high conversion (Ullman reaction).

In the formation of ferrocenyl Grignard reagents, mixtures of ferrocene and haloferrocene are recovered. Infrared spectra and melting points indicated the presence of ferrocene. The exact compo­ sition of these mixtures was not determined. No way of separating haloferrocenes from ferrocene has been found.

Formation of ferrocenecarboxylic acid 0-6%) from reaction of

1,1'- dibromoferrocene and magnesium may be attributed to abstraction of a single hydrogen atom from the solvent by the di-Grignard reagent and subsequent carbonation. 21

Attempts to form the 1'- bromoferrocenyl Grignard reagent by

reducing the ratio of magnesium to 1,1'- dibromoferrocene were unsuc­

cessful. The difficulty in making effective use of the small quantity

of magnesium required is thought to be at least partially responsible for the lack of success.

Reaction of ferrocenylmagnesium bromide and amyl nitrate did not

give nitroferrocene. Reaction of ferrocenylmagnesium bromide and

dinitrogen tetrcsxide produced a low yield of azoferrocene, identified by its infrared spectrum.

Iodoferrocene reacted with sodium amide in liquid ammonia (36) to

(36) Discussions of the reactions of halobenzenes with alkali amides are given in the following papersj R. Huisgen and J. Sauer, Angew. Chem., T2j 91 (i960); J. D„ Roberts, D. A. Semenow, H. E. Simmons, and L. A. Carlsmith, J. Am. Chem. Soc., 78, 601 (1958)j J. D. Roberts, C. W. Vaughan, L. A. Carlsmith, and~D. A. Semenow, J. Am. Chem. Soc., 78; 611 (1958).

give azoferrocene in 12% conversion. This unexpected product must

have been formed by oxidation of intermediate aminoferrocene. Under

the same conditions bromoferrocene gave no reaction. The difference

in reactivity is believed to be the result of solubility differences.

Iodoferrocene appears to be slightly soluble in ammonia; bromoferrocene

appears to be insoluble.

Replacement of iodine in iodoferrocene by reaction with sodium

amide may be viewed as a direct displacement or as proceeding through

a ferrocyne intermediate analogous to the benzyne intermediate (36).

In the absence of further evidence, no choice between these alterna­

tives is possible. 22

Recently Nesmeyanov et al. reported other reactions of haloferro- cenes (3.7). Reactions of bromo- or chloroferrocene with cuprous

(37) A. K. Nesmeyanov, 7. A. Sazonova, and V. N. Drozd, Doklady Akad. Nauk SSSR, 3JO, 1030 (i960). cyanide in pyridine produce cyanoferrocene. Reactions of bromo- or chloroferrocene with cupric phthalimide give N-ferrocenylphthalimide which may be hydrolyzed to aminoferrocene. Bromo- or chloroferrocene and cupric acetate in alcohol yield acetaxyferrocene.

The reactions reported by Nesmeyanov and those discovered in this investigation are the only examples of reactions involving replacement of halogens on the ferrocene nucleus. IV. EXPERIMENTAL

A. General Information

Infrared spectra were determined with a Baird model B recording spectrophotometer. Ultraviolet spectra were determined with a Beck­ man DU spectrophotometer. Elemental analyses were performed by

Galbraith Laboratories, Knoxville, Tennessee, and Schwarzkopf Micro- analytical Laboratory, Woodside, New York. Ferrocene (DuPont Company) was sublimed before use to remove a small, spongy residue.

B. Synthesis and Reactions of Nitroferrocene

Nitroferrocene

Butyllithium was prepared under nitrogen by reaction of butyl bromide (13.70 g., 0,10 mole) and lithium wire (1 .U57 g., 0.21 mole) in ethyl ether (E>0 ml.) (38). The solution was filtered through glass

(38) H. Gilman, J. A. Beel, C. G. Brannen, M, W. Bullock, G. E. Duim, and L. S. Miller, J. Am. Chem. Soc., 71> li*99 (19U9). wool, added gradually at roam temperature to a stirred solution of ferrocene (Hi.7 g., 0.079 mole) in ethyl ether (25>0 ml.), and stored overnight.

A special dropping funnel designed to permit a cooling bath to surround the funnel contents was attached to the reaction flask.

Dinitrogen tetroxide (7.h g., 0. 0 8 mole) (39) in ethyl ether (S>0 ml.)

(39) Before each experiment dinitrogen tetroxide was purified by distillation. Oxygen was then bubbled through it for two hours to oxidize any dinitrogen trioxide present.

23 was put in the dropping funnel and cooled to -70°, The dinitrogen tetroxide solution was added dropwise to the stirred ferrocenyllithium solution at -70° in 70 minutes. Reaction was instantaneous. A dark color developed. After stirring at -7 0 ° for HO minutes, the mixture was allowed to warm to room temperature.

The mixture was hydrolyzed with water and filtered to remove a dark brown solid believed to be ferric hydroxide. When the precipitate was dissolved in dilute hydrochloric acid and treated with ammonium thiocyanate, it gave a blood-red color. The colored aqueous layer of the filtrate showed the characteristic dichroism of the ferricinium ion.

Treatment of the aqueous solution with aqueous sodium bisulfite gave ferrocene (O.OH g.).

The ether solution was dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was dissolved in petroleum ether and chromatographed on alumina. Elution with petroleum ether gave ferrocene (7.19 g.; total recovery: 7.23 g., k9%).

