TECHNICAL REVIEW
Silylation of Organic Chemic Charles A. Roth Chemicals, Tedinical Service ana ueveropmenc, UMUw n m n g ~ o r p . imuiiana, , ivli
..
.
. ..
4 0 ~ 4 ~
..
The use of trimethyl and dimethyl chlorosilones ond silazaries as silylating agents far organic chemicals i s cited. Physical and chemical properties of commercially av ailable silanes are given, and the chemistry of silylation i s briefly described. Examples token from the putdished literature are given where solubility and stability of organic materials are modified with these materialr. In addition, silyloting agents are a means of temporarily blo,cking organic functional groups COI ntainin,g active hydrogen. Several examples ore given of the use of silylotion as o process aid in the pharmac:eutica I industry, primarily i n the synthesis of penicillins.
:..
CHARLES A. ROTHi s a supervisor in the Technical Service and Development Department of the Resins and Chemicals Division at Dow Corning Corp., Midland, M I . He holds a BS in chemistry from the University of Michigan and an M S from Michigan State University. I n addition to silylation chemicals, his interests include organofunctional silanes, and he is the coauthor of several articles dealing with these materials. He i s a member of the American Chemical Society.
T h e application of the term silylation to the process of silylating organic and inorganic materials has grown to encompass all types of chemical and surface modification hy organosilicon chemicals (Plueddemann, 1969). For the purpose of this article, silylation is defined as the operation by which a trimethylsilyl (Measi--, TMS) group is substituted for an active hydrogen in an organic malecule. A related but less frequently occurring form of silyIation which should he included is where two organic species containing active hydrogen may be connected by means of a dimethylsilyl (-Me2Si-, DMS) linkage. Such chemical modification of organic materials by the substitution of T M S or DMS groups for active hydrogen causes marked changes in the chemical and physical characteristics of many compounds. Silylation Chemicals
The silicon chemicals used for silylation may be roughly divided into two classes: those used as analytical reagents 134 Ind. Eng. Chem. Prod. Rer Develop., Vol. 1 1 . No. 2, 1972
on.,.mn..n:nl --"l:".,+:-.." FI". A.. &l..l" an(r1 -".L4Y l l Y D r ..-..a uucu 111 I"""" '1'SC, L"......~.u.a. "pp..Ya"."LL" ""J'ation. Some of the materials used in analytical work will be briefly described later. The commercially available silylating agents are chlorosilanes or silazanes-that is, compounds containing either -Sic1 or =SiN= bonds. Table I presents informat,ion eoncernine the nhvsical nronerties of these
e
Some Theoretical Concepts
Silicon, like carbon, forms tetravalent compounds with tetrahedral geometry. With a covalent radius of 1.17 A for silicon compared t o 0.77 A for carbon and the fact that the Si-C bond distance is approximately 25% greater than the C - C bond, the Me&- (TMS) group is somewhat larger than the Me3C- or tert-butyl group, but there is a good deal more freedom of motion of the Me-Si bonds. With the exception of the Si-0 bond, the bond energies of silicon to nitrogen and sulfur are approximately equivalent to the carbon bonds to these elements. The silicon-oxygen bond energy is about 20 kcal/mol greater than for the carbonoxygen linkage (Table 11). A discussion of the mechanism of the reaction of chlorosilanes or silasanes with species containing active hydrogen is beyond the scope of this article. The reader is referred to some excellent texts (Eahorn, 1960; Sommer, 1965) on this subject. Chemistry of Silylation
Fundamentally, the T M S group may be introduced into an organic molecule by the following chemical reactions:
