I N COORDINATION COMPOUNDS, ELECTRON DENSITY
PATTERNS CONTROL REACTIVITY. SHARING O F ELECTRONS T O F O R M u AND I B O N D S IS R E P R E S E N T E D B E L O W
. ,i'
i i
'A
14
INDUSTRIAL A N D ENGINEERING CHEMISTRY
ligand Reactivity and Catalysis M A R K M. JONES
c
oordination may hinder, aid, or have little effect on a pven .’ type of ligand reaction. It is the purpose of this paper to present a classification of coordination reactions which will enable the underlying principles to be applied to newly encountered reactions. The ultimate understanding and control of these processes must await a more thorough knowledge of the way in which coordination affects the electron density patterns. and hence reactivity patterns of the ligands. The first report on the effect of coordination on the reactivity of an organic ligand appeared over one hundred years ago. In 1856, Gibbs and Genth (77) noticed that oxalate coordinated to cobalt(II1) did not undergo many of the typical reactions of oxalate ion with oxidizing agents, such as cbloroauric acid. Since that time there have appeared numerous, but very scattered, reports on this same subject: the effect of coordination on the reactivity of organic ligands. Much of this information is of considerable practical use. The number of instances where coordination is essential to catalytic activity is very large. Some of these, such as the oxo process or the Friedel-Crafts reaction, are of considerable industrial importance. Others are involved primarily with reactions which take place within living organisms; still others may be cited whose usefulness are presently limited to laboratory preparations. The examples considered here are almost exclusively those in which coordinate bonds of the “classical” sort are formed. The sigma bond shown in the figure opposite represents this classical concept. Metal cyclopentadienyls, carbonyls, and related types of compounds exhibit behavior of a more complicated sort and will not be treated here. In this article, we are dealing with compounds in which a pair of electrons, originally on a donor atom (D3 such as nitrogen or oxygen, is used to form a coordinate bond with a metal ion (M). An example is the lone pair of electrons on the nitrcgen atom in pyridine, which is used to form a coordinate bond to mercuric ion when mercuric acetate and pyridine are brought together. While it is usual to consider this electron pair as equally
W I L L I A M A. CONNOR
shared between the two bonded atoms, this is usually not the case. In most coordinate bonds the donor atom has a larger share of control over the electron pair than does the acceptor atom. While a qualitative description of the electron distribution can be given in terms of such simple notions as these, a suitable quantitative description requires the use of molecular orbital theory. When pi bonds are formed between the metal and the donor, the prediction of the charge d i s ~ b u t i o nin the resulting complex is much more difficult (bonding by pi electrons is also represented in the figure). Because of this, most of the utility of the system of classification given on the next page is presently restricted to systems containing only simple Coordinate bonds. Some examples of ligands which form pi bonds are included to illustrate how such bonding modifies the behavior patterns, but it is not intended here to SUNV the enormous number of organic reactions where such bonding has been called into play. As has been stated coordination may hinder, aid, or have little effect on a given type of ligand reaction depending upon how it affects the ease with which the ligand may undergo the reaction. Thus, while coordination suppresses the oxidation of coordinated oxalate in the complex mentioned previously, the analogous reaction of EDTA with permanganate is much more rapid for the Cr(II1) and Bi(II1) complexes than for the free ligand ( 75). Coordination can frequently accelerate a reaction by providing an easier path for it than is otherwise available. This was clearly pointed out by Meerwein many years ago. This is a kinaic dfect. Coordination can also function by providing a favorable thenndynamic path for a reaction. This can most clearly be seen in the work of Eley and his coworkers on the GattennannKoch reaction (37, 50). Because of the paucity of information on the thermodynamics of coordination compounds, most of the examples cited will be examples of kinetic effects. These various effects can be most readily seen in the figure on page 19, which has been developed from Meerwein’s to show all of these thermodynamic and kinetis possibilities. VOL. 5 5
NO. 9
SEPTEMBER 1963
IS
ClassMlcaNon Methods
Reactions of Class 1
Other authors have classified the reactions of coordinated ligands in a differentway than we use here. Martell, Gustafson, and Chaberek (755) center their attention on the central metal ion and divide the reactions into two groups: -Those reactions in which the central metal ion undergoes a permanent change, e.g., redox reactions such as the permanganate-oxalate ion reaction. -Those reactions in which the central metal ion does not undergo a permanent change. These are the true metal ion catalyzed reactions and include the hydrolyses of amino-acid esters and transaminations of S c W s bases derived from pyridoxal.
A good and simple illustration is the cuprous chloridepyridine complex which acts as a catalyst for the autoxidation of aromatic amines by atmospheric oxygen. This reaction was studied by Terent’ev et d. (226229). It was found that other cuprous or cupric compounds were ineffectiveas catalysts and also that pyridine, which was used as a solvent, could not be replaced by alcohols, dioxane, dichloroethane, or quinoline. A typical reaction of this sort is the oxidation of aniline to ambenzene, which proceeds with 88 per cent yield. Presumably, a complex is formed in which cuprous ion, pyridine, and oxygen and the amine are brought together and the oxygen is simultaneously activated for attack’of the amine. A solution of cuprous chloride in pyridine absorbs one mole of oxygen per mole of CuCl and this is presumably the route by which the oxygen is transformed into a species which is both selective and effective.
While this classification is of considerable theoretical utility its form is such that it is difficult to use in a practical case in deciding whether coordination offers advantages in a specific reaction. Beck (74) classifies the catalytic phenomena of coordination chemistry into two groups: -Catalysis by complex compounds. -Catalysis of the formation of complex compounds, which includes coordination catalysis by both the ligand (83, 796) and the cation (31),catalysis connected with redox reactions, catalysis of a heterogeneous nature. The classification scheme above utilizes a completely different basis, which emphasizes the variations in ligand behavior which may arise on coordination. It is hoped that this presents the information in a form in which its practical applications are more obvious and in which possible extemions to analogous reactions can be more easily seen. The eight classes of reactions given above are developed on the basis of the manner in which coordination affects the reactivity of the ligand. From such examples as are presently known it can be demonstrated that coordination may find practical application in both the suppression of undesirable reactions and in the facilitation of certain reactions which occur more readily with coordinated ligands. 16
INDUSTRIAL A N D E N G I N E E R I N G CHEMISTRY
e
+
H
* CuCl
-$I.
+ 01
PyridiOC
[ e m s ,
2
H
2
O
1
pridine
05,
+
e
=
N
a
This is not an isolated case, but is a reasonably general procedure for formation of azo compounds from aromatic amines. A simiiar set of reactions was studied by Kinoshita (7 78). Here a solution of cuprous chloride in pyridine was used to catalyze the autoxidation of benzoin to benzil and then to benzoic acid. When cupric chloride was used, autoxidation of benzoin went only as far as b d :
-+-e H
cuca OI
d a i r
OH 0 0 0
cucl in
0
T h e use of cupric chloride here gives a n almost quantitative yield of benzil. For these reactions (but not those involving amines such as were studied by Terent'ev et al.) the cuprous acetate-pyridine complex was found to be a n effective catalyst. Kinoshita studied the amine oxidations and showed that a n intermediate in this reaction was an oxidizing agent derived from the cuprous complex. Kinoshita proposed the following scheme: CUCl2
+
-- CeHsNH2
in pyridine
0
2
Cu"-Cl
(CF,H~~H~CU")+C~(c6H6NH-c~')
+
( C ~ H ~ N H C U ' ) HC1
+ C6H6NHNHC6H5
+ 2Cu'
C ~ H ~ N H N H C -+ B HC~~ H Z N = N C ~ H ~ T h e oxidation of olefin-palladium chloride complexes is apparently a reaction of this type. For example, acetaldehyde can be readily prepared from ethylene (197) :
+ +
+ +
+ + +
CzH4 PdClz H20 -P CzH40 Pd 2HC1 Pd 2C~C12+ PdClz C~zClz 2CuC1 '/zOz 2HC1+ 2 C ~ C l z HzO
+
Brackman and his coworkers (25, 26) have investigated the oxidation of monohydric phenols using molecular oxygen as the oxidant and copper(I1) amines as catalysts. I t has been found that these reactions are rapid at room temperature and may be applied to a variety of phenols and employ a number of different primary and secondary amines as catalytic agents. T h e product with phenol itself is, initially, the corresponding orthoquinone. This in turn is subject to rapid addition reactions with the primary or secondary amines, which are present, to give a substituted catechol. This is then oxidized to a substituted orthoquinone. This series of reactions may be summarized as : OH
6
-+
'
Monohydric Phenol
Catalyst
Product and Yield
Phenol
Cu( 11)-morpholine complex
Alpha naphthol
Cu( 11)-morpholine complex
4,5-Dimorpholino1,2-benzoquinone, 64% 4-Morpholino-l,2naphthaquinone,
Beta naphthol
Cu( 11)-morpholine complex
2-Substituted alpha naphthol
Cu( I1)-collidine complex
4-Substituted alpha naphthol
Cu(I1)-collidine complex
37 % 4-Morpholino-l,2naphthaquinone, 84% 1,4-Naphthaquinone, 41% dinaphthanone, 38y0 Bisnaphthalene indigo
The molecular oxygen is required to reconvert the univalent copper, formed in the reaction, to the divalent state. This appears to be its sole function since the reactions are feasible only in the presence of oxygen. Hydrogen peroxide is generated in the process by the autoxidation of the phenol. I t has been noted that the induction period can be completely removed by the addition of a small amount of hydrogen peroxide. T h e amine, the peroxide, and the phenol then form a coordination complex which by suitable electronic rearrangement yields the dihydric phenol (catechol) derivative which then forms the end products. Brackman and his coworkers proposed a reaction intermediate which produces the final compounds by the following mechanism : X
Y
X
'0
?
