Grignard Route

RM can be a traditional Grignard reagent or an organolithium, 2inc, aluminum, or mercury compound. The Grignard route is employed commercially for production of tertiary phosphines, even though these reactions are subject to side reactions. Yields are often low, eg, 40—50% for (C4H )2P prepared via a Grignard reaction (18). A phosphoms—carbon bond can form from the metathetical reaction of a phosphoms haUde and a pseudohaUde salt. 

In the context of commercial silane production, these frequendy lead to by-product reactions, as for example the production of allyl dim ethyl sil a n e by a Grignard route (see Grignard reactions). 

Properties of zinc salts of inorganic and organic salts are Hsted in Table 1 with other commercially important zinc chemicals. In the dithiocarbamates, 2-mercaptobenzothiazole, and formaldehyde sulfoxylate, zinc is covalendy bound to sulfur. In compounds such as the oxide, borate, and sihcate, the covalent bonds with oxygen are very stable. Zinc—carbon bonds occur in diorganozinc compounds, eg, diethjizinc [557-20-0]. Such compounds were much used in organic synthesis prior to the development of the more convenient Grignard route (see Grignard reactions). 

All three routes are used on an industrial scale and the Grignard route (or the equivalent organo-Li reagent) is convenient for laboratory scale. Rather less used is the modified Wurtz-type reac-8 Na... 

The benzene layer is removed by decantation and the remaining mixture is rendered basic with 10% sodium hydroxide solution and is extracted with three 1,500 ml portions of benzene. The benzene extracts are washed, then dried with anhydrous sodium sulfate and concentrated in a vacuum leaving a residue of 1,530 grams, gas and thin layer chromatography analysis show this to be a cis/trans mixture (approx. 4 1) of 11-dimethylamino-propylidene-6,11-dihydrodibenz-(b,e)oxepin (90% yield). This mixture has substantially more activity pharmacologically than the cis/trans mixture obtained by the Grignard route disclosed in the Belgian Patent 641,498. This base is then converted to the hydrochloride with HCI. 

This phenol synthesis complements the analogous reaction (see below) from arylthallium ditrifluoroacetates (147). Although yields are only moderate, the procedure represents a viable conversion of aryl Grignard reagents to phenols. It is a practical method, however, only when the diarylthallium trifluoroacetate precursor is formed via the Grignard route the alternative synthesis via symmetrization of arylthallium ditrifluoroacetates is obviously circuitous, since the latter compounds may be converted directly to phenols. 

The reaction of [ Co"(DMG)2py 2] with B( -C4H,)3 in benzene followed by extraction with CH2Cl2/aq. NaOH produces [ -BuCo(DMG)2py] the reaction is less successful with [pyCo "(DMG)2Cl] 161). This may be a convenient method using the more stable arylboron derivatives, but is probably experimentally more difficult than the Grignard route if a lower alkyl is to be introduced, because the lower alkylboron compounds inflame spontaneously in air, though they do not react with water, while the aryls are stable in air. 

Answer Alcohol (2) will dehydrate to (1) and the Grignard route gives (2),... 

Example The lactone (8>, needed for a natural product synthesis, might be made from (6) via epoxide (7) and so a synthesis for (6) was required. Wittlg disconnection reveals a 1,5-dicarbonyl compound (9), best made by Michael addition of a substituted malonate (11) to enone (10). The enone was made by the simple but reliable Grignard route rather than risking a Mannich reaction of unknown regloselectivity. 

They avoided the obvious Friedel-Crafts synthesis of (33), presumably to avoid the separation of o and p isomers, and used instead either Grignard route to (34),... 

The product did indeed have the same structure as (34) but the stereochemistry was still unknown. If a carbonyl group is added (FGA) to give ketone (39), disconnection via standard Grignard routes to available optically active (40) is possible. 

Maximum yield was obtained when the applied voltage was 13.1 V, the cathode surface area was 4 cm2 and the total CH3I concentration was 35.2 pmol. The C-14 labelled tetramethyllead was isolated by the extraction procedures developed for the Grignard route (vide supra). It was next converted to 14CH3(CH3)2PbCl by controlled oxidation with HC1. 

The Grignard route to diorganyl ditellurides suffers from lack of generality and the mechanism of the oxidation seems to be uncertain. Alkylmagnesium halides demonstrate lack of reactivity towards elemental tellurium/ whereas aryhnagnesium halides in ether as the solvent furnish a mixture of ditellurides and tellurides. Satisfactory results are obtained by tellurium insertion in aryhnagnesium halides in THF followed by oxidation before or after aqueous work-up. ... 

The Grignard route is better it is a one-pot transformation. Converting the secondary bromide to a nitrile will be accompanied by elimination, and the procedure requires two separate operations. 

The aryl bromide cannot be converted to a carboxylic acid by way of the corresponding nitrile, because aryl bromides are not reactive toward nucleophilic substitution. The Grignard route is necessary. 

The nitrile route would involve an Sn2 displacement of bromide by cyanide, a highly unlikely step when the alkyl halide is tertiary. The Grignard route, on the other hand, works well for all alkyl halides—primary, secondary, and tertiary. 

A Grignard or organo-lithium reagent would attack at the less hindered end of the epoxide and the Grignard route gives the alcohol 53. In chapter 12 we shall see that this reaction is stereospecific. 

Shu, S., Husain, S. and Koros, W.J. (2007) Formation of nanostructured zeolite particle surfaces via a halide/Grignard route. Chemistry of Materials, 19 (16), 4000-4006. 

Several methods have been recommended for the preparation of pure methylcopper, each having advantages over previously reported methods. Costa et al. consider the [Pb(CH3)4 + Cu(N03)2] method superior to the Grignard route, as reproducible analyses are obtained 82). However, Thiele and Kohler recommend the reaction of zinc dialkyls with cop-per(II) chloride in ether at — 78°C for the preparation of pure yellow methylcopper, red-brown ethylcopper, and orange propylcopper, uncontaminated by copper alkoxides (277). The mechanism was considered to be a reduction of copper(II) to copper(I) chloride, followed by the reaction of the latter with the zinc dialkyl. The results from the recent... 

Though Grignard-based method appears economically preferable if possible, lithium-based procedures are much more widely employed, probably because it is free from trouble caused by Lewis acid-base interaction that is sometimes encountered with the corresponding Grignard route. Choice of the lithiation... 

The sandwich structure of bis (benzene) chromium (XXV) prepared by this new route was soon confirmed by Weiss and Fischer (242). Moreover, Fischer and Sens (98) prepared bis (phenyl) chromium iodide (XXII) by the Friedel-Crafts-type method, starting with biphenyl in place of benzene, and were able to show that the product obtained in this manner was identical to bis (biphenyl) chromium iodide (XXII) isolated via Heines Grignard route. A longstanding and vexing problem in coordination chemistry was thus finally solved. 

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