Deprotection reaction

Acid-C t lyzed Chemistry. Acid-catalyzed reactions form the basis for essentially all chemically amplified resist systems for microlithography appHcations (61). These reactions can be generally classified as either cross-linking (photopolymerization) or deprotection reactions. The latter are used to unmask acidic functionality such as phenohc or pendent carboxyhc acid groups, and thus lend themselves to positive tone resist apphcations. Acid-catalyzed polymer cross-linking and photopolymerization reactions, on the other hand, find appHcation in negative tone resist systems. Representative examples of each type of chemistry are Hsted below. 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The removal of carbobenzyloxy (Cbz or Z) groups from amines or alcohols is of high interest in the fine chemicals, agricultural and pharmaceutical industry. Palladium on activated carbon is the catalyst of choice for these deprotection reactions. Nitrogen containing modifiers are known to influence the selectivity for certain deprotection reactions. In this paper we show the rate accelerating effect of certain N-containing modifiers on the deprotection of carbobenzyloxy protected amino acids in the presence of palladium on activated carbon catalysts. The experiments show that certain modifiers like pyridine and ethylenediamine increase the reaction rate and therefore shorten the reaction times compared to non-modified palladium catalysts. Triethylamine does not have an influence on the rate of deprotection. 

Macke recently introduced a monoreactive DOTA prochelator (4,7,10-tricarboxymethyl-tert-butyl ester A, A, A", A "-tetraazacyclododecane-1 -acetate), which was coupled to Tyr3—Lys5 (BOQ-octreotide via solid-phase peptide synthesis. A one-step deprotection reaction generated the bioactive compound DOTATOC in about 65% yield.142 The 90Y and 177Lu DOTATOC complexes have shown promise for the treatment of neuroendocrine tumors in early clinical trials.143,444... 

With respect to application of MS to deprotection reactions, Mizuno et al.105 observed an unexpected O-acetyl cleavage in a building block of an N-glycopeptide by simple treatment with absolute methanol that had been stored over 3 A MS. When acetates from other sugars were submitted to the same conditions, similar results were obtained, whereas no O-acetyl cleavage was observed when using absolute methanol that had not been dried over 3 A MS. This deacetylation was evidently promoted by a... 

The protection-deprotection reaction sequences constitute an integral part of organic syntheses such as the preparation of monomers, fine chemicals, and reaction intermediates or precursors for pharmaceuticals. These reactions often involve the use of acidic, basic or hazardous reagents and toxic metal salts [30], The solvent-free MW-accelerated protection/deprotection of functional groups, developed during the last decade, provides an attractive alternative to the conventional cleavage reactions. 

A brief exposure of diacetate derivatives of aromatic aldehydes to MW irradiation on neutral alumina surface rapidly regenerates aldehydes (Scheme 6.5) [36], The selectivity in these deprotection reactions is achievable by merely adjusting the time of irradiation. As an example, for molecules bearing acetoxy functionality (R = OAc), the aldehyde diacetate is selectively removed in 30 s, whereas an extended period of 2 min is required to cleave both the diacetate and ester groups. The yields obtained are better than those possible by conventional heating methods and the procedure is applicable to compounds bearing olefmic moieties such as cinnamaldehyde diacetate [36],... 

Scheme 4 A La3 +-catalyzed deprotection reaction of 6-exo-acetoxybicyclo[2.2.2]octan-2-one, where the mild nature of the transesterification conditions does not promote rearrangement of the product (ref. 44).

Depressurization of an expanded liquid organic solution (DELOS), 24 17, 18 Depropanizer, 10 614, 615 Deprotection reactions, 15 168-169, 170, 172, 173, 183 Deprotonation, 15 654 alkylborane, 13 660 Depth filters, 15 827, 828 Depth filtration, in protein separation, 12 136... 

The chemically amplified resists reported here for deep-UV applications require a post-exposure thermal treatment process step to effect the deprotection reaction. This step has proven to be critical, and in order to understand the processing considerations it is instructive to discuss, qualitatively, the various primary and secondary reactions that occur with these systems during both exposure and PEB, ie ... 

The AG molecule is converted to a strong acid (AH) upon absorption of a photon and the rate of this reaction is fast, with the extent of reaction being governed by the quantum effeciency of the particular acid generator and flux. The acid proton affects the desired deprotection reaction (4) with a finite rate constant. This rate is a function of the acid concentration, [H4-], the temperature and most importantly, the diffusion rate of the acid in the polymer matrix. The diffusion rate in turn, depends on the temperature and the polarity of the polymer matirx. At room temperature, the rate of this reaction is typically slow and it is generally necessary to heat the film to well above room temperature to increase reaction rates and/or diffusion to acceptable levels. The acid (H+) is regenerated (reaction 4) and continues to be available for subsequent reaction, hence the amplification nature of the system. 

The rate and extent of the deprotection reaction (4) is critically dependent on the acid concentration, [H+], Side reactions (2 and 3) reduce the effective acid concentration and must be controlled. All of these reactions are thermally activated, however they do occur at a finite rate at room temperature. In order to assure a constant total extent of deprotection (reaction 4) it is necessary to control the elapsed time between exposure and PEB. 

The PEB temperature and temperature uniformity must be tightly controlled for the same reasons discussed above. It has been found that it is feasible to drive the deprotection reaction in t-butoxycarbonyl protected systems to completion, providing the side reactions are minimized or controlled. This is a necessary requirement for satisfactory lithographic performance. 

The precise structure subset, dendrimers are prepared using iterative protection-condensation-deprotection reaction cycles. These reiterative cycles incorporate ABn monomers (i.e. branch cell units) into structural domains referred to as dendrons. Assembly of these dendrons can proceed in a divergent [1] (core... 

An automated H-Cube platform was designed, constructed and validated by Clapham et al. [26], to perform deprotection reactions and produce compound libraries. This special instrument includes 48 starting material vials for automated injection into the flow reactor. In producing the Cbz deprotected library, complete conversions and a 93% average crude yield were obtained over Pd/C catalyst at 60°C using full hydrogen mode. For the second library, 4-benzyloxy benzoic acid was coupled with a series of amides. The deprotection performed in H-Cube resulted in eomplete conversions to the products and 88% average crude yield. 

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