Elution with benzene removed a purple band and gave a blood red solution. Removal of the solvent left a deep red, almost purple, crystalline solid, nitroferrocene (O.I4.O g., 0.0017 mole, 2.2%). After rechromatography and vacuum sublimation, it melted at 12H-125.50

(Ho, la).

(HO) A preliminary communication relating to this work (reference 1 9 ) erroneously listed the melting point as 9 6 -97°.

(Hi) Nitroferrocene, m.p. 125-126°, was reported at approximately the same time by Grubert and Rinehart (reference 20). 25

Anal. Calcd. for C^H^eNOg! C, 51.98; H, 3.93; N, 6.06.

Found: C, 52.09, 52.31; H, lt.12, 3.9k; N, 6.08, 6.30.

Nitroferrocene dissolves in benzene, chloroform, ethyl ether, acetone, and petroleum ether.

In isooctane nitroferrocene has ultraviolet absorption maxima at

238-239 mp, log€, 3.96; 272 mp, log€, 3.80; and 363 ifh log( ,

3.13.

The infrared spectrum (potassium bromide) of nitroferrocene has principal absorption bands at 6 .6 6 , 7.05, 7.31, 7 .U2 , 7.53, 9.03, 9 .8 1 ,

1 0 .0 1 , 1 2 .1 6 , 1 2 .5 2 , and 1 3 . 2 1 .

Elution of the alumina column ■with chloroform removed a trace amount of an unidentified orange compound.

Catalytic Reduction of Nitroferrocene

Nitroferrocene (0.07 g., 0.00030 mole) was hydrogenated in ben­ zene (25 ml.) with a W-5 Raney nickel catalyst. After having been

shaken for 1 . 5 hours at 30 psi, the mixture was filtered and benzene was removed under reduced pressure. Vacuum sublimation of the residue gave aminoferrocene (0 .0k g., 0 . 0 0 0 2 0 mole, 67%), m.p. 15U-155°

(sealed tube); lit. (h2 ), m.p. 1 5 5 °.

(U2) F. S. Arimoto and A. C. Haven, J. Am. Chem. Soc., 77j 6295 (1955). Aminoferrocene must be placed in an evacuated sealed tube immediately after sublimation in order to get a sharp melting point. Aminoferrocene darkens rapidly in air. 26

The structure of aminoferrocene was further verified by reaction with acetyl chloride in benzene to give acetamidoferrocene, m.p. 169-171°j lit. (U2), m.p. 170.5-172° (dec.).

Lithium Aluminum ffydride Reduction of I&troferrocene

Nitroferrocene (0.15 g., 0.00065 mole) in ethyl ether (25 ml.) was added under nitrogen to a stirred ether solution (25 ml.) of excess lithium aluminum hydride (U3). After standing overnight the

(U3) The lithium aluminum hydride solution was prepared by Paul Schickedantz and the exact concentration was not deteimined. reaction mixture was decomposed by addition of water. The ether solution was filtered, dried over anhydrous magnesium sulfate, and concentrated to dryness. The residue was dissolved in petroleum ether and chromatographed on alumina.

Elution with petroleum ether - ether (2:1 by volume) removed a purple band which gave azoferrocene (0 . 0 2 g., 0 . 0 0 0 0 5 mole, 7,7%).

After rechromatography on alumina with petroleum ether - ether (8:1 by volume) elution, the azoferrocene melted at 2l*9 °j lit. (Ui),

(UU) A. N. Nesmeyanov, E. G. Perevalova, and T. Y. Nikitina, Tetrahedron Letters, No. 1, 1 (i960). m.p. 256-258° (dec.). Its infrared spectrum was identical with that of authentic azoferrocene produced by other reactions.

Elution with ether removed a yellow band which gave aminof erro- 27 cene. Vacuum sublimation gave orange crystals (0.03 g., O.OOOlli mole,

23$) having an infrared spectrum identical with that of authentic aminoferrocene. A tarry residue indicated that same of the product was lost by oxidation (U5 ).

(U5) The reaction of lithium aluminum hydride with nitroferrocene is probably quantitative since no nitroferrocene could be detected during chromatography.

C. Unsuccessful Routes to IB.troferrocene

Reaction of Ferrocenyllithium and Amyl Nitrate

Ferrocenyllithium was prepared under nitrogen by reaction of butyllithium (c.a. 0 . 0 9 mole) and ferrocene (5.52 g., 0 . 0 3 mole) in ethyl ether (120 ml.). After having been filtered through glass wool, the mixture was added to a stirred solution of amyl nitrate (9.98 g.,

0.075 mole) in ethyl ether (2+0 ml.) at -70°. The mixture was allowed to warm to room temperature and stand overnight. The mixture, which was slightly darker, was decomposed with water.

The ether solution was dried over anhydrous magnesium sulfate.

After removal of ether the residue was dissolved in petroleum ether- benzene and chromatographed on alumina. Elution with petroleum ether gave ferrocene (1+.68 g., 85$ recovery). Elution with absolute ethanol removed a small; brown band which yielded a non-sublimable tar. Nitroferrocene was not detected. 28

Sodium Nitrocyclopentadienide

Sodium ethoxide was prepared under nitrogen by reaction of sodium

(13.8 g„, 0 . 6 0 mole) and absolute ethanol (382 ml., 6.5 moles). To the stirred solution of sodium ethoxide in ethanol at 0 ° were added dropwise amyl nitrate (79.9 g., 0.60 mole) and chilled cyclopentadiene * monomer (39.7 g. > 0.60 mole) in succession. After standing overnight the dark brown mixture did not react with water. It was concentrated to two-thirds the original volume with an air stream. After ligroin had been added, filtration yielded sodium nitrocyclopentadienide

(26.7 g., 0.20 mole, 33%) as a red-brown powder. The salt darkened but did not melt below 280°. It exploded when warmed with a flame (1*6 ).

