Here is a wonderful article that i just found that sheds new prespective on the particulars of the crossed Kolbe coupling scheme. Hopefully Rhodium will find it in his heart to post it on his website along side my other work...
Here is the text, i only included the bulk of the article, not the experimental section
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Page 2854
Linstead, Shephard
and Weedon:
634. Anodic Syntheses. Part V.* Electrolysis of N-Acylamino-acids.
A Novel Alkoxylation Reaction
.
By R. P. LINSTEAD, B. R. SKEPHMID, and B. C. L. WEEDON.
Electrolysis of N-acyl-glycines and -DL-[alpha]-alanines in methanol gives
N-methoxymethyl- and N-l'-methoxyethyl -amides respectively in good yields.
Analogous reactions occur in both ethanol and isopropanol.
Under similar conditions N-acyl derivatives of 6-aminohexanoic acid, [gamma]-
aminobutyric acid, and [beta]-alanine undergo the normal Kolbe reaction giving
the corresponding derivatives of polymethylenediamines in ca. 20— 40% yields.
THE Kolbe synthesis of compounds of the type R*R by electrolysis of the acids
R-CO,H is known to be accompanied by side reactions, a number of which were
described by Kolbe himself (Annaltn. 1849, 69, 257). The extent to which
by-products are formed is governed both by the experimental conditions and to
a marked degree, by the structure of the acid, to a electrolysed. A survey
of the literature reveals that presence of substituents [alpha] to the carboxyl
group has the most pronounced influence, as would be expected, and may result
in the Kolbe coupling reaction being largely or completely suppressed. Thus
although normal coupling occurs with alkyl hydrogen malonates (Brown and
Walker, ibid., 1891, 261, 107; Hickling and Westwood, /., 1938, 1039) and, to
a smaller extent, with [alpha]-phenyl- (Fichter and Stenzl, Helv. Chim. Ada,
1939, 22, 970) and [alpha]-aryloxy-acetic acids (idem, loc. cit.; Fichter and
Kesten-holz, ibid., 1942, 25, 785), and a few [alpha]-alkyl-acids, little or
no coupling has been reported for [alpha]-aklyl acids, for [alpha]-methoxy-,
[alpha]-hydroxy-, [alpha]-halogen-, a-keto, a-cyano-, and [alpha]-amino- acids
most (for a review see Brockman, " Electro-Organ c Chemistry," New York, 1926)
or for di-or tri-phenylacetic acid (van der Hoek and Nauta, Rec. Trav. Mm.,
1942, 61, 845; Riccoboni, Gazzetta, 1940, 70, 748). However as the experimental
conditions employed in much of the early work in this field cannot now be
regarded as the most suitable for coupling, further study seemed desirable.
Moreover an investigation of the competing reactions might well reveal new and
valuable synthetic processes. With these considerations in mind an exploratory
investigation of the electrolysis of a number of substituted acids has been
put in hand. The results with N-acylamino-acids are reported in the present
communication.
Fichter and Schmidt (Helv. Chim. Acta, 1920, 3, 704) demonstrated that
electrolysis, in aqueous solutions, of [alpha]-amino-acids or their N-acyl or
N-sulphonyl derivatives led to complete disruption of the molecule and not to
coupling of the Kolbe type. In the application of the Kolbe reaction to fatty
acids the use of methanolic either than aqueous solutions has frequently been
found advantageous, and the present work hits been confined to non-aqueous
solutions. These have yielded results quite different from those reported by
Fichter.
Electrolysis of N-benzoylglycine in methanol furnished in good yield (61%) a
neutral product which, on the basis of the analytical results and the
formation of bisbenzamidomethane (II) and formaldehyde on treatment with
mineral acid, is formulated as N-methoxymethyl-benzamide (I; R = Ph). This
structure was confirmed by treatment of N-hydroxymethyl-benzamide with
methanolic hydrogen chloride (cf. UiS.P. 2,364,737; B.P. 557,932), which gave
in 30% yield a product identical with that prepared anodically.
(I) R-CO-NH-CH2-CO2H --> R-CO-NH-CH2OMe
(III) R-CO-NH-CHMe-CO2H --> R-CONH-CHMe-OMe
(II) (Ph-CO-NH)2CH2
Anodic methoxylation also took place readily with N-acetyl- and
N-carbobenzyloxygylcine, giving N-methoxymethylacetamide (I; R = Me) and
-benzylurethane (I; R = PhCH2O) in 78 and 74% yield respectively. Similarly
N-acetyl- and N-benzoyl-DL-[alpha]-alanine gave the N-l'-methoxyethyl-
amides (III; R = Me and Ph) in 85 and 91% yield respectively.