+
-€I MeBiC1 +-&Me, Active hydrogen species -€I
+ '/l(MeaSi)lNH --+
+ HCI or -SiMes
+ I/zNHa
A similar set of chemical reactions can be written, exemplify-
ing the method by which the dimethylsilyl group acts as a linkage between active hydrogens of two molecules. 2-H
+ MezSiClz +- S i M e p + 2HC1
Active hydrogen species 2-H
Table 1. Properties of Silylation Chemicals MeaSiCl
or
+ (Me2SiNH)3,4 +-.SiMesW + NH3
Generally, the reaction of chlorosilanes such as MeaiCl or MesSiC12 with organic materials is performed in the presence of a tertiary amine. Pyridine, trimethylamine, or dimethylaniline are suitable acid acceptors. Silazanes such as (Me&)?" when utilized as silylating agents may be used separately or in the presence of a n acidic catalyst (Langer e t al., 1958). The type of molecules capable of undergoing silylation must possess active hydrogen species in one form or another. Thus, organic chemicals containing hydroxyl, carboxyl, hydroperoxyl, enol, amine, amide, or thiol groups may be silylated. The ease of silylation is approximately in the order listed, although a comprehensive competition study of a complete system has never been investigated. Steric crowding of groups on the carbon atom adjacent to the active hydrogen groups is obviously of considerable importance. Thus, although alcohols may be more easily silylated than amides, tert-butyl alcohol is considerably more difficult to silylate than acetamide. The order of reactivity of the commercially available silylating agents toward a given active hydrogen species is somewhat more difficult to categorize. Generally, the silazanes such as (hIe3Si)zNH and (Me2SiNH)3,4 are slow to react, and heat (in most cases) must be applied to force the evolution of ammonia. If acidic catalysts are used, such as Me3SiCl or ammonium salts, the reaction proceeds much more readily. Base catalysis retards the reaction (Langer et al., 1958). Chlorosiltines such as lCle3SiCl and MezSiClz readily silylate many organic species. For obvious reasons amines and other basic materials cannot be silylated with these reagents except when tertiary amines are used as acid acceptors. I n practice, tertiary amines are almost always utilized with chlorosilanes owing to the corrosive and damaging nature of free HCI. The combination of a chlorosilane and a tertiary amine is a n extremely effective and rapid means of silylating most materials. Another rapid and efficient utilization of silylating agents is to combine a chlorosilane and a silazane reagent in such a fashion t h a t the nitrogen to chlorine ratio is unity. I n this type of a system, the one reagent acts as a n acid (or base) acceptor for the by-products of the other reagent, and only neutral ammonium chloride is formed as a result. For example, the combination of (Me3Si)zNH and MesSiCl in equimolar amounts (Speier, 1956) can be used in the following silylation of a n alcohol ROH: Jle3SiiXHSiMe3
+ RlesSiCl + 3ROH + 3MeaSiOR
+ NH&l
No additional acid acceptors or catalysts are necessary. Commercial Utility of Silylation
The utility of the silylation reaction is in the early stages of commercial investigation. Of historical interest and still probably the most widely known application for silylation is in the area of analytical chemistry. Specifically, silylation has been a n invaluable tool in the derivatization of many
[Me&i)zNH
MezSiClz
(MezSiNH)3.4'
Molecular weight, g/mol 108.7 161.4 129.1 ... Specific gravity, 25OC 0.86 0.77 1.07 0.89 Refractive index, 25°C 1.389 1.403 1.402 1.469 Flash point, O F 0 77 16 74 Boiling point, "C, 1atm 57.2 126 70.3 ... a An experimental product from the Dow Corning Corp. consisting of a 507' solution in toluene of cyclotri- and tetrasilazanes.
