New Synthesis of Ferrocene Monocarboxylic Acid and Systematic Studies on the Preparation of Related Key-Intermediates Alberto Federman Neto a, *, Joseph Miller c , Va Ãnia Faria de Andrade a , Susana Yumi Fujimoto a , Ma Ârcia MaõÂsa de Freitas Afonso b , Fernando Costa Archanjo b , VõÂtor Andre  Darin b , Ma Ârcio LuõÂs Andrade e Silva d ,A  urea Donizete Lanchote Borges a , Gino Del Ponte a Ribeira Äo Preto, SP/Brasil,Universidade de Sa Äo Paulo, a Faculdade de Cie Ãncias Farmace Ãuticas and b Faculdade de Filosofia, Cie ÃnciaseLetrasdeRibeira ÄoPreto c Joa Äo Pessoa, PB/Brasil, Universidade Federal da ParaõÂba, DQ e LTF ± Depto. Ribeira Äo Preto SP, Brasil De QuõÂmica e Laborato ÂriodeTecnologiaFarmace Ãutica d Franca, SP/Brasil, Universidade de Franca, Laborato Ârio de Pesquisa em Quõ Âmica LABQUIM), Nu Âcleo de Pesquisas em Cie ÃnciasExataseTecnolo Âgicas ReceivedJuly25th,2001. Abstract. An improved technique for the preparation of fer- rocenecarboxaldehyde and two new methods for the synthe- sis of ferrocenemonocarboxylic acid from the aldehyde or from acetyl ferrocene are described. Using the aldehyde or the monocarboxylic acid as starting materials, some im- portant ferrocene key intermediates were prepared: mono- chlorocarbonyl ferrocene, alkali metal and ammonium ferro- cenoates, ferrocene carboxyaldehyde diethylacetal, ferro- cenecarboxamide, et..., as well as a new ferrocene deriva- tive: piperazinium diferrocenoate. Keywords: Ferrocene;Organometallics Eine neue Synthese von Ferrocenmonocarbonsa Èure und systematische Untersuchungen zur Darstellung von verwandten Zwischenprodukten Inhaltsu Èbersicht. Eine verbesserte Methode zur Darstellung von Ferrocencarboxylaldehyd und zwei neue Methoden zur Synthese von Ferrocenmonocarboxylsa Èure aus dem Aldehyd oder aus Acetylferrocen werden beschrieben. Beim Aldehyd oder der Monocarboxylsa ÈurealsEduktewerdeneinigewich- tige Ferrocen-Zwischenprodukte erhalten: Monochlorcarbo- nylferrocen, Alkalimetall- und Ammoniumferrocenata, Fer- rocencarboxylaldehyd-diethylacetal, Ferrocencarboxamid usw. sowie ein neues Ferrocenderivat: Piperazinium-diferrocenat. Introduction Ferrocene derivatives are important organometallic compounds, specially as building blocks for catalysts [1±4, 34], new pharmaceuticals [5, 6] and polymers. They are generally prepared from simple function- alized ferrocenes, such as ferrocenyl ketones or alde- hydes [1, 4, 11, 12, 17, 53], ferrocene carboxylic acids [13, 17], halogenocarbonyl ferrocenes [1, 46, 52], fer- rocenyl amides, mercurated ferrocenes [14, 15], halo- genoferrocenes[14]etc. Ferrocene carboxaldehyde is generally prepared by the direct Vilsmeier-Haack formylation of ferrocene with phosphorus oxychloride in the presence of N,N- dimethylformamide or better, N-methylformanilide [7±10, 55]. Less used older methods include: Somme- let reaction on amino ferrocenes, oxidation of ferroce- nyl alcohols by manganese oxide, etc. [7]. More re- cently, the reaction between ferrocenyl lithium and triethyl orthoformate or DMF has been used, but these two or multistep procedures are more suitable for the preparation of the substituted ferrocenyl alde- hydesorofthe1,1'-dialdehyde[47,48,72]. 1,1'-dicarboxyferrocene is easily obtained by the di- lithiation of ferrocene with n-butyl lithium and TMDA) followed by carboxylation with CO 2 [16, 24, 47] or by the oxidative cleavage of 1,1'-diacetyl ferro- cene [7, 17, 18]. On the other hand, it is not easy to prepare ferrocene monocarboxylic acid. The best knownmethodsare: a) Transmetallation between monochloromercurio- ferrocene [19] or a ferrocenyl stannane [20] and n-bu- tyllithium, followed by carboxylation of the ferrocenyl lithium thus formed disadvantages are the high cost andtoxicityoftheorgano-mercurycompounds). Z.Anorg.Allg.Chem. 2002, 628,209±216 Ó WILEY-VCHVerlagGmbH,D-69451Weinheim,2002 0044±2313/02/628209±216$17.50+.50/0 209 * Prof.AlbertoFedermanNeto, UniversityofSa ÄoPaulo, CollegeofPharmaceut.Sci.ofRibeira ÄoPreto, Dept. of Pharmaceutical Science, Labor. of Medic. Chemis- tryandOrganomet.Chemistry , ZeferinoVazAvenue,w.number,Campus , 14040-903±Ribeira ÄoPreto,S.P./Brazil, Fax:0055016)633-1092 e-mail:albfneto@fcfrp.usp.br