C ' U'
?/
'
Y
'cu/
'0
0
/OH --OH
-+
a
OH
=
o
Morpholine
x
___f
Y
X
Y
0
101 OH
0
4,5-dimorpholino-l,2-benzoquinone, in 64% yield
Mark M . Jones is an associate professor in the Department of Chemistry, Vanderbilt University, Nashville, Tenn. William A . Connor is a graduate student in the same department.
AUTHOR:
CATALYZED OXIDATIONS
-P
No mechanism was suggested for the subsequent step :
+
TABLE I .
The groups X and Y are generally amines, and in the example cited above they would both be morpholine. Table I lists the systems studied by Brackman. T h e introduction of hydroxyl groups into aromatic rings has an analog in the so-called oxidative coppering reaction which has received much attention from workers in the field of azo dyes (248). Much of this work was done at the laboratories of the Badisch Anilin und Soda Fabrik A.G., and is covered by patents. I n these reactions, ortho-hydroxyazo compounds are converted into 0 , O '-dihydroxyazo derivatives when treated with hydrogen peroxide in the presence of cupric acetate. Copper(1) and copper(I1) salts have been used widely as catalysts for a variety of oxidation reactions. C. W. VOL. 5 5
NO. 9 S E P T E M B E R 1963
17
Schwartz (272) found that cupric nitrate catalyzed the high temperature, high pressure oxidation of aliphatic substituents on the pyridine ring. A complex is presumably responsible for these reactions:
+ Cut2 Cu(I1) salt of isocincheromic acid CH3
I n addition to these reactions, several reactions using cuprous salts as catalysts can be run at high temperatures in the absence of a solvent. It should be recalled that the coordination of the nitrogen atom of pyridine generally results in a notable increase in the ease of ionization of a hydrogen from an attached methyl group. Thus zinc chloride catall-zes the condensation of the methyl group of a-picoline with aldehydes (72). The study of metal ion catalysis of autoxidation reactions has been pursued for many years and the literature is very extensive (49). Trace amounts of metals often catalyze the autoxidation of industrial and food products -control of such reactions may be an economic necessity-. For example, the oxidation of benzaldehyde in benzene-water mixtures is accelerated by ferric salts and, more effectively, by ferrous salts (730, 245). The principal product is benzoic acid. Other aldehydes undergo similar reactions, for example butanal, 3,5,5trimethylhexanal, and related compounds (705). These reactions are considered to be free radical reactions and the catalysts are instrumental in the initiation of the chain reaction (73). In the catalytic autoxidation of benzaldehyde by cobaltous acetate, the initial step is the oxidation of cobaltous to cobaltic ion, followed by:
-
+
C O + ~ C6H5CH0 CsHsCO.
+
0 2 ---t
CsHbC000.
limiting step
CsHsC000
+
C ~ H B C H -O + CsHsCOOOH CsHsCO.
+ CeH5COOOH
-
+
fast
very slow
+
CO+~
CsHSCOOO. 2CsH&000
-
-+
+
C O + ~ OHC~H~COO.
+ H+
molecular products
The second and third steps represent the propagation of the chain reaction. These steps are typical of many reactions of this type. A survey of the recent work is available (49),as is much of the older work (270). A series of cases where complexes catalyze hydrogenation reactions has been investigated in great detail by Halpern and his coworkers (85, 86). Halpern has studied the homogeneous catalytic activation of molecular hydrogen by many simple and complex species. This kind of reaction was first discovered by Calvin 18
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Activation Energy, Kcal.;/Mole
Heterolytic Splitting Probable
+ + +
+ +
CU" Hz + CUHH+ .4g+ Hz + AgH Hf Hgt2 Hz HgH+ Hf Mn04Hz + Hhfn04-2
+
+
-+
27 24 18 15
+ H+
Homolytic Splitting Probable
+ + +
2Ag+ Hz --t 2AgHt Hgz'? Hz + 2HgH7 Agy MnOdHz -+ AgH" HMnO;-
15 20
+
9
Complex formation may- either increase or decrease the activity of these metallic species as catalysts. Some of the data summarized by Halpern are given in Table 11. TABLE II.
RELATIVE CATALYTIC ACTIVITIES hlean Formation
Speczes Cu( butyrate)? Cu( propionate)2 Cu( acetate)l cusoi cuc14 -* c u +2
CO+z
+ CsH5COOOH Cof3
+ C s H 5 C 0 . + HS
(34, 35), who found that cupric acetate or benzoquinone dissolved in quinoline which contained cuprous acetate, suffered reduction by molecular hydrogen a t 100' C., an unusually low temperature for such a homogeneous reaction. Subsequently, many instances of the activation of molecular hydrogen by such materials have been reported. Some of the ions which are capable of activating hydrogen in aqueous solution are Cuf*, Ag', Hg+2, Hg2+2, and Mn0,-. This activation can be either by homolytic or heterolytic splitting of the hydrogen. Reactions believed to be rate determining are :
Hg Lz Hg( acetate)n HgCU2 HgCl? Hg(en)2i2 Ag( acetate) .4g( en), + Ag Ag(CN);.-
I
Constant
I 1
I
30
~
loo 1 about
,
~
1
22 1 6 X lo4 6 X IO3 4 x 106 5 1 x 10"
7
about 3 x 103
+
2 4
x
I ,
i
~
~
, ~
109
Relatzue Actztity
150 150 120 6 5 2 j 1 0 1.8 I
x x 2.5 x 1 x 4 3.2
10-2 10-3 10-3 10-3
80 25 1 inactive
In some complexes, designated bifunctional by Halpern, very pronounced catalytic activity is found. This is found for molecules which possess both electron accepting and proton accepting sites. These groups must be so disposed that they can interact simultaneously with a hydrogen molecule, but must nevertheless be in a rigid framework which prevents them from reacting with each other. A model system such as this may be present in some enzymes, Table I11 lists examples. Reactions of Class 2
There are a very large number of cases where polarization is the principal source of the change in reactivity
THERMODYNAMIC EFFECTS AE*
for simple or complexed reactants does not differ substantially
T' I
la) Coordination results in a more stable product
L Io) Complex provides a route of lower AF* by changes in AH* or AS*
Ib) Coordination results in reaction favoring complexed product formation
E
il Ib) Routi
3E' and stabilized prodowt
**-
I I
I'
I 1
-r,-
c
z
IC) Destabilization of reactant and stabilization of product
Id) Increased c - ..-:ion energy prevents reaction Imaskingl VOL 5 5
NO. 9
SEPTEMBER 1963
1
(see Table IV). This type of behavior was described by early workers in the field, especially Meerwein (156). This is, of course, a universal factor accompanying any coordination process. I t is also a very commonly utilized form of coordination catalysis. This mode of action is generally considered to be dominant in the catalytic decarboxylations of aliphatic keto acids in which the same keto group is alpha to one carboxyl group and beta to another one (72-76, 723, 128, 182, 785, 797, 221, 222, 246), and in some other organic acids such as dihydroxymaleic acid (68). It is also considered important in the catalytic hydrolysis of amino acid esters (79, 129, 244) and amides (160); the hydrolyses of Schiff bases (56, 57, 59),diisopropylphosphorofluoridate (240), and phosphate esters (32, 150-152, 233).