Table 11. Bond Energies (kcal/mol) for Si-X X=
Si C
and C-X
0
N
S
108 85.5
77 72.8
63 65
organic materials, allowing ready analysis by gas-liquid chromatography, mass spectrometry, and thin-layer chromatography. For such analytical processes, silylation refers almost exclusively to the introduction of the TMS group into a molecule to prepare derivatives for analysis. By such a technique, compIex organic molecules may be converted into stable derivatives which can be easily identified by conventional methods. Volatility of the T M S derivatives is increased, and hydrogen bonding is eliminated. The silylation of even polyhydroxy compounds, such as sugars, allows their analysis by gas-liquid chromatography (glc). This technique was first described in detail in the classic paper by Sweeley and coworkers (1963). This article describes the silylation and analysis of over one hundred compounds including mono- and oligosaccharides, glycosides, deovy sugars, ketoses, amino sugars, and lactams. Since this first major effort, many others have contributed to advances in this field. Noteworthy is the contribution by Vanden Heuvel and associates (1962) concerning the silylation of phenolic and hydroxy steroids a s well as 17ketosteroids and estrogens. The most important single compilation of methods, materials, and data regarding the analytical aspect of trimethylsilylation was the publication by Pierce (1968). H e documented the glc analysis of alcohols, amines, and acids, as well as the more complex steroids, catecholamines, carbohydrates, and many others. For details on techniques used for analytical silylation, see Pierce (1968). For this type of analytical silylation, specific reagents have been developed for the rapid, selective replacement of certain functional, active hydrogen groups. Materials such as those shown below have found utility for this application. CHIC [OSi (CH&]=NSi (CH3) (CH3)3SiN ( C H Z C H ~ Z N,O-bis(trimethylsily1)acetamide Trimethylsilyldiethylamine CH,SiNCH=NCH=CH Trimethylsilylimidazole The cost of these materials, however, has somewhat limited their utility to analytical work rather than commercial silylation. Ind. Eng. Chem. Prod. Res. Develop., Vol. 1 1, No. 2, 1972
135
Table 111. Dipole Moments I n Debye units at 25OC, see McClellan (1963) X=
-0Me
HX Me3SiX
-NMel
1.63 1.19
1.47 0.33
silylation, and the above reaction may then be performed in this solvent. I n peptide synthesis, trimethylsilylation has been employed as a blocking agent for the hydroxyl, sulfhydryl, and carboxyl groups in amino acids such as cysteine and serine. HOCHzCHCOOH NHz
+ 1.5(Me3Si)2NH+
A I n general, the use of silylation as a n analytical tool provides the research chemist with a method of preparing stable derivatives of organic materials which contain active hydrogen. I n commercial chemical synthesis, silylation may be viewed as a means of achieving many other desired results in addition to increased stability. The following points should be considered as major advantages \+-hen considering the properties of organic materials prepared via the silylation process: Blocked reactive sites Altered solubility Reduced hydrogen bonding Increased stability Ready removal of the silyl group Many examples of each of these points may be cited, and indeed in most cases, more than one of these advantages are simultaneously apparent. For example, silylation of a n unstable material containing an active hydrogen will improve its stability. If excessive hydrogen bonding imparts undesirable properties to a chemical system, silylation will reduce or eliminate this problem by capping or blocking the hydroxyl groups. If solubility or wetting of a species is impaired because of hydrophilicity of the material, silylation will chemically modify the material to become organic in nature. The following examples taken from the published literature are illustrative of the utility of the silylation technique. Silylation as Blocking Agent for Reactive Sites
The direct synthesis of cyclic ureas from a,w-diamines is a n excellent example of silylation as a useful means of partially blockiiig reactive sites of an organic molecule to perform a chemical synthesis not readily accomplished by other means. Birkhofer et al. (1960) has shown that when trimethyl silyl derivatives of certain a,w-diamines are prepared, ring closure may be readily effected by means of phosgene or even carbon dioxide.
yH2 (CH21n
2 M+CI lor lMe+I)2NH)
NHSMs3 I ICHzI, I NHSMa3
?ME3 C0Cl2
y
/N W ) .
'
y
c.0
Me3SiOCH2CHCOOSiMe3 S H S i Me3 B Silyl esters such as B are more conveniently employed in peptide synthesis than the corresponding alkyl esters. Numerous methods have been cited (Birkhofer and Ritter, 1965) for converting amino acid derivatives such as B into peptides. I n addition, Schoenwaldt (1969) has disclosed a method for the synthesis of heteropeptides and proteins employing trimethylsilylated N-carboxyanhydrides of hydroxylated a-amino acids. Here, the hydroxyl group of the anhydride is effectively blocked by silylation, and the resulting product coupIed with a n amino acid to give specific peptide linkages not readily accessible by conventional methods. For example, phenylalanine and O-trimethyl-silyl-L\r-carboxy serine anhydride gave upon hydrolysis serylphenylalanine. 0
PHENYLALANINE
'C'
8
O-TRIMETHYLSILYL-NCARBOXY SERINE ANHYDRIDE
Other techniques for preparing similar materials are not only more complex but produce lower yields owing to unavoidable side reactions. The synthesis of 1,2,3-triazoles from acetylenes and hydrazoic acid is well known (Hartzel and Benson, 1954). However, the difficulties in handling and storage of HKa make this a n undesirable reagent in most cases. Hydrazoic acid may be readily silylated with ;\leaSiC1 t o produce trimefhylsilylazide, MeaSiSa, a reagent which can be utilized (Birkhofer et al., 1963) with acetylenes to produce high yields of 1,2,3-triazoles. MeJS'N3
t
PhCsCH+Me3S,N-N
t i
%
*/
HC
HN-N
i
i
Hc*
PA
+
lMa3Sd20
/
PI:
SMe3
Alcoholysis of the final product results in quantitative removal of the TlIS groups. Overall yields of 60 and 75y0 for n being two and three, respectively, are reported. I n a similar fashion 4,5-diaminouracil map be converted to uric acid with such a mild reagent as carbon dioxide in 87% yield.