(1*6) Thiele (reference ll*) reports that the salt explodes when heated.

Attempts to obtain additional sodium nitrocyclopentadienide by concentrating the filtrate on a steam bath gave a tarry residue.

Reaction of Sodium Nitrocyclopentadienide And Ferrous Ion

Mixing aqueous solutions of ferrous sulfate and sodium nitrocyclo­ pentadienide produced a dark precipitate. It was insoluble in such representative organic solvents as benzene, ethyl ether, chloroform, and petroleum ether. It did not melt but could be burned. The infra­ red spectrum of the dry salt showed strong water absorption indicating that it was a hydrate. This evidence suggests that the compound was 29 ionic iron nitrocyclopentadienide rather than the desired 1 ,1 '- dinitro- ferrocene.

Acetylferrocene

Acetylferrocene, m.p. 8 U-8 6 0, was prepared in 6b% conversion by reaction of ferrocene and acetic anhydride with boron trifluoride etherate as a catalyst (U7 ).

(hi) C. R. Hauser and J. K. Lindsay, J. Org. Chem., 22j k82 (1957).

Reaction of Acetylferrocene and Hydrazoic AcicT

A stirred mixture of acetylferrocene (2.0 g., 0.0088 mole), trichloroacetic acid (25 g.> 0.15 mole), and chloroform (5 ml.) was heated to U5° (25). Addition of a small amount of sodium azide to the blood-red solution gave no Schmidt reaction so sulfuric acid (3 drops) was added. Sodium azide (0 . 8 6 g., 0.0132 mole) was added in portions in 2.5 hours during which nitrogen was evolved steadily. , Stirring was continued for an additional 1+.5 hours. The total volume of nitrogen collected was 210 ml. (9 5 # of theory).

Water and Skellysolve B-benzene (Usl by volume) were added to the mixture. Both the aqueous layer and the organic layer were very dark colored. The organic layer was washed with 10# aqueous potassium carbonate and dried over anhydrous magnesium sulfate. Chromatography on silica-celite indicated that no ferrocene derivatives remained. 30

O-Benzylhydroxylamine

O-Benzylhydroxylamine, b.p. 98-99°/l5 mm., was prepared in 30$ conversion (from acetaxime) by the laborious procedure described

(U8, U9) for the synthesis and acid hydrolysis of O-benzylacetoxime.

(U8 ) A. Janny, Ber., 16, 170 (1883).

(U9) R. Behrend and K. Leuchs, Ann., 257, 203 (1890).

The time required for the synthesis of O-benzylacetoxime can be shortened by using commercial sodium methaxide rather than preparing sodium ethoxide.

Aminoferrocene

Aminoferrocene, m.p. l5U-l55°, was prepared in 10$ conversion by reaction of O-benzylhydroxylamine and ferrocenyllithium in ethyl ether (2k).

Oxidation of Aminoferrocene

Aminoferrocene (0.75 g.» 0.0037 mole) in methylene chloride (15 ml.) was added dropwise at 0 ° to a stirred solution of trifluoroacetic anhydride (2.5 ml., 3.78 g., 0 . 0 1 8 mole) and 90$ hydrogen peroxide

(O.Ul ml., 0.57 g., 0.015 mole) in methylene chloride (12 ml.) (23).

The mixture was stirred for 30 minutes at 0 ° and was then washed with water and aqueous sodium bicarbonate. Filtration of the mixture and treatment of the water washing with base gave a red-brown precipitate

(0 . 3 0 g.) which would not burn, melt or dissolve in organic solvents. 31

Concentration of the methylene chloride solution gave a tarry residue which was not identified.

D. Synthesis and Reactions of Haloferrocenes

Chloromercuriferrocene

Chloromercuriferrocene was prepared by the procedure of Rausch,

Vogel, and Rosenberg (50). Mercuric acetate (79.8 g., 0.25 mole)

(50) M. Rausch, M. Vogel, and H. Rosenberg, J. Org. Chem. , 22, 900 (1957). in 9$% ethanol (1025 ml.) was added all at once to ferrocene (U6 g.,

0.25 mole) in benzene (375 ml.). The solution was stirred for 8 hours at room temperature and then concentrated to one-half the original volume. Potassium chloride (18.7 g., 0.25 mole) in aqueous ethanol

(1:1 by volume, 300 ml.) was added all at once with stirring. After standing overnight the reaction mixture was filtered to isolate the insoluble organomercury compounds.

The residue was washed with petroleum ether and water and then extracted with a large volume of methylene chloride. There remained

1 ,1 '- di chloromercurif errocene (5 6 . 0 g., 0.085 mole, 3h%), a yellow powder having no melting point below 290°• lit. (5 0 ), no m.p. below

300°.

The methylene chloride solution was dried over anhydrous magnesium sulfate and evaporated to dryness. After removal of a trace of ferro­ cene by vacuum sublimation, chloromercurif errocene (35.0 g., 0 . 0 8 3 mole, 33$) was obtained as a yellow powder, m.p. 192-195° (dec.); lit.