The type of effect which is invoked here can be clearly seen in an example from the work of Meerwein. He showed how coordination facilitates the ionization of a
TABLE 1 1 1 .
hydrogen from the donor atom in a complex. Thus, the complex of BF3 and acetic acid is an acid comparable in strength to sulfuric acid. This particular effect can be used for synthetic purposes. Meerwein (108) showed that alcoholic groups which are normally unreactive toward diazomethane could be rendered reactive : CHzh-2 ROH A1(OR)3 -+ H[Al(OR),] .41(OR)3 ROCH3 The essential role of coordination in processes such as this is to provide an intermediate which can form an activated complex with a much smaller requirement for activation energy. The mechanism proposed by Kroll (129) for the catalytic hydrolysis of amino acid esters is typical in many respects of the way in which the ionic charge of the metal is assumed to influence the course of the reaction. It provides for the attack of a coordination compound rather than the simple substrate:
-+
+
REACTIONS WHERE COORDINATION ALLOWS THE LIGANDS AND A T H I R D REACTANT TO COME TOGETHER MORE EASILY
Reactants
Metal Ions
Products
Reaction Type
Reference
Fe and Cu chelates
Oxidation
1
cu+2
Oxidation
I
Zn+z
Oxidation
Tetrazolium salts
63
Fe+2
Oxidation
Tetrazane (dimerization)
64
Pyrogallol and phloroglucinol
Copper complexes with amines such as isopropanolamine
Oxidation
Allylic chlorides
CueClz
Hydrolysis
Alcohol
a-Ketoglutarate
C O ' ~ ,and Mnf2
Oxidation
COz, succinate, malate, oxalate, and acetate
7 99
Decarboxylation
Diacetyl and acetone
754
Dihydroxyphenylamino acids and their derivatives 2 : 3, 2 :4, and 2 :5 dihydroxyphenyl alanine 3 :4 Dopa methyl esters and amides DL-leucyl DL 3 :4 dihydroxyphenyl alanine 3 :4 Dihydroxyphenylacetic acid +Phenylenediamine Formazyl compounds 1-Hydrazine-phthalazine
a-Acetolactic acid Hydroxylamine
1
~
I
Fe+3,
CU'~, Al+S
cui2
o-Diphenols formed which undergo ring closure to give indole derivatives
I49
62
724
Q5
Oxidation
771 703
Hydrazine
Fe +2
Oxidation
Ascorbic acid
FeEDTA
With He02
79
Adrenaline, linoleic acid, and ascorbic acid
Fe( 1I)EDTA
Oxidation
67
Oxidation
Salicylate
I
Fe(II1)EDTA
Secondary amines
j
cuciz
Alkylcarbamates
28
CUClZ
N,N'-Disubstituted ureas
30
Primary and secondary amines
I I
80
X,N'-Disubstituted amines
27
Aromatic amines
Cu'2 complexes
Oxidation
2-Amino-5-anilinoquinone ani1
67
Primary and secondary alcohols
C U + as ~ primary or secondary amine complex
Oxidation
Aldehyde from primary alcohol Ketone from secondary alcohol
29
CU(I1)
Oxidation
Liquid amines
4-Hvdroxvbenzoxazole 20
~
cuc12
I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
66
R
O
TABLE IV.
I / / M+2 + H2N-C-C-OR‘
EXAMPLES
O F CLASS 2 REACTIONS
Example
I
H
H2N
0
Galactouronic acid Oxaloacetic acid
\M/.2
c--
+
R I H-c-&-oR/ 1 HiN,+,O
11
M -OH]
Reference
Decarboxylations
I+OH-
249 59, 72-75, 728, 173, 220, 243, 246 227, 222 62, 63, 197, 237, 232 66, 67, 207-209 786 123
Dimethyloxaloacetic acid Acetone-dicarboxylic acid Pyruvic acid Dihydroxytartaric acid Beta keto acids
Hydrolyses of phosphates and phosphate esters
This ligand polarization must be present in all complexes. I t presumably is important for reactions such as some Friedel-Crafts reactions, the Fries reaction, and many other examples treated below in other classes. Note that while this effect is always present, it need not always play a leading role in the catalytic process. Since polarization of the donor atom is a general phenomenon which accompanies coordination, its effects are to be seen in a large number of examples in an indirect way. One such example may be found in the catalytic splitting of ethers by Lewis acids such as zinc chloride, aluminum chloride, stannic chloride, and related compounds. An early example is (20): CzH50CzH5
ZnCll
C2H6Cl
+ ClZnOCZH5
and another is the corresponding reaction with the dimethyl ether of anthraquinone (189). The catalytic effects of mercury(I1) on the hydrolysis of halides is another reaction in this group (224). The catalytic action of metals on the hydrolysis of pyrophosphate is also probably in this class (40),as is the catalytic hydrolysis of fluorophosphates and their derivatives (87). More recent discussions of this effect are available (741, 243) and the name “super acid” catalysis has been applied to such cases by Westheimer. This is somewhat misleading. Metal ions allow one to carry out what are essentially acid catalyzed reactions under basic conditions by such a process, but when comparative data are available it is found that mole for mole, such metals are sometimes less effective as catalysts than the proton. In general, the proton exerts a much more profound polarization effect on a donor molecule than does a metal ion. However, the commercial applications of replacing hydrogen ions with metals to carry out acid catalyzed reactions of compounds not stable in acidic solution should be quite numerous. Further examples are given in Table IV. Reactions of Class 3
There are a number of instances where a ligand can exist in two or more tautomeric forms, only one of which forms stable chelates. In these cases the reactions of the complexed ligand are those characteristic of the form of
Acetyl phosphates Ethyl phosphates and related compounds Thiophosphinic esters Sarin and D F P (diisopropyl phosphorfluoridate) DFP Sarin Summarizing review ATP (adenosine triphosphate) Phosphate esters (and 32 references to other work) ATP with Mg+2 A T P with MgEDTA (ethylenediamine) tetraacetic acid Pyrophosphate hydrolysis
125 40 7 76 46 240 742 233 243 6 187 70 706
Deaminations Pyridoxamine, amino acids Cu-glycine complexes Cu-amino acid complexes Cu-alanine complexes Cu complexes with polyamines Alanine Acetylacetone and derivatives Deamination of serine Amides and amino acids catalyzed by rare earth ions
7 72 7 76 178 7 77 7 79 126 76 161 7
Hydrolyses of Schiff bases Bis( 2-thiophena1)ethylenediamine 6-Succino amino purine and derivatives Pyridoxal -alanine Schiff bases and ethylenediamine complexes with Cu( 11)
56, 57, 59, 84, 85
5 79, 58, 59, 65 109
Ester hydrolyses Glycine esters Glycine amide Potassium ethyl oxalate, malonate, adipate, and sebacate Glycine-containing peptides Amino acids and sulfur-containing amino acid esters Rare earth ions as catalysts Synthesis of hydroxamates
79 760 708 722 244 8 157
Amide hydrolyses Peptidase action on amides C~+~-nitriloacetic acid and triamide Rare earth ion catalyzed hydrolyses of dipeptides Amides
70 795 9 194
the ligand present in the complex, modified by the stereochemical and electronic changes accompanying coordination. This is seen in the bromination of ethyl acetoacetate (783),in which the first step of the reaction is catalyzed by cupric ions which stabilize the enol form of the compound upon coordination. The same general VOL. 5 5
NO. 9
SEPTEMBER 1963
21
H
H
I I
C"
2Hfi-CHrCHrCHrC-COOH ornithine
NHz
+I
*
HdG-CHrCHrCHr
A -c)
0
,,
\ o \ eoodiated/HrN\ unreactive amino L H Z \ O
unwardinated rcaetivc
EQUATION 1
Hfi-CHrcHrcHrA-L
I
nI
N
H
H
I
/
Hsk
O \
NHrCNH-CHrCHrCH-C-C
0 II
H O NHG-NH-CHrCH
II
I
0 citrulline
NHI
O
\ /
+ CuS c HB -
A F I r &-&-OH
r (urea)
HzNC~H-CH,-cHrCH+LL
II
H
I
H I
0
6
+ ?.€IEQUATION + 2
features may be seen in the numerous reactions of betadiketones and their complexes. In these cases (77, 4745, 57, 727, 209, 277, 238) the observed reactions are essentially those of the enol form of the ligand. The conscious use of this principle in the preparation of a m dyes may be traced back in the literature for over sixty years. In the c a m cited, phenols were coupled with diazonium salts. Here it is the phenolate anion which is the literal reactant, and this can be stabilized by coordination to a metal ion. The complex which is formed undergoes diazo coupling with less accompanying oxidation than does the free ligand. When the coupling is complete, the metal can be removed and the dye recovered in good yield (722). Further examples of this class are collected in Table V. TABLE V.
