3,712,911 United States Patent Office Patented Jan. 23, 1973 1. 2 Another possibility is for R1 and R2 to jointly form an 3,712,911 alkylidene radical, as in the compound METALLIZED SOCYANDES Ulrich Schoellkopf, Bovenden, and Fritz Gerhart, Gottin EC-CEI-CE=C-N=C gen, Germany, assignors to Badische Anilin- & Soda Fabrik Aktiengesellschaft, Ludwigshafen (Rhine), Ger Me many or to denote a carboxylic radical together with the alpha No Drawing. Filed Oct. 20, 1969, Ser. No. 867,941 carbon atom of the isocyanide, as in cyclohexylisocyanide. Int, C. C07c 119/02 The radicals R in the ROOC- and ROC-groups may U.S. C. 260-464 8 Claims in principle have the same meanings as the radicals R and R. In ROOC-R may also be a metal ion (Me) and in O ov-ROC-hydrogen. ABSTRACT OF THE DISCLOSURE Me in the first-mentioned general formula stands for ov-Metalated isocyanides containing the radical alkali metal, i.e. lithium, sodium or potassium, or an equivalent of magnesium, zinc or cadmium. 5 As can be seen from the details given above, the metal lized isocyanides of this invention constitute a new class Me of compounds characterized by the as an essential portion of the molecule. Me stands for alkali or an equivalent of magnesium, zinc or cadmium. Their manufacture is accomplished by replacing hydrogen 20 on the cy-carbon of an isocyanide with said metals. The portion of the molecule. compounds open up new routes for organic synthesis and Examples of individual compounds of this class are therefore have outstanding importance as intermediates, c-metal methyl isocyanide, a-metal ethyl isocyanide, c e.g. for the manufacture of olefins, amino acids and 25 metal isopropyl isocyanide, ox-metal cyclopropyl isocya heterocycles. nide, ox-metal cyclopentyl isocyanide, or-metal cyclohexyl isocyanide, or-metal allyl isocyanide, c-metal crotyl iso cyanide, a-metal methallyl isocyanide, or-metal pentadien This invention relates to new compounds, viz. iso 2,4-yl isocyanide, a-metal benzyl isocyanide, a-metyl fur cyanides metallized in the a-position, which open up new 30 furyl isocyanide, a-metal-2-pyridyl methyl isocyanide, oz possibilities for organic synthesis and therefore have out metal ethynyl methyl isocyanide, a-metal vinyl isocyanide, Standing importance as intermediates for such reactions, -o-metal ethoxymethyl isocyanide, c-metal phenoxymethyl for example for the manufacture of olefins, amino acids isocyanide, cy-metal ethylmercaptomethyl isocyanide, ox and heterocycles. The invention also relates to the manu metal phenylmercaptomethyl isocyanide, c-metal dimeth facture of the said cy-metallized isocyanides, which are ylaminomethyl isocyanide. ethyl a-metal isocyanoacetate, also referred to as isonitriles or carbylamines. ethyl ox-metal a-isocyanopropionate, D-metal oz-isocyano The new compounds have the general formula acetone, a-metal o-isocyanoacetophenone and O-metal iso cyanoacetonitrile. R The metallized isocyanides may be obtained by treating 40 isocyanides bearing at least one hydrogen atom on the alpha carbon atom with a metallizing agent. Metallizing agents are especially basic agents of the type Mex where where R1 and R may be identical or different and each Me is an equivalent of one of the said metals and X an denotes hydrogen and/or an inorganic or organic radical aliphatic or aromatic hydrocarbon radical, the radical of Such as may occur in isocyanides, and Me is alkali, mag 45 an alcohol or acetylenic compound, or OH. Metallizing nesium, zinc or cadmium. agents therefore include organometallic compounds, alco R1 and R2 may be for example hydrogen saturated or holates, acetylides, hydroxides and Grignard compounds. unsaturated aliphatic or cycloaliphatic hydrocarbon radi Metal hydrides and metal amides may also be successfully cals or aromatic-aliphatic, aliphatic-aromatic, aromatic or used, and in some cases the isocyanides can be reacted heterocyclic radicals. The radicals themselves may be sub 50 direct with a metal to form metallized isocyanides. stituted by hydroxyl, alkoxy, ROOC-, ROC-, isonitrile Examples of metallizing agents are butyllithium, phenyl or nitrile groups or by halogen. Aliphatic radicals are for lithium, phenylsodium, sodium methylate, sodium ethyl example alkyl radicals such as methyl, ethyl, propyl or ate, potassium tert-butylate, lithium tert-butylate, potas butyl. Examples of unsaturated aliphatic radicals are samide, sodium acetylide, phenyl magnesium bromide, alkenyl radicals such as propylene or isoprenoid radicals. 55 magnesium hydroxide, sodium hydride, sodamide and so Other unsaturated aliphatic radicals for the purposes of dium metal. the above general formula are for example alkynyl radi It goes without saying that the radicals R1 and R2 in cals, such as the radical of acetylene. An aromatic radical the starting materials is for example, phenyl, which may be substituted, e.g. by alkyl groups. 