(9), m.p. 1 9 U-1 9 6 0 (dec.) (5l).

(5l) Some magnesium sulfate is believed to have dissolved in the methylene chloride solution during drying causing the total recovery to appear to be 1 0 2 $.

The initial filtrate and washings were combined and extracted with petroleum ether. After the petroleum ether solution had been

dried over anhydrous magnesium sulfate, evaporation to dryness and

vacuum sublimation of the residue gave crude ferrocene (1 6 . 5 g., 35$), m.p. 150-167°; lit. (l), m.p. 173-17U0.

Iodoferrocene

Iodoferrocene was prepared by an improved modification of the

published procedure (7). A slurry of iodine (6 6 . 6 g., 0.27 mole) in methylene chloride (600 ml.) was added in portions to a stirred slurry

of chloromercurif errocene (3 5 . 0 g., 0 . 0 8 3 mole) in methylene chloride

(600 ml.). A green precipitate formed which turned black. After

stirring 30 minutes at roam temperature, the iodine complexes were

partially destroyed by warming with excess aqueous sodium thiosulfate.

Attempts to extract the product with petroleum ether showed that

insoluble complexes remained. The residue was then stirred at roam

temperature with aqueous sodium thiosulfate and petroleum ether until

only a red residue of mercuric iodide remained. The petroleum ether

solution was dried over anhydrous magnesium sulfate, passed through an

alumina column, and concentrated to a red oil. Vacuum sublimation of 33 the residue yielded iodoferrocene (18.1 g., 0.058 mole, 70$) as orange crystals, m.p. U3-U50; lit. (7), m.p. UU-U5°.

Ferrocenylboronic Acid and l,!1- Ferrocenylenediboronlc Acid

Ferrocenylboronic acid and 1,1'- ferrocenylenediboronic acid were prepared by an improved modification of the published procedure (15).

Butyllithium was prepared in an atmosphere of oxygen-free (52), dry

(52) L. F. Fieser, "Experiments in Organic Chemistry," 3d Ed., D. C. Heath and Co., Boston, 1957, p. 299. nitrogen from butyl bromide (37.0 g., 0. 2 7 mole) and lithium wire

(3.7U8 g., 0.51i mole) in ethyl ether (110 ml.) Ferrocene (16.7 g.,

0,09 mole) in tetrahydrofuran (110 ml.) was added to the magnetically stirred solution in 15 minutes at 0°. After U5 minutes of stirring at

0 °, the mixture was stored overnight at room temperature.

The mixture was filtered through glass wool and then added drop- wise in 2 hours to butyl borate (7 2 . 5 g., 0 .315 mole) in ethyl ether

(50 ml.) at -70°. Formation of a solid caused stirring to cease.

After having been warmed to room temperature in 1.5 hours, the mixture was decomposed with 1 0 $ aqueous sodium hydroxide (100 ml.) and , filtered. The ether solution was extracted nine additional times with

1 0 $ aqueous sodium hydroxide (additional volumes U0 0 ml.).

Acidification of the basic solution with 10$ sulfuric acid at 0° gave a yellow precipitate which was filtered and washed with water.

Scxhlet extraction of the air-dried precipitate with ethyl ether for k days removed ferrocenylboronic acid (9.02 g., 0 . 0 3 9 mole, U3 .6 $) which was obtained as a yellow powder after evaporation of solvent, m.p. 136-lUO0 (dec.)j lit. (53)> m.p. lU3-lU8° (sealed tube.)

(53) Nesmeyanov et al. (reference 15) report that the melting point varies greatly with the rate of heating.

1,1'- Ferrocenylenediboronic acid (U.l*2 g., 0.016 mole, 18$) remained as an insoluble yellow powder from the Soxhlet extraction, dec. c.a. 200°} lit. (l5), dec. 180°.

Concentration of the base-washed ether solution followed by filtra­ tion and vacuum sublimation of the precipitate gave crude ferrocene

(U.93 g., 29$).

Bromoferrocene

Bromoferrocene was synthesized by the procedure of Nesmeyanov,

Sazonova, and Drozd (15). A solution of cupric bromide (5.69 g.,

0.0 2 5 5 mole) in water (20 ml.) was added to a slurry of ferrocenylboronic acid (1 . 9 6 g., 0 . 0 0 8 5 mole) in water (2i*0 ml.) in a flask fitted with

a steam distillation apparatus (5U). After the mixture had been gradu-

(5U) F. T. Wallenberger, W. F. O'Connor, and E. J. Mori cord, J. Chem. Ed., 36, 25l (1959).

ally heated to boiling, the product was steam distilled and collected

in petroleum ether. The solution of the product and petroleum ether

extracts of the distillation flask contents were combined, dried over

anhydrous magnesium sulfate, and evaporated to a red oil. Vacuum

sublimation gave bromoferrocene (1 . 8 0 g., 0.00 6 8 mole, 80$) as orange

crystals, m.p. 32-33°; lit. (l5), m.p. 32-33°. Chloroferrocene

Chloroferrocene was prepared by the published procedure (l5), a procedure similar to that described for bromoferrocene. Reaction of ferrocenylboronic acid (1.56 g., 0.0068 mole) and cupric chloride

(CuCl2 *2 H2 0 , 2.11 g., 0.020lj. mole) in water (250 ml.) yielded chloro­ ferrocene (1.18 g., 0.005U mole, 19%) as orange crystals, m.p. 60.5-

61.5°, after vacuum sublimation; lit. (l5), m.p. 59-60°.