I n this case the substitution of the TMS group for hydrogen in HNa imparts a degree of stability to the otherwise unstable HYS but also acts as a blocking agent allowing the direct synthesis of the triazole. Silylation for Altering Solubility
Polar groups such as -OH,
-SH,
-S"2,
-CONH?, or
-C02H limit the solubility of many organic compounds in
SMa3
This reaction also illustrates the solubility changes that occur upon silylation. The 4,B-diaminouracil, normally insoluble in hydrocarbons, can be dissolved in toluene after 136 Ind. Eng. Chem. Prod. Res. Develop., Vol. 11, No. 2, 1972
nonpolar solvents. On the other hand, silanes and silicones possess excellent solubility characteristics in both aliphatic and aromatic hydrocarbons, chlorinated solvents, and ethers. Consequently, the silylation process greatly improves the solubility of many organic materials by conversion of the polar -XH of the above groupings to the less polar -XSiMe3. Table I11 lists the dipole moments of a n alcohol and an amine,
as well as the TMS derivative. Note the decrease of polarity in both cases for the silylated analog. The silylation of cellulose and cellulosic materials by conventional means provides products with interesting and unusual properties. Trimethylsilylated cellulose (Klebe and Finkbeiner, 1969) is soluble in aliphatic, aromatic, and chlorinated solvents and may be used as a coating to provide hydrophobic surfaces. CHIOH
CHzOLMe3
I
No. of carbon atoms
1 2 3 4
5
I
CH-0
CH-0
Table IV. Boiling Points of Alcohols and Acids Minus Trimethylsilylated Derivative, "C
6
7 *n-
*I.
8
"
I..
L
JCYCLIC
ACYCLIC
The changes in solubility of silylated compounds may also be used to advantage in the medicinal field. For example, lincomycin has a low solubility in chlorinated solvents, ethers, and the vegetable oils used as carriers for the antimicrobial treatment of fabric, paper, and animal feeds. Silylation (Houtman, 1968) allows one to four T M S groups to be introduced. Me
M4 H~OH
I
P r - h
:-;!CH
y' M~JS,CI/R~N
HO LINCOMYCIN
k0\,
(Me3S1)2NH
'
qwo
N prfi
I?"
HCOSMe3 O H 1
LN-CH
M . 3 d - O \ I
The example above s h o w the incorporation of three T h l S groups into lincomycin. These products are soluble in such oils and solvents as are necessary for the administration of this antimicrobial. More important, t h e silylated lincomycin, although stable in basic solutions, is said to release its antimicrobial activity slo~vlyin the presence of a n acidic medium. Thus, controlled release of the active species is accomplished by silylation. I n a n analogous fashion chloramphenicol has been partially or completely silylated without impairing its activity as an antibacterial agent. The silylated materials (Houtman, 1969) do not possess the bitterness normally associated with chloramphenicol but are soluble and may be administered either as solutions in vegetable oils or as stable aqueous suspensions. Chloramphenicol is not sufficiently soluble in such oils as to be admiiiistered in this fashion. CH20H
CHLORAMPHENICOL
Primary acids
7 4
-7 3 -8 - 15 - 14 - 17
28 42 22 .. 10 ..
11
16 19 24 23 23
I .
Cyclic dextrins (Shardinger resins) , often used as chemical entrapping agents, have one serious drawback: their water solubility destroys their utility in removing materials from liquid or gas streams containing significant amounts of water. Silylation of these soluble dextrins (Buckler et al., 1969) produces a material which retains its aroma aiid chemical trapping ability but with far less sensitivity to moisture.
