16808-41-6

Usage

Molecular class

Isoindoline-1,3-dione compounds

Structural feature

Contains an adamantane group

Known for

Diverse range of pharmaceutical and biological activities

Importance in drug design

Adds steric and conformational properties

Potential for further research

Synthesis and potential applications in medicinal chemistry

InChI:InChI=1/C18H19NO2/c20-16-14-3-1-2-4-15(14)17(21)19(16)18-8-11-5-12(9-18)7-13(6-11)10-18/h1-4,11-13H,5-10H2

Upstream product

• 85-44-9 phthalic anhydride 
• 768-94-5 1-Adamantanamine 
• 136918-14-4 phthalimide 
• 768-95-6 1-adamanthanol 
• 930-68-7 cyclohexenone 
• 1333108-05-6 3-(N-phthalimido)-1-adamantane carboxylic acid 
• 106-95-6 allyl bromide 
• 292638-85-8 acrylic acid methyl ester 
• 6240-10-4 3-amino-1-adamantanecarboxylic acid 
• 25995-06-6 ethyl 2-oxoadamantane-1-carboxylate 
• 1064664-26-1 ethyl 2-cyanotricyclo[3.3.1.1^3,7]decane-1-carboxylate 
• 1581695-79-5 2-cyanotricyclo[3.3.1.1^3,7]decane-1-carboxylic acid 
• 107-13-1 acrylonitrile 
• 6221-58-5 bicyclo[3.3.1]nonane-3,7-dicarboxylic acid 

Relevant academic research and scientific papers

Tumor necrosis factor-alpha production-regulating activity of phthalimide derivatives in genetically modified murine melanoma cells B78H1

The effect of imides, monothioimides, trimellitimides, as well as 5′-deoxy-5′-phthaloylamino-derivatives of azidothymidine on tumor necrosis factor-alpha (TNF-α) production by genetically modified murine B78H1 melanoma cells transduced with the gene for human TNF-α (B78/TNF) was investigated. It was found that N-(adamant-1-yl)monothiophthalimide (1e) and N-(adamant-2-yl)-monothiophthalimide (1f) showed over 200% enhancing of TNF-α production while some of imides were inhibitors.

Photophysical properties and electron transfer photochemical reactivity of substituted phthalimides

The photochemical reactivity and photophysical and electrochemical properties of a series of N-adamantylphthalimides bearing carboxylic functional groups were investigated. Upon irradiation (with or without a triplet sensitizer), the compounds undergo decarboxylation via photoinduced electron transfer (PET) from the carboxylate to the phthalimide. UV-vis and fluorescence pH titrations were used to determine pKa values for the prototropic forms, which were put in connection with the quantum yields of the reaction (ΦR). The compounds bearing electron donors OH and OCH3 at the phthalimide 4 position are fluorescent (ΦF = 0.02-0.49) and PET takes place from both singlet and triplet excited states. The estimated rate constants for PET in the singlet excited states for the methoxy- A nd amino-substituted phthalimides are (2.0 ± 0.1) × 109 s-1 and (3.4 ± 1.0) × 107 s-1, respectively. Laser flash photolysis (LFP) was conducted to characterize the triplet excited states, which are populated less efficiently for compounds with electron donors. The PET is reversible and the overall ΦR depends on the rates for back electron transfer, protonation of the phthalimide radical anion and decarboxylation. The plausible photochemical and photophysical pathways depend on the phthalimide substituents, which is important for the use of phthalimide derivatives in organic synthesis and photocatalysis. This journal is

Cyclic (Aryl)(Amido)Carbenes: NHCs with Triplet-like Reactivity

The synthesis and study of a library of cyclic (aryl)(amido)carbenes (CArAmCs), which represent a class of electrophilic NHCs that feature low calculated singlet-triplet gaps (ΔEST=19.9 kcal mol?1; B3LYP/def2-TZVP) and exhibit reactivity profiles expected from triplet carbenes, are described. The electrophilic properties of the CArAmCs were quantified by analyzing their respective selenium adducts, which exhibited the largest downfield 77Se NMR chemical shifts (up to 1645 ppm) measured for any NHC derivative known to date, as well as their Ir carbonyl complexes, from which large Tolman electronic parameter (TEP) values (up to 2064 cm?1) were ascertained. The CArAmCs were found to engage in reactions that are typically observed with triplet carbenes, including C?H insertions, [2+1] cycloadditions with alkenes as well as alkynes, and spontaneous oxidation upon exposure to oxygen.