1 ,1 f- Dibromoferrocene

1,1'- Dibromof errocene was prepared by the published procedure

(15). 1,1'- Ferrocenylenediboronic acid (2.12 g., 0.0077 mole) was

reacted with cupric bromide (l3»7k g.» 0 .06 l6 mole) in water (675 ml.).

The product was steam distilled and collected in petroleum ether.

After having been dried with anhydrous magnesium sulfate, the solution was passed through an alumina column. The solvent was removed below

room temperature with a dry air stream to give 1 ,1 '- dibromof errocene

(1.61* g., 0 .00U8 mole, 62%) as fluffy, orange crystals, m.p. 37-3 9 °.

Recrystallization frcrn cold methanol gave needles, m.p. ii-7—U8°« lit.

(15), m.p. 5o-5i°.

Ferrocenylmagnesium Bromide (Methyl Iodide As Entrainer)

Magnesium powder (0.36 g., 0.01U8 gram-atam, 80-200 mesh) was put

in an oven-dried flask and flamed briefly under oxygen-free, dry

nitrogen. After addition of anhydrous tetrahydrofuran (5 ml.), the

magnesium was activated with a drop of methyl iedide. A solution of 36 bromoferrocene (1 . 0 0 g., 0 . 0 0 3 8 mole) and methyl iodide (0 . 5 3 g.»

0.0037 mole) in tetrahydrofuran (10 ml.) was added dropwise with magnetic stirring at 31-33°. The mixture was stirred at 37-39° for two hours and then cooled to 0°. Dry Ice was added.

After the mixture had been hydrolyzed with 3N hydrochloric acid and diluted with ether, the organic layer was extracted with 1 0 % aqueous sodium hydroxide (2 x 1 0 ml.). The orange, basic solution was cooled to 0° and neutralized with cold 6N hydrochloric acid. The voluminous^ yellow precipitate formed was extracted with ether. The ether solution was dried over anhydrous magnesium sulfate and evaporated to dryness leaving ferrocenecarboxylic acid (0 . 7 3 g.> 0 . 0 0 3 2 mole, 81$). After recrystallization from ether-petroleum ether, it melted at 19h-197° (dec.); lit. (9), m.p. 192-205° (dec.); (55),

(55) J. K. Lindsay and C. R. Hauser, J. Org. Chem., 22, 355 (1957). m.p. 219-225° (dec.).

The initial ether solution, following washing with base, was washed with water, dried over anhydrous magnesium sulfate, and evapor­ ated to dryness. Vacuum sublimation of the residue gave a mixture of bromoferrocene and ferrocene (0 . 1 1 g., 1 1 # calculated as bromoferrocene,

15# calculated as ferrocene), m.p. 75-125° (5 6 ).

(56) The percentage composition was not determined because of the difficulty in separating haloferrocenes from ferrocene. 3?

Ferrocenylmagnesium Bromide (Trace Amount of Methyl Iodide)

Ferrocenylmagnesium bromide was prepared as previously described with the exceptions that no methyl iodide was used as an entrainer and the reaction was run at 38-1*2° for 3.5 hours. Bromoferrocene (0.96 g.,

0 . 0 0 3 6 mole) and magnesium powder (0 . 2 6 g., 0. 0 1 0 8 gram-atom) in tetra­ hydrofuran (l5 ml.) gave ferrocenecarboxylic acid (0 .1*1 g., 0 . 0 0 1 8 mole, 1*9$). After recrystallization from ether-petroleum ether, it melted at 19U-1970 (dec.).

Vacuum sublimation of the non-acidic products gave mixed bromo- ferrocene and ferrocene (0 . 3 3 g.» 3h% calculated as bromoferrocene) (56).

Remaining as a non-sublimable residue was biferrocenyl (0.06 g.,

0 . 0 0 0 1 6 mole, 9%) which melted at 233-237° after recrystallization from benzene-ligroinj lit. (3U)> m.p. 239-21*0°. It was identified by its infrared spectrum (5 7 ).

(57) S. I. Goldberg and D. ¥. Mayo, Chem. and Ind., 671 (1959).

Ferrocenylmagnesium Iodide (Methyl Iodide As Entrainer)

Ferrocenylmagnesium iodide was prepared by a modification of the procedure described for ferrocenylmagnesium bromide. Magnesium powder

(0 . 3 1 g., 0 . 0 1 2 8 gram-atom) in tetrahydrofuran (5 ml.) under oxygen- free, dry nitrogen was activated with a drop of methyl iodide. A

solution of iodoferrocene (1 . 0 0 g., 0 . 0 0 3 2 mole) and methyl iodide

(0.1*6 g., 0 . 0 0 3 2 mole) in tetrahydrofuran (15 ml.) was added dropwise with stirring at 11-12°. The mixture was stirred for one hour at 38

11-12° and then cooled to 0 °. Dry Ice was added.

The products were Isolated by the procedure described for the ferrocenylmagnesium bromide experiments. Ferrocenecarboxylic acid

(0 .U8 g., 0 . 0 0 2 1 mole, 6$%) was obtained and melted at 19U-1970 (dec.) after recrystallization from ether-petroleum etherj lit. (9), m.p.