The use of solvents other than methanol was also briefly investigated, and
by electrolysis of N-benzoylglycine in ethanol and isopropanol, and of N-
benzoyl-DL-[alpha]-alanine in ethanol, the corresponding ethoxy- and
isoopropoxy-alkylamides were obtained (56—70%).
[Page 2855]
These reactions can be generalised as follows :
X-NH-CHR-CO2H + R'-OH ——> X-NH-CHR-OR' + CO2
where X is acyl, R hydrogen or methyl, and R' alkyl. The alkoxyalkyl-amides
(acylaminoethers) so produced are of a rare type hard to prepare in other ways.
The yields are high aid the products easily obtained as crystalline solids
or colourless distillable liquids.
Electrolysis of N-phenylacetylglycine in acetic acid solution yielded N-
(acetoxymethyl) phenylacetamide (IV) (38%), previously prepared by the action
of lead tetra-acetate on phenylacetylglycine (Sus, Annvlen, 1949, 564, 137).
From a few of the electrolyses in alcohols described above, small amounts
(<15%) [alpha]-diamine derivatives, the products of normal coupling, were also
isolated.
Ph-CH2-CONH-CH2-OAc
(IV)
Ph-CO-NH-CH2-N(CO)2(C6H4)
(V)
When N-methoxymethylbenzamide (I; R = Ph) and the corresponding ethoxy- and
isopropoxy-compounds were heated with phthalimide, N-phthalimidomethylbenzamide
was obtained. A number of the other l-alkoxyalkyl derivatives described above
were also shown to react similarly with phthalimide and were conveniently
characterised in this way.
The only previous well-authenticated example of anodic alkoxylation was reported
by van der Hoek and Nauta (loc. cit.) who isolated methoxydiphenylmethane
(36% yield) from the products formed by electrolysis of diphenylacetic acid in a
mixture of methanol and pyridine. Anodic alkoxylations, in general, are
reminiscent of the formation of alcohols on electrolysis of fatty acids in
aqueous solution (Hofer and Moest, Annalen, 1902, 828, 284). The Hofer-Moest
reaction is promoted by various inorganic anions and can involve attack at
positions both [alpha] and [beta] to the eliminated carboxyl group (Kruis and
Schanzer, Z. physikal. Chem., 1942, 191, A, 301). In the present work, however,
no evidence was obtained of [beta]-attack on derivatives of DL-[alpha]-alanine.
Several plausible mechanisms could be put forward to account for these anodic
alkoxylations is but it is not proposed to speculate on these at present.
Experiments designed to provide information on this aspect are in hand. It is
hoped to determine also the structural features which favour alkoxylation and
related reactions.
After the study of derivatives of [alpha]-amino-acids, attention was directed to
acids with the amino- and carboxyl groups separated from one another. Fichter
and Schmidt (loc. cit.) were unable to detect the normal Kolbe reaction on
electrolysis of [beta]-alanine or its N-benzo rl derivative in aqueous solution,
but, more recently, Ofie (Z. Naturforsch, 1947, 2b, 182, 18 5) has stated that
electrolysis in methanol of N-acyl or N-alkylsulphonyl derivatives of amino-acids
other than those of the [alpha]-series leads to the corresponding derivatives of
diamines by normal coupling. This conclusion was based on the results of
electrolysing [gamma]-phthalimido- butyric acid and derivatives of 6-
aminohexanoic acid but yields were given in one case only. We find that normal
Kolbe coupling occurs in the electrolysis in methanol of a considerable range
of acylamino-acids other than those of the [alpha]-series. The reaction
X-NH[CH2]n-CO2H ——> X-NH-[CH2]2n-NHX
proceeds in about 30% yield where n is 2, 4, or 6. Thus 6-acetamido-,
6-benzamido-, and 6-carbobenzyloxyamino-hexanoic acids yielded the corresponding
derivatives of 1 : 10-diamino-decane (31, 23, and 38% respectively). 1 :6-Bis-
carbobenzyloxyaminohexane was similarly prepared (35%) from [gamma]-carbobenzyl-
oxyaminobutyric acid. Electrolysis of N-benzoyl- and N-carbobenzyloxy-[beta]-
alanine furnished the derivatives of 1 : 4-diaminobutane in 20 and 33 % yield.
From N-benzoyl-[beta]-alanine a small amount of 2-phenyloxazoline was isolated
(in the form of its picrate) as by-product. In general, however, the nature of
the side products these reactions remains to be determined.
EXPERIMENTAL.
... [truncated for brevity]
