HONB | N-Hydroxynorbornene Dicarboximide | CAS 21715-90-2 | ≥98%

HOBN / HONB (N-hydroxy-5-norbornene-2,3-dicarboximide) is a non-benzotriazole N-hydroxyimide coupling additive used with carbodiimide reagents such as DCC, DIC, and EDC for amide and peptide bond formation. The compound is structurally unrelated to HOBt: it contains no benzotriazole ring and is built instead on a rigid bicyclic norbornene-dicarboximide scaffold. In carbodiimide activation, HOBN forms N-hydroxy-norbornene-dicarboximide active esters that undergo aminolysis with low racemisation while suppressing N-acylurea formation. Its active esters are unusually resistant to hydrolysis for N-hydroxyimide esters, enabling peptide-forming reactions that can tolerate aqueous media, while liberated HOBN is sufficiently soluble in water and common organic solvents to simplify removal during work-up.

Racemisation suppression in carbodiimide couplings

In carbodiimide activation, an N-protected amino acid or peptide first forms an O-acylisourea intermediate, which can undergo side reactions including oxazolone formation and O→N acyl migration. HOBN diverts this intermediate into the corresponding N-hydroxy-norbornene-dicarboximide active ester, reducing racemisation during subsequent amine coupling. Racemisation-test studies show that HOBN markedly lowers racemisation while delivering peptides in high yield and purity.

Inhibition of N-acylurea formation

A major loss pathway in carbodiimide couplings is irreversible O→N acyl migration of the O-acylisourea to the unreactive N-acylurea, a dead-end by-product that consumes both the activated acid and the carbodiimide. HOBN diverts the O-acylisourea into the corresponding active ester before significant O→N acyl migration can occur, increasing the fraction of activated acid that proceeds to productive amide formation. The effect matters most in fragment condensation and longer coupling sequences, where small per-cycle losses compound across many steps.

Non-benzotriazole alternative to HOBt

Benzotriazole additives such as HOBt can carry explosive-classification and transport constraints, particularly for anhydrous or inadequately desensitised material. HOBN provides a non-benzotriazole active-ester route for carbodiimide coupling: its norbornene-dicarboximide framework lacks the benzotriazole motif associated with HOBt’s energetic handling profile while retaining the racemisation-control and active-ester benefits expected from auxiliary N-hydroxyimide additives.

Resistance to Lossen rearrangement

N-hydroxysuccinimide-derived activation chemistry can suffer from Lossen-rearrangement side reactions that generate β-alanine-derived by-products. HOBN rarely undergoes this side reaction because its rigid bicyclic framework disfavours the geometry required for the rearrangement, reducing a side-reaction pathway associated with HOSu/DCC activation chemistry.

Peptide fragment condensation and stereochemically sensitive coupling

HOBN/carbodiimide protocols have been applied to stepwise elongation and fragment condensation of stereochemically sensitive peptide targets, where high coupling efficiency and low racemisation are required. The combination of hydrolysis-resistant active-ester formation, racemisation suppression, N-acylurea control, and non-benzotriazole structure suits HOBN to research-scale peptide synthesis, fragment condensation, and larger-scale coupling work where benzotriazole additives are undesirable.