192-20$° (dec.)j ($$), m.p. 219-22$° (dec.). Also recovered was a mixture of iodoferrocene and ferrocene (0.27 g., 27$ calculated as iodoferrocene) which melted at approximately 2$-30° ($6 ).

Ferrocenylmagnesium Iodide (Trace Amount of Methyl Iodide)

Ferrocenylmagnesium iodide was prepared as previously described with the exceptions that no methyl iodide was used as an entrainer and the reaction was run at 11-13° for 2.$ hours. Iodoferrocene (0.75 g.s

0,002k mole) and magnesium powder (0 . 1 8 g., 0 . 0 0 7 2 gram-atom) in tetrahydrofuran (l$ ml.) gave ferrocenecarboxylic acid (0.26 g.,

0 . 0 0 1 1 mole, h7%) which melted at 19U-1970 (dec.) after recrystalliza­ tion from ether-petroleum ether.

Also recovered was impure iodoferrocene (0.33 g.» hh%) melting at

39-U30.

Ferrocenylmagnesium Chloride

Ferrocenylmagnesium chloride was synthesized by a procedure

similar to that described for ferrocenylmagnesium bromide. Chloro­ ferrocene (0 . 9 0 g., 0 .0 0 ^ 1 mole), methyl iodide (0.$8 g., O.OOUl mole),

and magnesium powder (O.iiO g., 0.0163 mole) were stirred in tetrahydro- 39 fur an (l5 ml.) at U6-U8 ° for h hours. After carbonation, hydrolysis, and separation of products, there was obtained ferrocenecarboxylic acid

(O.ll* g., 0.0006 mole, 1 5$). After recrystallization from ether-petro­ leum ether, it melted at 19U-197° (dec.); lit. (9), m.p. 192-205°

(dec.); (5 5 ), m.p. 219-2 2 5 ° (dec.).

Also recovered wa3 impure chloroferrocene (0.71 g., 79$) melting at 6 0 -78°.

Attempted Reaction of Bromoferrocene with Methylmagne slum Iodide

Methylmagnesium iodide was prepared under oxygen-free, dry nitrogen by reaction of methyl iodide (0 . 8 8 g., 0 . 0 0 6 2 mole) and magnesium powder

(0.13 g., 0.0056 mole) in tetrahydrofuran (15 ml.) at 27° for 1.5 hours.

Only traces of magnesium remained. Bromoferrocene (0.50 g., 0.00187 mole) in tetrahydrofuran (5 ml.) was added dropwise with stirring at

27°. The mixture was stirred at 3 7 -U0 ° for 2 hours and then was cooled to 0°. Dry Ice was added. After the mixture had been hydrolyzed with

3N hydrochloric acid and diluted with ether, the organic layer was extracted with 10$ aqueous sodium hydroxide. The colorless basic solu­ tion gave no ferrocenecarboxylic acid on acidification. The ether solution subsequently gave bromoferrocene (0 . 3 8 g., 76$), m.p. 29-3 0 °.

Reaction of Ferrocenylmagnesium Bromide And Cobalt ous Chloride

Magnesium powder (0.33 g., 0.0135 gram-atom) under oxygen-free, dry nitrogen was activated with a drop of methyl iodide. A solution of bromoferrocene (0.72 g., 0.0027 mole) and ethylene bromide

(0 .5l g., 0 . 0 0 2 7 mole) (3 2 ) in tetrahydrofuran (10 ml.) was added in

30 minutes at 29-30°. After the mixture had been stirred for 2.5 hours at 37-39°, anhydrous cobaltous chloride (0.23 g., 0 . 0 0 1 8 mole)

(58, 59) was added all at once at 0°. The mixture was warmed to

(58) A. R. Pray, “Inorganic Synthesis, 11 Vol. V, McGraw-Hill Book Co., Inc., New York, 1957, p. 153.

(59) M. S. Kharasch and E. K. Fields, J. Am. Chem. Soc., 63, 2316 (19U1). roam temperature, allowed to stand overnight, decomposed with hydro­ chloric acid and worked up in the usual manner. Vacuum sublimation of the residue gave a mixture of ferrocene and bromoferrocene (0.13 g.,

1 8 $ calculated as bromoferrocene), m.p. 35-95°. Remaining as a red- orange residue was biferrocenyl (0 .U0 g., 0 . 0 0 1 1 mole, 80$) which melted at 230-23U0 after recrystallization from benzene-ethanolj lit. (3U), m.p. 239-2U00 (dec.).

Reaction of 1,1*- Dibromoferrocene with Magnesium

Magnesium powder (0.20 g., 0.0080 gram-atcm) in tetrahydrofuran

(5 ml.) under oxygen-free, dry nitrogen was activated with a drop of methyl iodide. A solution of 1,1'- dibromoferrocene (0.55 g., 0.0016 mole) and methyl iodide (0 .U5 g., 0.0032 mole) in tetrahydrofuran

(10 ml.) was added dropwise with stirring at 29-32°. The mixture was stirred at 33-3U0 for 5.25 hours and then cooled to 0°. Dry Ice was added. After the mixture had been hydrolyzed with 3N hydrochloric acid and diluted with ether and tetrahydrofuran, the organic layer was extracted with 1 0 $ aqueous sodium hydroxide (3 x 20 ml.). The basic solution was cooled to 0° and neutralized with cold 6 N hydrochloric acid. The yellow precipitate which formed was extracted with tetra­ hydrofuran with the aid of added saturated sodium chloride solution and then recrystallized by addition of petroleum ether.