EXAMPLES
OF
CLASS 3 REACTIONS
Rmtion
Substituted @-diketonesfrom wppcr wmplacs of @diketonesand nitmbenmyl chlorides Reparation of thioacetyl and benzoyl cthm Halogenation of @-diketonewmplexea Substitutionson acetoacetic acid Bromination of ethyl acetoacetate and related wmpaunda Acylation of a wordinated oxime group
Refmmc.
11
238 42, 772
767, 168 727, 183, 784 127
In particular, the large scale application of the third type of reaction listed in the table should be very attractive as it allows the preparation of many halogen derivatives of beta diketonea which can be obtained only in a low yield by direct reaction. 22
INDUSTRIAL A N D E N G I N E E R I N G CHEMISTRY
Reactions of Closs 4
At least some of the reactions of a ligand will be modified by the steric changes which accompany coordination. In many cases, coordination will either prevent or enormously retard reactions which involve the atoms linked directly to the metal ion. Hesse (702) cites as examples of this the resistance to oxidation found in the complexes of boron trialkyls and ammonia (RxB:NHx) and the greatly decreased sensitivity of FxB:NHa to hydrolysis when compared to BFx. This same principle can also be put to use in the design of new preparative methods. One such case is the synthesis of citrulline from ornithine via the inner complex salt which copper forms with ornithine. Thus chelate formation removes one of the reactive amino groups of ornithine from the reaction and allows the desired reaction site to be the sole reaction site. This synthesis (735, 736) is now used on a small s c a l e i t would appear to be of interest in production of amino acid derivatives (Equation 1 above). The same principle has been used in a number of other syntheses involving both aliphatic and aromatic ligands. The effectivenessof the masking is to a very considerable extent dependent upon the specific reaction as well as the stability of the complex. For example, the masking of the amino group of alpha amino acids by chelate formation with copper(I1) is effective in preventing the acetylation of this group (779, 773, its reaction with fluorodinitrobenzene (788), urea (135, 736), carbobenzoxyl chloride (175),or 0-methylisourea (236). In these cases the masking may be utilized for synthem which involve a reactive but unchelated group in the molecule. Similar studies of nickel dimethylglyoxime
I
show that masking may be dective toward some reagents but not toward others. Thus, in this complex, the oxime groups do not react with phenylisocyanate (2?4), but the complex is disrupted by acetyl chloride (727). I n the case of nickel(I1) complexes with substituted dithiooxamides, acetylation of a group not involved in the chelate ring can be effected. Thus half of the free hydroxy groups in N,N’-bis(2-hydroxyethyl)dithiooxamide &el(II) can be replaced by an acetylation reaction with acetic anhydride (7 70). The occurrence of masking is quite difficult to predict for it is determined by both the stereochemistry and the lability of the complex. Sacconi (207) demonstrated how NHI could be replaced by OH- in dihydrazone complexes. This is a reaction involving small ligands which are exchanged in a square planar complex. He also showed that a much larger group could attack such complexes. Thus when b.(salicylaldehyde)nickel(II) is treated with hydrazides of the type N H Z ” C 0 (CH&,R, one gets ultimately the dihydrazone complex (zo2). Other reactions of this type have also been reported by Sacconi (203-206). In the square planar complexes of copper(I1) with Schiff bases, the C==N bond can add methanol without an apparent mpture in the d i t e bonds (84). The proximity of the reactive center to the metal ion also has an d e c t which is somewhat difficult to predict. Thus, the saponification of coordinated cyanide groups has long been known to be v a y much more difficult than that of free cyanide or free isonitrile (8&94, 701, 107, 154). The reactions of coordinated amines indicate that the nitrogen may not be so thoroughly inactivated. Kukushkin repom that the nitrogen-
I1
hydrogen bond in platinum(1V) complexes can be transformed into a nitrogen-chlorine bond by treatment with chlorine, and the nitrogen remains coordinated to the platinum (737-733). Similarly, the reactions of sulfur, cited earlier, indicated that its reactivity may be affected very little by coordination. With aromatic compounds the use of coordination to mask reactive groups has been used, perhaps unconsciously, for over sixty years. It is hown that coordination of polyphenols allows them to be diazotized with a much smaller amount of concurrent oxidation than is found for the free ligands. This has been utilized in the preparation of diaw compounds of many types (745, 219-222). As an example, the reaction of 4-diiazodimethylaniline with chromotropic acid results in a 58% yield of the dye in which coupling has occurred at the 4 position of chromotropic acid (1,8-dihydroxynaphthalene-3,6ddonic acid). By using the calcium complex, the yield may he increased to 90% (740). When the coordination is to a donor atom external to the aromatic system, there is no change in the orientation for such substitution reactions (225). The effectiveness of the masking process is dependent on the stability of the complex which is formed and the tenacity with which susceptible reaction sites are held in the complex. In the case of the isonitrile complexes of iron, it is found that these undergo none of the typical reactions of isonitriles with water, dilute acids or bases, or halogens (8&94, 701, 707). Thus, the usual reaction of benzyl isonitrile with a halogen is addition to the isonitrile carbon. In the.benq-1 isonitrile ligands in these complexes, however, the aromatic rings undergo substitution and the isonitrile function is masked. V O L 5 5 NO. 9 S E P T E M B E R 1 9 6 3
23
--t
EQUATION 6
0
CHIOH
R
R EQUATION 7 40
Py ridoxaminc
Reactions of Class 5
I n at least some instances, the formation of a complex, or more usually of a chelate, may result in the stabilization of a compound which would otherwise break down into its constituents. In these instances, the new coordinate bonds seem to furnish the additional s t a b i i t i o n needed to hold the compound together. The behavior of many Schiff bases is an excellent illustration; that formed by salicylaldehyde and ammonia furnishes one of the older examples ( 7 9 0 ) . Subsequently, other examples have been noted (753). I n this situation, the hydrolysis of the Schiff base is prevented by the precipitation of an insoluble metal chelate, Equation 2, page 22. It must be noted that in many instances, coordination has been found to accelerate the hydrolysis of Schiff bases (78, 79, 753,245). I t is quite possible that metal ions*can catalyze the equilibrium between the Schiff base and the reactants which form it so that the stabilization or destabilization which is observed will be determined by the relative concentrations and solubilities of the species involved. In recent years several carboxylation reactions have been studied by Stiles and his collaborators (223). An example is the carboxylation of ketones which possess enolizable methyl or methylene groups in the presence of magnesium methyl carbonate (MMC), Equation 3, page 23. 24
I N D U S T R I A L A N D ENGINEERING C H E M I S T R Y
The same kind of reaction was used by Stiles to prepare nitroacetic acid. Such a method of synthesis is certainly suitable for large scale preparations, and may have commercial promise (Equation 4, page 23). Another example of this sort is the preparation of Schiff bases-as the nickel(I1) chelates which are quite insolubleby the interaction of alpha diketones and beta mercaptoethylamine. This reaction takes quite a different course when no nickel is present (230). Class 5 Reactions Involving Internal Reanangement
Instances where coordmtion allows an internal rearrangement of the ligand are of considerable interest. Most of the examples considered below involve Schiff bases. If the copper(I1) chelates of Schiff bases derived from an optically active amino acid ester and salicylaldehyde are prepared, rapid racemization is found to mcur (797). This is postulated to proceed thmugh a tautomeridshift assisted by coordination, as shown in Equation 5, page 23. The asymmetry of the optically active carbon is lost in structure I1 and the regeneration of structure I would lead to equal amounts of both enantiomorphic forms. The catalysis, by metals, of transamination and transesterification reactions probably falls in this same category (239). Thus transsterification reactions of compounds such as I may be effected by merely retluxing the complex in an alcohol, while transaminations may be
effected by the same operation with an amine. The mechanism proposed by Verter and Frost is different from that suggested by the earlier workers and may be illustrated by a typical case in Equation 6. The second methyl group is released in another process of the same type. The transamination and deamination reactions involving a n amino acid, pyridoxal, and a metal ion are related to these and involve what is presumably a n internal tautomeric shift, such as that proposed by Pfeiffer which is then followed by hydrolysis (766, 277) as shown in Equation 7, page 23. If another alpha keto acid is present, R’COCOOH, it can enter similar intermediates and be transformed into R’CH(NH2)COOH. The synthetic possibilities of these reactions are considerable even though the mechanisms are still the subject of some dispute. Further examples of reactions of this class are given in Table VI. TABLE VI.