Alkylphosphinites as Synthons for Stabilized Carbocations

We present a new acid-free method for the generation of carbocations based on a redox condensation reaction that enables SN1 reactions with a variety of nucleophiles. We utilize readily synthesized phosphinites that are activated by diisopropyl azodicarboxylate to form betaine structures that collapse upon adding a pronucleophile, thereby yielding reactive carbocation intermediates. We also employ this approach for the alkylation of some bioactive molecules.

The effect of the rate of photoinduced electron transfer on the photodecarboxylation efficiency in phthalimide photochemistry

Reactivity in photoinduced electron transfer reactions (PET) has been investigated in a series of molecules possessing different distances between the electron donor (carboxylate or alkoxyphenyl) and the phthalimide as the electron acceptor. The molecules

NEW CRBN MODULATORS

Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by dysregulated or dysfunctional protein activity that can be targeted by cereblon.

Unmasking Amides: Ruthenium-Catalyzed Protodecarbonylation of N-Substituted Phthalimide Derivatives

The unprecedented transformation of a wide range of synthetically appealing phthalimides into amides in a single-step operation has been achieved in high yields and short reaction times using a ruthenium catalyst. Mechanistic studies revealed a unique, homogeneous pathway involving five-membered ring opening and CO2 release with water being the source of protons.

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

Adamantane α-, β-, and δ-amino acids activated by phthalimide (i.e., 3–6) were synthesized, and their photochemical reactivities were investigated. Amino acid derivatives 3–6 underwent a photoinduced electron transfer (PET) and decarboxylation reaction sequence, most probably through a triplet excited state. The decarboxylations of the β-amino acid derivatives were succeeded by cyclization reactions that afforded complex polycyclic molecules with potential biological interest. The adamantyl radical that is produced by the photoinduced decarboxylation could be trapped by alkenes or oxygen to deliver adducts or alcohols, respectively. The photodecarboxylation process was shown to be more efficient under acetone sensitization conditions (with quantum yields, Φ = 0.02–0.5) than upon direct excitation, and the reactivity was dependent on the chain length (intramolecular distance) between the electron donor (carboxylate) and acceptor (phthalimide in the triplet excited state) of the derivative. The formation of different radicals, that is, the 1- or 2-adamantyl intermediate, probably does not affect the overall rate of the decarboxylation This current report provides a better understanding of photodecarboxylation and the rational design of molecular systems to undergo photoinduced decarboxylation and cyclization reactions.

Silver-mediated oxidative aliphatic C-H trifluoromethylthiolation

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic C-H bonds employs a silver-based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional-group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural-product derivatives.

Photoinduced decarboxylation of 3-(N-phthalimido)adamantane-1-carboxylic acid and radical addition to electron deficient alkenes

Direct and sensitized excitation of 3-(N-phthalimido)adamantane-1- carboxylic acid (1) leads to the population of the triplet state that, in the presence of a base, decarboxylates, giving N-(1-adamantyl)phthalimide (2) cleanly and efficiently (Φ = 0.11). The radical initially formed by decarboxylation adds regiospecifically to electron deficient alkenes, whereas radical addition was not observed for electron rich alkenes. The radical addition can also be applied to molecules not bearing adamantanes wherein the electron donor (carboxylate) and the acceptor (phthalimide) are separated by a rigid spacer. The photodecarboxylation induced radical addition of phthalimide derivative 1 to alkenes takes place in good to excellent yields and represents a mild and efficient method for C-C bond formation. The Royal Society of Chemistry and Owner Societies 2011.