The acid was filtered and washed with ether. After having been dried over anhydrous magnesium sulfate and evaporated to dryness, the ether washing gave ferrocenecarboxylic acid (0 . 0 6 g., 0 . 0 0 0 2 6 mole,

16%). Even after recrystallization from benzene and ether-petroleum ether, the acid melted at 168-171°; lit. (9), m.p. 192-205° (dec.); (55) > m.p. 219-225° (dec.). Its infrared spectrum showed ferrocene mono­

substitution bands near 9 and 1 0 microns. The acid gave a negative test for bromine following sodium fusion.

Anal. Calcd. for C^H^FeOg: C, 57.UU; H, U.38; Fe, 2U.28.

Found: C, 57.1*0; H, U.53j Fe, 2U.02.

Remaining as a residue from the ether washing was 1,1'- ferro-

cenedicarbaxylic acid (0 . 2 6 g., 0 . 0 0 1 6 mole, 5 9 $) which did not melt

or decompose below 2 8 0 °; lit. (9 ), no melting or decomposition below

250°. Its infrared spectrum was identical with that of authentic

1 ,1 '- ferrocenedicarboxylic acid.

The identity of 1,1'- ferrocenedicarboxylic acid was further proved

by esterification with methanol using a trace of hydrochloric acid as

a catalyst. After chromatography on alumina and vacuum sublimation,

dimethyl 1,1'- ferrocenedicarboxylate was isolated in 73$ conversion. After recrystallization from aqueous methanol, it melted at

112-113°; lit. (9), nup. Ili*-ll5°.

Coupling of Iodoferrocene with Magnesium

Magnesium turnings (0.57 g., 0.0233 mole) in tetrahydrofuran

(10 ml.) were activated by addition of a small quantity of ethylene bromide. Iodoferrocene (2.3U g., 0.0075 mole) in tetrahydrofuran

(20 ml.) was added dropwise with stirring under oxygen-free, dry nitro­ gen at room temperature. Following slow, dropwise addition of ethylene bromide (2.82 g., 0 . 0 1 5 0 mole) in tetrahydrofuran (25 ml.), the mixture was stirred 3 hours and then cooled to 0°. Dry Ice was added.

Following treatment with 3N hydrochloric acid, dilution with ether, and filtration, the organic layer was extracted with 1 0 $ aqueous sodium hydroxide (30 ml.). The colorless extract contained no ferrocene derivatives.

The ether solution was washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness. Vacuum sublimation of the residue gave ferrocene (0 . 8 6 g., 0.002*5 mole, 6 2 $), m.p. 168-172*°; lit. (1 ), m.p. 173-171*°.

Remaining as a non-sublimable residue was biferrocenyl (0.2*7 g.,

0.0012 mole, 3l*$). After recrystallization from benzene-ethanol, it melted at 236.5-237.5°; lit. (3i*), nup. 239-21*0°. U3

Reaction of Iodoferrocene and Butyllithium

Butyllithium was prepared under nitrogen by reaction of butyl bromide (0.96 g., 0.007 mole) and lithium wire (0.0972 g., O.OlU mole) in ethyl ether (10 ml.). Iodoferrocene (1.09 g., 0.0035 mole) in

ethyl ether (15 ml.) was added dropwise with stirring at 0 °. The mixture was stirred one hour at 0° and then Dry Ice was added. After

a washing with 3N hydrochloric acid, the mixture was extracted with

1 0 $ aqueous sodium hydroxide.

The ether layer was washed with water, dried over anhydrous mag­

nesium sulfate, and concentrated to dryness. Vacuum sublimation of

the residue gave impure ferrocene (0 . 3 9 g., 0 . 0 0 2 1 mole, 6 0 $) melting

at 1UO-1650; lit. (l), m.p. 173-17U0.

Biferrocenyl (0.13 g.> 0.00035 mole, 20$) remained as a red-

orange residue. After recrystallization from benzene-petroleum ether,

it melted at 236-237°; lit. (3U), m.p. 239-21*0°.

Acidification of the basic extract gave a yellow precipitate which

was extracted with ethyl ether. After the extract had been dried over

anhydrous magnesium sulfate, ferrocenecarboxylic acid (O.lli g., 0.00060

mole, 17$) was crystallized by addition of petroleum etherj m.p. 19U-

197° (dec.)jlit. (9), m.p. 192-205° (dec.), (55), m.p. 219-225° (dec.).

Reaction of Iodoferrocene And Sodium Amide

Sodium amide was prepared by reaction of sodium (0 . 2 6 g., 0 . 0 1 1 2

mole) and liquid ammonia (l5 ml., large excess). Iodoferrocene (0.50 g . , 0 . 0 0 1 6 mole) was added and stirred in partial solution for one hour at

-33°. After addition of ethyl ether (10 ml.), the mixture was warmed to room temperature and was washed with water and then with 6N hydro­ chloric acid (3 x 1 0 ml.).

The acid extract was made basic with 1 0 $ aqueous sodium hydroxide and gave a small, dark precipitate which was ether insoluble.

The ether solution was dried over anhydrous magnesium sulfate and solvent was removed. Vacuum sublimation of the residue gave iodoferrocene (0.39 g.j 7 8 $) with m.p. 33-37°.