REACTIONS INVOLVING PYRIDOXAL Reaction
1
Reference
cupric ion. The polarization of the ligand by the cupric ion occurs under conditions favorable to the complete transfer of the electron to the copper to produce copper (I) and H A ’ . This is the rate determining step. Both of these species are then oxidized by molecular oxygen. The effect of adding chelating agents indicates that at least two coordination sites must be available for the critical electron transfer step (33). Thus EDTA can completely prevent the reaction from following its normal course by simply preventing the ascorbate ion from occupying two adjacent coordination sites. The chelates with dipyridyl and orthophenanthroline seem to exhibit some of the same peculiarities in this system that have been noted previously in simpler cases : Electron transfer is apparently possible through the aromatic system of the chelate so chelation does not result in a complete stoppage of the reaction. Some of the reactions of this class which have been reported are listed in Table VII. This list contains only a very small fraction of the reactions which are in the literature. Such reactions provide a very convenient means of oxidation at mild conditions and would appear to have commercial possibilities.
Transaminations using vitamin Be
162
Racemizations of amino acids
780
Cleavage of hydroxamic acids
763, 164
Transaminations using glyoxilic acid
165
Reaction
General mechanism for vitamin BEcatalyzed reactions
166
Decomposition of diazoketones
Reactions using analogs of vitamin BE Pyridoxal catalyzed reactions with metal ions Alpha-beta elimination reactions of serine-3 phosphate and related compounds Cleavage of alpha-methyl serine and alpharnethylol serine
1
TABLE V I I .
EXAMPLES OF CLASS 6 REACTIONS
1
Various oxidations 117
146
Reference 96 2
Oxidations with ferric ion
48
Phenol oxidation via copper( 11)
66
747 Reactions of Class 7 748
Reactions of Class 6
In many cases coordination is a prerequisite to the facile transfer of electrons as it opens up many mechanisms by which electrons may be transferred (69). Unfortunately, most of the systems whose mechanisms have been elucidated in some detail are rather different from the typical catalytic processes. Nevertheless, the general conditions favoring the electron transfer process are known and are given in detail by Fraser (69). One condition is that the reaction path should not require the close approach of two ions of similar charge. This is usually the condition which determines the mechanism of electron transfer between complex ions. Most of the catalytically interesting reactions involve the oxidation of a neutral or negatively charged organic species by a metallic cation. In these reactions the cation usually extracts an electron from the ligand and it is then subsequently oxidized by oxygen to regenerate the oxidized form. There are an enormous number of reactions which may be of this type and many autoxidations catalyzed by copper(II), iron(I1) and (111), and similar ions will probably be found to be of this type. A reaction of this type which has been studied in detail is the cupric ion catalyzed autoxidation of ascorbic acid (33, 156). Here the mechanism seems to involve a complex between the ascorbate ion, HA-, and the
Instances where the stereospecific nature of the coordination act is critical in determining the course of a reaction are not numerous, though the phenomenon has been known for some time. A long series of studies of such reactions has been published by Bailar and his students-e.g. (7, 4, 77)-and these contain citations to much of the earlier work. An extensive series of very recent studies is that of Dwyer and his coworkers (52-55) and these also contain most of the previous literature. It has been recognized for some time that when a metal ion forms complexes with an optically active ligand, not all possible complexes can be prepared. Thus cobalt(II1) will react with a mixture of the d and 1 forms of a bidentate ligand to give the compounds Co(Z11) or Go(&), but rarely complexes in which the d and I forms of the ligand are present in the same coordination sphere. The use of the resolved ligand in a pure form is also found to lead to one of the possible forms of the complex with a certain degree of preference. Thus Dwyer and his coworkers found that the reaction D
Co(1-propylenediamine)3 + 3 + L Co(1-propylenediamine)3 + 3
had an equilibrium constant of 5.75 and hence a standard free energy change of - 1.02 Kcal./mole. In many of the cases cited by Dwyer, the preponderance of one isomer, isolated as a solid salt, is more striking. When this same pair of complex ions is isolated as the hydrated VOL. 5 5
NO. 9
S E P T E M B E R 1963
25
bromides, one obtains only D Co(d-pn)3Br3.2Hz0 from d-propylenediamine and L Co(I-pn) 3Br3 2H20 from 1-propylenediamine. When the iodides are isolated, both D and L forms of each complex ion may be isolated as a solid salt. The effort to find differences in the behavior of enantiomorphs has lead to the study of the oxidation of some racemic mixtures of amino acids in the presence of optically active complex salts (213, 274). It has been reported that one isomer of the racemic mixture is more rapidly oxidized by atmospheric oxygen in the presence of a n optically active complex. The effect, if present, is apparently small as Pugh (798) obtained results which were not in agreement with these results. Bailar ( 3 ) suggested that a possible mechanism for such a process might involve a complexation reaction in which one antipode of the mixture is preferentially coordinated. While such processes are presumably responsible for some of the stereospecificity found in some metal activated enzyme systems, they have rarely been used for more typical chemical reactions (other than as a possible resolution procedure). For labile complexes, the degree of stereospecificity which is observed in the coordination act is far less pronounced in its exclusiveness [Bennett, private communication (20)1. For such systems as have been studied, the evidence indicates that only by careful design of the metal-ligand combination can we obtain a useful template which functions in this manner. Reactions of Class 8
There are a few ~7ellauthenticated cases where coordination has the effect of making an over-all reaction either favorable or more favorable from a thermodynamic viewpoint than it would be otherwise. T h e free energy change resulting from coordination then makes the total free energy change of the ligand-forming reaction more favorable. This class is related to Class 5 but shows some significant differences. The chief examples in this class are those in which aluminum chloride, acting as a Lewis acid, forms stable complexes with an aromatic species and subsequently or simultaneously catalyzes a substitution reaction on the ring. Since aluminum chloride also catalyzes aromatic rearrangements, the final products are often equilibrium products. These are quite different from the kinetically determined products in many reactions. A very obvious example of this type of reaction may be seen in the Fries reaction (24),where the amounts (relative) ofortho and para substitution are determined by the temperature at which the reaction is carried out. There are some examples which are even more striking. The Gattermann-Koch reaction proceeds via a path involving aluminum chloride, an aromatic hydrocarbon (such as benzene), carbon monoxide, and hydrochloric acid (47). The product, an aldehyde (such as benzaldehyde) forms a complex with aluminum chloride present. This complexation helps in making the overall reaction one with a more favorable free energy change (50). Another reaction which is apparently in this category is the Kolbe (and the Kolbe-Schmidt) reaction in which phenolate salts are carboxylated at tempera26