60 Examples of heterocyclic radicals are pyridyl and furyl. R may moreover denote substituents or groups such as alkoxy, aroxy, metaloxy, halogen, nitrile, alkylmercapto, and any substituents of R1 and R2 should not interfere arylmercapto, dialkylamino, ROOC-, ROC-, carboxyl with the substitution of the metal for the hydrogen atom ate, phosphinoxy, phosphate or phosphonium. R* may 65 or the alpha carbon atom. Although the manufacture of have the same meaning as long as the resultant compound the oz-metallized isocyanides and the metallized isocya has a realizable structure. Those skilled in the art after nides themselves are new, those skilled in the art having reading the present specification will have no difficulty read the present detailed disclosure will, thanks to their in deciding whether any starting material (an isocyanide general chemical knowledge, have no difficulty in distin having the above formula, but hydrogen in place of Me) is 70 guishing in the starting materials those radicals and sub suitable, so that no further explanations need be given. stituents that would interfere with or even prevent metal 3,712,911 3 4. lization in all circumstances or when using particular acts with component II to form the olefin. In some cases metallizing agents. it is possible first to combine the carbonyl compound with Metallization is carried out in a liquid medium, i.e. the metallizing agent and only then to add the isocyanide. one which is liquid during the metallization. The medium The medium in which this reaction may be carried out should be inert to the metallization agent and not interfere is one which is inert to the reactants and does not inter with the metallization. Preferred liquids are therefore fere with the reaction. Preferred liquids in which the re hydrocarbons, such as ligroin or benzene, ethers, such as action may be carried out are hydrocarbons, such as diethyl ether or tetrahydrofuran, dimethylformamide, di ligroin or benzene, ethers, such as diethyl ether, dioxane methylsulfoxide, acetonitrile, and if desired alcohols, such or tetrahydrofuran, dimethylformamide, dimethylsul as methyl or ethyl alcohol. Mixtures of the said liquids O foxide, acetonitrile, and if desired alcohols, such as methyl may also be used. Those skilled in the art having read the or ethyl alcohol. Mixtures of the said liquids may also present specification will have no difficulty in Selecting be used. Component II may also serve as reaction medium further liquids suitable as reaction media. or Solvent as long as it is liquid under the reaction con Unmetallized isocyanides may be obtained by the ditions. In order to avoid yield losses the solvent used method of Ugi and coworkers, Angew. Chem., 77, 492 should be substantially anhydrous. (1965); International Ed., 4, 472 (1965). The reaction temperature may be varied within a wide The reaction temperature may be varied within a wide range, but is usually between -80° and --80° C. In gen range. In general, temperatures below -80 C. and eral, temperatures below or around room temperature are above --80° C. are of no industrial importance; ten preferred. In many cases it may be expedient first to peratures below or around room temperature are pre 20 combine the reactants at a low temperature, e.g. at -80 ferred. to -40 C., and then to heat the mixture to room tem Compounds that are sensitive to atmospheric OXygen perature and if desired for a few minutes or hours to a are conveniently reacted under nitrogen. higher temperture up to about 80° C. or higher. It is preferred to use stoichiometric amounts of iso Compounds that are sensitive to atmospheric oxygen cyanide and metallizing agent, although in many cases the are conveniently reacted under nitrogen. reaction will more readily proceed to completion if an ex For economic reasons the reactants are used in stoichio cess of metallizing agent is used. metric amounts, but deviations of +5% are not detri There are various possibilities of following the progress mental. Moreover, component II may be used as solvent of metallization. While in some cases color changes can provided it is liquid under the reaction conditions. be observed, the metallized isocyanides sometimes occur as The solvent or liquid medium may be any of the liquids precipitates in the reaction mixture. Occasionally the com" 30 Specified above for the manufacture of the metallized pleteness of metallization can be ascertained by the nega isocyanides. tive Gilman test. Deuteration can also be used to show With regard to the contacting of the two reactants no the formation of metallized isocyanide. The said methods Special explanations are required. Incidentally, various are well known to those skilled in the art. The metallized possibilities are outlined above. isocyanides can immediately be used for further reactions The progress or end of the reaction may be ascertained in the form of the reaction mixtures, they may however by Well-known physical or chemical methods, if one be isolated, e.g. by evaporation of the liquid phase, i.e. wishes to go beyond isolating the olefin formed.