L
a,w-diols
dLMs3
/
AH
Primary alcohols
CHz0LMe3
S,Me3
The silylation of many pharmaceuticals such as lincomycin and chloramphenicol is becoming of increasing importance. Silylation here is used to permanently modify the nature of many medicinals. This type of application for silylation differs from the silylation which is used to temporarily block reactive protons and modify solubility. I n other words, silyla-
tion may be viewed as a process aid to accomplish some desirable means and later be quantitatively removed. If the removal of the T h l S or DMS group can be controlled as in these drug modifications, new and previously unavailable properties may be achieved. The unique properties of such silylated drugs would indicate t h a t this area of silylation holds a good deal of future potential both in pharmaceuticals and in the general chemical process industry. For example, the bitter taste associated with erythromycin is eliminated by silylation (Speier, 1956) without impairing its antimicrobial action. Silylated steroids such as testosterone and progesterone (Cereghetti et al., 1971) are claimed to have a sustained and delayed hormonal activity in the body. Silylated heparin (Speier, 1956) prevents blood from clotting for a substantially longer period of time than the nonsilylated sodium salt of heparin normally used for this treatment. Silylation for Reducing Hydrogen Bonding
The concept of reduced hydrogen bonding can best be shown by the changes in solubility and stability in silylated compounds when compared to the nonsilylated materials. Some of these examples have already been discussed. It is appropriate, however, to review the effect of silylation on the volatility of mono- and polyhydroxy compounds. Thus, although the replacement of a T M S group for a n active hydrogen adds a significant amount of weight to a molecule (73.2 gjmol of active hydrogen replaced), the boiling points of such molecules are generally reduced. Table IV shows the difference in boiling points of a series of alcohols and acids compared to the TMS derivative. For the primary alcohols, trimethylsilylatiori reduces the boiling point only slightly for the lower members and increases it beyond % butanol. Silylation does impart a significant reduction in the boiling points of diols and acids. The negative values indicate a greater boiling point for the derivatives than the parent compound. Even more striking are the boiling points of the polyols such as glycerine and pentaerythritol, which when trimethylsilylated, are dropped 60' and 112'C, respectively (Pierce, 1968). Increased Stability b y Silylation
The increased stability imparted to many sugars and other polyhydroxy compounds by trimethylsilylation has already been shown by the fact t h a t these derivatives may be analyzed by gas chromatography. The silyl esters are able t o survive the volatilization necessary without loss through decomposition. Another example of such stability was also mentioned earlier in the use of trimethylsilylazide, l\lesSir\'a (Birkhofer and Ritter, 1960) which can be distilled a t atmospheric pressure without decomposltion, bp 95'C. Ind. Eng. Chem. Prod. Res. Develop., Vol. 1 1, No. 2, 1972
137
Although increased thermal stability is enhanced by silylation for most compounds, the effect is particularly noteworthy in the case of the T M S derivatives of hydroperoxides. Buncel and Davies (1956) have shown that the silylation of twt-butylhydroperoxides provides a product with improved thermal stability. The TMS derivative was significantly more stable than the carbon analog (Hiatt, 1964). Me3SiOOCMe3 t1/22030 N 1 h r
-
Me3COOCMe3 tl/21470 1 hr
The silyl derivatives of hydroperoxides maintain their utility as free radical sources since they initiate the polymerization of styrene and methyl methacrylate (Buncel and Davies, 1958). Removal of Silyl Groups
I n the first step, any 6-acyl aminopenicillanic acid may be used with a trimethyl or dimethyl silylating agent and an acid acceptor in those cases where chlorosilanes are used. Phosphorus pentachloride is then added a t -4OOC or lower to form the imino halide. While keeping this intermediate a t this low temperature, an alcohol is introduced to convert the halide to a n imino ether. The final step is to add water and adjust the p H to about 4. The 6-APA in a high degree of purity (96-99%) readily precipitates in an overall yield of greater than 90%. The other process in which silylation performs an important function is the synthesis of useful penicillins from 6-APA. As early as 1961, patent activity began (Chemi Grunenthal, 1965) in Germany in which the silylation of 6-APA was cited as a key step in the preparation of semisynthetic penicillins. Schematically, this route can be shown as:
Because of the reversible nature of bonds between silicon and Group V and V I elements, the TMS and DMS groups may be readily and quantitatively removed by the addition of water or simple alcohols. These materials desilylate organic compounds to form siloxanes or alkoxysilanes, allowing the organic compounds, free of silicon, to be isolated in some suitable fashion.