INDUSTRIAL A N D E N G I N E E R I N G CHEMISTRY
tures above 100’ C., through a chelate intermediate (84, 144, 275). Presumably the formation of this chelate is an important part of the mechanism by which the thermodynamically favored product is formed. The general character of this reaction indicates that the normal products (obtained usually at 120-140’ C.) are the most stable compounds in the reacting system. Although the Gattermann synthesis is similar in some respects to the Gattermann-Koch reaction, the mechanism is quite different. In the Gattermann reaction, complexation favors the formation of a reactive intermediate of composition AlC13.2HCN. HC1, but whose structure is probably ClCH=NCH=NH AICIP. This, in turn, attacks the aromatic ring t o produce a final product which is still complexed with aluminum chloride. Hydrolysis of this results in the aromatic aldehyde. Here, coordination stabilizes successive products. As a rule of thumb, then, one may say that when reactants which form only weak complexes or none a t all interact to give a product which forms stable complexes, then coordination may be used to stabilize the product and perhaps increase the ease with w-hich it may be isolated. Coordination may be used here without having any profound effect on the kinetics of the reaction which forms the product. SUMMARY
The number of ways in which coordination may effect the course of a ligand reaction has been divided into eight classes. In general, when either the reactants or the products (or both) form coordination compounds the possibility exists for utilizing known phenomena for increasing the yield or the purity of desired products. It is safe to say that the number of such examples presently known is but a small fraction of those where coordination may be used to advantage. BIBLIOGRAPHY (1) Archer, R. D., Bailar, J. C., Jr., J . Am. Chem. Soc. 83, 812 (1961). (2) Bacon, R. G. R., Chem. Ind. LondoiL 1952, 19. (3) Bailar, J. C., Jr., Chem. Reo. 19, 82 (1936). (4) Bailar, J. C., Jr., Jonassen, H. B. Gott, A. D., J . Am. Chem. SOC.74, 3131 (1952). (5) Baddiley, J., Buchanan, J. G.?Stephenson, J . E., Arch. Biochem. Biophys. 83, 54 (1959). (6) Bamann, E., Riehl, J., Sicolai, R., Biochem. 2.328,12 (1956). (7) Bamann, E., Trapmann, H., Rother, A., ivuturwissenschaften 44, 232 (1957). (8) Bamann, E., Steber, M., Trapmann, H., Braum-Krasncy, I., Ibid.,44, 328 (1957). (9) Bamann, E., Trapmann, H.: Rother. A , , Ber. 91, 1744 (1958). (10) Bamann, E., Hass, J. G., Trapmann, H., Nuturwissenshaiten 46, 73 (1953). (11) Barry, W. J., J. Chem. SOC.1960, 670. (12) Baurath, H., Ber. 20, 2719 (1888). (13) Bawn, C. E. H., Jolley, J.,Proc. Roy. SOC. A237, 297 (1956). (14) Beck, M. T., J . Inorg. N u d . Chem. 15, 250 (1960). (15) Beck, M. T., Kling, O., Acta Chem. Scand. 15, 453 (1961). (16) Belford, R. L.: Martell, A. E.. Calvin, M., J . Inorg. AVucl. Chem. 2, 11 (1956). (17) Ibid., 5, 170 (1958). (18) Ibid., 14, 173 (1960). (19) Bender, M. L., Turnquest, B. it’.; J. .4m. Chem. Soc. 79, 1889 (1957). (20) Bennett, W., State University of Iowa, private communication. (21) Berger, H., Bickel, A. F., T r a n s . Faraday SOG.57, 1325 (1961)
(22) Blaise, E., Compt. Rend. 139, 1211 (1904). (23) Zbid., 140, 661 (1905). (24) Blatt, A. H . , “Organic Reactions” 5, 290, Wiley, New York, 1949. Chim. 74, 937, 1021, (25) Brackman, W., Havinga, E., Rec. TTQV. 1070, 1100, 1107 (1955). (26) Brackman, W., “International Conference on Coordination Chemistry,” London, Spec. Publication #13, The Chemical Society, London (1959). (27) Brackman, W. (to Bataafsche Petroleum Maatschappij, N.V.), Dutch Patent 94,612 (see C A 55:22343i). (28) Zbid., 94,613 (see C A 55: 22345e). (29) Brackman, W. (to Shell International Research, Maatschappij, N.V.), Brit. Patent 868,460, (see C A 5 6 : 1 4 3 4 ~ ) . (30) Brackman W. (to Shell Development Co.), U. S. Patent 2,883,426. (31) Bronsted, J. N., Livingstone, R., J . Am. Chem. SOC.49, 435 (1927). (32) Butcher, W. W., Westheimer, F. H., Zbid., 77, 2420 (1955). (33) Butt, V. S., Hallaway, M., Arch. Biochem. Biophys. 92, 24 (1961). (34) Calvin, M., Trans. Faraday Soc. 34, 1181 (1938). (35) Calvin, M., J . Anz. Chem. SOC.61, 2230 (1959). (36) Calvin M., Pon, N. G., J . Cellular Comp. Physiol. 54, Supplement 51 (1959). (37) Campbell, H., Eley, D. C., Nature 154, 85 (1944). (38) Chalk, A. J., Smith, J. F., Zbid., 174, 802 (1954). (39) Chatt, J., Duncanson, L. A., J . Chem. SOC.1953, 2942. (40) Cherbuliez, E., Leber, J. P., Stucki, R., Helv. Chim. Acta ’ 36, 537 (1953). Goldbv, G. D.. Trahanovskv. 141) Collman. J. P.. Moss. R . &4.. ,, ‘ S., Chem‘. Znd. London 43, 1213 (1960):’ (42) Collman, J. P., Moss, R. A., Maltz, H., Heindel, C. C., J . Am. Chem. SOC. 83, 531 (1961). (43) Collman, J. P., Kittleman, E. T., Ibid., 83, 3529 (1961). (44) Collman, J. P., Marshall, R . I., Young, W.L., 111, Goldby, S. D., Inorg. Chem. 1, 704 (1962). (45) Collman, J. P., Kittleman, E. T., Zbid., 1, 704 (1962). (46) Courtney, R. G., Gustafson, R. L., Westerback, S. J., Hyytianinen, H . , Charbarek, S. C., Martell, A. E., J . Am. Chem. SOC.79, 3030, 3036 (1957). (47) Crounse, N. H.: “Organic Reactions” 5 , 290, Wiley, New York, 1949. (48) Dainton, F. S., Chem. SOC.,London, Spec. Publ. #18, 47 (1954). (49) Denisov, E. T., Emanuel, N. M., Russ. Chem. Rev. 29, 645 (1960). 1949, 2613. (50) Dilke, M . H., Eley, D. D., J . Chem. SOC. (51) Djordjevic, C., Lewis, J., hTyholm, R . S., Chem. 2nd. London 1959, 122. (52) Dwyer, F. P., Garvan, F. L., J . Am. Chem. Soc. 81, 290 (1959). Zbid., 81, 1043 (53) Dwyer, F. P., Garvan, F. L., Shulman, .4., (1959). (54) Dwyer, F. P., Sargeson, A. M., Zbid., 81, 5269, 5272 (1959). (55) Dwyer, F. P., Garvan, F. L., Ibid., 83, 2610 (1961). (56) Eichorn, G. L., Bailar, J. C., Jr., Zbid., 75, 2905 (1953). (57) Eichorn, G. L., Trachtenberg, I. M., Ibid., 76, 5183 (1954). (58) Eichorn, G. L., Dawes, J. W., Zbid., 76, 5663 (1954). (59) Zbid., 78, 2688 (1956). (60) Eichorn, G. L., Dawes, J. W., Biochem. Biophys Acta 23, 417 (1957). (61) Engelsma, G., Havinga, E., Tetrahedron 2, 289 (1958). (62) Fallab, S., J . Inorg. Nucl. Chem. 8, 631 (1958). (63) Fallab, S., Erlenmeyer, H . , Helu. Chim. Acta 42, 1152 (1959). (64) Fallab, S., Walz, D., Ibid., 43, 540 (1960). (65) Fasella, P., Lis, H., Baglioni, C., Siliprandi, N., J . Znorg. Nucl. Chem. 8, 620 (1958). (66) Fernando, Q., Resnik, R., Cohen, T., J . Am. Chem. SOC. 83, 3344 (1961). (67) Flesch, C., Schuler, W., Meier, R., Helv. Chim. Acta 43, 2014 (1960). (68) Francke, W., Brathuhn, O., Ann. 487, 1 (1931). (69) Fraser, R. T. M., Rev, Pure Appl. ChPm. 11, 64 (1961). (70) Friess, E. T., Morales, M . F., Bowen, W. J., Arch. Biochem. Biophys. 53, 311 (1954). (71) Gott, A. D., Bailar, J. C., Jr., J . Am. Chem. Sot. 74, 4820 (1952). (72) Gelles, E., Pitzer, K. S., Ibid., 77, 1947 (1955).
