Sensitive substrates

Sihcone polymer plasticizers have historically been used in many formulations. These plasticizers (qv) are of the same Si—O backbone as the functional polymers but generally are terrninated with trimethyl groups which are unreactive to the cure system. This nonreactivity means that, if improperly used, the plasticizer can migrate from the sealant and stain certain substrates. Staining has been a widely pubHcized flaw of sihcone sealants, but the potential of a formulation to stain a substrate can be minimized or eliminated with proper formulation work. In general, this is accompHshed by not using plasticizers for formulations developed for stain-sensitive substrates. 

Initiation. Free-radical initiators are produced by several processes. The high temperatures and shearing stresses required for compounding, extmsion, and molding of polymeric materials can produce alkyl radicals by homolytic chain cleavage. Oxidatively sensitive substrates can react directly with oxygen, particularly at elevated temperatures, to yield radicals. 

CH3CH(Cl)OEt, PhNMc2, CH2CI2, 0°, 10-60 min. These conditions are effective for extremely acid-sensitive substrates or where conditions 1 and 2 fail. 

The introduction of the BDT group proceeds under these rather neutral conditions, and this may prove advantageous for acid-sensitive substrates. The BDT group can also be reduced with Raney nickel to a methyl group or with Bu3SnH to a 2-[(methylthio)phenylthio]methyl ether (MTPM ether)... 

Bu4N F , THF, 25°, 1 h, >90% yield. Fluoride ion is very basic especially under anhydrous conditions and thus may cause side reactions with base-sensitive substrates. ArOTBDMS ethers can be cleaved in the presence of alkyl OTBDMS ethers. ... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable... 

The TBDMS ester can be converted directly to an acid chloride [DMF, (COCl)2, It, CH2CI2] and then converted to another ester, with different properties, by standard means. This procedure avoids the generation of HCl during the acid chloride formation and is thus suitable for acid-sensitive substrates. ... 

E-beam is a relatively cold process and so is more suitable for heat-sensitive substrates. UV lamps emit about one third UV light and the rest is visible and IR. Consequently substrates can get very hot, even causing fires if they become stuck beneath the lamp. Safety shutters which close if the line stops are installed on many UV bulbs. 

Reactions of alcohols with sulfur tetrafluoride, because of decomposition and/or polymerization, usually do not give fluorinated products However, in the presence of a hydrogen fluoride scavenger like triethylamine or pyridine, even such sensitive substrates as benzylic alcohols [555], 2-phenylethanol, and 2-furylmethanol [554] can be fluorinated to give the expected fluoro derivatives (equation 73)... 

HgCl2, CaCO, MeCN, H2O. The calcium carbonate is used as an acid scavenger for acid-sensitive substrates. 

HF, CH3CN. In certain sensitive substrates it may be advisable to run this reaction in a polypropylene vessel, as was the case in Schreiber s synthesis of FK-506, where the yield increased from 35% to 73% after switching from the standard glass vessel. This is presumably because of the products formed when HF reacts with glass. 

BZOSO2CF3, —78°, CH2CI2, few min. With acid-sensitive substrates, pyridine is used as a cosolvent. This reagent also reacts with ketals, epoxides, and aldehydes. ... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Substituents R, R at the starting oxime 1 can be H, alkyl, or aryl. The reaction conditions for the Beckmann rearrangement often are quite drastic (e.g. concentrated sulfuric acid at 120 °C), which generally limits the scope to less sensitive substrates. The required oxime can be easily prepared from the respective aldehyde or ketone and hydroxylamine. 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

The Wolff rearrangement is a versatile reaction R can be alkyl as well as aryl most functional groups do not interfere. The generally mild reaction conditions permit an application to sensitive substrates. 

The introduction of halogen into organic molecules can be carried out by a variety of addition or substitution reactions. The classical methods for the addition of halogen to double bonds or the substitution of halogen for hydroxyl by hydrohalic acids are too well known to bear repetition here. Discussed below, then, are methods that are of interest because of their stereospecific outcome or because they may be used on sensitive substrates. 

When carbon tetrabromide is used, the alkyl bromide is formed. Providing moisture is excluded from the reaction mixture (HX is formed otherwise), the reaction conditions are completely neutral, affording a convenient preparation of the halides of acid-sensitive substrates (for example, sugars). 

The acid catalyzed hydration of olefins is frequently attended by decomposition or rearrangement of the acid-sensitive substrate. A simple and mild procedure for the Markovnikov hydration of double bonds has recently been devised by Brown and co-workers 13). This reaction, which appears to be remarkably free of rearrangements, initially involves the addition of mercuric acetate to the double bond to give the 1,2-... 

Note. This method is recommended for sensitive substrates that would not tolerate KOH or MeLi, such as enynes. 

Trost published a desulphonylation procedure for aryl alkyl sulphones using an excess of sodium amalgam in buffered ethanol126 (equation 52). Trost claimed that this is superior to earlier reactions using sodium amalgam in ethanol because of a couple of factors the use of the acid phosphate buffer to prevent formation of significant amounts of sodium methoxide is particularly important, since this can cause isomerizations in base-sensitive substrates, and the temperature should be kept low, but optimized for each substrate. 

It minimizes the risk of damaging heat-sensitive substrates since it operates at a relatively low temperature (as low as 300°C in the case of Si02 deposition). 

Not all sensitized photochemical reactions occur by electronic energy transfer. Schenck<77,78) has proposed that many sensitized photoreactions involve a sensitizer-substrate complex. The nature of this interaction could vary from case to case. At one extreme this interaction could involve a-bond formation and at the other extreme involve loose charge transfer or exciton interaction (exciplex formation). The Schenck mechanism for a photosensitized reaction is illustrated by the following hypothetical reaction ... 

BP Hughes, JN Crofts, AM Auld, LC Read, GJ Barritt. (1987). Evidence that a pertussis-toxin-sensitive substrate is involved in the stimulation by epidermal growth factor and vasopressin of plasma-membrane Ca2+ inflow in hepatocytes. Biochem J 248 911-918. 

Cage effects in SDS depend on sensitizer, substrate structure and magnetic field... 

A limitation to the use of the Tebbe reagent 93 was observed during the attempted conversion of substrates 139 and 142 to the tricyclic systems 141 and 144 respectively (Scheme 21). The major products from these reactions were olefinic alcohols 140 and 143. These products presumably resulted from sequential hydrolysis and olefination of the initially formed cyclic enol ethers. The problem associated with these sensitive substrates was overcome through use of the less Lewis-acidic Petasis reagent 110, which provided access to the desired products 141 and 144 [34a]. 

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