t SILYLATING AGENT
y,”” 4 R3N MONO
OR OlSlLYLATED S A P A
1
ACYLATING AGENT X I!#,
04&YLISILVLATEOI AMlNOPENlClLLANlC ACID
Other Important Uses for Silylation
Silylation has found wide utility in the commercial synthesis of penicillins. The blocking effect of trimethylsilyl and dimethylsilyl groups on 6-aminopenicillanic acid (6APA) has played
c-on
0
d
Numerous patents in this area quickly followed, covering many variations of this synthesis. Kotable among the researchers who contributed to this effort were Sjoeberg and Ekstrom (1966) a t Beecham Laboratories and Robinson and Nescio (1969) a t Wyeth. Of particular interest was the synthesis of ampicillin by this route:
n2Nlzq4“ 0e
a
SAPA
an important role in a t least two aspects of the total synthetic production of “semisynthetic” penicillins. The first of these (Weissenburger and van der Hoeven, 1970) relates to the synthesis of 6-APA in greater than 90% yields from naturally occurring penicillins. The second employs 6-APA as a starting material for the preparation of numerous penicillin derivatives (Herrling and Mueckter, 1966), many of which are not possible by other synthetic or natural methods. I n the preparation of 6-XPA, the following sequential reactions are performed:
H2Nr12 e
E-OH 0
+
me$jcl
CH2C12
a2
M.*:
Me1NPh Et3N
’
rwe3
0
I PhCH C-CI
AMPICILLIN
SILYLATED AMPICILLIN
Several key points typified in this synthesis are worthy of note. Firstly, the silylated 6-APA may be conveniently handled in many organic solvents, whereas the unmodified 6-4PA may be used only in water or solvents containing water. As a consequence, the acylating agents are a t least partially destroyed in the aqueous system before any acylation occurs. By the utilization of the silylated 6-APA, chlorinated solvents, hydrocarbons and ethers may be used which do not interact with the acylating agents. Secondly, the silyl groups are readily removed in the final step, allowing the penicillin to be recovered in high yields. If the silylated ampicillin intermediate is treated sequentially with an anhydrous alcohol, a tertiary amine, and an aqueous alcohol, crystalline anhydrous ampicillin is obtained in good yields and in a high degree of purity (Adams, 1969). Conventional techniques of isolating ampicillin from ampicillin trihydrate are tedious (-4lburn and Grant, 1967) and result in reduced yields. The anhydrous form of ampicillin is claimed to have better storage stability, slower absorption 138 Ind. Eng. Chem. Prod. Res. Develop., Vol. 1 1 , No. 2, 1972
into the body, and a prolonged blood level than the hydrated form. I n a fashion analogous to t h e above two processes for penicillins, the same silylation techniques have proved useful in the production of cephalosporins. Both the synthesis (Bickel et al., 1970) of 7-amino-cephalosporonic acid (7--4CA) and the preparation of the 7-acyl derivatives by use of 7-ACA as a starting material (Ekstrom and Sjoeberg, 1970) have utilized silylation as a key step in t h e overall synthesis.
“‘“a7 P
CHZOCCHQ
I
HOIC*O
?-ACA
I n essence, t h e preparation of 7-ACA parallels t h e earlier route outlined for 6-APX. A silyl ester of a naturally occurring 7-acylaminocephalosporin is treated with PC1s and a n alcohol. The resulting imino ether is then hydrolyzed under acidic conditions causing cleavage of the imine as well as the silyl ester. 7-ACX is recovered in high yield and purity. The 7-ACA may also be acylated a t the 7 position after first preparing t h e mono- or disilyl ester of 7-ACA in a manner identical to the synthesis of ampicillin. The utility of silylation as a cost savings might well be inferred from some of the earlier examples. A specific case of this has been shown by Gauri (1969) in the synthesis of a n antiviral uracil derivative from a uracil and deoxyribose. I n conventional synthesis the molar ratio of the uracil to t h e deoxyribose must be 1: 2. Trimethylsilylation of the starting uracil allows equimolar amounts of these two materials t o be successfully employed. Summary
Silylation is a useful means of accomplishing many chemical modifications of organic materials. Silylation is a means of achieving either permanent modification of a molecule or, in a temporary sense, as a process aid t o provide some useful property. KO attempt has been made in this article t o exhaustively review t h e literature but rather to illustrate specific examples of t h e utility of silylation chemistry.