6’.
(73) Gelles, E., Clayton, J. P., Trans. Faraday SOC.52, 353 (1956). (74) Gelles, E., J.Inorg. Nucl. Chem. 8, 625 (1958). 1958, 3673. (75) Gelles, E., Hay, R. W., J.Chem. SOC. (76) Gelles, E., Salama, A., Ibid., 3683, 3689. (77) Gibbs, W., Genth, F. A., Amer. J . Sei. 2, 241 (1857). (78) Goudot, A,, Comfit. Rend. 242, 1614 (1960). (79) Grinstead, R., J.Am. Chem. SOC. 82, 3464 (1960). (80) Zbid., 82, 3472 (1960). (81) Gustafson, R. L., Martell, A. E., J . Am. Chem. SOC.84, 2309 (1962). (82) Haggett, M. L., Jones, P., Wynne-Jones, W. F. D., Discussions Faraday SOC.29, 153 (1960). (83) Hamm, R. E., J . Am. Chem. SOC. 75, 5670 (1953). (84) Hales, J. L., Jones, J. I., Lindsey, Chem. Znd. London 1954, 49. (85) Halpern, J., “Advances in Catalysis,” Vol. XI, Academic Press, New York, 1959. (86) Halpern, J., J . Phys. Chem. 63, 398 (1959). (87) Harris, C. M., McKenzie, E. D., Nature 196, 670 (1962). (88) Hartley, E. G. J., Proc. Chem. SOC.26, 90 (1910). (89) Zbzd., 28, 107 (1912). (90) Ibzd., 29, 188 (1913). (91) Hartley, E. G. J., J . Chem. SOC. 97, 1066, 1725 (1910). (92) Ibzd., 101, 705 (1913). (93) Zbzd., 103, 1196 (1913). (94) Zbzd., 101 (1933). (95) Hatch, L. F., Ballin, S . G., J.Am. Chem. SOL.71, 1037 (1949). (96) Haupter, F., Pucek, A., Ber. 93,249 (1960). (97) Heldt, W. Z . , J.Znorg. Nucl. Chem. 22, 305 (1961). (98) Heldt, W. Z., J . Org. Chem. 26, 3226 (1961). (99) Heldt, W. Z . , J . Znorg. N u l . Chem. 24, 73 (1962). (100) Heldt, W.Z . , J . Org. Chem. 27,2604, 2608 (1962). (101) Heldt, W. Z . , “Advances in the Cheistry of Coordination Compounds,” S. Kirchner, ed., 321, McMillan, N. Y., 1961. (102) Hesse, G., “Katalyse durch Komplexbildung” in G. M. Schwab, “Handbuch der Katalyse,” Vol. VI, 68, Springer Verlag, Vienna, 1943. (103) Higginson, W. C., Wright, P., J. Chem. SOC.1955, 1551. (104) Hoare, D. S., Snell, E. E., Proc. International Symposium on Enzyme Chemistry, Kyoto and Tokyo, 2, 142 (1957). (105) Hock, H., Kropf, H., J.Prakt. Chem. 4, 14, 71 (1961). 81, 4461 (106) Hofstetter, R., Martell, A. E., J . Am. Chem. SOC. (1959). (107) Holzl, F., Monatsh, 48, 72 (1927). (108) Hoppe, J. I., Prue, J. E., J. Chem. Soc. 1957, 1775. (109) Hoyer, E., Naturwissenschaften 46, 1 4 (1959). (110) Hurd, R. N., DeLa Mater, G., McElheny, G. C., Pfeiffer, L.V., J . Am. Chem. SOC. 82,4454 (1960). (111) Ikawa, M., Snell, E. E., Ibid., 76, 653 (1954). (112) Zbid., 76, 4900 (1954). (113) Joy, I. K., Orchin, M., 2. Anorg. Allgem. Chem. 305, 236 (1960). (114) Kaufmann, 0. (to Badische Anilin und Soda-Fabrik), Ger. Patent 889,196. (115) Zbid., 893,699. (116) Ketelaar,. J. A. A., Gersman, H. R., Beck, M. M., Nature 177, 392 (1956). (117) .Kharasch, ‘M. S., Seyler, R. C., Mayo, F. R., J . Am. Chem. SOC.60, 882 (1938). (118) Kinoshita, K., Bull. Chem. SOC.Japan 32, 777, 780, 783 (19 59). (119) Klement, R., Ber. 66, 1312 (1933). (120) Klotz, I. M., Loh Ming, W. L., J . Am. Chem. Soc. 76, 805 (1954). (121) Kluiber, R . W., Zbid., 82,4839 (1960). (122) Koltun, W. L., Fried, M., Gurd, F. R. N., Zbid., 82, 233 (1960). (123) Kornberg, A., Ochoa, S., Meller, A. L., J. B i d . Chem. 174, 159 (1948). (124) Korpusova, R. D., Nauchn. Dokl. Vyyshei Shkoly Khim. i Khim. Tekhnol. 1, 94 (1958). (125) Koshland, D. E., J.Am. Chem. SOC. 74, 2286 (1952). (126) Krause, H. W., Ber. 92, 1914 (1959). (127) Krause, R. A., Jicha, D. C., Busch, D. H., J . Am. Chem. SOC.83, 528 (1961). (128) Krebs, H. A., Biochem. J . 36, 303 (1942). (129) Kroll, H., J. Am. Chem. SOC.74, 2036 (1952). (130) Kuhn, R., Meyer, K., Naturwissenschaften 16, 1028 (1928). (131) Kukushkin, Y . N., Zh. Neorgan. Khim. 2, 2371 (1957).
(Continued on next page) VOL. 5 5
NO. 9
SEPTEMBER 1963
27
(132) Zbid.,4, 2460 (1959). (133) Ibid.,5 , 1943 (1960). (134) Kurtz, A. C., J . Biol.Chem. 180, 1255 (1949). (135) Kurtz, A. C., Am. J.Med. Sci.194,875 (1937) (136) Kurtz, A. C., J . Biol. Chem. 122,447 (1938). (137) Kuznetsov, V. I., Nemodruk, .A4. A:, Sbornik Statei Obschei Khim. 2. 1378 (1953). (138) Kuznetsov, V. I., J. Gen. Chem. C’.S.S.R., Suppl. (11) 1378 (1953). (139) Kuznetsov, V. I., J.Gen. Chem. U.S.S.R. 25, 117 (1955). (140) Ibid.,26, 3657 (1956). (141) Langenbeck, W., Ber. Deutsch. Akad. 357 (1960). (142) Larsson, L., Acta Chem. Scand. 12, 1226 (1958). 1955, 2936. (143) Leden, I., Chatt, J., J.Chem. SOC. (144) Lindsey, A. S., Jeskey, H., Chem. Reu. 57, 583 (1957). (145) Longenecker, J. B., Snell: E. E., Proc. 2Vatl. Acad. Sci. 42,221 (1956). (146) Longenecker, J. B., Snell, E. E.: J. Am. Chem. Soc. 79, 142 (1957). (147) Longenecker, J. B., Snell, E. E., J . Bid. Chem. 225, 409 (1957). (148) Longenecker, J. B., Ikawa, M., Snell, E. E.: Ibid.,226,663 (1957). (149) Losse, G., Barth, A . , Langenbeck, IV.: Ber. 95, 918 (1962). (150) Lowenstein, J. M., Biochem. J.70,222 (1958). (151) Lowenstein, J. M., Biochem. Biophys. Acta 28, 206 (1958). (152) Lowenstein, J. M., Nature 187, 570 (1960). (153) McCarthy, P. J., Hovey, R . J., Ueno, K . , Martell, A. E., J . Am. Chem. Soc. 77, 5820 (1955). (154) deMan, J. C.: Rec. Trav. Chim. 78, 480 (1959). (155) Martell, A. E., Gustafson, R., Chaberek, S., “Advances in Catalysis,” Vol IX, 319, Academic Press, New York, 1957. (156) Martell, A. E., Calvin, M., “Chemistry of the Metal Chelate Compounds,” 389, Prentice-Hall, New York, 1952. (157) Meerwein, H., Ann. 455, 227 (1927). (158) Zbid.,484, 1 (1931). (159) Meisenheimer, J., Ber. 58, 1 3 (1925). (160) Meriwether, L., Westheimer, F. H., J . Am. Chem. Soc. 78, ‘ 5119 (1956). 