Azoferrocene (0.0U g., 0.00010 mole, 12$) was left as a sublima­ tion residue. The product was dissolved in petroleum ether and chromatographed on alumina. Elution with 8 : 1 petroleum ether-ether gave deep purple crystals, m.p. 2 5 3 -25 5 ° (dec.); lit. (UU), m.p. 256-2 5 8 ° (dec.).

Anal. Calcd. for C20Hl8Fe2N2: 7.0U. Found: N, 6.89.

Reaction of Ferrocenylmagnesium Bromide and Amyl Sitrate

Ferrocenylmagnesium bromide was prepared from bromoferroeene

(0 . 7 5 g.» 0 . 0 0 2 8 mole) and magnesium powder (0.20 g., 0 .008U mole) in tetrahydrofuran (l5 ml.) with methyl iodide (O.liD g., 0.0028 mole) as an entrainer according to the procedure previously described. The

Grignard slurry was diluted with tetrahydrofuran (5 ml.) and was then added dropwise at 0 ° to a stirred solution of amyl nitrate (0 . 7 5 g.»

0.0056 mole) in tetrahydrofuran (5 ml.). The reaction was stirred at

0 ° for 15 minutes, warmed to U5° over 2 hours, and held at U5° Tor Ii5

3.25 hours. There was no change in appearance.

The mixture was cooled and decomposed with water. After addition of ether, filtration to remove a small, dark precipitate, and several washings with water, the organic layer was washed briefly with 3N hydrochloric acid. Some decomposition appeared to occur in the presence of acid.

The ether solution was dried over anhydrous magnesium sulfate and concentrated to dryness. Vacuum sublimation of the residue gave ferrocene (0 . 3 8 g., 0 . 0 0 2 0 mole, 13%) melting at 1 2 2 -lU5°} lit. (l), m.p. 173-17U0. Its infrared spectrum contained only those absorption bands characteristic of ferrocene and brcmoferrocene.

A brown residue remaining was identified by its infrared spectrum as crude biferrocenyl ( 0 . 0 2 g., k%) and melted at 220-223° (dec.)j lit. (3k)t m.p. 239-2itO° (dec.).

E. Miscellaneous Preliminary Experiments

Reaction of Ferrocenyllithium and Acetone Cyanohydrin Hitrate

Acetone cyanohydrin nitrate (21, 22) was dissolved in ethyl ether

and added dropwise at room temperature to stirred ferrocenyllithium in

ether. An exothermic reaction ensued. The color became dark brown

and a brown precipitate formed. No good procedure could be developed

for isolation of the products. Several ferrocene derivatives were

detected by alumina chromatography, some of which could not be crystal­

lized. There was no nitroferrocene.

Cyanoferrocene was identified by its infrared spectrum. After purification by vacuum sublimation and chromatography, it melted at

1 0 7 -1 0 8 °; lit. (6 0 ), m.p. 1 0 6 .5 -1 0 7 .5 °.

(60) N. A. Nesmeyanov and 0. A. Reutov, Doklady Akad. Nauk SSSR, 120, 1267 (1958).

Anal. Calcd. for 0-^H^FeN: C, 62.60; H, U.30; N, 6 .61+. Found:

C, 63.15; H, 1+.63; N, 6.90.

Reaction of Ferrocenylmagnesium Bromide and binitrogen Tetroxide

Ferrocenylmagnesium bromide was prepared in tetrahydrofuran with methyl iodide as an entrainer by the procedure previously described.

It was added dropwise at -70° to a stirred solution of dinitrogen tetroxide in ethyl ether. Substantial oxidative decomposition occurred to give iron salts. Azoferrocene was produced in h% conversion and was identified by its infrared spectrum. No other ferrocene derivatives were isolated. APPENDIX PERCENT TRANSMITTANCE 100 3000 AE UBR I CM-' IN NUMBERS WAVE AE EGH N MICRONS IN LENGTH WAVE 2000 : e n e NO< IUEI Infraredspectrum ofnitroferrocene. FIGUREI.

1500

1400

1300 1200 1100 9.724 1000 900 11.035 AE UBR I CM-> IN NUMBERS WAVE AE EGH N MICRONS IN LENGTH WAVE 7 QO 625 100 40 ■pr co PERCENT TRANSMITTANCE OPTICAL DENSITY 0 0 3 . 0 0 0 9 . 0 0 0 5 . 0 0 0 8 . 0 0.200 0 0 6 . 0 0.700 0.100 1.000 0 3 2 0 7 2 ULTRAVIOLET SPECTRUM OF OF SPECTRUM ULTRAVIOLET OVN: ISOOCTANE SOLVENT: OC : 4 L.ter / g : 24m CONC. NITROFERROCENE 310 WAVELENGTH WAVELENGTH FIGURE II FIGURE 0 3 4 0 9 3 0 5 3 (m|JL)

0 7 4 AUTOBIOGRAPHY

I, John Frederic Helling, was b o m in Madelia, Minnesota,

June It, 1933. After completion of my secondary school education in the Madelia public schools, I attended St. Olaf College, North- field, Minnesota, and graduated with the Bachelor of Arts degree, cum laude, in June, 19$$. From 19$$ to I960 I studied for the degree Doctor of Philosophy in the Department of Chemistry of The

Ohio State University. During this time I held appointments as teaching assistant, assistant instructor, DuPont Teaching Fellow,

National Science Foundation Cooperative Graduate Fellow, and National

Science Foundation Summer Teaching Fellow.

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