literature Cited
Adam?, -4.C., U S . Patent 3,479,338 (1969). Auburn, H. E., Grant, K. H., U.S.Patent 3,299,046 (1967). Bickel, H., Fechtig, B., Bosshardt, G., Sheller, J., Peter, H., Canadian Patent 851,183 (1970). Birkhofer, L., Ritter, A., Angew. Chem., Int. Ed., 4 ( 5 ) , 417 (1965). Birkhofer, L., Ritter, A.,Chem. Ber., 93,424 (1960). Birkhofer, L., Ritter, A,, Kuehlthau, H., ibid., 2810 (1960). Birkhofer, L., Ritter, A., Uhlenbrauck, H., ibzd., 96, 2750, 3280 (1963). Buckler, S. A., Martel, R. F., Moshy, R. J., U.S. Patent 3,472,835 (1969). Buncel, E., Davies, A. G., Chem. Ind., 1052 (1956). Buncel, E., Davies, A. G., J . Chem. Soc., 1958,p 1550. Cereghetti, AI., Furst, A,, Vecchi, RI., Vetter, W., U.S. Patent 3,560,532 (1971). Chemi Grunenthal GmbH, British Patent 1,008,468 (1965). Eaborn, C., “Organosilicon Compounds,” Butterworths, London, England, 1960. Ekstrom, B. A., Sjoeberg, B. O., German Patent 1,445,434 (1970). Gauri, K . K., British Patent 1,170,565 (1969). Hartzel, L. W., Benson, F. R., J . Amer. Chem. Soc., 76, 667 119543. Herding, S., Mueckter, H., Canadian Patent 733,104 (1966). Hiatt, R. R., Can. J . Chem., 42, 985 (1964). Houtman, R. L., U.S. Patent 3,418,414 (1968). Houtman, R. L., U.S. Patent 3,442,926 (1969). Klebe, J. F., Finkbeiner, H. L., J . Polym. Sci., A-1 (i),1947 (1969). Langer,’S. H., Connell, S., Wender, I., J . Org. Chem., 23, 50 (1958). McClellan, W., “Tables of Experimental Dipole lIoments,” W.H. Freeman and Co., San Francisco, CB, 1963: Cumper, C., J . Chem. Soc., 1966, p 246; Kokoreva, I., Zh. Strukt. Khtm., 8, 1102 (1967). Pierce, A. E., “Silylation of Organic Compounds,” Pierce Chemical Co.. Rockford. IL. 1968. Pluedderffann, E . P., ’“Kirk-Othmar Encyclopedia of Chem. Tech., 2nd ed., Vol 18, 1969, p 260. Robinson, C. A., Nescio, J. J., U.S. Patent 3,478,018 (1969). Schoenwaldt, E. F., U.S. Patent 3.435.046 11969). Sjoebera, B. 0..Ekstrom. B. A.. Canadian‘Patent 726.717 (1966). Sommec L. H., “Stereochemistry, Mechanism and Silicon:” RIcGraw-Hill, New York, NY, 1965. Speier, J. L., C.S. Patent 2,746,956 (1956). Sweeley, C. C., Bentley, R., Makita, AI., Wells, W. W., J . Amer. Chem. Soc., 85, 2497-(1963). Vanden Heuvel, W. J. A., Creech, B. G., Homing, E. C., Anal. Biochem.. 4. 191 11962). Weissenburger, H. W. O., van der Hoeven, 31. G., Recueil, 89, 1081 (1970). RECEIVED for review August 23, 1971 ACCEPTED March 20, 1972
Ind. Eng. Chem. Prod. Res. Develop., Vol. 1 1, No. 2, 1972
139
