                Grignard reactions in solvents other than ether

              From Grignard Reactions of Non-metallic Substances,
        by M.S. Kharasch and Otto Reinmuth, yr 1954 (posted by Chem Guy)

"Tertary Amines. Tschelinzeff [146] remarked the simarity betwwen the reactions
of Grignard reagents with many oxygen compounds, on the one hand and their
nitrogen analogs, on the other hand, e.g. water and ammonia, alcohols and amines
(primary and secondary), ketones and nitriles, esters and amides. From this he
reasoned that the nitrogen analog of an ether (e.i. a tertiary amine) might well
play the same role as an ether in the preparation of a grignard reagent." [In
short this worked. Specificly he speaks of dimethylaniline. Reference, 146:
Tschelinzeff, Ber., 37, 2081-5 (1904) ]

"Hydrocarbons. ...Tschelinzeff [149] attempted the preparation of of Grignard
reagents from a series of iodides (not specified) in benzene, both
thiophene-free and thiophene contaminated, but noted no preceptible reaction
after forty-eight hours at the boiling point. In xylene, he was able to prepare
reagents from, ethyl, n-propyl, n-butyl, and n-amyl iodides without the use of a
"catalyst".

When a few drops of a tertiary amine (suitable dimethylaniline) was added such
preparations could be carried out in benzene, toluene, xylene, hexane, petroleum
ether, benzine, and terpenoid hydrocarbons. Reaction often begin spontaneously,
but always could be initiated by warming to 30-40 , or by adding a crystal of
iodine.... Simialr tertiary amine promoted Grignard reagents preparations in
hydrocarbon solvents are described b Tschelinzeff [150], by Stadnikoff [151],
and Hess and Rheinboldt [152].

...A comparative study of the effectiveness of various ethers and their sulfur
analogs in facilitating Grignard reagent formation in benzene solution has been
made by Hepworth [156].... In general oxygen compounds are much more effective
thantheir sulfur analogs. Open-chain compounds are more effective than the
related hetrocycles: e.g. ethyl n-propyl ether is more effective than
pentamethylene oxide; ethyl n-propyl sulfide is more effective than
pentamethylene sulfide...

Gilman and McCracken [157] have reviewed earlier work on the preparation of
Grgnard reagents in solvents other than ethyl ether, and have investigated the
effect on Grignard yields of various hydrocarbon-ethyl ether mixtures. They
conclude that in general, the use of a mixed solvent results in a drop in yeild
of about 10 percent below that obtained with the optmum ethyl ether
concentration....

Barr'e and Repentigny [160] describe the preparation of several Grignard
reagents in hydrocarbon solvents with dimethylaniline as "catalyst"....

TABLE II-XII

PREPARATIONS OF SEVERAL GRIGANRD REAGENTS IN HYDROCARBON SOLVENTS WITH THE AID
OF DIMETHYLANILINE

Halide/Solvent/Grams-Amine/Hours refluxed/Temp/Yield
...

C6H5CH2Cl*/C6H6/1.25/14hr/80 C/20-30%

...
* - Benzyl Chloride quaternizes to some extent; neither allyl bromide nor
t-butyl chloride give appreciable yeilds of Grignard reagent."

References:
-----------

149: Tschelinzeff, Ber., 37, 4534-40, (1904)

150: Tschelineff, Ber., 3664-73, (1905)
151: Stadnikoff, Ber., 44, 1157, (1911),
152: Hess and Rheinboldt, Ber., 54B, 2043-55, (1921)
156: Hepworth, J. Chem. Soc., 119, 1249-56, (1921)
157: Gilman and McCracken, Rec. Trav. Chim., 46, 463-72, (1927)
160: Barr'e and Repentigny, Can. J. Research, 27B, 716-20, (1949)

Also, concerning ketone formation by Grignard reagent addition to an excess of
acid halide...

"'The order of activity of the three acid halides, benzoyl flouride, chloride,
and bromide,...Since the acid flouride is actually found to be the most
reactive, it is obvious that the reaction occurs through addition to the
carbonyl group not through a metathetical reaction of the halogen atom....

It may or may not be significant in this connection that the order of reactivity
of acyl halides toward the organoainc, -cadmium, and -mercury compounds (Which
do not under go carbonyl double bond addition, which is very slowly indeed) is
said to be the reverse of that toward Grignard reagents....

PREPARATION OF KETONES BY GRIGNARD-HALIDE INTERACTION
...For that purpose low operating tempatures, reverse adition (e.i. addition of
the Grignard reagent to the acid chloride, or it's solution), and the use of an
excess of the acid chloride are obviously indicated. The reaction has indeed
been employed by, amoung others, Gilman et al [13], Helferich and Malkomes [14],
Darzens and Rost [15], Acree [16], Schmidlin [17], Karrer [18], and Whitmore and
Badertscher [19]....
When applicable, however, the organozinc halides or the diorganocadmium,
compounds give superior results.

KETONE PREPARATION WITH THE AID OF ZINC AND CADMIUM SALTS
...
The advantage claimed for the use of organocadmium compounds are: that they are
readily prepared form from Grignard reagents and the relativly economical,
nonhydroscoopic cadmium chloride; that the preparation and subsequent reaction
can be carried out in ether solution (although benzene, or toluene is preferred
solvent for acid chloride reactions); that, although they react readily with
acid chloride and acid anhydrides, they are are very unreactive towards other
functional groups (including the carbonyl) that react more or less readily with
Grignard reagents. The R2Cd and RCdX compounds appear to be equally satisfac-
tory, but the former are most often used as requiring less cadmium chloride.

The Organozinc compounds are similar in chemical properties to the corresponding
organocadmium compounds, but notwithstanding the recommondations of Blaise [25],
who gives no experimental detail, are alleged to to be comparatively disadvant-
ageous because of greater difficultly of preparation; the undesireableity of
using ether as a solvent in acid chloride reactions )because of ether cleavage
and ester formation) ; and the geatwerreactivity of the zinc compounds
particularly towards carbonyl groups. ...It is possible, however, to affect the
preparation by a method analogous to that commonly employed for the preparation
of organocadmium compounds, namely, the addition of anhydrous zinc chloride to a
Grignard reagent solution, a method that has been used with good sucess by Jones
[27] and others."

"TABLE IX-I
PREPARATION OF KETONES FROM ACID HALIDES WITH THE AID OF CADMIUM OR ZINC SALTS

Halide/RMgX/Cd or Zn salt/% Yeild Ketone
...
CH3COCl/C6H5CH2MgCl/CdCl2/18%


Conclusion: Ketone preparation from Cd of Zn SUCKS, no matter how you do it...

References:
-----------

13: Gilman, "Organic Chemistry", 2nd Ed,Chapter 5, page 501-2,1943
14: Chem. Abstr., 41, 41, 3444, 1947
15: Rec. trav. chim., 48, 748-51, 1929
16: Ber.,625-8, 1904
17: Ber., 42, 2377-92, 1909
18: Ber., 50, 1499-508, 1917
19: J. Amer. Chem. Soc., 55, 1559-67, 1933
25: Bull. soc. chim., [4], 9, I-XXVI, 1911
27: J. Amer. Chem. Soc., 69, 2350-4, 1947

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