1161) Metzler. D. E.. Snell. E. E.. J.Biol. Chem. 198. 353 11952). (162j Metzler: D . E., Snell, E.‘ E., J . .4m. Chem: Soc.‘74, 979 (1952) (163) Metzler, D. E., Longenecker, J. B., Snell, E. E., Ibid., 75, 2786 (1953). 1164) Zbid.. 76. 639 (1954). (165j Metzler,’ D. E., Olivand, J., Snell, E. E.: Zbid., 76, 644 (1954). (166) Metzler, D. E., Ikawa, M., Snell, E. E., Zbid.,76, 648 (1954). (167) Michael, A., Carlson, G. H., Zbid.,57, 159 (1935). (168) Zbid.,58, 353 (1936). (169) Mix, H., Z. Physiol. Chem. 315, 1 (1959). (170) Zbid., 325, 106 (1961). (171) Moews, P. C., Audrieth, L. F., J . Inorg. ~Vucl.Chem. 11, 242 (1959). (172) Morgan, G. T., Drew, H. D. K ~ J. , Chem. Soc. 121, 2456 (1922). (173) Nassal, M., Xature 163, 405 (1949). (174) Nemodruk, A. A,, J . Gen. Chem. U.S.S.R. 28, 1051 (1958). (175) Neuberger, A,, Sanger, F., Biochem. J . 37, 515 (1943). (176) Nyilasi, J., Acta Chim. Acad. Sci. Hung. 17, 265 (1958). (177) Nyilasi, J., Magy. Kem. Folyoirat 63, 192 (1957). (178) Zbid., 64, 474 (1958). (179) Zbid., 65, 341 (1959). (180) Olivard, J., Metzler, D. E., Snell, E. E., J.Biol. Chem. 199, 669 (1952). (181) Orgel, L. E., Quart. Rev. 8, 422 (1954). (182) Pedersen, K. J., J.Am. Chem. SOG.51, 2098 (1929). (183) Pedersen, K. J., Acta Chem. Scand. 2, 252 (1948). (184) Zbid.,383 (1948). (185) Zbid.,6, 285 (1952). (186) Zbid.,9, 1640 (1955). (187) Perry, S. V., Grey, T. C., Biochem. J.64, 184 (1956). (188) Peters, T., Biochem. Biophys. Acta 39, 546 (1960). (189) Pfeiffer, P., Ann. 398, 141 (1913). (190) Pfeiffer, P., Bucholz, E., Bauer, O., J. Prakt. Chem. 129, 163 (1931). (191) Pfeiffer, P., Offerman, I$:.> IVerner, H., Zbid., 159, 313 (1942). ~I
\
28
I
I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
(192) Pfitzner, H . , Baumann, H. (to Badische Anilin und SodaFabrik), Ger. Patent 900,600. (193) Pfitzner, H., Baumann, H., Angert.. Chern. 70, 232 (1958). (194) Photaki, I., Fallab, S., Erlenmeyer, H., Chzm. Chronzka Athens. Greece 23, 209 (1958). (195) Photaki, I , Fallab, S , Erlenmeyer. H , Helo. Chzm. Acta 39, 1484 11956). Postmus, C., King: E. L., J. Phys. Cheni. 59, 1216 (1955). Prue, J. E., J.Chem. SOC.2331 (1952). Pugh, C. E. M., Biochm. J . 27, 480 (1933). Rachis, J. J., Kalnitsky, G., J. B i d . Chem. 225, 751 (1957). Reihlen: H., Illig, R., IYittig, R., Ber. 58, 12 (1925). Sacconi, L., J. Chem. SOC.1954, 1326. Sacconi, L., J . Am. Chem. Soc. 74, 4503 (1952). Sacconi, L., Gazz. Chim. Ital. 83, 884 (1953). Zbid.,83, 894 (1953). Sacconi, L.: 2. Anorg. Allg. Chem. 271, 176 (1953). Ibid.,275, 249 (1954). Schellenberger, A,, Podany, E.: Ber. 91, 1781 (1958). Schellenberger, A,, !$:inter: K., Zbid.. 92, 793 (1953). Schellenberger, A,, 2.Physiol. Chem. 309, 16 (1957). Schoberl, A., ”Handbuch der Katalvse.” G. M . Schwab, ed., Vol. VII,’ part 1, 494, Springer Verlag, Vienna; 1943. (211) Schonbrodt, R . , Ann. 253, 171 (1889). (212) Schwartz, C. W. (to Deutsche Gold- und Silber- Scheideanstalt vorm. Roessler), Ger. Patent 1,010,524. (213) Shibata, Y., Tsuchida, R., Bull. Chem. SGC.Jafian 4, 142 (1929). (214) Zbid.,6, 120 (1931). (215) Shilov, E. A , Smirnov-Zamkov, I. V.: Matsovskii, K . I., Lrkrain. Khim. Zhur. 21, 600 (1955). (216) Smidt, J., Hafner, !V.: Jira, R., Sieber? R.:Sedlemeyer, J.? Sabel, A,, Angew. Chern., International Edition 1 , 80, (1960). (217) Snell, E. E., Physiol. Rev. 33, 509 (1953). (218) Snell, E. E., Special Lectures in Biochemistry, University College, London, 1 (1954-55). (219) Snell, E. E., Jenkins, W, T., J . Cellular Comnp. Physiol. 54, Supplement 1, 161 (1959). (220) Speck, J. F., J . Bid. Chem. 178, 315 (1948). (221) Steinberger, R., Sliestheimer, F. H.: J. A m . Chem. Soc. 71, 4158 (1949). (222) Ibid.,73, 429 (1951). (223) Stiles, M., Ann. .V. Y . Acad. Sci.88, No.2, 332 (1960). (224) Streitwieser, .4., Chem. Rev. 56, 621 (1956). (225) Taft, J. C., Jones, M . M., J . Am. Chern. Soc. 83, 4196 (1960). (226) Terenriev, A. P., Bull. Soc. Chim. Fraiice 35, 1164 (1924). (227) Terentiev, A. P., Mogilyanskii, Ya. D., Doklady dkad. N a u k . U.S.S.R. 103, 91 (1955). (228) Terentiev, A . P., Mogilyanskii, Ya. D.? J. Gen. Chem. U.S.S.R. 28, 2002 (1958). (229) Zbid., 31, 298 (1961). (230) Thompson, M . C., Busch, D. H., J.-Ira. Chem. SOC.84, 1762 (1962). (231) Toyama, O., Kubokawa, Y., Yoshida, Y.:J . Chem. Soc. Japan 74, 955 (1953). (232) Ibid.,75, 879 (1954). (233) Trapmann, H., Arzneimittel-Forsch. 9, 341, 403 (1959). (234) Tschugaev, L. A,, J . Chem. SOC.105, 2192 (1914). (235) Turba, F., Schuster, K . H.? A’aturwissenschaften 33, 370 (1946). (236) Turba, F., Schuster, K. H., 2. Physiol. Chem. 283, 27 (1948). (237) Uri, N., Chem. Rea. 50, 375 (1952). (238) Vaillant, V., Compt. Rend. 119, 647 (1894). (239) Verter, H. S., Frost, A. E., J . Am. Chem. Soc. 82, 85 (1960). (240) Wagner-Jauregg, T., Hackley, B. E., Lies, T. A., Owens, 0. O., Proper, R., Zbid.,77, 922 (1955). (241) Wang, J. H., Zbid.,77, 4715 (1955). (242) Weber, A., J . Bid. Chem. 234, 2764 (1959). (243) Westheimer, F., Trans. N . Y. Acad. Si.18, 15 (1955). (244) White, J. M., Manning, R.A., Li, S.C., J..4m’. Chem. Soc. 78, 2367 (1956). (245) WielAd, H.,Richter, D., Ann. 486, 227 (1931). (246) Williams, R. J. P., Nature 171,304 (1953). (247) Williams, R. J. P., “Special Lectures in Biochemistry,” University College, London, 43 (1954-55). (248) Zollinger, H., “Azo and Diazo Chemistry,” 299, Interscience. New York, 1961. (249) Zweifel. G., Deuel; H., Helv. Chim. Acta 39, 662 (1956). \
I
,
I
